Calcaneogenesis.
We report a case in which Ilizarov distraction osteogenesis was used to lengthen the portion of calcaneum that remained after a radical debridement for osteomyelitis. The patient was able to walk normally in unmodified shoes at the end of his treatment.


Medical expulsive therapy for pediatric urolithiasis: Systematic review and meta-analysis.
Kidney stone disease has become more common among children and young adults. Despite its well-documented success in adults, published success rates of medical expulsive therapy (MET) for pediatric urolithiasis vary widely. Our objective was to determine whether the aggregated evidence supports the use of MET in children. We searched the Cochrane Controlled Trials Register, clinicaltrials.gov, MEDLINE, and EMBASE databases, and recently presented meeting abstracts for reports in any language. In addition, the bibliographies of included studies were then hand-searched. The protocol was prospectively registered at PROSPERO (CRD42013005960). Inclusion criteria were children (aged ≤ 18 years) with urolithiasis treated with medications with the specific goal of increasing spontaneous stone passage rate, including but not limited to alpha-adrenergic blockers (e.g., tamsulosin or doxazosin), calcium channel blockers (e.g., nifedipine), or other adjuvant medications (e.g., steroids or tolterodine). Manuscripts were then assessed and data abstracted in duplicate, with differences resolved by the senior author. Risk of bias was assessed using standardized instruments. Descriptive statistical analyses were performed as appropriate. We identified 11,197 studies, five of which (3 randomized controlled trials, 2 retrospective cohorts) were included in the pooled meta-analysis. Although we found little evidence of significant publication bias, we were unable to assess the likelihood of other forms of bias (allocation, selection) for most included studies due to reporting limitations. The pooled results demonstrate that MET significantly increased the odds of spontaneous stone passage (OR 2.21, 95% CI 1.40-3.49). Between-study heterogeneity was not statistically significant (I(2) = 14%, p = 0.36). Bivariate meta-regression models revealed no significant association between the likelihood of stone passage and study COI (p = 0.9), study country (p = 0.7), patient age (p = 0.4), patient gender (p = 0.4), duration of follow-up (p = 0.3), or stone size (p = 0.7). Side effects of MET were reported to be minimal. Relatively few patients reported any adverse effects at all; the most commonly reported issue was somnolence. Concerns about biases affecting the published outcomes of the included studies exist due to the low quality of the randomized controlled trials reviewed for analysis. However, there was little visual evidence of publication bias noted on the funnel plot, as confirmed by the Begg test (p = 0.5). Consistent with the adult literature, pediatric studies demonstrate that treatment with MET results in increased odds of spontaneous ureteral stone passage and a low rate of adverse events. Although the accumulated literature is limited by inconsistent and/or incomplete reporting, there is nonetheless a clear, cumulative positive effect of MET on stone passage among children. The available evidence thus supports a prominent role for MET in treatment algorithms for pediatric urolithiasis.


A truncated herpes simplex virus origin binding protein which contains the carboxyl terminal origin binding domain binds to the origin of replication but does not alter its conformation.
We have studied the DNA binding properties of a polypeptide consisting of the carboxyl terminal 37% of UL9, the herpes simplex virus type 1 (HSV-1) origin of replication binding protein. Using a Sindbis virus expression system, we expressed and partially purified this truncated form of UL9 (UL9CT) which contains the site-specific DNA binding domain. UL9CT specifically recognized UL9 binding sites on a 200 base pair DNA fragment containing the HSV origin ori(s) and appeared to bind as a dimer to each site. DNAse I footprint analysis showed that UL9CT protected the two high affinity binding sites of ori(s), but unlike full-length UL9, UL9CT did not induce a conformational change in the origin. Addition of anti-UL9CT antibody to the UL9CT-origin complex, however, caused a conformational change in the origin to be evident. Our results suggest that a domain, or domains, in the amino terminus are necessary for a UL9-induced origin conformational change to occur and that UL9-UL9 interactions between binding sites are involved.


Bayesian analysis for cystic fibrosis risks in prenatal and carrier screening.
Risk assessment is an essential component of genetic counseling and testing, and Bayesian analysis plays a central role in complex risk calculations. We previously developed generalizable Bayesian methods to calculate the autosomal recessive disease risk of a fetus when one or no mutation is detected, and another, independent risk factor is present. Our methods are particularly useful for calculating the CF disease risk for a fetus with echogenic bowel. In genetics practice, however, there are other scenarios for which our previous methods are inadequate. We provide herein methods for calculating genetic risks in a variety of common clinical scenarios. These scenarios include the following: (1) different mutation panels that have been used for the parents and for a fetus; (2) genetic testing results available on the proband or other relatives, in addition to the consultand; (3) fetal ultrasound negative for echogenic bowel with a positive family history; and (4) a consultand with a mixed ethnic background. Our Bayesian methods have proven their versatility through application to many different common genetic counseling scenarios. These methods permit autosomal recessive disease and carrier probabilities to be calculated accurately, taking into account all relevant information. Our methods allow accurate genetic risk estimates for patients and their family members for CF or other autosomal recessive disorders.


A systematic review and meta-analysis suggests obesity predicts onset of chronic kidney disease in the general population.
Obesity and chronic kidney disease (CKD) are public health priorities that share core pathophysiological mechanisms. However, whether high body mass index (BMI) increases risk of CKD de novo remains ill-defined. To evaluate the role of BMI in predicting CKD onset in the general adult population, we performed a systematic review and meta-analysis of PubMed and ISI Web of Science databases articles published between January 2000 and August 2016 without language restriction. We selected studies in adult individuals from a general population with normal renal function at baseline that reported the risk of low estimated glomerular filtration (eGFR) (under 60 mL/min/1.73m2) and/or albuminuria (1+ at dipstick or an albumin creatinine ratio of 3.4 mg/mmol or more) as hazard ratio, odds ratio or relative risk related to obesity, overweight, or BMI as continuous value. A total of 39 cohorts covering 630, 677 participants with a mean follow-up of 6.8 years were selected. Obesity increased the relative risk, 95% confidence interval and heterogeneity (I2) of developing low eGFR (1.28, 1.07-1.54, [I2: 95.0%]) and albuminuria (1.51, 1.36-1.67, [I2: 62.7%]). Increase of BMI unit was also associated with higher risk of low eGFR (1.02, 1.01-1.03, [I2: 24.3%]) and albuminuria (1.02, 1.00-1.04, [I2: 0%]). Conversely, overweight did not predict onset of either low eGFR (1.06, 0.94-1.21, [I2: 50.0%]) or albuminuria (1.24, 0.98-1.58, [I2: 49.4%]). Thus, a high BMI predicts onset of albuminuria without kidney failure (CKD stages 1-2) as well as CKD stages 3 and higher, the effect being significant only in obese individuals. Hence, our findings may have implications to improve risk stratification and recommendations on body weight control in the general population.


Visualizing resonances in the complex plane with vibrational phase contrast coherent anti-Stokes Raman scattering.
In coherent anti-Stokes Raman scattering (CARS), the emitted signal carries both amplitude and phase information of the molecules in the focal volume. Most CARS experiments ignore the phase component, but its detection allows for two advantages over intensity-only CARS. First, the pure resonant response can be determined, and the nonresonant background rejected, by extracting the imaginary component of the complex response, enhancing the sensitivity of CARS measurements. Second, selectivity is increased via determination of the phase and amplitude, allowing separation of individual molecular components of a sample even when their vibrational bands overlap. Here, using vibrational phase contrast CARS (VPC-CARS), we demonstrate enhanced sensitivity in quantitative measurements of ethanol/methanol mixtures and increased selectivity in a heterogeneous mixture of plastics and water. This powerful technique opens a wide range of possibilities for studies of complicated systems where overlapping resonances limit standard methodologies.


A validated quantitative assay to detect occult micrometastases by reverse transcriptase-polymerase chain reaction of guanylyl cyclase C in patients with colorectal cancer.
Guanylyl cyclase C (GCC), a receptor for bacterial diarrheagenic enterotoxins, may be a prognostic and predictive marker to detect occult micrometastases in patients undergoing staging for colorectal cancer. However, quantification of GCC expression in tissues by the quantitative reverse transcription-PCR (qRT-PCR) has not undergone analytic and clinicopathologic validation. A technique to quantify GCC mRNA in tissues employing RT-PCR was developed and validated employing external calibration standards of RNA complementary to GCC. GCC qRT-PCR exhibited reaction efficiencies >92%, coefficients of variations <5%, linearity >6 orders of magnitude, and a limit of quantification of >25 copies of GCC cRNA. This assay confirmed that GCC mRNA was overexpressed by colorectal tumors from 41 patients, which correlated with increased GCC protein quantified by immunohistochemistry. Analyses obtained with 164 lymph nodes from patients free of cancer and 15 nodes harboring metastases established a threshold for metastatic disease of approximately 200 GCC mRNA copies/mug total RNA, with a sensitivity of 93% and specificity of 97%. GCC mRNA above that threshold was detected in 76 of 367 (approximately 21%) nodes free of disease by histopathology from 6 of 23 (26%) patients, suggesting the presence of occult micrometastases. Quantifying GCC mRNA in tissues by RT-PCR employing external calibration standards is analytically robust and reproducible, with high clinicopathologic sensitivity and specificity. This validated assay is being applied to approximately 10,000 lymph nodes in a prospective trial to define the sensitivity of GCC qRT-PCR for staging patients with colorectal cancer.


