Managing alcohol problems and risky drinking.
While overall alcohol consumption and alcohol-related automobile deaths have declined, rates of alcohol dependence, liver cirrhosis, and alcohol-related problems remain high among adults, and binge drinking continues as a major health risk for high school and college students. Some individual-level downstream interventions have been evaluated with sufficient rigor to recommend widespread dissemination, and widened availability of new pharmacotherapies could further increase effectiveness. Midstream population-based programs, such as screening and brief interventions in hospitals and managed care organizations, may have greater public health impact than tertiary treatment because of early identification and low cost. Upstream programs and policies that place limits on alcohol availability (e.g., higher legal purchasing age) have the greatest potential to reduce morbidity and mortality at the least cost to society.


A novel route for F-box protein-mediated ubiquitination links CHIP to glycoprotein quality control.
In SCF (Skp1/Cullin/F-box protein) ubiquitin ligases, substrate specificity is conferred by a diverse array of F-box proteins. Only in fully assembled SCF complexes, it is believed, can substrates bound to F-box proteins become ubiquitinated. Here we show that Fbx2, a brain-enriched F-box protein implicated in the ubiquitination of glycoproteins discarded from the endoplasmic reticulum, binds the co-chaperone/ubiquitin ligase CHIP (C terminus of Hsc-70-interacting protein) through a unique N-terminal PEST domain in Fbx2. CHIP facilitates the ubiquitination and degradation of Fbx2-bound glycoproteins, including unassembled NMDA receptor subunits. These findings indicate that CHIP acts with Fbx2 in a novel ubiquitination pathway that links CHIP to glycoprotein quality control in neurons. In addition, they expand the repertoire of pathways by which F-box proteins can regulate ubiquitination and suggest a new role for PEST domains as a protein interaction motif.


The emerging role of estrogen receptor-β in human reproduction.
Knowledge surrounding estrogen and estrogen receptor biology continues to evolve, and the diversity of their actions and complexity of their mechanisms are becoming increasingly evident. Estrogen receptor (ER) regulation of reproduction is no exception. Although it is well established that estrogen and ERα play key roles in mediating several reproductive biological processes, such as myometrial and endometrial growth, increasing evidence suggests that ERβ is also an important factor. ERβ is a key mediator in folliculogenesis and may also play a role in stimulating ovulation and regulating aspects of luteinization. ERβ is also expressed in higher quantities than ERα in the human myometrium and cervix during pregnancy, and thus it may play a part in the initiation of labor and parturition. Finally, ERβ is the sole ER expressed within the endothelium of the endometrium and the fetoplacental vasculature, and studies suggest that its role may contribute to angiogenic and vasomotor changes that play a role in both implantation and regulation of fetoplacental blood flow.


Plasma membrane calcium fluxes in intact rods are inconsistent with the "calcium hypothesis".
The temporal relationship between the extracellular rod photovoltage and light-induced net Ca fluxes across the rod plasma membrane is investigated. The net Ca flux measurements are derived from extracellular Ca concentration measurements at the receptor surface of the isolated bullfrog retina. As reported previously, illumination leads to a net Ca efflux, which is followed by a net influx, during which the released Ca is taken back up. However, the net Ca flux has two characteristics that are inconsistent with the hypothesis that intracellular free Ca is the intracellular messenger for phototransduction in rods. First, during maintained photovoltage saturation, the net Ca efflux is transient, declining with a stereotypic time course that is independent of stimulus intensity and duration. Second, the significant rate of net influx during Ca uptake has no correlate in the photovoltage waveform. These observations are not consistent with the "Ca hypothesis." Rather, these data corroborate recent findings suggesting that light causes a decrease rather than an increase in intracellular free Ca concentration.


Beyond the aortic bifurcation: branched endovascular grafts for thoracoabdominal and aortoiliac aneurysms.
To evaluate the use of novel technology to treat complex aortic aneurysms involving branches that provide critical end-organ blood supply. A prospective study was conducted in patients with thoracoabdominal, suprarenal, or common iliac aneurysms (TAA, SRA, or CIA) at high risk for open surgical repair. An endovascular graft using the Zenith platform was customized to fit patient anatomy (TAA or SRA) and combined with Jomed balloon-expandable stent-grafts. Prefabricated hypogastric branches were used with a Zenith abdominal aortic aneurysm (AAA) or Fluency self-expanding fenestrated device in conjunction with a self-expanding stent-graft. Analyses were conducted in accordance with the endovascular aneurysm reporting standards document. Follow-up studies occurred at discharge, 1, 6, and 12 months, and included computed tomography and duplex ultrasound scans, and flat plate radiography. Fifty patients were treated (9 TAA, 20 SRA, 21 CIA). The mean aneurysm size was 7.6 cm (TAA), 7.2 cm (SRA), and 6.1 cm AAA size associated with a mean CIA size of 3.8 cm. Bilateral CIA aneurysms were present in 86% (18/21) of patients with CIA aneurysms. Perioperative mortality was 2% (1/50) and resulted from a myocardial infarction after a planned conduit and iliac endarterectomy required for device access. Five late deaths occurred (2 TAA, 2 SRA, 1 CIA), three of which (2 TAA, 1 SRA) were aneurysm related. Failure to access internal iliac arteries occurred in three cases, and two late hypogastric branch thromboses occurred. No visceral branches were lost acutely or occluded during follow-up. Sac shrinkage (>5 mm) was noted in 65% of patients at 6 months and in all patients (10/10) by 12 months. There were no ruptures or conversions, but nine patients required secondary interventions. Branch vessel technology has made it technically feasible to preserve critical end-organ perfusion in the setting of CIA, SRA, and TAA aneurysms. The relatively low acute mortality rate and lack of short-term branch vessel loss are encouraging and merit further investigation. These advances have the potential to markedly diminish the complications associated with conventional management of complex aneurysms.


The urgent case for expanded development assistance for health.
The low-income developing countries require increased development assistance for health (DAH) to achieve Sustainable Development Goal 3, 'Healthy Lives for All'. DAH has a proven track record. DAH expanded during 2001-2008, with significant health gains in the LIDCs, but then stopped expanding in the wake of the 2008 financial crisis. The Global Fund to Fight AIDS, TB and Malaria requires around US$31.8 billion during 2021-2023 to maintain a trajectory to end the three epidemics by 2030, yet donors have so far signaled that they are prepared to offer less than half that sum, around US$14 billion.


Effect of organic nitrates on ex vivo platelet aggregation and fibrinolysis in man.
Previous in vitro studies have suggested that nitric oxide-releasing agents can increase the fibrinolytic capacity while platelet aggregability is decreased. We have therefore directly compared the influence of organic nitrates on ex vivo platelet aggregation and the fibrinolytic system in 16 healthy volunteers. Each subject received glyceryl trinitrate (GTN, 2 x 32 mg patches), isosorbide-dinitrate (ISDN, 120 mg p.o.), isosorbide-5-mononitrate (ISMN, 50 mg p.o.), and placebo in a randomized double-blind manner. Ex vivo platelet aggregation, activities and concentrations of tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) were measured before, 90 and 150 minutes after drug intake. GTN, ISDN, and ISMN were equipotent in respect to their hemodynamic responses. Platelet aggregation induced with a low (1 microM) but not with a high (4 microM) agonist concentration (adenosine diphosphate, ADP) was reduced after GTN and ISDN. ISMN had no influence on aggregation. An increase of t-PA activity was significantly reduced after GTN and ISDN (p<0.05), whereas t-PA concentrations were not affected by the nitrates. A decrease of PAI-1 activity after ISMN and placebo was not apparent after GTN and ISDN. In the case of GTN, the decrease of PAI-1 concentration was delayed. In conclusion, GTN and ISDN did not increase the fibrinolytic capacity but decreased the reversible phase of ADP-induced platelet aggregation, while ISMN had neither an effect on the fibrinolytic system nor on platelet aggregation.


Monitoring of liver metabolic function during interferon-alpha therapy and its relationship to treatment outcome in chronic hepatitis C patients.
Interferon is considered the cornerstone in the therapy of chronic hepatitis C patients. Experimental studies have shown that interferon administration may influence liver metabolic activity. However, data concerning the monitoring of liver metabolic function during a therapeutic course of interferon in chronic hepatitis C patients are scanty. The MEGX (monoethylglycinexylidide) test has been used in diagnostic and prognostic assessment of chronic liver disease as a quantitative liver function test. In this study our aim was to non-invasively monitor liver function in chronic hepatitis C patients during a course of interferon-alpha therapy and to evaluate whether the presence of modifications in liver metabolic function might influence the therapeutic outcome. We studied 22 patients with biopsy-proven chronic hepatitis C before, during (1st, 3rd and 6th month of therapy), and three months after interferon-alpha (3 million units thrice weekly for six months) using MEGX test to monitor liver function. During the longitudinal study no significant differences were observed between pretreatment MEGX30 values and those obtained during interferon treatment or at the end of follow-up, both considering patients together or grouped according to treatment outcome (Responders vs. Non-responders). Analysis of the MEGX30 variations during therapy showed that they were evenly distributed between responder and non-responder patients. Furthermore, during interferon therapy none of the patients reached a MEGX30 value compatible with severely impaired liver function. Our results suggest that although a discrete prevalence of modifications in liver metabolic function occurs in chronic hepatitis C patients during interferon therapy they do not seem to have clinical relevance or influence therapeutic outcome.


Serum Levels of miR-148a and miR-21-5p Are Increased in Type 1 Diabetic Patients and Correlated with Markers of Bone Strength and Metabolism.
Type 1 diabetes (T1D) is characterized by bone loss and altered bone remodeling, resulting into reduction of bone mineral density (BMD) and increased risk of fractures. Identification of specific biomarkers and/or causative factors of diabetic bone fragility is of fundamental importance for an early detection of such alterations and to envisage appropriate therapeutic interventions. MicroRNAs (miRNAs) are small non-coding RNAs which negatively regulate genes expression. Of note, miRNAs can be secreted in biological fluids through their association with different cellular components and, in such context, they may represent both candidate biomarkers and/or mediators of bone metabolism alterations. Here, we aimed at identifying miRNAs differentially expressed in serum of T1D patients and potentially involved in bone loss in type 1 diabetes. We selected six miRNAs previously associated with T1D and bone metabolism: miR-21; miR-24; miR-27a; miR-148a; miR-214; and miR-375. Selected miRNAs were analyzed in sera of 15 T1D patients (age: 33.57 ± 8.17; BMI: 21.4 ± 1.65) and 14 non-diabetic subjects (age: 31.7 ± 8.2; BMI: 24.6 ± 4.34). Calcium, osteocalcin, parathormone (PTH), bone ALkaline Phoshatase (bALP), and Vitamin D (VitD) as well as main parameters of bone health were measured in each patient. We observed an increased expression of miR-148a (p = 0.012) and miR-21-5p (p = 0.034) in sera of T1D patients vs non-diabetic subjects. The correlation analysis between miRNAs expression and the main parameters of bone metabolism, showed a correlation between miR-148a and Bone Mineral Density (BMD) total body (TB) values (p = 0.042) and PTH circulating levels (p = 0.033) and the association of miR-21-5p to Bone Mineral Content-Femur (BMC-FEM). Finally, miR-148a and miR-21-5p target genes prediction analysis revealed several factors involved in bone development and remodeling, such as MAFB, WNT1, TGFB2, STAT3, or PDCD4, and the co-modulation of common pathways involved in bone homeostasis thus potentially assigning a role to both miR-148a and miR-21-5p in bone metabolism alterations. In conclusion, these results lead us to hypothesize a potential role for miR-148a and miR-21-5p in bone remodeling, thus representing potential biomarkers of bone fragility in T1D.


Tissue Barriers to Arbovirus Infection in Mosquitoes.
Arthropod-borne viruses (arboviruses) circulate in nature between arthropod vectors and vertebrate hosts. Arboviruses often cause devastating diseases in vertebrate hosts, but they typically do not cause significant pathology in their arthropod vectors. Following oral acquisition of a viremic bloodmeal from a vertebrate host, the arbovirus disease cycle requires replication in the cellular environment of the arthropod vector. Once the vector has become systemically and persistently infected, the vector is able to transmit the virus to an uninfected vertebrate host. In order to systemically infect the vector, the virus must cope with innate immune responses and overcome several tissue barriers associated with the midgut and the salivary glands. In this review we describe, in detail, the typical arbovirus infection route in competent mosquito vectors. Based on what is known from the literature, we explain the nature of the tissue barriers that arboviruses are confronted with in a mosquito vector and how arboviruses might surmount these barriers. We also point out controversial findings to highlight particular areas that are not well understood and require further research efforts.


Comparing endoscopic thyroidectomy using the breast approach and conventional open thyroidectomy: A retrospective analysis.
Endoscopic thyroidectomy (ET) using the breast approach and conventional open thyroidectomy (OT) are effective approaches to treating thyroid tumors. This study evaluates the effectiveness of ET and OT regarding safety, cosmetic effects, and feasibility. Four hundred and fifty-six patients who underwent thyroidectomy in our department from January 2019 to August 2020 were included in this study. Based on the intraoperative rapid pathology, all patients with papillary thyroid carcinoma underwent unilateral thyroid lobectomy and central neck lymph node dissection. Whereas all benign patients underwent unilateral thyroid lobectomy. Differences in various factors such as clinical characteristics, operation time, postoperative drainage volume, parathyroid hormone (PTH) levels, calcium (Ca) levels, total number of central lymph nodes resected, the number of metastatic central lymph nodes resected, hospital duration, hospitalization costs, and cosmetic effects were compared in each group. Baseline characteristics among the four groups were similar, except for patient age and tumor size. Patients in the malignant ET group were younger than those in the malignant OT group with smaller tumors (P < 0.05). There were no significant differences between the OT and ET groups in postoperative Ca levels, PTH levels, the total number of lymph nodes resected, and the number of metastatic central lymph nodes resected. Compared with conventional OT, ET is a feasible, practical, and safe procedure with excellent cosmetic benefits.


The Molecular Basis for Ca2+ Signalling by NAADP: Two-Pore Channels in a Complex?
NAADP is a potent Ca2+ mobilizing messenger in a variety of cells but its molecular mechanism of action is incompletely understood. Accumulating evidence indicates that the poorly characterized two-pore channels (TPCs) in animals are NAADP sensitive Ca2+-permeable channels. TPCs localize to the endo-lysosomal system but are functionally coupled to the better characterized endoplasmic reticulum Ca2+ channels to generate physiologically relevant complex Ca2+ signals. Whether TPCs directly bind NAADP is not clear. Here we discuss the idea based on recent studies that TPCs are the pore-forming subunits of a protein complex that includes tightly associated, low molecular weight NAADP-binding proteins.


The association between serotonin transporter gene promoter polymorphism (5-HTTLPR), self-reported symptoms, and dental mercury exposure.
The associations between a polymorphism of the serotonin transporter gene (5-HTTLPR), dental mercury exposure, and self-reported symptoms were evaluated among 157 male dentists and 84 female dental assistants. Self-reported symptoms and detailed work histories were obtained by computerized questionnaire. Spot urine samples were collected and analyzed for mercury concentrations to evaluate recent exposures, whereas a chronic mercury exposure index was created from the work histories. 5-HTTLPR polymorphism status was determined using a polymerase chain reaction (PCR)-based assay. Scores for current, recent, and chronic self-reported symptom groups were evaluated with respect to recent and chronic mercury exposure and 5-HTTLPR polymorphism status. Multiple regression analysis controlled for age, socioeconomic status, tobacco and alcohol use, self-reported health problems, and medications. Analyses were restricted to Caucasian subjects due to the highly skewed distribution of the 5-HTTLPR polymorphism. Separate evaluations were conducted for dentists and dental assistants. In contrast to previous reports, no consistent associations were found between either urinary mercury concentration or the chronic index of mercury exposure and any category of symptoms. However, both significant and consistent associations were observed between increased symptoms and the 5-HTTLPR polymorphism involving two copies of the short or "s" allele (full mutation), but not with the polymorphism involving only one copy (heterozygous), demonstrating a gene-dose relationship for symptom reporting. These findings suggest that within this restricted population increased symptoms of depression, anxiety, and memory are associated with the 5-HTTLPR polymorphism among both males and females.


MFI zeolite nanosheets with post-synthetic Ti grafting for catalytic epoxidation of bulky olefins using H2O2.
The external surfaces of the surfactant-directed, 2.5 nm MFI zeolite nanosheets were grafted with Ti using titanium(IV) butoxide. The Ti/MFI nanosheets exhibited a remarkable catalytic performance for epoxidation of bulky olefins using H2O2 as an oxidant, in comparison to the mesoporous silicas with amorphous frameworks.


Amelin: an enamel-related protein, transcribed in the cells of epithelial root sheath.
Since 1974, when Slavkin and his collaborators proposed the epithelial origin of cementum, many experiments have been carried out to provide evidence for deposition of enamel-related proteins along the root surface. However, neither amelogenin nor other proteins have fully satisfied expectations. In previous studies, we have identified a novel mRNA coding for an extracellular-like protein which we called amelin. It was expressed at high levels in secretory and postsecretory ameloblasts in rat molars and incisors. In situ hybridization experiments described in the present study also localized the amelin message to epithelial cells adjacent to the peripheral surface of newly deposited dentin in the root end and to cells embedded in cellular cementum in molars. In incisors, the amelin RNA positive cells were detected in the area where cementum formation had been initiated. No amelogenin RNA signal was found in the cells at the root surface. We postulate that the epithelial cells of the root sheath as well as the ameloblasts are synthesizing amelin which might be one of the key proteins coupled to the process of cementogenesis.


[Design and application of an opening and breaking device of ampoule bottle].
Ampoule bottles are common clinical containers forliquid medicine. After use, ampoules occupy a lot of space, which will not only consume a large number of sharp boxes, but also lead to low work efficiency and easy to scratch the hands of medical staff by changing the sharp boxes frequently. In order to overcome the problems mentioned above, the neurosurgery medical staff of Yuechi County People's Hospital designed a new type of ampoule bottle opening and crushing device, and won the national utility model patent. The device includes a bottle-opening structure and a crushing structure, and has both ampoule opening and crushing function, the device is convenient to use, has high safety performance, and is suitable for clinical promotion.


Emergency psychiatric assessments: do outcomes match priorities?
The targeting of scarce mental health resources is currently organised around three broad areas: treating severe mental illness; reducing suicide; and obviating risk to the wider community. High priority clients are those who present with either psychotic symptoms, or who are perceived to be high risk to self or others. This study examined records of emergency assessments at a mental health trust in the south-east of England over a three-month period (n = 336) to see whether clients with these characteristics are more likely than others to be offered hospital admission or treatment. It was found that clients presenting with psychosis are much more likely to be offered admission than those assessed as non-psychotic, that those assessed as a suicide risk are also significantly more likely to be offered admission, and that those assessed as presenting a risk to the public at large are no more likely to be admitted than those presenting no risk. This investigation indicates that the emergency service of the trust studied is addressing the first two target areas, but may be underperforming in the third.


Comparison of the 3 Different Injection Techniques Used in a Randomized Controlled Study Evaluating a Cross-Linked Sodium Hyaluronate Combined With Triamcinolone Hexacetonide (Cingal) for Osteoarthritis of the Knee: A Subgroup Analysis.
A recent trial demonstrated that patients with knee osteoarthritis treated with a sodium hyaluronate and corticosteroid combination (Cingal) experienced greater pain reductions compared with those treated with sodium hyaluronate alone (Monovisc) or saline up to 3 weeks postinjection. In this study, injections were administered by 1 of 3 approaches; however, there is currently no consensus on which, if any, of these techniques produce a more favorable outcome. To provide additional insight on this topic, the results of the previous trial were reanalyzed to determine whether (1) the effect of Cingal was significant within each injection technique and (2) pain reductions were similar between injection techniques across all treatment groups. Greater pain reductions with Cingal up to 3 weeks were only significant in the anteromedial subgroup. Across all therapies, both the anteromedial and anterolateral techniques demonstrated significantly greater pain reductions than the lateral midpatellar approach at 18 and 26 weeks.