Use of Mpc-amino acids in solid phase peptide synthesis leads to improved coupling efficiencies.
The Mpc-group has a somewhat better stability than the Fmoc-group, resists catalytic hydrogenolysis, is highly stable in acidic media and its elimination product does not polymerize spontaneously. In a direct comparison of coupling efficiencies obtained in solid phase peptide syntheses using Mpc- or Fmoc-amino acids it is shown that the use of Mpc-amino acids leads to better coupling efficiencies and, consequently, a more homogeneous peptide. An improved synthesis of Mpc-ONSu and of Mpc-amino acid derivatives is presented.


Fetal growth and the lifetime risk of generalized anxiety disorder.
Anxiety disorders are thought to have their origins in early childhood, though they have not yet been studied as a potential outcome of impaired fetal growth, which has been implicated in the developmental etiologies of many psychopathologies. This study investigated the association between indicators of fetal growth and the development of generalized anxiety disorder (GAD). Indicators of fetal growth, including birth weight (BW) and ponderal index (PI), were assessed among 682 offspring of participants in Providence, Rhode Island, site of the Collaborative Perinatal Project. Participants were interviewed as adults, and their lifetime histories of GAD were assessed using the Diagnostic Interview Schedule. We used Cox regression to estimate the association between fetal growth indicators and development of GAD. The lifetime risk of GAD differed between infants in the highest category of BW, PI, and all others. Newborns with birth weights below 3.5 kg (hazard ratio, HR: 2.38; CI=1.25, 4.55), in the lowest four BW Z-score quintiles (HR=2.49; CI=1.14, 5.45) or a PI in the lowest four quintiles (HR=2.33; CI=1.04, 5.00) had higher lifetime risks of GAD. In contrast to earlier studies on psychiatric outcomes in relation to fetal growth, there was no linear relationship between birth weight and GAD. Although these results generally support the hypothesis that a healthy nutritional fetal uptake, as indicated by BW and PI, is associated with better lifetime mental health, further work is needed to characterize the nature of the association between fetal growth and subsequent psychopathology.


Apoptosis induced by X-irradiation of rec-myc cells is postmitotic and not predicted by the time after irradiation or behavior of sister cells.
Rat embryo cells expressing the c-myc oncogene (rec-myc) were studied by time-lapse microscopy to determine whether radiation-induced apoptosis occurred before or after mitosis. Following X-irradiation with 9.5 Gy, cells were imaged every 3 min for 6 days. Episodes of apoptotic blebbing were very consistent from cell to cell, lasting 30-60 min, followed by cessation of movement and cell death. In contrast, the time of initiation of apoptotic blebbing was unpredictable. At least 96% of the apoptotic episodes were postmitotic, after one to four cell divisions and 2-97 h after a given division. Sister cells often behaved differently from one another, with apoptosis in one sister occurring many h or several divisions after apoptosis in the other. Thus, the onset of radiation-induced apoptosis in rec-myc cells is not strictly programmed but may result from the segregation of chromosome aberrations in the postirradiation generations.


Selective cytotoxicity against human osteosarcoma cells by a novel synthetic C-1 analogue of 7-deoxypancratistatin is potentiated by curcumin.
The natural compound pancratistatin (PST) is a non-genotoxic inducer of apoptosis in a variety of cancers. It exhibits cancer selectivity as non-cancerous cells are markedly less sensitive to PST. Nonetheless, PST is not readily synthesized and is present in very low quantities in its natural source to be applied clinically. We have previously synthesized and evaluated several synthetic analogues of 7-deoxypancratistatin, and found that JC-TH-acetate-4 (JCTH-4), a C-1 acetoxymethyl analogue, possessed similar apoptosis inducing activity compared to PST. In this study, notoriously chemoresistant osteosarcoma (OS) cells (Saos-2, U-2 OS) were substantially susceptible to JCTH-4-induced apoptosis through mitochondrial targeting; JCTH-4 induced collapse of mitochondrial membrane potential (MMP), increased reactive oxygen species (ROS) production in isolated mitochondria, and caused release of apoptosis inducing factor (AIF) and endonuclease G (EndoG) from isolated mitochondria. Furthermore, JCTH-4 selectively induced autophagy in OS cells. Additionally, we investigated the combinatory effect of JCTH-4 with the natural compound curcumin (CC), a compound found in turmeric spice, previously shown to possess antiproliferative properties. CC alone had no observable effect on Saos-2 and U-2 OS cells. However, when present with JCTH-4, CC was able to enhance the cytotoxicity of JCTH-4 selectively in OS cells. Such cytotoxicity by JCTH-4 alone and in combination with CC was not observed in normal human osteoblasts (HOb) and normal human fetal fibroblasts (NFF). Therefore, this report illustrates a new window in combination therapy, utilizing a novel synthetic analogue of PST with the natural compound CC, for the treatment of OS.


Genes potentially involved in plaque rupture.
Rupture of an atherosclerotic plaque is the predominant underlying event in the pathogenesis of acute coronary syndromes and stroke. While ruptured plaques are morphologically well described, the precise molecular mechanisms involved in plaque rupture are still incompletely understood. Over the last few years, techniques like microarray, suppression subtractive hybridization and differential display enabled us to study complex gene expression profiles that occur during the process of atherogenesis. In this review we focus on recent large-scale gene expression profiles performed on whole mount vascular specimens. The gene expression profiles on whole mount vascular tissue confirmed that at least three mechanisms are involved in plaque rupture: (1) a disturbed balance in extracellular matrix turnover, (2) disturbed regulation of cell turnover and (3) processes involved in lipid metabolism. Animal models exhibiting features of plaque rupture reflect the involvement of these three mechanisms. The most dramatic mouse phenotypes were observed after interventions in at least two of these mechanisms. The observation of plaque rupture in recent mice models is indicative of the multifactorial process of plaque rupture. This multifactorial character of plaque rupture suggests that interventions may be most effective when they influence more than one mechanisms at a time.


Recognition of Extracellular Bacteria by NLRs and Its Role in the Development of Adaptive Immunity.
Innate immune recognition of bacteria is the first requirement for mounting an effective immune response able to control infection. Over the previous decade, the general paradigm was that extracellular bacteria were only sensed by cell surface-expressed Toll-like receptors (TLRs), whereas cytoplasmic sensors, including members of the Nod-like receptor (NLR) family, were specific to pathogens capable of breaching the host cell membrane. It has become apparent, however, that intracellular innate immune molecules, such as the NLRs, play key roles in the sensing of not only intracellular, but also extracellular bacterial pathogens or their components. In this review, we will discuss the various mechanisms used by bacteria to activate NLR signaling in host cells. These mechanisms include bacterial secretion systems, pore-forming toxins, and outer membrane vesicles. We will then focus on the influence of NLR activation on the development of adaptive immune responses in different cell types.


Knockdown of MKL1 ameliorates oxidative stress-induced chondrocyte apoptosis and cartilage matrix degeneration by activating TWIST1-mediated PI3K/AKT signaling pathway in rats.
Studies have reported that megakaryocytic leukemia 1 (MKL1) is closely related to the pathological process of a variety of inflammatory diseases, but its role in osteoarthritis (OA) needs to be clarified. This study aimed to investigate the regulatory role of MKL1 in oxidative stress-induced chondrocyte apoptosis and cartilage matrix degeneration. The expressions of target mRNAs and proteins were measured by using reverse transcription-quantitative polymerase chain reaction and western blotting. ELISA assay was used to measure the levels of IL-6, IL-8, and TNF-α in chondrocytes. And commercial kits based on different spectrophotometry or colorimetry methods were performed to validate oxidative stress. CCK-8 and apoptosis kits were used to determine cell viability and apoptosis. Rat OA model was established by anterior cruciate ligament transection (ACLT), and the expression of MKL1 was interfered by injecting sh-MKL1 lentiviral vector into caudal vein. The results showed that the expression of MKL1was induced by H2O2 in chondrocytes. Knockdown of MKL1 alleviated H2O2-induced inflammation and cell apoptosis, reduced H2O2-induced oxidative stress, and improved cartilage matrix degeneration of chondrocytes. Besides, inhibition of MKL1 regulated the activation of TWIST1-mediated PI3K/AKT signaling. Further studies have found that TWIST1-mediated PI3K/AKT signaling was involved in the regulation mechanism of MKL1 on chondrocyte apoptosis and cartilage matrix degeneration. Next, intervention with MKL1 inhibited the progression of OA in rats. These results demonstrated that MKL1 regulate the apoptosis and cartilage matrix degeneration of chondrocytes via TWIST1-mediated PI3K/AKT signaling.


Detection of DNA of W. bancrofti in blood samples by QC-PCR-ELISA-based.
An internal control was used in a polymerase chain reaction PCR-ELISA-based technique to detect the DNA repeat of the filarial parasite W. bancrofti. The sensitivity of the test could detect as low as one single microfilaria added to 200 ul of blood. The assay was evaluated on field samples from persons living in areas endemic for filariasis. Examination of night blood of 113 individuals for the presence of microfilaria by filtration revealed 44 microfilaria carriers. All microfilaria carriers were positive in the PCR-ELISA and, in addition, 14 more samples were proven to contain parasite DNA. All the 58 proven cases had circulating filarial antigens in their serum samples. Assuming a sensitivity of PCR-ELISA on night blood of 100%, the sensitivity of night blood filtration was 74% and that of circulating filarial antigens is 100%. The data showed that the described PCR-ELISA method was capable of detecting the filarial infections. Consequently, this method facilitated the identification of the filarial endemic areas and the monitoring of control programs.