[A clinical review of 449 cases with fever of unknown origin].
To investigate the causes of fever of unknown origin (FUO). The clinical data were retrospectively analyzed from patients with FUO hospitalized in Peking Union Medical College Hospital from January 2000 to December 2003. During that period of time, 449 cases fulfilled the criteria of FUO. Out of the 449 FUO cases, definite diagnosis was eventually achieved in 387 patients (86.9%). The most common causes of FUO were infectious diseases (56.8%), with tuberculosis accounting for 43.6% of cases of infection. Seventy-six patients were suffered from collagen vascular diseases (CVD): with Still's disease, systemic lupus erythematosus and vasculitis accounting for 34.2% (26/76), 18.4% (14/76) and 13.2% (10/76) of the this category, respectively. 16.5% (64/449) of the FUO cases were diagnosed as malignancy. Miscellaneous causes were found in 7.0% of the FUO cases. However, no definite diagnosis had been made in the remaining 62 (13.8%) cases until they discharged from the hospital. In most FUO cases the causes can be diagnosed eventually after careful analysis of clinical data. While infectious diseases, especially tuberculosis, were still the most common causes of FUO, CVD and malignancy were also major causes of FUO and the incidence of malignancy were increased with the time.


Lessons from MPO deficiency about functionally important structural features.
Genetic abnormalities often serve as the catalyst to stimulate critical insights into normal biology. In many cases, examining such experiments of Nature explicates not only the abnormal but also serves to illustrate underlying normal principles. Within the context of myeloperoxidase biosynthesis, we have examined the impact of specific missense mutations that cause inherited myeloperoxidase deficiency. Such studies have provided novel insights not otherwise possible. We have described three such mutations and are completing the analysis of a fourth.


Mass spectrometry imaging with high resolution in mass and space.
Mass spectrometry (MS) imaging links molecular information and the spatial distribution of analytes within a sample. In contrast to most histochemical techniques, mass spectrometry imaging can differentiate molecular modifications and does not require labeling of targeted compounds. We have recently introduced the first mass spectrometry imaging method that provides highly specific molecular information (high resolution and accuracy in mass) at cellular dimensions (high resolution in space). This method is based on a matrix-assisted laser desorption/ionization (MALDI) imaging source working at atmospheric pressure which is coupled to an orbital trapping mass spectrometer. Here, we present a number of application examples and demonstrate the benefit of 'mass spectrometry imaging with high resolution in mass and space.' Phospholipids, peptides and drug compounds were imaged in a number of tissue samples at a spatial resolution of 5-10 μm. Proteins were analyzed after on-tissue tryptic digestion at 50-μm resolution. Additional applications include the analysis of single cells and of human lung carcinoma tissue as well as the first MALDI imaging measurement of tissue at 3 μm pixel size. MS image analysis for all these experiments showed excellent correlation with histological staining evaluation. The high mass resolution (R = 30,000) and mass accuracy (typically 1 ppm) proved to be essential for specific image generation and reliable identification of analytes in tissue samples. The ability to combine the required high-quality mass analysis with spatial resolution in the range of single cells is a unique feature of our method. With that, it has the potential to supplement classical histochemical protocols and to provide new insights about molecular processes on the cellular level.


Anti-amyloid β autoantibodies in cerebral amyloid angiopathy-related inflammation: implications for amyloid-modifying therapies.
Cerebral amyloid angiopathy-related inflammation (CAA-ri) is characterized by vasogenic edema and multiple cortical/subcortical microbleeds, sharing several aspects with the recently defined amyloid-related imaging abnormalities (ARIA) reported in Alzheimer's disease (AD) passive immunization therapies. Herein, we investigated the role of anti-amyloid β (Aβ) autoantibodies in the acute and remission phases of CAA-ri. We used a novel ultrasensitive technique on patients from a retrospective multicenter case-control study, and evaluated the anti-Aβ autoantibody concentration in the cerebrospinal fluid (CSF) of 10 CAA-ri, 8 CAA, 14 multiple sclerosis, and 25 control subjects. Levels of soluble Aβ40, Aβ42, tau, P-181 tau, and APOE genotype were also investigated. During the acute phase of CAA-ri, anti-Aβ autoantibodies were specifically increased and directly correlated with Aβ mobilization, together with augmented tau and P-181 tau. Following clinical and radiological remission, autoantibodies progressively returned to control levels, and both soluble Aβ and axonal degeneration markers decreased in parallel. Our data support the hypothesis that the pathogenesis of CAA-ri may be mediated by a selective autoimmune reaction against cerebrovascular Aβ, directly related to autoantibody concentration and soluble Aβ. The CSF dosage of anti-Aβ autoantibodies with the technique here described can thus be proposed as a valid alternative tool for the diagnosis of CAA-ri. Moreover, given the similarities between ARIA developing spontaneously and those observed during immunization trials, anti-Aβ autoantibodies can be considered as novel potential biomarkers in future amyloid-modifying therapies for the treatment of AD and CAA.


Modeling nuclear volume isotope effects in crystals.
Mass-independent isotope fractionations driven by differences in volumes and shapes of nuclei (the field shift effect) are known in several elements and are likely to be found in more. All-electron relativistic electronic structure calculations can predict this effect but at present are computationally intensive and limited to modeling small gas phase molecules and clusters. Density functional theory, using the projector augmented wave method (DFT-PAW), has advantages in greater speed and compatibility with a three-dimensional periodic boundary condition while preserving information about the effects of chemistry on electron densities within nuclei. These electron density variations determine the volume component of the field shift effect. In this study, DFT-PAW calculations are calibrated against all-electron, relativistic Dirac-Hartree-Fock, and coupled-cluster with single, double (triple) excitation methods for estimating nuclear volume isotope effects. DFT-PAW calculations accurately reproduce changes in electron densities within nuclei in typical molecules, when PAW datasets constructed with finite nuclei are used. Nuclear volume contributions to vapor-crystal isotope fractionation are calculated for elemental cadmium and mercury, showing good agreement with experiments. The nuclear-volume component of mercury and cadmium isotope fractionations between atomic vapor and montroydite (HgO), cinnabar (HgS), calomel (Hg2Cl2), monteponite (CdO), and the CdS polymorphs hawleyite and greenockite are calculated, indicating preferential incorporation of neutron-rich isotopes in more oxidized, ionically bonded phases. Finally, field shift energies are related to Mössbauer isomer shifts, and equilibrium mass-independent fractionations for several tin-bearing crystals are calculated from (119)Sn spectra. Isomer shift data should simplify calculations of mass-independent isotope fractionations in other elements with Mössbauer isotopes, such as platinum and uranium.


Multivariate one-sided multiple comparison procedure with a control based on the approximate likelihood ratio test.
In this study, we discuss a multiple comparison procedure with a control for multivariate one-sided test in each pairwise comparison. For pairwise comparisons, we use the approximate likelihood ratio test statistics derived by Tang et al. (An approximate likelihood ratio test for a normal mean vector with nonnegative components with application to clinical trials. Biometrika 1989, 76, 577-583). We derive a formula to determine the critical value for pairwise comparisons satisfying a specified significance level. Furthermore, we formulate the power of the test for our multiple comparison procedure. Finally, we give some numerical examples regarding the critical values and the power of the test.


An update on the validation of whole slide imaging systems following FDA approval of a system for a routine pathology diagnostic service in the United States.
Pathologists have used light microscopes and glass slides to interpret the histologic appearance of normal and diseased tissues for more than 150 years. The quality of both microtomes used to cut tissue sections and microscopes has improved significantly during the past few decades, but the process of rendering diagnoses has changed little. By contrast, major advances in digital technology have occurred since the introduction of hand held electronic devices, including the development of whole slide imaging (WSI) systems with software packages that can convert microscope images into virtual (digital) slides that can be viewed on computer monitors and via the internet. To date, however, these technological developments have had minimal impact on the way pathologists perform their daily work, with the exception of using computers to access electronic medical records and scholarly web sites for pertinent information to assist interpretation of cases. Traditional practice is likely to change significantly during the next decade, especially since the Federal Drug Administration in the USA has approved the first WSI system for routine diagnostic practice. I review here the development and slow acceptance of WSI by pathology departments. I focus on recent advances in validation of WSI systems that is required for routine diagnostic reporting of pathology cases using this technology.


Norovirus Detection at Oualidia Lagoon, a Moroccan Shellfish Harvesting Area, by Reverse Transcription PCR Analysis.
Norovirus (NoV) is the leading cause of acute viral gastroenteritis outbreaks in the world. These outbreaks are frequently associated with bivalve shellfish consumption, particularly because these products are often eaten raw or only slightly cooked. In Morocco, regulations concerning the acceptable levels of enteric bacteria indicator organisms in these products have been put in place. However, these regulations do not take into account the risk of viral contamination, and many gastroenteritis outbreaks have been linked to the ingestion of bivalve shellfish from areas that comply with the current food safety criteria. The aim of this study was to investigate NoV presence in shellfish samples (n = 104) collected at four sites owcff Oualidia lagoon (Moroccan Atlantic coast) from November 2015 to February 2017. Samples were analysed using real-time RT-PCR in accordance with the ISO 15216-2 method. NoVs of the genogroup II were detected in 7% of samples that were all collected during the winter months. Moreover, 71% of NoV-positive samples were harvested at sites upstream of the lagoon. These results highlight the need of regularly monitoring viral contamination in bivalve shellfish to limit the risk of viral gastroenteritis outbreaks.


[Rapid and simultaneous determination method for analysis of minerals in infant formula using ICP-MS].
A rapid and simultaneous method by using inductively coupled plasma mass spectrometry (ICP-MS) was developed for determination of 19 elements in infant formula. Fast and efficient sample digestion was achieved by a microwave-assisted nitric acid procedure. An acetic acid was added to both these treated solutions and standard solutions as a countermeasure for carbon charge transfer in As, Se elements. The observed calibration curves showed good linearity (r(2)>0.9993) and the quantification limit was low. The recoveries of elements were 95.0-108% and the relative standard deviations (RSD) of this method were 0.3-4.2%. The analyzed values were in good agreement with the certified values in a NIST standard reference material. This study showed that the ICP-MS method is useful for major to trace multi-elemental determination in infant formula.


Early afterdepolarizations and arrhythmogenesis. Experimental and clinical aspects.
There is growing evidence that early afterdepolarizations (EADs) and EAD-induced triggered activity play a significant role in the clinical syndrome of long QTU and polymorphic ventricular tachyarrhythmias better known as Torsade de Pointes (TdP). This evidence is briefly examined in this report. The three steps required for the manifestation of EAD-induced triggered activity are: 1) critical prolongation of the repolarization phase, 2) a net depolarizing current carrying the charge for EAD, and 3) propagation of EADs which are locally generated to capture the entire heart resulting in one or more extrasystoles. The majority of pharmaceutical interventions associated with EADs could be grouped as acting predominantly through one of three different mechanisms 1) a delay of one or both potassium currents IK and Ikl, 2) an increase of transsarcolemmal calcium current (ICa), and 3) a delay of sodium current (INa) inactivation. Two experimental models in the dog utilized cesium and anthopleurin-A to produce bradycardia-dependent long QTU and polymorphic ventricular tachyarrhythmias that may resemble the clinical syndrome of long QTU and TdP. In both in vivo models, monophasic action potential (MAP) recordings demonstrated EADs-like deflections more prominent in endocardial than in epicardial recordings. The clinical syndrome of long QTU and TdP can be either congenital, idiopathic or acquired. Several observations suggest a common underlying mechanism with a greater predominance of adrenergic influence in the congenital or idiopathic long QTU syndrome. Adrenergic influence can act by enhancing the depolarizing current of EAD as well as EAD transmission in the intact heart.(ABSTRACT TRUNCATED AT 250 WORDS)


Hospital Frailty Risk Score Is Independently Associated with Mortality and Encephalopathy in Hospitalized Patients with Hepatocellular Carcinoma.
Frailty represents a state of vulnerability to multiple internal physiologic factors, as well as external pressures, and has been associated with clinical outcomes. We aim to understand the impact of frailty on patients admitted with hepatocellular carcinoma (HCC) by using the validated Hospital Frailty Risk Score, which is implemented in several hospitals worldwide. We conducted a nation-wide retrospective cohort study to determine the effect of frailty on the risk of in-patient mortality, hepatic encephalopathy, length of stay and cost. Frailty was associated with a 4.5-fold increased risk of mortality and a 2.3-fold increased risk of hepatic encephalopathy. Adjusted Cox regression showed that frailty was correlated with increased risk of in-patient mortality (hazard ratio: 2.3, 95% CI 1.9-2.8, p < 0.001). Frail HCC patients had longer hospital stay (median 5 days) vs. non-frail HCC patients (median 3 days). Additionally, frail patients had higher total costs of hospitalization ($40,875) compared with non-frail patients ($31,667). Frailty is an independent predictor of hepatic encephalopathy and in-patient mortality. Frailty is a surrogate marker of hospital length of stay and cost.


An immunohistochemical study of endocrine cells in the digestive tract of Varanus salvator (Reptile: Varanidae).
The aim of the study was to identify the distribution pattern and frequency of endocrine cell types in the digestive tract of Varanus salvator. The presence of endocrine cells (glucagon, somatostatin, and serotonin) in the digestive tract (esophagus, stomach, and intestine) was detected using the avidin-biotin complex (ABC) method. Three types of endocrine cells immunoreactive to antisera glucagon, serotonin, and somatostatin were found in the caudal portion of the small and large intestines but were not observed in the esophagus, stomach, and caput and medial sections of the small intestine. Endocrine cells distributed in the digestive tract of V. salvator vary in color intensity, from weak to sharp, in response to the primer antibody. Endocrine cells in the digestive tract that is immunoreactive to glucagon, somatostatin, and serotonin are those found in the caudal portion of the small and large intestines. They are varied in distribution pattern, frequency, and color intensity.


Lifespan Extension and Sustained Expression of Stem Cell Phenotype of Human Breast Epithelial Stem Cells in a Medium with Antioxidants.
We have previously reported the isolation and culture of a human breast epithelial cell type with stem cell characteristics (Type I HBEC) from reduction mammoplasty using the MSU-1 medium. Subsequently, we have developed several different normal human adult stem cell types from different tissues using the K-NAC medium. In this study, we determined whether this low calcium K-NAC medium with antioxidants (N-acetyl-L-cysteine and L-ascorbic acid-2-phosphate) is a better medium to grow human breast epithelial cells. The results clearly show that the K-NAC medium is a superior medium for prolonged growth (cumulative population doubling levels ranged from 30 to 40) of normal breast epithelial cells that expressed stem cell phenotypes. The characteristics of these mammary stem cells include deficiency in gap junctional intercellular communication, expression of Oct-4, and the ability to differentiate into basal epithelial cells and to form organoid showing mammary ductal and terminal end bud-like structures. Thus, this new method of growing Type I HBECs will be very useful in future studies of mammary development, breast carcinogenesis, chemoprevention, and cancer therapy.


Simple models for two-dimensional tunable colloidal crystals in rotating ac electric fields.
We compare the behavior of a new two-dimensional aqueous colloidal model system with a simple numerical treatment. To the first order the attractive interaction between the colloids induced by an in-plane rotating ac electric field is dipolar, while the charge stabilization leads to a shorter ranged, Yukawa-like repulsion. In the crystal-like "rafts" formed at sufficient field strengths, we find quantitative agreement between experiment and Monte Carlo simulation, except in the case of strongly interacting systems, where the well depth of the effective potential exceeds 250 times the thermal energy. The "lattice constant" of the crystal-like raft is located approximately at the minimum of the effective potential, resulting from the sum of the Yukawa and dipolar interactions. The experimental system has display applications, owing to the possibility of tuning the lattice spacing with the external electric field. Limitations in the applied field strength and relative range of the electrostatic interactions of the particles result in a reduction in tunable lattice spacing for small and large particles, respectively. The optimal particle size for maximizing the lattice spacing tunability was found to be around 1000 nm.


Documentation proficiency of patients who leave the emergency department against medical advice.
This study describes the current documentation practices of health-care providers in the emergency department (ED) during the discharge against medical advice (AMA) process. This retrospective cohort study reviewed health care provider documentation of adult patients who left an ED AMA in one year. Each encounter documentation was reviewed for eight medicolegal standards including the documentation of 1) the patient's capacity; 2) the signs and symptoms; 3) the extent and limitation of the evaluation; 4) the current treatment plan, risks, and benefits; 5) the risks and benefits of forgoing treatment; 6) the alternatives to suggested treatment; 7) the explicit statement made by the patient who left AMA, as well as the explicit documentation of what the patient was refusing; and 8) the follow-up care including discharge instructions. There were 81,038 eligible ED encounters with a total of 418 patients identified as having left AMA resulting in an AMA discharge rate of 0.52%. No single chart fulfilled all eight medicolegal standards. Minimal standards established by the Emergency Medical Treatment and Active Labor Act (EMTALA) were fulfilled in only 17 charts (4.1%). Despite general acceptance in the legal and policy literature on the need to ensure capacity to make decisions, only 22.0% of the charts documented that the patient had such capacity. This study revealed suboptimal documentation in AMA cases by clinicians at a single ED and confirms disparities between federal and academic quality (safety documentation requirements and actual provider documentation).


Antipsychotic medication utilization trends among Texas veterans: 1997-2002.
An antipsychotic utilization pattern has evolved substantially over the past 20 years or so due to the introduction of the second-generation antipsychotics (SGAs) and the increasing understanding of their adverse effect profile. To understand antipsychotic utilization trends (including monotherapy, antipsychotic switching, and combination therapy) and to investigate factors associated with antipsychotic index medication selection (SGAs vs first-generation antipsychotics [FGAs]) among Texas veterans. Data were taken from the Veterans Administration North Texas Health Care System (VANTHCS) and South Texas Veterans Health Care System (STVHCS) from January 1996 to December 2003. Adults with continuous enrollment (1 y before and after the index date) who had newly initiated antipsychotic therapy were included. Prescriptions were followed for up to 12 months. Descriptive analyses examined utilization trends; logistic regression evaluated factors associated with antipsychotic index medication selection. A total of 8096 patients were included in the study (VANTHCS n = 4477; STVHCS n = 3619), with the majority being male (93.6%) and white (62.6%) and nearly half aged 55 years or older (44.1%). Between 1997 and 2002, antipsychotic prescriptions changed from primarily FGAs (1997: 71.7%; 1999: 25.2%; 2002: 5.7%) to SGAs. Over the 6-year time frame, risperidone (31.0%) and olanzapine (30.7%) were most commonly prescribed. The overall combination therapy slightly increased over time (4.3%), switching to another antipsychotic remained stable (14.2%), and antipsychotic monotherapy remained dominant (81.5%). Hispanic and black patients were less likely than white patients to be initiated on SGAs. Patients who were older, had hypertension, and were in STVHCS were less likely to start on SGAs. Patients with dyslipidemia, bipolar disorder, and treatment in recent years were more likely to start on SGAs. SGAs have replaced FGAs as first-line medications for patients with mental disorders. Race, age, physical comorbidities (ie, dyslipidemia, hypertension), and treatment initiation year were important factors in index medication selection.


Quantification of EUGR as a Measure of the Quality of Nutritional Care of Premature Infants.
To develop an index of the quality of nutritional care of premature infants based on the change in weight Z score from birth to discharge and to illustrate the use of this index in comparing the performance of different NICUs. Retrospective data analysis was performed to compare the growth of premature infants born in three perinatal centers. Infants with gestational age ≤ 32 weeks who survived to discharge from 2006 to 2010 were included. Weight Z scores at birth and discharge were calculated by the method of Fenton. Using data from one NICU as the reference, a multivariable linear regression model of change in weight Z score from birth to discharge was developed. Employing this model, a benchmark value of change in weight Z score was calculated for each baby. The difference between this calculated benchmark value and the baby's observed change in weight Z score was defined as the performance gap for that infant. The average value of the performance gaps in a NICU serves as its quality care index. 1,714 infants were included for analysis. Change in weight Z score is influenced by birth weight Z score and completed weeks of gestation; thus the model for calculating the benchmark change in weight Z score was adjusted for these two variables. We found statistically significant differences in the average performance gaps for the three units. A quality care index was developed based on change in weight Z score from birth to discharge adjusted for two initial risk factors. This objective, easily calculated index may be used as a measurement of the quality of nutritional care to rank the performance of different NICUs.