International experiences with ceftriaxone in the treatment of lower respiratory tract infections.
The clinical efficacy and tolerability of ceftriaxone in the treatment of pneumonia and other lower respiratory tract infections were evaluated in 827 patients (515 pneumonia, 312 other lower respiratory tract infections) reported in the international literature (daily dose: 1 of 2 g.i.v. or i.m. in most patients). Therapeutic success was achieved in 738 patients (89.2%). Microbiological results were evaluated in 295 patients. Eradication of the most common respiratory pathogens was achieved in 100% of cases and of Enterobacteriaceae in 85.7%-100%. Adverse effects occurred in 4.9% of patients. A large multicenter trial was carried out in Italy using a single daily dose of 1-2 g by i.v. or i.m. Six hundred ninety-six patients were admitted to the study (370 pneumonia, and 326 other lower respiratory tract infections). Therapeutic success was achieved in 668 cases (96%). Pathogens were eradicated in 88% of cases (184 pts evaluated). Side effects were observed in 4.6% of cases.


An Insider View of the Cancer Radiation Experience Through the Eyes of a Cancer Patient.
While oncology providers see and treat thousands of cancer patients every year, few have had cancer themselves, or know what's it like to be in the shoes of a cancer patient days in and days out. This article written by a cancer survivor, writer, and experience design consultant lifts the lid on the cancer patient experience, for the benefit of noncancer patients. Through visual imageries, the author helps oncology providers and caregivers visualize and realize the vulnerability of the cancer experience and discover the treatment experience through new eyes. The article reveals emotional, mental, and somatic stressors, which add stress and/or trauma to the treatment experience and have been largely overlooked by health-care providers.


Inactivation of blasticidin S by Bacillus cereus. VI. Structure and comparison of the bsr gene from a blasticidin S-resistant Bacillus cereus.
Two types of recombinant plasmids containing 600 bp Nde I fragments that coded the bsr gene in opposite directions were obtained. Nucleotide sequencing shows that the bsr encodes a 140 amino acid protein with a putative molecular weight of 15560, the same as that of purified blasticidin S (BS)-deaminase (BSR), on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) (15500). Upstream of the open reading frame, a Shine-Dalgarno (SD) sequence, frequent inverted repeats, and the sigmaA and sigmaB promoter sequences are observed. The transcriptional start point was determined to be the A located 7 bases downstream from the putative sigmaA promoter (91TTGATC and 113TAAAAT) by the primer extension method and site directed mutagenesis at the -10 or -35 promoter region. A comparison of the amino acid sequence of BSR with that of BS-deaminase from Aspergillus terreus (BSD) showed 27.2% homology. Low degrees of homology were also observed with cytidine deaminase and deoxy cytidine monophosphate (CMP) deaminase. Four conserved amino acid motifs were observed, VGAx6G, C(orH)AEx6A, SPCGxCR, and Gx8ELIP (x(n) indicates a nonspecific residue and its position). It is possible that the three Cys residues and the Glu in the conserved motifs comprise the active center. Site-directed mutagenesis of the Cys residues supports this possibility.


Brunei epidemiological stroke study: patterns of hypertension and stroke risk.
Hypertension is the most important known risk factor for cardiovascular diseases. A cross-sectional study was conducted in Brunei Darussalam to estimate the prevalence of hypertension and its association with socioeconomic and life-style factors and impact on stroke incidence. Five thousand and sixty-three participants aged above 18 years from 2103 randomly selected households in the Brunei-Muara district of Brunei Darussalam were surveyed. Hypertension was defined as mean SBP at least 140 mmHg, DBP at least 90 mmHg, or taking antihypertensive medication and blood pressure was measured twice. Logistic regression models are used to analyze the association between hypertension/medication for hypertension and sex, age, overweight, education, smoking, family history of hypertension, and employment. A total of 48.3% [95% confidence interval (CI): 46.9-49.7%] of all respondents were identified as hypertensive. Prevalence of hypertension was higher in men (52.8%; 95% CI: 50.7-54.9%) compared to women (45.0%; 95% CI: 43.2-46.8%) and women seek treatment more often than men. Age, overweight, lower levels of education, and a family history of high blood pressure are positively associated with the prevalence of hypertension. The prevalence of overweight (57.3%) and obesity (23.7%) is high and the attributable risk of hypertension for stroke is large. The prevalence of hypertension in Brunei is high in both women and men. Information campaigns and prevention programs are needed to be able to cope with the increasing problem of hypertension and resulting diseases like stroke in Brunei in the near future.


[Patients with lung diseases and sports].
Lung patients are suffering from dyspnea. These symptoms make any physical exertion unpleasant, and patients become sedentary. This behaviour leads to a deconditioning of the cardiocirculatory and muscular system which renders activity even more unpleasant, thus reinforcing the sedentary life style. This downward spiral can be interrupted by a program of progressive exercise which should be adapted to the type and severity of the pulmonary disease. In this context, the value of sport therapy in the treatment of asthma bronchiale and COPD is redefined. The possibilities and limitations for this form of treatment are explained.


Clinicopathological characteristics of immunoglobulin G4-related sialadenitis.
Immunoglobulin G4-related disease (IgG4-RD) is a newly recognized fibro-inflammatory condition. Forty-two cases with immunoglobulin G4-related sialadenitis (IgG4-RS) confirmed by histopathological and immunohistochemical assessment were studied to clarify the clinicopathologic characteristics of the salivary glands involved in IgG4-RS, especially the relationship between the histopathologic features and function of salivary glands or serum levels of IgG4. Clinical, serologic, imaging and histopathological data of these cases were analyzed. CT volumes of submandibular, parotid, and lacrimal glands were calculated. The saliva flow rate was measured. Scintigraphy with 99mTc-pertechnetate was undertaken in 31 cases, and the concentration index (CI) and secretion index (SI) was calculated. Relationships between fibrosis severity and salivary gland function or serum IgG4 levels were analyzed. The first symptom was swelling of bilateral submandibular or lacrimal glands. Physical examination showed multiple bilateral major salivary glands (including sublingual and accessory parotid glands) and lacrimal glands were enlarged in IgG4 RS. Multiple enlarged cervical lymph nodes were noted in 30 patients. Saliva flow at rest was lower than normal in 34 cases; stimulated saliva flow was lower than normal in 15 cases. Secretory function was reduced more severely in the submandibular glands than in the parotid glands. Serum levels of IgG4 were elevated in 95.2% of cases and 78.6% patients had increased IgE levels. Serum IgG4 level was higher and saliva secretion lower as glandular fibrosis increased. Prominent changes in the morphology, histology, immunohistochemistry and secretion of the major salivary glands of IgG4-RS patients were accompanied by involvement of the lacrimal glands and cervical lymph nodes. Elevated IgE, allergic history, eosinophil infiltration suggest allergic reactions as a potential pathogenesis of IgG4-RS. Severity of glandular fibrosis correlated with salivary function and serum levels of IgG4.


Dissolved Microcystin Release Coincident with Lysis of a Bloom Dominated by Microcystis spp. in Western Lake Erie Attributed to a Novel Cyanophage.
Western Lake Erie (Laurentian Great Lakes) is prone to annual cyanobacterial harmful algal blooms (cHABs) dominated by Microcystis spp. that often yield microcystin toxin concentrations exceeding the federal EPA recreational contact advisory of 8 μg liter-1 In August 2014, microcystin levels were detected in finished drinking water above the World Health Organization 1.0 μg liter-1 threshold for consumption, leading to a 2-day disruption in the supply of drinking water for >400,000 residents of Toledo, Ohio (USA). Subsequent metatranscriptomic analysis of the 2014 bloom event provided evidence that release of toxin into the water supply was likely caused by cyanophage lysis that transformed a portion of the intracellular microcystin pool into the dissolved fraction, rendering it more difficult to eliminate during treatment. In August 2019, a similar increase in dissolved microcystins at the Toledo water intake was coincident with a viral lytic event caused by a phage consortium different in composition from what was detected following the 2014 Toledo water crisis. The most abundant viral sequence in metagenomic data sets was a scaffold from a putative member of the Siphoviridae, distinct from the Ma-LMM01-like Myoviridae that are typically documented to occur in western Lake Erie. This study provides further evidence that viral activity in western Lake Erie plays a significant role in transformation of microcystins from the particulate to the dissolved fraction and therefore requires monitoring efforts from local water treatment plants. Additionally, identification of multiple lytic cyanophages will enable the development of a quantitative PCR toolbox to assess viral activity during cHABs.IMPORTANCE Viral attack on cHABs may contribute to changes in community composition during blooms, as well as bloom decline, yet loss of bloom biomass does not eliminate the threat of cHAB toxicity. Rather, it may increase risks to the public by delivering a pool of dissolved toxin directly into water treatment utilities when the dominating Microcystis spp. are capable of producing microcystins. Detecting, characterizing, and quantifying the major cyanophages involved in lytic events will assist water treatment plant operators in making rapid decisions regarding the pool of microcystins entering the plant and the corresponding best practices to neutralize the toxin.


[High-risk pulmonary surgery in potential candidates for a heart transplant].
Severe ventricular dysfunction and concomitant infection are considered absolute contraindications for major thoracic operations and immunosuppressive therapy, respectively. However, cardiac transplantation represents the first-choice treatment in advanced heart failure. We report the case of a patient with dilated cardiomyopathy and severe left ventricular dysfunction (ejection fraction = 25%), initially not considered as a potential heart transplant candidate due to the presence of a lung abscess. The patient subsequently underwent atypical pulmonary resection with intraoperative and perioperative intraaortic balloon counter-pulsation for circulatory support and was then listed for cardiac transplant. Pitfalls and intra/postoperative strategy, all of which are potentially important aspects in minimizing operative risk, are discussed.


Complementary role of chest roentgenogram in interpretation of Tc-99m sulfur colloid liver scan.
Correlation of a chest roentgenogram and a radionuclide scan facilitated the interpretation of a liver scan with a defect in the dome that was due to an extrinsic compression and photon attenuation by a metastatic tumor in the right lung base.


A Review of Facebook Research in the Social Sciences.
With over 800 million active users, Facebook is changing the way hundreds of millions of people relate to one another and share information. A rapidly growing body of research has accompanied the meteoric rise of Facebook as social scientists assess the impact of Facebook on social life. In addition, researchers have recognized the utility of Facebook as a novel tool to observe behavior in a naturalistic setting, test hypotheses, and recruit participants. However, research on Facebook emanates from a wide variety of disciplines, with results being published in a broad range of journals and conference proceedings, making it difficult to keep track of various findings. And because Facebook is a relatively recent phenomenon, uncertainty still exists about the most effective ways to do Facebook research. To address these issues, the authors conducted a comprehensive literature search, identifying 412 relevant articles, which were sorted into 5 categories: descriptive analysis of users, motivations for using Facebook, identity presentation, the role of Facebook in social interactions, and privacy and information disclosure. The literature review serves as the foundation from which to assess current findings and offer recommendations to the field for future research on Facebook and online social networks more broadly.


Association and interaction of APOA5, BUD13, CETP, LIPA and health-related behavior with metabolic syndrome in a Taiwanese population.
Increased risk of developing metabolic syndrome (MetS) has been associated with the APOA5, APOC1, BRAP, BUD13, CETP, LIPA, LPL, PLCG1, and ZPR1 genes. In this replication study, we reassessed whether these genes are associated with MetS and its individual components independently and/or through complex interactions in a Taiwanese population. We also analyzed the interactions between environmental factors and these genes in influencing MetS and its individual components. A total of 3,000 Taiwanese subjects were assessed in this study. Metabolic traits such as waist circumference, triglyceride, high-density lipoprotein (HDL) cholesterol, systolic and diastolic blood pressure, and fasting glucose were measured. Our data showed a nominal association of MetS with the APOA5 rs662799, BUD13 rs11216129, BUD13 rs623908, CETP rs820299, and LIPA rs1412444 single nucleotide polymorphisms (SNPs). Moreover, APOA5 rs662799, BUD13 rs11216129, and BUD13 rs623908 were significantly associated with high triglyceride, low HDL, triglyceride, and HDL levels. Additionally, we found the interactions of APOA5 rs662799, BUD13 rs11216129, BUD13 rs623908, CETP rs820299, LIPA rs1412444, alcohol consumption, smoking status, or physical activity on MetS and its individual components. Our study indicates that the APOA5, BUD13, CETP, and LIPA genes may contribute to the risk of MetS independently as well as through gene-gene and gene-environment interactions.


Highspeed multiplexed heterodyne interferometry.
Digitally enhanced heterodyne interferometry is a metrology technique that uses pseudo-random noise codes for modulating the phase of the laser light. Multiple interferometric signals from the same beam path can thereby be isolated based on their propagation delay, allowing one to use advantageous optical layouts in comparison to classic laser interferometers. We present here a high speed version of this technique for measuring multiple targets spatially separated by only a few centimetres. This allows measurements of multiplexed signals using free beams, making the technique attractive for several applications requiring compact optical set-ups like for example space-based interferometers. In an experiment using a modulation and sampling rate of 1.25 GHz we are able to demonstrate multiplexing between targets only separated by 36 cm and we achieve a displacement measurement noise floor of <3 pm/√Hz at 10 Hz between them. We identify a limiting excess noise at low frequencies which is unique to this technique and is probably caused by the finite bandwidth in our measurement set-up. Utilising an active clock jitter correction scheme we are also able to reduce this noise in a null measurement configuration by one order of magnitude.


The benefits of ultrasound-guided continuous sensory nerve blockade in the setting of burn injury: a case report of bilateral continuous superficial peroneal nerve blockade in a patient with severe sleep apnea.
The management of pain after burn injuries is a clinical challenge magnified in patients with significant comorbidities. Presently, burn pain is treated via a wide variety of modalities, including systemic pharmacotherapy and regional analgesia. Although the latter can provide effective pain control in patients with burn injuries, it is relatively underused. Furthermore, the development of ultrasound guidance has allowed for novel approaches and sparing of motor nerve blockade with preference toward sensory-specific analgesia that has not been possible previously. This can result in decreased opiate use and shorter latency to initiation of rehabilitation. In this report, we describe a patient with chronic pain, morbid obesity, and severe sleep apnea who presented with uncontrolled pain resulting from a burn injury to the dorsum of his feet. The treatment consisted of multimodal analgesia and placement of bilateral continuous superficial peroneal nerve catheters, as he underwent skin grafting and postprocedural hydrotherapy. This novel approach allowed for sparing of postprocedural opiates with positive clinical results.


[Chinese expert consensus on the imaging diagnosis of severe pneumonia of influenza A (H1N1) flu].
In March 2009, influenza A(H1N1) flu broke out and spread rapidly worldwide, and it has been circulating in local areas with various scales since then. Particularly, the outbreak and prevalence have occurred in China during 2023 extensively. At present, there is an absence of unified consensus on imaging diagnosis of severe influenza A (H1N1) flu pneumonia, which is not conducive to the standardized imaging diagnosis and clinical practice. Chinese experts including the Infection and Inflammatory Radiology Committee of the Chinese Research Hospital Association jointly formulate this consensus based on numerous references related to influenza A (H1N1) flu, meanwhile combining the methodological requirements of evidence-based medicine for guideline and standard formulation. This consensus aims to form a consensus on the diagnostic evidence, recommended imaging methods, diagnostic standard and differential diagnosis of severe influenza A(H1N1) flu pneumonia, and it is ought to provide clear diagnostic information and basis for relevant professional physicians and guide the clinical diagnosis and treatment of severe pneumonia caused by influenza A(H1N1) flu.


Binding of mutagens by fractions of the cell wall skeleton of lactic acid bacteria on mutagens.
The binding effect of cells and cell fractions, cell wall skeleton, cytoplasm, whole cells, and cell wall skeleton treated by lysozyme and alpha-amylase at 37 degrees C for 5 h, on Trp-P-1 (3-amino-1,4-dimethyl-[5H]pyrido [4,3-b]indole) and Trp-P-2 (3-amino-1-methyl-[5H]-pyrido[4,3-b]indole) were investigated. The cell and cell wall skeleton of Streptococcus cremoris Z-25 had greater binding activity, but cytoplasm and extract of cell wall skeleton did not bind Trp-P-1 and Trp-P-2. When the cells or cell wall skeleton were treated with lysozyme and alpha-amylase, unbound Trp-P-1 and Trp-P-2 concentrations were greater than that of the untreated control. It is possible that cell walls may be involved in the binding of mutagenic pyrolyzates to lactic acid bacteria. The cell wall skeleton of S. cremoris Z-25, Lactobacillus acidophilus IFO 13951, and Bifidobacterium bifidum IFO 14252 showed binding of Trp-P-1, 2-amino-6-methyldipyrido(1,2-a:3',2'- d)imidazole, 2-amino-5-phenylpyridine, 2-amino-3-methylimidazo(4,5-f)quinoline, 2-amino-3,4-dimethylimidazo(4,5-f) quinoline, and 2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline. The cell wall skeleton of S. cremoris group and Streptococcus lactis also showed the binding activity with A N-nitrosodimethylamine. The binding of Trp-P-1 to cell walls was very high, and the binding of mutagenic pyrolyzates was variable with different bacterial species. The peptidoglycan complex and polysaccharides liberated from cell wall skeleton of S. cremoris Z-25 showed strong binding of Trp-P-2. Peptidoglycans has a binding effect of about 19.86 micrograms/mg; polysaccharides had a binding effect of 14 micrograms/mg.