[Candida dubliniensis studies and isolation of Candida types in oropharyngeal specimens from oncologic patients].
Fungal opportunistic infections, and in particular those caused by the various Candida species, have gained considerable significance as a cause of morbidity and, often, mortality. Although Candida albicans remains to be the most frequently isolated fungal species as an opportunistic oral pathogen, other yeast species are often identified in immunocompromised patients. C. dubliniensis, the recently described species, has been recovered primarily from oropharyngeal candidasis in Human Immunodeficiency Virus (HIV)-infected patients. C. dubliniensis shares many phenotypic characteristics with, and is phylogenetically closely related to, C. albicans. The aim of the present study was to investigate the colonization rates of fungal species, and especially C. dubliniensis, in the oropharyngeal samples from cancer patients. The oropharyngeal swabs of 543 patients were collected during their visits to oncology clinic in 9 months period, and a total of 209 Candida species have been isolated. Of them, 147 isolates were found to be positive for germ tube and chlamydospore formation, and they were tested for the growth inability at 42 degrees C and 45 degrees C, colony morphology in Staib agar and the intracellular beta-glucosidase activity, in order to identify C. dubliniensis. The results of these tests and carbohydrate assimilation tests by API 20C AUX yeast identification system, yielded that all these 147 (70.3%) isolates were C. albicans. The other isolates were identified as follows; 16 C. parapsilosis (7.6%), 13 C. tropicalis (6.2%), 10 C. glabrata (4.7%), 5 C. guilliermondii (2.3%), 4 C. krusei (1.9%), 3 C. keyfr (1.4%), 3 C. famata (1.4%), 2 S. cerevisiae (0.9%), 2 C. pelliculosa (0.9%), 1 C. utiles (0.4%), 1 C. neoformans (0.4%) and 1 Hansenula polymorpha (0.4%), while no C. dubliniensis was isolated.


Immunochemical and biomolecular studies of circulating immune complexes isolated from patients with acute and chronic hepatitis C virus infection.
Circulating immune complexes (ICs) were isolated by affinity chromatography and sucrose density gradient fractionation during acute and chronic hepatitis C virus (HCV) infection. Immunochemical and biomolecular studies showed that they basically consist of the virus component, IgG with specific anti-HCV activity and IgM bearing 17.109 epitope (IgM 17.109), an antigenic determinant common to rheumatoid factors (RFs) with WA cross-idiotype (XId). An antigen-specific IC assay was used to demonstrate IgG anti-HCV/IgM 17.109 ICs (IgG-IgM ICs) in five out of the five patients with acute and in 8 out of the 10 patients with chronic hepatitis C who mounted an IgG anti-HCV immune response. They were not detected in patients with no IgG anti-HCV response. IgG-IgM ICs appeared in step with IgG anti-HCV seroconversion and remained detectable for a long period irrespective of clinical outcome, in that they were demonstrated over a 4-year follow-up of patients with chronic hepatitis C. Their presence was unrelated to the severity and progression of liver histology. Despite similar serum levels of IgM 17.109 XId, antigen-specific IgG-IgM ICs were not found in acute and chronic hepatitis B or in acute hepatitis A. Thus, these ICs appear to be uniquely associated with HCV infection, supporting the view that IgM 17.109 XId derive from an antigen-driven response strictly related to the involved antigen. Even although they have no apparent effects on the progression of HCV-related liver disease, their presence may help to explain the immunological abnormalities and extrahepatic disorders observed in HCV infection.


Extracellular matrix-resident basic fibroblast growth factor: implication for the control of angiogenesis.
Despite the ubiquitous presence of basic fibroblast growth factor (bFGF) in normal tissues, endothelial cell proliferation in these tissues is usually very low, suggesting that bFGF is somehow sequestered from its site of action. Immunohistochemical staining revealed the localization of bFGF in basement membranes of diverse tissues, suggesting that the extracellular matrix (ECM) may serve as a reservoir for bFGF. Moreover, functional studies indicated that bFGF is an ECM component required for supporting endothelial cell proliferation and neuronal differentiation. We have found that bFGF is bound to heparan sulfate (HS) in the ECM and is released in an active form when the ECM-HS is degraded by heparanase expressed by normal and malignant cells (i.e. platelets, neutrophils, lymphoma cells). It is proposed that restriction of bFGF bioavailability by binding to ECM and local regulation of its release provide a novel mechanism for neovascularization in normal and pathological situations. The subendothelial ECM contains also tissue type- and urokinase type-plasminogen activators which participate in cell invasion and tissue remodeling. These results and studies on the properties of other ECM-immobilized enzymes (i.e. thrombin, plasmin, lipoprotein lipase) and growth factors (GM-CSF, IL-3, osteogenin), suggest that the ECM provides a storage depot for biologically active molecules which are thereby stabilized and protected. This may allow a more localized and persistent mode of action, as compared to the same molecules in a fluid phase.


Effects of chronic ethanol ingestion on mouse brain beta-adrenergic receptors (BAR) and adenylate cyclase.
Previous work showed that chronic ethanol ingestion by C57BL mice resulted in reduced stimulation of cerebral cortical adenylate cyclase (AC) activity by isoproterenol (ISO) and guanine nucleotides (GN). To investigate the mechanism of this change we have assessed the effect of chronic ethanol ingestion on agonist and antagonist binding to BAR in cerebral cortex (mainly beta 1-AR) and cerebellum (mainly beta 2-AR). C57BL mice were fed ethanol in a liquid diet for seven days and were withdrawn for various intervals. Agonist (ISO) binding data were best fit by a two-site model (high and low affinity states) in cortical membranes of control mice. GN induced conversion to a one site model (low affinity state). At the time of withdrawal, ISO binding data in cortical membranes were best fit by a one-site model even in the absence of GN. Antagonist binding was not affected. These results resemble those seen after heterologous desensitization, indicating "uncoupling" of receptor and AC. Control cerebellar ISO binding data were similar to cortical data. Chronic ethanol ingestion, however, did not produce data fit by a one site model in cerebellum. The affinity for ISO of the high affinity state of the BAR was significantly decreased at the time of withdrawal. ISO-stimulated AC-activity in cerebellar membranes was not affected by chronic ethanol ingestion, indicating that, in contrast to cerebral cortex, the cerebellar BAR was not uncoupled from AC.


Antifreeze Proteins: Novel Applications and Navigation towards Their Clinical Application in Cryobanking.
Antifreeze proteins (AFPs) or thermal hysteresis (TH) proteins are biomolecular gifts of nature to sustain life in extremely cold environments. This family of peptides, glycopeptides and proteins produced by diverse organisms including bacteria, yeast, insects and fish act by non-colligatively depressing the freezing temperature of the water below its melting point in a process termed thermal hysteresis which is then responsible for ice crystal equilibrium and inhibition of ice recrystallisation; the major cause of cell dehydration, membrane rupture and subsequent cryodamage. Scientists on the other hand have been exploring various substances as cryoprotectants. Some of the cryoprotectants in use include trehalose, dimethyl sulfoxide (DMSO), ethylene glycol (EG), sucrose, propylene glycol (PG) and glycerol but their extensive application is limited mostly by toxicity, thus fueling the quest for better cryoprotectants. Hence, extracting or synthesizing antifreeze protein and testing their cryoprotective activity has become a popular topic among researchers. Research concerning AFPs encompasses lots of effort ranging from understanding their sources and mechanism of action, extraction and purification/synthesis to structural elucidation with the aim of achieving better outcomes in cryopreservation. This review explores the potential clinical application of AFPs in the cryopreservation of different cells, tissues and organs. Here, we discuss novel approaches, identify research gaps and propose future research directions in the application of AFPs based on recent studies with the aim of achieving successful clinical and commercial use of AFPs in the future.


[Effect of tea polyphenols on expression of nuclear factor kappa B].
To investigate the effect of tea polyphenols (TP) on expression of nuclear factor kappa B (NF-kB) in rats with alcoholic liver diseases and in cells treated with alcohol. 22 female Wistar rats were randomly divided into three groups: a control group, an alcohol model group and a TP plus alcohol group. All treatments were injected into stomach through intragastric tube. L02 cells were divided into five groups: a control group, an alcohol treated group, a prevention group (cells were treated with TP for 3 days, and then treated with alcohol), an intervention group (cells treated with TP and alcohol), and a therapeutic group (cells were treated with alcohol for 3 days, and then treated with TP). Histopathology was observed under light microscope (LM); serum MDA, ROS in cells were quantified by optical density measurement; the expression of NF-kB and IkB was determined by RT-PCR; and the activity of NF-kB was checked with Electrophoretic Mobility Shift Assay (EMSA). LM indicated hepatocytes were injured obviously in the model group. Serum MDA and cells ROS in TP treated groups were significantly lower than the alcohol treated group. The level of NF-kB mRNA expression in TP treated groups(rats: 0.58+/-0.16, cells: 0.60+/-0.03, 0.59+/-0.01, 0.59+/-0.01) were significantly lower than the alcohol treated group (rats: 1.15+/-0.03, cells: 0.76+/-0.03) (P<0.01), the level of IkB mRNA expression in the prevention group, intervention group, and therapeutic group (0.51+/-0.01, 0.50+/-0.01, 0.50+/-0.12) were significantly higher than the alcohol treated group (0.61+/-0.03) (P<0.05), the difference among the three groups was not significant (P>0.05). The activity of NF-kB in TP treated rats(DNA stain: 669.85+/-41.34, Protein stain: 675.35+/-18.27) was significantly lower than the alcohol treated rats(DNA stain: 1410.78+/-22.19, Protein stain:1426.08+/-33.15) (P<0.01); NF-kB activity in cells of the prevention, intervention, therapeutic groups (DNA stain: 713.07+/-11.91, 710.79+/-14.99, 693.45+/-71.69; Protein stain: 758.88+/-34.65, 753.07+/-76.78, 725.77+/-36.09) was significantly lower than the alcohol treated cells (DNA stain: 849.94+/-12.45, Protein stain: 925.96+/-5.78) (P<0.01), the difference among the three TP treated groups was not significant (P>0.01). TP can alleviate and prevent alcohol-induced liver injury via inhibiting NF-kB activation.


Nutrition and chemosensory perception in the elderly.
The elderly person's perception of foods and food flavor is affected by age-associated changes in the chemical senses (taste, smell, and trigeminal sensation). Both classic and modern psychophysical techniques have been applied to achieve some understanding of these changes. Taste threshold sensitivity declines with age; however, the magnitude of the decline and the degree to which taste qualities are differentially affected remains to be understood. Suprathreshold taste intensity perception is affected by age, but there is a differential effect of taste quality. Experiments with blended foods have indicated that both olfactory and taste deficits contribute to older people's difficulty with food identification. Experiments assessing threshold sensitivity, suprathreshold intensity, and suprathreshold identification have all demonstrated significant impairment in olfaction in old age. In fact, these effects are far greater than in the taste system. Patients with Alzheimer's disease show even greater olfactory deficits than normal elderly and the effect is related to the degree of dementia. We have ruled out nasal disease in these patients as the primary causes of olfactory insensitivity, because significant impairment remains when the influence of nasal airflow and nasal cytology has been removed statistically. Both normal elderly and patients with Alzheimer's disease show impairment in odor memory. Sensitivity to, familiarity with, and identifiability of the odors all play a role in odor memory performance. Flavor preference also changes over the lifespan. Older subjects, for instance, rate high concentration of sugar and salt as pleasanter than young subjects do. Multiple influences contribute to this phenomenon. Elderly persons and those of lower nutritional status have shown preferences for higher concentrations of casein hydrolysate than young persons and those of higher nutritional status, suggesting that dietary preference can be related to chemosensory cues. There are significant age-associated changes in chemosensory perception that have the potential to interact with dietary selection and nutrition in the elderly. A better understanding of these phenomena may promote health and well-being in the elderly.