Metabolic syndrome, its components, and mortality in the elderly.
The metabolic syndrome (MetS) has been shown to predict mortality in the middle-aged, but less is known on the impact of MetS and its components on mortality risk in the elderly. Our objectives were 1) to examine the association of MetS with the risk of all-cause and cause-specific mortality in a French elderly community-dweller cohort and 2) to determine the main components driving these associations. Prospective analyses were carried out on 7118 men and women aged 65 yr and over from the Three-City cohort. Association between MetS (defined using the National Cholesterol Education Program Adult Treatment Panel III criteria) and mortality risk over the 7-yr follow-up was assessed using Cox proportional hazards models. After adjusting for sociodemographic variables, health behaviors, and health status, a 50% increased risk for all-cause mortality was observed in participants with MetS at baseline compared with those without, with a hazard ratio of 1.54 [95% confidence interval (CI) = 1.24-1.92]. Elevated fasting blood glucose, high triglycerides, and low high-density lipoprotein cholesterol were the major contributors to this association, acting synergistically on mortality risk. For coronary heart disease mortality and cancer mortality, the hazard ratios associated with MetS were 2.21 (95% CI = 1.07-4.55) and 1.49 (95% CI = 1.04-2.14), respectively. By showing that an elevated fasting blood glucose potentiates the excess mortality risk associated with lipid abnormality, our study supports the status of MetS as a risk factor for mortality in the elderly. Our findings emphasize the importance of MetS screening and managing dyslipidemia and hyperglycemia in older persons in general practice.


Dental maturation in children with shunt-treated hydrocephalus.
The aim of this study was to examine the relationship between dental maturation and somatic development and to discover their possible deviations in children with shunt-treated hydrocephalus. Radiographs (orthopantomogram and hand-wrist radiograph) from children with shunt-treated hydrocephalus were analyzed with respect to the dental maturation and compared with values of an age- and sex-matched control group and population standards. Forty-one children with shunt-treated hydrocephalus (27 boys and 14 girls) aged from 5 to 16 years (median age 11.0 years). The mean deviation of dental age from chronological age was significantly greater in the hydrocephalic group than in the control group. The mean value of dental age deviation was advanced in early pubertal stages but reduced in later pubertal stages. These findings can be explained by changes in the endocrinological conditions, which are due to disturbed pituitary secretion. The present results could also partly reflect an adaptable developmental pathway in an otherwise strictly genetically determined process.


Mass spectrometry for the study of protein-protein interactions.
The identification of subpicomolar amounts of protein by mass spectrometry (MS) coupled with two-dimensional methods to separate complex protein mixtures is fueling the field of proteomics, and making feasible the notion of cataloging and comparing all of the expressed proteins in a biological sample. Functional proteomics is a complementary effort aimed at the characterization of functional features of proteins, such as their interactions with other proteins. Proteins comprise modular domains, many of which are noncatalytic modules that direct protein-protein interactions. Capturing proteins of interest and their interacting proteins by using high-affinity antibodies presents a simple method to prepare relatively simple protein mixtures easily resolved in one-dimensional formats. Individual or mixtures of proteins identified as stained bands in polyacrylamide gels are subjected to in situ digestion with the protease trypsin, and the extracted peptide fragments are analyzed by MS. The quality, quantity, and complexity of the tryptic digest, the species origin of the proteins, and the quality of the corresponding databases of genomic and protein information greatly influence the subsequent MS analysis in terms of degree of difficulty and methodological approach required to make an unambiguous protein identification. In this article we report the isolation of associated proteins from a complex cell-derived lysate by using an epitope-directed antibody. The protein pICLn engineered to carry an epitope tag was purified from cultured human embryonic kidney cells, and found to associate with a variety of proteins including the spliceosomal proteins smE and smG. By application of this general approach, the systematic identification of protein complexes and assignment of protein function are possible.


[Value of sentinel lymph node metastasis status in predicting the presence of residual disease in the non-sentinel lymph node of breast cancer patients].
To explore the value of sentinel lymph nodes (SLN) metastasis status in predicting the presence of residual disease in non-sentinel lymph nodes (nSLN) and the feasibility of avoiding or reducing the scope of axillary lymph node dissection (ALND) for patients with single positive SLN. A retrospective study was conducted for 2265 patients with invasive breast carcinomas undergoing sentinel lymph nodes biopsy (SLNB) at Shandong Cancer Hospital between November 1999 and December 2011. And 1228 patients with axillary dissection were screened and divided into 5 groups of (-), (1/n), (1/1), (n/N), (n/n) (n ≥ 2, N ≥ 3, N > n) according to the status of SLN metastasis. The nSLN metastasis rate of SLN(-), (1/n), (1/1), (n/N) and (n/n) groups was 11.8%(73/618), 25.2%(65/258), 49.6%(67/135), 48.4%(60/124)and 65.6%(61/93)respectively. A comparison of SLN(-), (1/n), (1/1), (n/N), and (n/n) groups of nSLN metastasis showed a significant difference (P = 0.000). The differences of nSLN metastasis between SLN(-) and other groups (including 1/n, 1/1, n/N, n/n group) were significant (P = 0.000). This difference was also significant between SLN (1/n) and other positive groups (include 1/1, n/N, n/n group) (P = 0.000), but not significant between SLN(1/1), (n/N) and (n/n) groups (P = 0.842, 0.017, 0.042 respectively, Chi-square segmentation). No significant difference existed between axillary lymph node metastasis on Level II and III of SLN 1/n group and SLN(-) group (P = 0.012, 0.570,χ(2) segmentation). The status of SLN metastasis is one of influencing factors for the nSLN metastasis of patients with invasive breast cancer. The possibility of non-sentinel lymph node involvement for patients with single SLN metastasis was smaller than that of other SLN-positive patients. It is safe for some SLN 1/n patients to undergo low lymph node dissection. But ALND is not avoided for patients with single positive SLN (SLN 1/n n ≥ 2). Their clinicopathological variables should be also considered.


Design and test of a compact beam current monitor based on a passive RF cavity for a proton therapy linear accelerator.
In a medical accelerator, real-time monitoring systems of the beam and dose delivered to the patient are mandatory. In this work, we present a compact current profile detector that has been designed and tested in the framework of the TOP-IMPLART (Intensity Modulated Proton Linear Accelerator for RadioTerapy) project. This project foresees the realization of a proton linear accelerator, currently under construction at ENEA Frascati, for proton therapy applications. The linac produces a pulsed proton beam with 3 µs duration at 50 Hz repetition rate with a pulse current between 0.5 and 50 μA. A large dynamic range and spatial constraints make the use of usual noninterceptive beam diagnostics unfeasible. Therefore, the use of a beam current monitor based on a passive RF cavity working in the TM010 mode has been proposed. This paper reports the electromagnetic design of the device guided by a simplified analytical model. A prototype of such a device has been realized, characterized, and tested on the linac with a 35 MeV beam varying the beam current. The test results in air and in vacuum, together with the signal detection systems used, are presented.


Reversible CO Scavenging via Adsorbate-Dependent Spin State Transitions in an Iron(II)-Triazolate Metal-Organic Framework.
A new metal-organic framework, Fe-BTTri (Fe3[(Fe4Cl)3(BTTri)8]2·18CH3OH, H3BTTri =1,3,5-tris(1H-1,2,3-triazol-5-yl)benzene)), is found to be highly selective in the adsorption of CO over a variety of other gas molecules, making it extremely effective, for example, in the removal of trace CO from mixtures with H2, N2, and CH4. This framework not only displays significant CO adsorption capacity at very low pressures (1.45 mmol/g at just 100 μbar), but, importantly, also exhibits readily reversible CO binding. Fe-BTTri utilizes a unique spin state change mechanism to bind CO in which the coordinatively unsaturated, high-spin Fe(II) centers of the framework convert to octahedral, low-spin Fe(II) centers upon CO coordination. Desorption of CO converts the Fe(II) sites back to a high-spin ground state, enabling the facile regeneration and recyclability of the material. This spin state change is supported by characterization via infrared spectroscopy, single crystal X-ray analysis, Mössbauer spectroscopy, and magnetic susceptibility measurements. Importantly, the spin state change is selective for CO and is not observed in the presence of other gases, such as H2, N2, CO2, CH4, or other hydrocarbons, resulting in unprecedentedly high selectivities for CO adsorption for use in CO/H2, CO/N2, and CO/CH4 separations and in preferential CO adsorption over typical strongly adsorbing gases like CO2 and ethylene. While adsorbate-induced spin state transitions are well-known in molecular chemistry, particularly for CO, to our knowledge this is the first time such behavior has been observed in a porous material suitable for use in a gas separation process. Potentially, this effect can be extended to selective separations involving other π-acids.


MondoA senses adenine nucleotides: transcriptional induction of thioredoxin-interacting protein.
The MondoA-Mlx transcription complex plays a pivotal role in glucose homoeostasis by activating target gene expression in response to G6P (glucose 6-phosphate), the first reaction intermediate in glycolysis. TXNIP (thioredoxin-interacting protein) is a direct and glucose-responsive target of MondoA that triggers a negative-feedback loop by restricting glucose uptake when G6P levels increase. We show in the present study that TXNIP expression is also activated by AICAR (5-amino-4-imidazolecarboxamide ribofuranoside) and adenosine. Using pharmacological inhibitors and genetic knockdowns of purine metabolic enzymes, we establish that TXNIP induction by AICAR and adenosine requires their cellular uptake and metabolism to adenine nucleotides. AICAR induction of TXNIP depended on MondoA, but was independent of AMPK (AMP-activated protein kinase) activation and calcium. The findings of the present study have two important implications. First, in addition to activating AMPK, AICAR may have AMPK-independent effects on gene expression by regulating MondoA-Mlx activity following its flux into the adenine nucleotide pool. Secondly, MondoA-Mlx complexes sense elevated levels of G6P and adenine nucleotides to trigger a TXNIP-dependent feedback inhibition of glycolysis. We propose that this mechanism serves as a checkpoint to restore metabolic homoeostasis.