Inferring Very Recent Population Growth Rate from Population-Scale Sequencing Data: Using a Large-Sample Coalescent Estimator.
Large-sample or population-level sequencing data provide unprecedented opportunities for inferring detailed population histories, especially recent demographic histories. On the other hand, it challenges most existing population genetic methods: Simulation-based approaches require intensive computation, and analytical approaches are often numerically intractable when the sample size is large. We propose a computationally efficient method for simultaneous estimation of population size, the rate, and onset time of population growth in the very recent history, using the pattern of the total number of segregating sites as a function of sample size. Coalescent simulation shows that it can accurately and efficiently estimate the parameters of recent population growth from large-scale data. This approach has the flexibility to model population history with multiple growth stages or other epochs, and it is robust when the sample size is very large or at the population scale, for which the Kingman's coalescent assumption is not valid. This approach is applied to recently published data and estimates the recent population growth rate in the European population to be 1.49% with the onset time 7.26 ka, and the rate in the African population to be 0.735% with the onset time 10.01 ka.


Identification of a species specific regulatory site in human pancreatic cholesterol esterase.
All mammalian pancreatic cholesterol esterases (CEase) bind to membrane-associated heparin at a single site on the intestinal brush border membrane with a dissociation constant of 100 nM. While the enzyme is bound to the membrane, the activity of the human and bovine enzymes is enhanced 2-fold when compared to the activity of the enzyme in solution. On the other hand, soluble heparin potently inhibits the human CEase-catalyzed hydrolysis of cholesterol oleate with an IC50 of 2 x 10(-4) mg/mL, a value that is about 10(4) times more potent than that found with the bovine enzyme. The C-terminal portion of the human enzyme contains 16 proline-rich repeats of 11 amino acids each, while that from other species contains only a few of these repeat units. To determine if the unique human C-terminus is responsible for this inhibition, two chimeras containing either the human N-terminus (residues 1-445) and the bovine C-terminus (residues 446-557), HB, or the bovine N-terminus (residues 1-445) and the human C-terminus (residues 446-722), BH, were prepared. The cholesterol oleate hydrolytic activity of these chimeras was similar to that for the recombinant human and bovine enzymes. Importantly, each chimera was inhibited by heparin with IC50 values of 0.03 and 0.1 mg/mL for HB and BH, respectively. These intermediate IC50 values indicate that human CEase has two structural regions that contribute to is unique inhibition by this sulfated glycosaminoglycan, and these could regulate cholesterol uptake in humans.


Three-Dimensional Bending Analysis of Multi-Layered Orthotropic Plates by Two-Dimensional Numerical Model.
The paper presents effective numerical modelling of multi-layered plates with orthotropic properties. The method called the FEM23 is employed to construct the numerical model. The approach enables a full 3D analysis to be performed while using a 2D finite element mesh. The numerical model for a multi-layered plate is constructed by an assembling procedure, where each layer with orthotropic properties is added to the global numerical model. The paper demonstrates that the FEM23 method is very flexible in defining the multilayered plate, where the thickness of each layer as well as its mechanical orthotropic properties can be defined independently. Several examples of three-layered or nine-layered plates are analyzed in this paper. The results obtained by the FEM23 method coincide with the ones taken from the published papers or calculated with the standard 3D FEM approach. The orthotropic version of the FEM23 can be quite easily applied for other kinds of problems including thermo-mechanics, free vibrations, buckling analysis, or delamination.


Measles-induced respiratory distress, air-leak and ARDS.
Young infants with measles requiring respiratory support have a significant risk for death and long-term complications. Even in developed countries, the occurrence of spontaneous air-leaks and acute respiratory distress syndrome (ARDS) still represent the most severe clinical presentation in early childhood, with a high fatality rate. A clinical series review from a tertiary university paediatric intensive care unit (PICU) was undertaken. During the 2006-2007 outbreak in Rome, Italy, a young infant presented with ARDS/spontaneous air-leak and needed aggressive ventilatory management and haemodynamic support. Both nebulised iloprost and intravenous pentoxifylline were administered during the acute hypoxaemic phase; the role of this pharmacologic approach in critically ill patients is still under debate. We observed four further cases of respiratory impairment requiring a non-invasive approach. Clinical-radiological findings ranged from interstitial pneumonia to bronchiolitis-like pictures. All patients were imported cases, representing an important epidemiological factor and future medical issue, though they were not malnourished nor affected by chronic diseases. We conclude that early respiratory assessment and timely PICU referral is of mainstem importance in the youngest infants with measles-induced respiratory failure. The protean nature of clinical presentation and the possibility of rapid respiratory deterioration should be highlighted, and infants from immigrant families may represent a susceptible high-risk group.


Assessment of a multi-marker risk score for predicting cause-specific mortality at three years in older patients with heart failure and reduced ejection fraction.
Due to increasing co-morbidity associated with aging, heart failure (HF) has become more prevalent and heterogeneous in older individuals, and non-cardiovascular (CV) mortality has increased. Previously, we defined a multi-marker modality that included cystatin C (CysC), troponin T (TnT), and age. Here, we validated this multi-marker risk score by evaluating its predictions of all-cause mortality and CV mortality in an independent population of older individuals with HF and reduced ejection fraction (HFrEF). This prospective cohort study included 124 patients, median age 73 years, that had HFrEF. We determined all-cause mortality and CV mortality at a 3-year follow-up. We compared the risk score to the N-terminal prohormone of B-type natriuretic peptide (NT-proBNP) for predicting all-cause mortality and CV mortality. High risk scores were associated with both all-cause mortality (HR 4.2, 95% CI 2.2-8.1, p < 0.001) and CV mortality (HR 3.6, 95% CI 1.7-8.0, p = 0.0015). Receiver operating characteristics showed similar efficacy for the risk score and NT-proBNP in predicting all-cause mortality (HR 0.74, 95% CI 0.65-0.81 vs. HR 0.74, 95% CI 0.65-0.81, p = 0.99) and CV mortality (HR 0.68, 95% CI 0.59-0.76 vs. HR 0.67, 95% CI 0.58-0.75, p = 0.95). When the risk score was added to the NT-proBNP, the continuous net reclassification improvement was 56% for predicting all-cause mortality (95% CI 18-95%, p = 0.004) and 45% for predicting CV mortality (95% CI 2-89%, p = 0.040). In HFrEF, a risk score that included age, TnT, and CysC showed efficacy similar to the NT-proBNP for predicting all-cause mortality and CV mortality in an older population.


Dependence of control coefficient distribution on the boundaries of a metabolic system: a generalized analysis of the effects of additional input and output reactions to a linear pathway.
Both experimental and theoretical studies of metabolism are likely to relate to a segment that has been isolated for analytical purposes. In practice, it will be embedded in the whole of cellular metabolism. Thus, it is necessary to consider how conclusions about the control of an isolated pathway may be modified in this wider context where the input and output metabolites are considered as variables of cellular metabolism. Here, we analyse the effect of expanding a linear metabolic pathway by adding an extra input or an extra output. In particular, we analyse the effect of the elasticities of the extra steps on control coefficients. We derive matrix algebraic relationships for obtaining flux and concentration control coefficients from expressions depending on these extra elasticities and on parameters (elasticities and control coefficients) of the original pathway. These equations can be shown in certain cases to be generalized versions of earlier rescaling relationships and to be related to top-down analysis, but also apply where the new variable metabolite of the expanded pathway is an effector of more than one step of the original pathway. We use our relationships to analyse the dependence or independence of control coefficients upon these extra elasticities for the published analyses of the pathway of mammalian serine biosynthesis (Fell & Snell, 1988) and Escherischia coli threonine biosynthesis (Chassagnole et al., 2001). The same analysis can be applied to determine whether the transport reactions of substrates and products of a pathway in and out of a cell need to be included in estimations of the control coefficients of the enzymes.


Limb salvage procedures in osteosarcomas around the knee joint.
Surgical techniques developed for restoring skeletal continuity after a local resection of a bone tumor (limb salvage procedures) revolutionized the management of the patient suffering from osteosarcomas around the knee. In this article the authors review the current status of various reconstruction procedures; they include osteoarticular allograft arthrodesis, rotation plasty, expandable prosthesis and knee arthroplasty. In summary they suggest that the knee arthrodesis is the preferred procedure for young and active patients, the rotation plasty should be recommended as the alternative to amputation for very young patients, and the customized prostheses are preferred for patients with limited longevity.


The development of professional practice standards for Australian general practice nurses.
The aim of this study was to explore the current role of general practice nurses and the scope of nursing practice to inform the development of national professional practice standards for Australian general practice nurses. Increasing numbers of nurses have been employed in Australian general practice to meet the growing demand for primary care services. This has brought significant changes to the nursing role. Competency standards for nurses working in general practice were first developed in Australia in 2005, but limited attention has been placed on articulating the contemporary scope of practice for nurses in this setting. Concurrent mixed methods design. Data collection was conducted during 2013-2014 and involved two online surveys of Registered and Enrolled Nurses currently working in general practice, a series of 14 focus groups across Australia and a series of consultations with key experts. Data collection enabled the development of 22 Practice Standards separated into four domains: (i) Professional Practice; (ii) Nursing Care; (iii) General Practice Environment and (iv) Collaborative Practice. To differentiate the variations in enacting these Standards, performance indicators for the Enrolled Nurse, Registered Nurse and Registered Nurse Advanced Practice are provided under each Standard. The development of national professional practice standards for nurses working in Australian general practice will support ongoing workforce development. These Standards are also an important means of articulating the role and scope of the nurses' practice for both consumers and other health professionals, as well as being a guide for curriculum development and measurement of performance.