Attitudes of healthy volunteers to genetic testing in phase 1 clinical trials.
Background: Genetic testing in clinical trials introduces several ethical and logistical issues to discuss with potential participants when taking informed consent. The aim of this study was to explore the attitudes of healthy volunteers in phase 1 studies to the topics of genetic security, genetic privacy and incidental genetic findings. Methods: Healthy volunteers presenting for screening appointments at a phase 1 clinical trial unit (CMAX Clinical Research, Adelaide, Australia) took an anonymous paper survey about genetic testing. Results: There were 275 respondents to the survey. The mean age was 27 years (range 18-73); 54% were male and 53% were of North/Western European ethnicity. Just over half the healthy volunteers thought genetic security (56%) and genetic privacy (57%) were "important" or "very important". However, the security of their genetic information was ranked less important than other personal information, including mobile phone number, internet browser search history and email address. Two-thirds of respondents would trade genetic privacy for re-identifiability if information relevant to their health were discovered by genetic testing. Healthy volunteers favoured the return of incidental genetic findings (90% indicated this was "important" or "very important"). A level of risk (10 to 90%) for developing a serious medical condition that would "trigger" the return of incidental genetic findings to participants was not identified. Conclusions: Healthy volunteers screening for phase 1 clinical trials have mixed views about the importance of genetic security and genetic privacy, but they strongly favour the return of incidental genetic findings that could affect their health. These issues should be discussed with potential participants during informed consent for phase 1 clinical trials with genetic testing.


Differential activity of trans-acting hammerhead ribozymes targeted to beta amyloid peptide precursor mRNA by altering the symmetry of helices I and III.
In order to determine whether distributing the pairing bases in helices I and III of a hammerhead ribozyme asymmetrically would enhance the cleavage of trans-acting ribozymes designed to degrade cellular mRNAs, we measured the cleavage properties of symmetric and asymmetric ribozymes targeted to the amyloid peptide precursor (beta APP) mRNA. Five ribozymes were formed from three beta APP synthetic mRNA analogs and two ribozyme RNA core sequences. Symmetric ribozymes beta 133/Rz133 and beta 125/Rz133 contained 8 bp in helix I and 7 bp in helix III. Asymmetric ribozyme beta 125/Rz125 had 13 bp in helix I and 4 bp in helix III, asymmetric ribozyme beta 123/Rz125 had 11 bp in helix I and 4 bp in helix III, while asymmetric ribozyme beta 133/Rz125 contained 8 bp in helix I and 4 bp in helix III. The ability of each ribozyme to cleave its substrate RNA was first assessed under single-turnover conditions at 37 degrees C. These studies revealed that only symmetric ribozyme, beta 133/Rz133, and asymmetric ribozyme beta 123/Rz125 effectively cleaved their substrates. Further studies using a 80 degrees C, 1-min-->37 degrees C, 1-min temperature cycling paradigm were performed to increase the cleavage efficiency of the ribozymes. Under these conditions ribozymes beta 133/Rz133, beta 125/Rz125, and beta 123/Rz125 were kinetically well behaved. Therefore, the fact that the symmetric ribozyme beta 133/Rz133 was more active than its asymmetric counterparts indicates that symmetrically distributing the pairing bases in helices I and III around this cleavage site is preferred.


NH3 permeability of principal cells and intercalated cells measured by confocal fluorescence imaging.
The cortical collecting duct (CCD) is an important site for NH3 secretion in mammalian nephron. However, given the cellular heterogeneity of this epithelium, the transcellular sites for NH3 secretion are unknown. In the present study, a dual-excitation confocal microscope was designed and optimized to have sufficient temporal resolution to measure the permeability of ammonia (PNH3) across the basolateral and apical membrane of principal cells (PCs) and intercalated cells (ICs) in perfused rabbit CCDs. The rate of cellular NH3 influx was calculated from the time course of increase in intracellular pH (pHi), measured with 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein after 20 mM NH4Cl was added to the bath or luminal perfusate. The time course of increase in pHi was calculated from 488/442 image pairs stored at a rate of 4 Hz. The apparent basolateral and apical PNH3 values of PCs were 36 +/- 5 and 113 +/- 11 microns/s, respectively. The values were 5.0 +/- 0.7 and 34 +/- 3 microns/s after membrane folding correction. The apparent basolateral and apical PNH3 values of ICs were 38 +/- 6 and 132 +/- 15 microns/s. Corrected for membrane folding, the values were 9.0 +/- 1.0 and 47 +/- 5 microns/s, respectively. The results demonstrate that the apical surface was more permeable than the basolateral surface in both cell types. In addition, ICs were more permeable to NH3 than PCs across both membranes. The transcellular PNH3 of PCs and ICs were 27.3 and 29.5 microns/s, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)


Steady-state kinetics of the glutaminase reaction of CTP synthase from Lactococcus lactis. The role of the allosteric activator GTP incoupling between glutamine hydrolysis and CTP synthesis.
CTP synthase catalyzes the reaction glutamine + UTP + ATP --> glutamate + CTP + ADP + Pi. The rate of the reaction is greatly enhanced by the allosteric activator GTP. We have studied the glutaminase half-reaction of CTP synthase from Lactococcus lactis and its response to the allosteric activator GTP and nucleotides that bind to the active site. In contrast to what has been found for the Escherichia coli enzyme, GTP activation of the L. lactis enzyme did not result in similar kcat values for the glutaminase activity and glutamine hydrolysis coupled to CTP synthesis. GTP activation of the glutaminase reaction never reached the levels of GTP-activated CTP synthesis, not even when the active site was saturated with UTP and the nonhydrolyzeable ATP-binding analog adenosine 5'-[gamma-thio]triphosphate. Furthermore, under conditions where the rate of glutamine hydrolysis exceeded that of CTP synthesis, GTP would stimulate CTP synthesis. These results indicate that the L. lactis enzyme differs significantly from the E. coli enzyme. For the E. coli enzyme, activation by GTP was found to stimulate glutamine hydrolysis and CTP synthesis to the same extent, suggesting that the major function of GTP binding is to activate the chemical steps of glutamine hydrolysis. An alternative mechanism for the action of GTP on L. lactis CTP synthase is suggested. Here the binding of GTP to the allosteric site promotes coordination of the phosphorylation of UTP and hydrolysis of glutamine for optimal efficiency in CTP synthesis rather than just acting to increase the rate of glutamine hydrolysis itself.


The relative economic progress of male foreign workers in Kuwait.
"A human capital framework is utilized to examine the economic progress of nine nationality groups of foreign workers [in Kuwait] using data from the 1983 national Labor Survey. The sources of earnings' variations of particular interest to us included different degrees of education and experience transferability, occupational affiliation and ethnic background. In general, the results derived from the analysis suggest that 1) foreign workers achieve a discernible economic progress as their residence lengthens; 2) the rate of economic progress varies depending on worker's education, home and Kuwait-specific experience, occupational status and ethnic background; and 3) about one third of the earnings inequality is due to unexplained factors including discrimination."


[Management of intracanal separated instruments with the microsonic technique and its clinical outcome].
To evaluate the clinical effect of microsonic technique on removal of intracanal separated instruments. Forty-four teeth with 47 intracanal separated instruments, which could not be successfully managed by conventional methods, were endodontically treated with ultrasonic instruments under dental operating microscope. The success rate was calculated and the cases were reviewed 5 to 19 months after retreatment. Thirty-four (34/47) separated instruments in 33 (33/44) teeth were completely removed with a success rate of 75%. Thirteen separated instruments in 11 teeth, however, could not be eliminated from the canals. Root canal perforation or vertical fracture was not found. None of these teeth showed periapical deterioration in the follow-up. The combined use of dental operating microscope and ultrasonic instruments in endodontic treatment enriched the way of managing complicated cases of intracanal separated instruments.


Crystal structure of the Lactococcus lactis formamidopyrimidine-DNA glycosylase bound to an abasic site analogue-containing DNA.
The formamidopyrimidine-DNA glycosylase (Fpg, MutM) is a bifunctional base excision repair enzyme (DNA glycosylase/AP lyase) that removes a wide range of oxidized purines, such as 8-oxoguanine and imidazole ring-opened purines, from oxidatively damaged DNA. The structure of a non-covalent complex between the Lactoccocus lactis Fpg and a 1,3-propanediol (Pr) abasic site analogue-containing DNA has been solved. Through an asymmetric interaction along the damaged strand and the intercalation of the triad (M75/R109/F111), Fpg pushes out the Pr site from the DNA double helix, recognizing the cytosine opposite the lesion and inducing a 60 degrees bend of the DNA. The specific recognition of this cytosine provides some structural basis for understanding the divergence between Fpg and its structural homologue endo nuclease VIII towards their substrate specificities. In addition, the modelling of the 8-oxoguanine residue allows us to define an enzyme pocket that may accommodate the extrahelical oxidized base.