In vivo differentiation of magnetically labeled mesenchymal stem cells into hepatocytes for cell therapy to repair damaged liver.
It was unclear whether systemically administered mesenchymal stem cells (MSCs) labeled with magnetic nanoparticles can transdifferentiate into hepatocytes. In the present study, we built a new in vivo murine model for monitoring the transdifferentiation of magnetically labeled green fluorescent protein (GFP) positive MSCs into albumin-positive hepatocytes, under the carbon tetrachloride (CCl4) induced persistent liver damage. We also tracked magnetically labeled MSCs by using magnetic resonance imaging (MRI) in vivo. Among the liver damage groups, magnetically labeled GFP-positive MSCs (group A), GFP-positive MSCs (group B), and saline alone (group C) were intravenously injected. In control groups without CCl4 administration magnetically labeled GFP-positive MSCs (group D) were infused, whereas nothing was given in group E. MRI examinations were performed 24 hours and 4 weeks after cell injection in group A, B, and C. Liver-to-muscle contrast-to-noise ratios on T2*-weighted MR images were measured. At 4 weeks, 3 serum biologic liver function markers were analyzed, and mice in all groups were killed for histologic examination. The results showed that migration of transplanted magnetic labeled cells to the liver was successfully documented with in vivo MRI. Serum liver function markers were changed for all liver damage groups than nondamage control groups (P < 0.05), but still insignificant compared with group C (P > 0.05). Hematoxylin and eosin and Masson staining confirmed the presence of liver damage and hepatic fibrosis in group A, B, and C. Positive Prussian blue stained cells were highly correlated with GFP-positive cells in group A with an average matching rate of 95%. In group D, no iron-GFP-positive cells can be found in the liver. Albumin was expressed in (34% ± 6%) and (35% ± 7%) of GFP-positive cells in group A and B, respectively, and there was no significant difference between the 2 groups. Our data demonstrate that magnetic labeling technique synchronized well in GFP expressing MSCs and did not interfere with the transdifferentiation process and amending function of MSCs in vivo. Both magnetically labeled and unlabeled MSCs appeared to have the potential to differentiate into hepatocytes.


Altered left ventricular chamber stiffness and isovolumic relaxation in dogs with chronic pulmonary hypertension caused by emphysema.
In chronic obstructive lung disease, a right to left ventricular septal shift that occurs as a consequence of right ventricular pressure overload is the usual mechanism given to explain a decrease in left ventricular (LV) diastolic performance. The purpose of the present study was to examine the extent to which this mechanism could account for a decrease in LV diastolic function in a canine model in which pulmonary artery pressure was elevated to a level found in human disease. Severe emphysema was produced in dogs by repeated instillations of the enzyme papain into the lung. To assess LV diastolic function, we used sonomicrometry, in which three pairs of subendocardial crystal transducers were implanted along the three orthogonal axes of the LV. LV end-diastolic dimensions and pressure-strain relations along the three axes, as well as the time constant of LV isovolumic relaxation (T), were measured before (baseline) and after 1 year of emphysema (post-1-year study). The results showed that after 1 year of pulmonary hypertension, LV pressure-strain relations were decreased along the septal-lateral and anterior-posterior axes, but a right to left ventricular septal shift was not detected. The relation of average midwall circumferential stress to midwall circumferential strain was used to describe the intrinsic compliance of the LV. The results showed that myocardial stiffness increased in emphysema but that chamber volume was not reduced. At the post-1-year study, T was abnormally increased in the emphysema group in response to augmented preload and afterload compared with preemphysema measurements. We conclude that mechanisms other than ventricular interdependence may be operative in leading to altered LV diastolic filling in chronic emphysema.


Rosai-Dorfman Disease: Breast Involvement-Case Report and Literature Review.
Background and objectives: Rosai-Dorfman disease (RDD) is a type of histiocytosis that usually appears in young adults or children as bilateral cervical lymphadenopathy, but extranodal involvement in not uncommon. Although the pathogenesis is not entirely elucidated, recent studies showed a possible neoplastic process. Materials and methods: Our manuscript presents a rare case of Rosai-Dorfman disease of the breast, the management of this rare case, and a literature review. There are few cases reported of RDD of the breast (around 90 globally reported cases); the data is poor, and the management not yet standardized for these cases. The case reported here shows the importance of correct breast investigation, breast imaging, and ultrasound-guided biopsy that provided an accurate diagnosis and guided further management. Results: Although RDD of the breast was rarely presented as bilateral disease in other case reports, our case showed bilateral breast disease with the suspicion of breast cancer on imaging. Pathology and immunohistochemistry were of critical importance and showed a specific pattern for histiocytosis. A multidisciplinary approach was taken into consideration for these cases in order to establish the approach. Some patients underwent surgery, but watchful waiting and close follow-up were the preferred approach. Conclusions: RDD of the breast is a rare form of histiocytosis, with fewer than 100 globally published cases. Although the management of this disease is not established yet by guidelines, a follow-up approach should be enough for these patients, and surgery might be overtreatment. Mortality from RDD is very low due to comorbidities. A multidisciplinary team decision is important, and abstinence might significantly benefit these patients.


Enzymes of Nitrogen Assimilation Undergo Seasonal Fluctuations in the Roots of the Persistent Weedy Perennial Cichorium intybus.
Chicory (Cichorium intybus), a deep rooted weed, grows in regions with temperate climates. Seasonal partitioning of compounds between the root and shoot results in fluctuations in the soluble carbohydrate, nitrate, amino acid, and protein pools within the roots. The activities of nitrate reductase (NR) (EC 22.214.171.124), glutamine synthetase (EC 184.108.40.206), NADH (EC 126.96.36.199), ferrodoxin glutamate synthase (EC 18.104.22.168), and glutamate dehydrogenase (GDH) (EC 126.96.36.199-4) vary throughout the year and coincide with seasonal alterations in nitrate, fructose, and sucrose. During the winter, NR, glutamine synthetase and ferrodoxin glutamate synthase activities increase in the root, while GDH displays the opposite trend with elevated activity in the summer months. All of these enzymes exhibit seasonal alterations in abundance as detected by Western blot analysis, increasing during the winter and, therefore, contributing to the seasonally dynamic protein pool. Extensive fluctuations in abundance and activity of these enzymes in the root occur during the spring and fall and coincide with shoot growth and senescence, respectively. Several observations indicate that posttranslational modifications of NR and GDH are taking place throughout the year; for example, NR is particularly unstable during the spring and fall, and seasonal GDH activity does not correlate with protein abundance.


Caregiver-reported dementia as a predictor of oral health among patients receiving home-visit dental treatment: A retrospective cohort study.
To assess caregiver-reported dementia as a risk factor for retained roots, an indicator of poor oral hygiene, among patients receiving home-visit dental treatment in Japan. The medical records of 231 dentate patients who received home-visit dental treatment (covered by public medical insurance) for more than 2 years were retrospectively analyzed. The number of teeth and retained roots at the initial and final examinations were obtained from the dental charts, and the "change in the number of retained roots from initial to final examination" was determined. The presence or absence of caregiver-reported dementia, diabetes, and osteoporosis, as well as the level of long-term care needed, were used as indicators of general health condition at the initial interview. Multiple regression analyses were conducted in five models that tested the association of independent variables (age, gender, observation period, general health, presence or absence of caregiver-reported dementia at the initial interview) with changes in the number of retained roots. In all models, the presence of caregiver-reported dementia at the initial interview was significantly associated with the change in the number of retained roots (p < .05). The adjusted coefficient of determination (R2 ) of model 5, which included all the predetermined independent factors, was .168. Caregiver-reported dementia may be a risk factor for an increase in the number of retained roots among patients who receive home-visit dental treatment and may serve as an indicator of the need for regular and proactive oral hygiene management.


Metastatic gastroesophageal adenocarcinoma to skeletal muscle: a unique event.
Skeletal muscle is rarely the site of metastatic cancer, though a few such cases have been reported. Esophageal adenocarcinoma metastasic to skeletal muscle has not previously been reported in the literature. We describe the case of 71-year-old African American male with stage IV adenocarcinoma of the gastroesophageal junction. He had severe and disabling pain in the right thigh, which was tender to palpation. The pain was unresponsive to nonsteroidal anti-inflammatory drugs and full-dose narcotics. Plain x-ray films and bone scan were nondiagnostic. Magnetic resonance imaging showed a soft tissue mass involving the thigh muscles, anterior and medial to the right femur. Computed tomography (CT)-guided biopsy revealed that the thigh mass was metastatic adenocarcinoma consistent with the primary gastroesophageal cancer. Metastasis to muscle is rare, but physicians should be aware of the possibility because detection requires specific tests. We discuss the role of these tests, as well as available treatment options.


Prostaglandin E2 inhibits the activation of cloned T cell hybridomas.
To minimize complicating interactions inherent in heterogeneous cell populations, we used a panel of cloned murine autoreactive (E8.A1) and antigen-specific (HEL.C10, HEL.B14) T cell hybridomas to examine the effect of prostaglandin E2 (PGE2) on T cell activation. These T cells secrete interleukin 2 (IL 2) when co-cultured with a cloned population of I region-matched stimulator cells (TA3), or with mitogenic signals in the absence of TA3 stimulator cells. Physiologic concentrations of PGE2 inhibited the induction of IL 2 secretion by the T cell hybridomas tested, when they were activated either by TA3 cells or by mitogenic signals. IL 2 production was inhibited in a dose-dependent manner by concentrations of PGE2 between 10(-7) and 10(-11) M, with 50% inhibition occurring at 10(-10) M. Pretreatment of the T hybridoma cells with 10(-7) M PGE2 for 1 hr before culture also resulted in marked inhibition of IL 2 secretion. Similar pretreatment of the TA3 cells did not affect their ability to activate the T cell hybridomas. PGE2 at 10(-8) M induced a 30-fold increase in cAMP levels within 25 min of addition to culture of the E8.A1 T cell hybridoma, but caused no significant elevation of cAMP levels in TA3 cells. The direct addition of dibutyryl cAMP (dcAMP) to cultures of E8.A1 cells resulted in marked inhibition of IL 2 secretion when stimulated by TA3 or by mitogenic signals, with an average of 80% inhibition occurring at 10(-4) M dcAMP. PGE2 and dcAMP also inhibited the growth of E8.A1 cells. Initially, cell growth was virtually halted, but began to recover between 24 and 48 hr after the addition of either PGE2 or dcAMP. Neither PGE2 nor dcAMP inhibited the division of TA3 cells. High affinity binding sites for PGE2 were detected in the E8.A1 T cell hybridomas with an apparent Kd of 7.6 X 10(-10) M, which is consistent with the functional data. No specific binding was detected in the TA3 stimulator cells. These findings suggest that the immunosuppressive effects of PGE2 are localized to the T cell, are receptor regulated, and may be mediated by the associated increase of cAMP levels in the T cell hybridomas.


An exposure to the oxidized DNA enhances both instability of genome and survival in cancer cells.
Cell free DNA (cfDNA) circulates throughout the bloodstream of both healthy people and patients with various diseases and acts upon the cells. Response to cfDNA depends on concentrations and levels of the damage within cfDNA. Oxidized extracellular DNA acts as a stress signal and elicits an adaptive response. Here we show that oxidized extracellular DNA stimulates the survival of MCF-7 tumor cells. Importantly, in cells exposed to oxidized DNA, the suppression of cell death is accompanied by an increase in the markers of genome instability. Short-term exposure to oxidized DNA results in both single- and double strand DNA breaks. Longer treatments evoke a compensatory response that leads to a decrease in the levels of chromatin fragmentations across cell populations. Exposure to oxidized DNA leads to a decrease in the activity of NRF2 and an increase in the activity of NF-kB and STAT3. A model that describes the role of oxidized DNA released from apoptotic cells in tumor biology is proposed. Survival of cells with an unstable genome may substantially augment progression of malignancy. Further studies of the effects of extracellular DNA on malignant and normal cells are warranted.


Misconceptions about AIDS among children who can identify the major routes of HIV transmission.
Described knowledge about HIV transmission among 1,048 third, fourth, fifth, and sixth graders from a multiethnic urban school district. Participants answered questions about behaviors leading to HIV transmission and about mechanisms of transmission. Children at all grade levels demonstrated a high level of recognition of the three primary routes of HIV transmission (through sex, through drug needle sharing, and in utero). However, children who knew about these routes also had many misconceptions about the mechanisms involved in acquiring HIV through these routes and about the ways HIV is not transmitted. Misconceptions decreased with grade and socioeconomic status (SES). Although there were no race/ethnicity differences in knowledge of actual routes and mechanisms of HIV transmission, there were more misconceptions about routes and mechanisms of HIV transmission among African American and Asian American children than among white children.


Reproductive immunology: biomarkers of compromised pregnancies.
The objective of this paper is to consider several categories of biomarkers of human pregnancy. The design of the report is to discuss useful and promising markers and techniques. Research gaps, needs, and priorities are also defined. Useful markers are mixed lymphocyte culture reactions, measures of lymphocytotoxic antibodies, histocompatibility (HLA) typing, and immunohematological evaluations. Promising markers are measures of major basic protein and early pregnancy factor, as well as determinations of trophoblast-lymphocyte cross-reactive (TLX) antigens. Promising techniques are fluorescence-activated cell-sorter analysis of maternal blood for fetal and extraembryonic tissues and immunotherapy with TLX and other antigens to prevent spontaneous abortion. It is concluded that immunology has much to offer the development of biomarkers of human pregnancy.


Purification and properties of acyl coenzyme A thioesterase II from Rhodopseudomonas sphaeroides.
A high molecular weight acyl coenzyme A (acyl-CoA) thioesterase, designated thioesterase II, has been purified 5300-fold from photoheterotrophically grown cells of Rhodopseudomonas sphaeroides. In contrast to R. sphaeroides acyl-CoA thioesterase I [Boyce, S.G., & Lueking, D.R. (1984) Biochemistry 23, 141-147], thioesterase II has a native molecular mass (Mr) of 120,000, is capable of hydrolyzing saturated and unsaturated acyl-CoA substrates with acyl chain lengths ranging from C4 to C18, and is completely insensitive to the serine esterase inhibitor diisopropyl fluorophosphate. Palmitoyl-CoA and stearoyl-CoA are the preferred (lowest Km) saturated acyl-CoA substrates and vaccenoyl-CoA is the preferred unsaturated substrate. However, comparable Vmax values were obtained with a variety of acyl-CoA substrates. Unlike a similar thioesterase present in cells of Escherichia coli [Bonner, W.M., & Bloch, K. (1972) J. Biol. Chem. 247, 3123-3133], R. sphaeroides thioesterase II displays a high ratio of decanoyl-CoA to palmitoyl-CoA activities and exhibits little ability to hydrolyze 3-hydroxyacyl-CoA substrates. Only 3-hydroxydodecanoyl-CoA supported a measurable rate of enzyme activity. With the purification of thioesterase II, the enzymes responsible for greater than 90% of the acyl-CoA thioesterase activity present in cell-free extracts of R. sphaeroides have now been identified.


Genotyping analysis of Helicobacter pylori using multiple-locus variable-number tandem-repeats analysis in five regions of China and Japan.
H. pylori (Helicobacter pylori) is the major causative agent of chronic active gastritis. The population of H. pylori shows a high genomic variability among isolates. And the polymorphism of repeat-units of genomics had participated the important process of evolution. Its long term colonization of the stomach caused different clinical outcomes, which may relate to the high degree of genetic variation of H. pylori. A variety of molecular typing tools have been developed to access genetic relatedness in H. pylori isolates. However, there is still no standard genotyping system of this bacterium. The MLVA (Multi-locus of variable number of tandem repeat analysis) method is useful for performing phylogenetic analysis and is widely used in bacteria genotyping; however, there's little application in H. pylori analysis. This article is the first application of the MLVA method to investigate H. pylori from different districts and ethnic groups of China. MLVA of 12 VNTR loci with high discrimination power based on 30 candidates were performed on a collection of 202 strains of H. pylori which originated from five regions of China and Japan. Phylogenetic tree was constructed using MLVA profiles. 12 VNTR loci presented with high various polymorphisms, and the results demonstrated very close relationships between genotypes and ethnic groups. This study used MLVA methodology providing a new perspective on the ethnic groups and distribution characteristics of H. pylori.


The role of oophoropexy in patients with gynecological cancer who need radiation therapy.
Pelvic radiotherapy is an essential component of cancer therapy for patients with cervical and other gynecological malignancies. The ovaries are particularly radiosensitive, and even low radiotherapy doses may result in impaired or complete loss of ovarian function, causing hormonal disturbances and infertility. Recent advances in both surgery and radiotherapy have facilitated the ability of some patients to maintain ovarian function through ovarian transposition and careful radiotherapy planning. Multidisciplinary discussions should be undertaken to consider which candidates are appropriate for transposition. Generally, patients under age 35 should be considered due to ovarian reserve, likelihood of oophoropexy success, and radioresistance of ovaries. Those patients with small squamous cell tumors, minimal extra-uterine extension, and no lymphovascular invasion or lymph node involvement are ideal candidates to minimize risk of ovarian metastasis. Patients should be assessed and counseled about the risks of ovarian metastasis and the likelihood of successful ovarian preservation before undergoing oophoropexy and starting treatment. Oophoropexy should be bilateral if possible, and ovaries should be placed superior and lateral to the radiotherapy field. Studies limiting the mean ovarian dose to less than 2-3 Gray have demonstrated excellent preservation of ovarian function. Intensity modulated radiotherapy and volumetric modulated arc therapy techniques have the potential to further minimize the dose to the ovary with excellent outcomes. The addition of brachytherapy to the treatment regimen will probably cause minimal risk to transposed ovaries. Oophoropexy before radiotherapy may preserve the hormonal function of ovaries for a duration, and fertility might be possible through surrogate pregnancy. Successful ovarian transposition has the potential to improve the overall health and wellbeing, reproductive options, and potentially quality of life in patients with cervical and other gynecological cancers.


Nosocomial infections in surgical intensive care unit: A retrospective single-center study.
This study aims to study the incidence, microbiological and antibiotic sensitivity and resistance profile and impact on intensive care units (ICUs) stay and mortality of nosocomial infections in patients admitted to surgical ICU of our hospital. A retrospective analysis of all patients admitted, over the course of 1 year, in the surgical ICU was undertaken. All patients who developed nosocomial infections were included in the study. Incidence, sites, common organisms of nosocomial infection were identified. The antibiotic sensitivity pattern of the microorganisms which were cultured was identified. This group of patients with nosocomial infections was matched with group of patients without nosocomial infections with respect to age, gender, and clinical diagnosis and the impact of nosocomial infections on ICU stay, and mortality was studied. Of 1051 patients admitted to the ICU during the study, 350 patients developed nosocomial infections and were included in the study group. Of the remaining patients, 350 patients matching the patients in the study group were included in the control group. The prevalence of nosocomial infections in our study was 33.30%. Skin and soft tissue infections (36.30%), including postoperative wound infections were the most common nosocomial infection, followed by respiratory infections (24.46%) and genitourinary infections (23.40%). The most common organisms causing nosocomial infections were Escherichia coli (26.59%) and Acinetobacter species (18.08%). About 40% of all Gram-negative organisms isolated were multidrug resistant. The average length of stay in ICU was 14.4 days for patients with nosocomial infections and 5.4 days (P < 0.05) for matched patients without nosocomial infections. The mortality in patients with nosocomial infections was 25.14% while that in patients without nosocomial infections was 10.57% (P < 0.05). Overall ICU mortality was 14.27%. Nosocomial infections in surgical ICU patients significantly increase ICU length of stay and mortality.


Comparative Compressibility of Smectite Group under Anhydrous and Hydrous Environments.
High-pressure synchrotron X-ray powder diffraction studies of smectite group minerals (beidellite, montmorillonite, and nontronite) reveal comparative volumetric changes in the presence of different fluids, as pressure transmitting media (PTM) of silicone oil and distilled water for anhydrous and hydrous environments at room temperature. Using silicone oil PTM, all minerals show gradual contraction of unit-cell volumes and atomistic interplane distances. They, however, show abrupt collapse near 1.0 GPa under distilled water conditions due to hydrostatic to quasi-hydrostatic environmental changes of water PTM around samples concomitant with the transition from liquid to ICE-VI and ICE-VII. The degrees of volume contractions of beidellite, montmorillonite, and nontronite up to ca. 3 GPa are ca. 6.6%, 8.9%, and 7.5% with bulk moduli of ca. 38(1) GPa, 31(2) GPa, and 26(1) GPa under silicone oil pressure, whereas 13(1) GPa, 13(2) GPa, and 17(2) GPa, and 17(1) GPa, 20(1) GPa, and 21(1) GPa under hydrostatic and quasi-hydrostatic environments before and after 1.50 GPa, respectively.