Anterior cervical discectomy: an analysis on clinical long-term results in 153 cases.
During the last three decades, the anterior approach to the cervical spine with interbody fusion has been increasingly preferred in the operative treatment of herniated cervical disc. Most studies on surgical procedure without interbody fusion are retrospective and reported that the bone graft is not important for the success of this technique. Between 1983 and 1993, 153 patients underwent surgery for the treatment of cervical degenerative disc disease: in 139 cases the technique without fusion was applied. This retrospective study analyze clinical and radiological parameters in order to verify any possible prognostic factor. 108 patients with radiculopathy and 31 patients with myelopathy were followed up clinically for at least 12 months up to 10 years. An excellent or good long-term result was achieved in 90.9% of patients with radiculopathy and 58.1% of those with myelopathy. The age of the patients, the duration of symptoms before diagnosis and the pathogenesis of disc herniation did not represent significant parameters influencing the outcome of patients. The results of the present study show that anterior discectomy without fusion lead to good clinical long-term results, either in patients with pure radicular syndrome, or in cases with myelopathy. The presentation with pure radicular signs is the most important factor in predicting a good overall outcome.


Evaluation of Anti-Diabetic and Anti-Hyperlipidemic Activities of Hydro-Alcoholic Crude Extract of the Shoot Tips of Crinum abyssinicum Hochst. ex A. Rich (Amaryllidaceae) in Mice.
Despite the availability of synthetic antihyperglycaemic medications on the market, diabetes is on the rise. Though not scientifically proven, the Crinum abyssinicum Hochst. ex A. Rich. (Amaryllidaceae) has been used traditionally to treat diabetes. Crinum abyssinicum was tested in mice to see if it had anti-diabetic and anti-hyperlipidemic properties. The hydro-alcoholic extract of Crinum abyssinicum shoot tips doses (100 mg/kg, 200 mg/kg, and 400 mg/kg) were administered to normoglycemic, oral glucose-loaded mice, and single and repeated dose-treated streptozotocin-induced diabetic model. Then, the blood glucose levels were measured for normoglycemic, oral glucose loaded and single dose treated streptozotocin model. Whereas in repeated dose-treated streptozotocin induced diabetic model, blood glucose level, body weight, and lipid profiles were measured. After oral administration, all extract doses (100 mg/kg (p < 0.01), 200 mg/kg (p < 0.001), and 400 mg/kg (p < 0.001)) significantly reduced blood glucose level of normal mice as compared to the control group. Significant reduction of post-prandial glucose was achieved with crude extract at a tested dose of 100 mg/kg (p < 0.05) both at 1st and 2nd hours; 200 mg/kg (p < 0.01) at the 1st hour and (p < 0.001) 2nd hours, and 400 mg/kg (p < 0.001) at the 1st and 2nd hours as compared to the negative control. In diabetic mice, the crude extract 200 mg/kg and 400 mg/kg; and glibenclamide 5 mg/kg significantly reduced (p < 0.001) blood glucose level on the 14th day as compared to the negative control. All doses of crude extract significantly improved the lipid profiles and the bodyweight of diabetic mice. These findings revealed that the hydro-alcoholic extract of Crinum abyssinicum shoot tips possess significant antihyperglycemic, antihyperlipidemic, and body weight improvements in streptozotocin-induced diabetic mice. Besides, it showed hypoglycaemic and anti-hyperglycaemic activities on normoglycemic and oral glucose loaded mice, respectively. These justify the claimed use of the plant in ameliorating diabetes mellitus in Ethiopian folk medicine.


Structured Water Molecules on Membrane Proteins Resolved by Atomic Force Microscopy.
Water structuring on the outer surface of protein molecules called the hydration shell is essential as well as the internal water structures for higher-order structuring of protein molecules and their biological activities in vivo. We now show the molecular-scale hydration structure measurements of native purple membrane patches composed of proton pump proteins by a noninvasive three-dimensional force mapping technique based on frequency modulation atomic force microscopy. We successfully resolved the ordered water molecules localized near the proton uptake channels on the cytoplasmic side of the individual bacteriorhodopsin proteins in the purple membrane. We demonstrate that the three-dimensional force mapping can be widely applicable for molecular-scale investigations of the solid-liquid interfaces of various soft nanomaterials.


Managing Early Childhood Caries with Atraumatic Restorative Treatment and Topical Silver and Fluoride Agents.
Early childhood caries (ECC) is a significant global health problem affecting millions of preschool children worldwide. In general, preschool children from families with 20% of the lowest family incomes suffered about 80% of the ECC. Most, if not all, surveys indicated that the great majority of ECC was left untreated. Untreated caries progresses into the dental pulp, causing pain and infection. It can spread systemically, affecting a child's growth, development and general health. Fundamental caries management is based on the conventional restorative approach. Because preschool children are too young to cope with lengthy dental treatment, they often receive dental treatment under general anaesthesia from a specialist dentist. However, treatment under general anaesthesia poses a life-threatening risk to young children. Moreover, there are few dentists in rural areas, where ECC is prevalent. Hence, conventional dental care is unaffordable, inaccessible or unavailable in many communities. However, studies showed that the atraumatic restorative treatment had a very good success rate in treating dentine caries in young children. Silver diamine fluoride is considered safe and effective in arresting dentine caries in primary teeth. The aim of this paper is to review and discuss updated evidence of these alternative approaches in order to manage cavitated ECC.


Palladin, an actin-associated protein, is required for adherens junction formation and intercellular adhesion in HCT116 colorectal cancer cells.
Palladin is a scaffold protein involved in the formation of actin-associated protein complexes. Gene expression array analysis on the poorly metastatic HCT116 colon cancer cell line and a metastatic derivative cell line (E1) with EMT (epithelial-mesenchymal transition) features showed a down-regulation of palladin gene expression in the latter. Knockdown of palladin expression in the HCT116 cells suppressed junctional localization of E-cadherin, reduced intercellular adhesion and collective cell migration, showing that palladin plays an important role in maintaining the integrity of adherens junctions. The acquisition of the EMT features by the E1 cell line was dependent on the Erk pathway. Inhibition of this pathway by U0126 treatment in E1 cells resulted in the re-expression of palladin, relocalization of E-cadherin to the adherens junctions and a reversal of EMT features. The re-establishment of intercellular adhesion was dependent on palladin expression. The down-regulation of palladin was also observed in poorly-differentiated tumor tubules and dissociated tumor cells that have undergone de-differentiation in human primary colon tumors. Our data show that palladin is an integral component of adherens junctions and plays a role in the localization of E-cadherin to the junctions. The loss of palladin may be an integral part of EMT, an early step in the metastatic spread of colon carcinoma.


The application and mechanisms of polyethylene glycol 8000 on stabilizing lactate dehydrogenase during lyophilization.
The purpose of this paper is to explore the application and mechanisms of polyethylene glycol 8000 (PEG 8000) on stabilizing lactate dehydrogenase (LDH) during lyophilization. In earlier freeze-thawing experiments, different molecular weights and concentrations of PEGs were formulated with LDH, and ultraviolet (UV) enzymatic activity and circular dichroism (CD) wavelength scanning studies were conducted. In lyophilization studies, different molecular weights of saccharides, e.g., glucose, sucrose, dextran 37,000 (D 37K), and dextran 160,000 (D 160K), with or without PEG 8000, were formulated with LDH at various molar ratios. UV assays, size exclusion chromatography -high performance liquid chromatography (SEC-HPLC), CD, fourier transform infrared spectroscopy (FTIR) were conducted for LDH. Upon lyophilization, enzymatic activity and tetrameric structure recoveries of LDH-saccharide formulations reached over 90% with PEG 8000 vs. 60-80% without PEG 8000. LDH-PEG 8000-saccharide formulations shifted the melting temperature (Tm) to higher temperatures than did LDH-saccharide formulations. Most LDH-PEG 8000-saccharide formulations at 1:100:1000 molar ratio showed better preservation of LDH secondary structures than did LDH-saccharide formulations at 1:1000 molar ratio. Since PEG 8000 was confirmed an effective cryoprotectant, saccharides were assumed to be protecting LDH from destabilization during drying. However, LDH-PEG 8000-dextran formulations preserved more LDH secondary structure than did LDH-dextran formulations, but preserved less LDH secondary structures than did LDH-PEG 8000 formulations. This indicated that dextrans not only did not stabilize LDH during drying, but they disrupted the stabilization effect of PEG 8000 on LDH during freezing. After reconstitution, CD wavelength scanning showed that some of the unfolded or denatured structures of LDH were refolded. Based on the steric hindrance of the bulky dextrans and the "water replacement mechanism", sucrose with PEG 8000 had synergistic protective effects, and dextrans with PEG 8000 had antagonistic effects, on stabilization of LDH during lyophilization.


Quantifying Remission Probability in Type 2 Diabetes Mellitus.
Type 2 diabetes mellitus (T2DM) is a chronic progressive disorder and is associated with significant morbidity and mortality. The concept of T2DM remission and the reversal of diabetic parameters to normal levels has been gaining momentum over the past years. T2DM remission is increasingly being recognized by various global guidelines. Multiple models have been developed and validated for quantifying the extent of remission achieved. Based on favorable clinical evidence, T2DM remission can be considered as the therapeutic goal in diabetes management and, in select cases, as an alternative to expensive treatment options, which can be burdensome as T2DM progresses. This narrative review discusses the available strategies, such as lifestyle interventions, physical activity, bariatric surgery, medical nutrition therapy, and non-insulin glucose-lowering medications, for achieving T2DM remission. Although the concept of T2DM remission has emerged as a real-world option, effective implementation in routine clinical practice may not be feasible until long-term studies prove the efficacy of different approaches in this regard.


Lactose enhances cellulase production by the filamentous fungus Acremonium cellulolyticus.
Acremonium cellulolyticus is a fungus that produces cellulase and has been exploited by enzyme industry. To promote cellulase production by A. cellulolyticus strain C-1, we evaluated the effects of the saccharides: Solka Floc (cellulose), soluble soybean polysaccharide (SSPS), pullulan, lactose, trehalose, sophorose, cellobiose, galactose, sorbose, lactobionic acid, and mixtures as carbon sources for cellulase production. Solka Floc with SSPS enhanced cellulase production. Lactose as the sole carbon source induced cellulase synthesis in this fungus, and the synergistic effects between lactose and Solka Floc was observed. Various enzyme activities and the protein composition of crude enzyme produced by cultures with or without addition of lactose were analyzed. The results showed that lactose addition greatly improves the production of various proteins with cellulase activity by A. cellulolyticus. To our knowledge, this is the first report on production of cellulases by lactose in the A. cellulolyticus.


Ultra-Small Air-Stable Triplet-Triplet Annihilation Upconversion Nanoparticles for Anti-Stokes Time-Resolved Imaging.
Image contrast is often limited by background autofluorescence in steady-state bioimaging microscopy. Upconversion bioimaging can overcome this by shifting the emission lifetime and wavelength beyond the autofluorescence window. Here we demonstrate the first example of triplet-triplet annihilation upconversion (TTA-UC) based lifetime imaging microscopy. A new class of ultra-small nanoparticle (NP) probes based on TTA-UC chromophores encapsulated in an organic-inorganic host has been synthesised. The NPs exhibit bright UC emission (400-500 nm) in aerated aqueous media with a UC lifetime of ≈1 μs, excellent colloidal stability and little cytotoxicity. Proof-of-concept demonstration of TTA-UC lifetime imaging using these NPs shows that the long-lived anti-Stokes emission is easily discriminable from typical autofluorescence. Moreover, fluctuations in the UC lifetime can be used to map local oxygen diffusion across the subcellular structure. Our TTA-UC NPs are highly promising stains for lifetime imaging microscopy, affording excellent image contrast and potential for oxygen mapping that is ripe for further exploitation.


A Pdx-1-Regulated Soluble Factor Activates Rat and Human Islet Cell Proliferation.
The homeodomain transcription factor Pdx-1 has important roles in pancreas and islet development as well as in β-cell function and survival. We previously reported that Pdx-1 overexpression stimulates islet cell proliferation, but the mechanism remains unclear. Here, we demonstrate that overexpression of Pdx-1 triggers proliferation largely by a non-cell-autonomous mechanism mediated by soluble factors. Consistent with this idea, overexpression of Pdx-1 under the control of a β-cell-specific promoter (rat insulin promoter [RIP]) stimulates proliferation of both α and β cells, and overexpression of Pdx-1 in islets separated by a Transwell membrane from islets lacking Pdx-1 overexpression activates proliferation in the untreated islets. Microarray and gene ontology (GO) analysis identified inhibin beta-B (Inhbb), an activin subunit and member of the transforming growth factor β (TGF-β) superfamily, as a Pdx-1-responsive gene. Overexpression of Inhbb or addition of activin B stimulates rat islet cell and β-cell proliferation, and the activin receptors RIIA and RIIB are required for the full proliferative effects of Pdx-1 in rat islets. In human islets, Inhbb overexpression stimulates total islet cell proliferation and potentiates Pdx-1-stimulated proliferation of total islet cells and β cells. In sum, this study identifies a mechanism by which Pdx-1 induces a soluble factor that is sufficient to stimulate both rat and human islet cell proliferation.


The consequences of a generic approach to teaching nursing in a multicultural world.
This paper describes the Generic approach to teaching identified in a qualitative study that investigated the processes by which nurse educators teach ethnically diverse nursing students. Data were obtained through in-depth interviews with faculty and ethnic nurses. The study's findings are derived from refining the categories and themes and ongoing theory development. The conditions, actions, and consequences involved in the Generic approach to teaching are described and examples that emerged from the data are presented as illustrations. Examination of the consequences of the Generic teaching approach may assist educators to analyze their own approach to teaching ethnically diverse students.


Assessment of freshwater discharge into a coastal bay through multi-basin ensemble hydrological modelling.
Coastal basins of the Brittany peninsula (France) are hydrological hot spots. A high level of nutrient pollution affects many of these basins and causes algal blooms in several coastal bays; nine have been a specific focus of the European Commission since 2007. The flux of each contributing basin flowing into these bays must be examined to assess the conditions and explore mitigation options. However, this task encounters a large lack of data since most of the basins are ungauged. In this context, this study developed a method which facilitates transposition of hydrographs from gauged basins to ungauged neighbouring basins of interest. Inverting a simple geomorphology-based transfer function of the gauged basin which describes travel time through channels enables the net rainfall time-series to be estimated from the discharge time-series of donor basins. To estimate the net rainfall of a given ungauged catchment, several net rainfall time series of gauged catchments are averaged. The resulting net rainfall is then transposed onto the ungauged target basin and convoluted by its own transfer function to estimate the hydrograph. This allows the transposition of as many hydrographs as there are different donor basins. This ensemble prediction enables the proportion of prediction uncertainty that is due to the heterogeneity in hydrological behaviour to be estimated. Moreover, the time-series of the donor basins are combined to estimate the ungauged net rainfall time-series. This provides a discharge prediction which values all available measurements. The method was applied to the highly controversial Saint Brieuc Bay, where it was possible to quantify the contribution of each coastal basin, even those influenced by dams, and ultimately the entire volume of fresh water entering the bay at an hourly time step. This work opens perspectives to additionally refine estimation of the associated nutrient fluxes.


Core-shell structured PEO-chitosan nanofibers by coaxial electrospinning.
Core-shell structured PEO-chitosan nanofibers have been produced using a coaxial electrospinning setup. PEO and chitosan solutions, both in an aqueous acetic acid solvent, were used as the inner (core) and outer (shell) layer, respectively. Uniform-sized defect-free nanofibers of 150-190 nm diameter were produced. In addition, hollow nanofibers could be obtained subsequent to PEO washing of the membranes. The core-shell nanostructure and existence of chitosan on the shell layer were confirmed by TEM images obtained before and after washing the PEO content with water. The presence of chitosan on the surface of the composite nanofibers was further supported by XPS studies. The chitosan and PEO compositions in the nanofibrous mats were determined by TGA analysis, which were similar to their ratio in the feed solutions. The local compositional homogeneity of the membranes and the efficiency of the washing step to remove PEO were also verified by FTIR. In addition, DSC and XRD were used to characterize the crystalline structure and morphology of the co-electrospun nonwoven mats. The prepared coaxial nanofibers (hollow and solid) have several potential applications due to the presence of chitosan on their outer surfaces.


Dimerization of protein G B1 domain at low pH: a conformational switch caused by loss of a single hydrogen bond.
A number of signals in the NMR spectrum of the B1 domain of staphylococcal protein G (GB1) show a chemical shift dependence on the concentration of the protein at pH 3 but not at neutral pH, implying the existence of self-association at low pH. NMR backbone relaxation experiments show that GB1 undergoes a slow conformational exchange at pH 3, which is not seen at higher pH. Analysis of relaxation dispersion experiments yields a self-association constant of 50 mM, and shows that (15)N chemical shift changes in the dimer interface are up to 3 ppm. The shift changes measured from concentration-dependent HSQC spectra and from relaxation dispersion show good consistency. Measurements of chemical shifts as a function of pH show that a hydrogen bond between the sidechains of Asp44 and Gln40 is broken when Asp44 is protonated, and that loss of this hydrogen bond leads to the breaking of the (i, i + 4) backbone helical hydrogen bond from Asp44 HN to Gln40 O, and therefore to a loss of two residues from the C-terminal end of the helix. This weakens the helix structure and facilitates the loss of further helical structure thus permitting dimerization, which is suggested to occur in the same way as observed for the A42F mutant of GB1 (Jee et al., Proteins 2007;71:1420-1431), by formation of an antiparallel beta-sheet between the edge strands 2 in two monomers. The monomer/dimer ratio is thus a finely balanced equilibrium even in the wild type protein.


Pinwheel-Shaped Titanium Plates Should Be Fixed to the Skull Using All Screw Holes to Protect the Plates from Being Bent.
In cranioplasty, pinwheel-shaped titanium mini plates are frequently used to cover bone defects produced by burr holes, and it is common to insert screws through only a few of the holes in cranial flap fixation. A 69-year-old man who had undergone clipping surgery for subarachnoid hemorrhage 16 years previously visited our clinic because a titanium plate had penetrated his scalp one month after he was hit on the head by a wall cabinet. Imaging studies revealed that part of the titanium plate had bent outwards and penetrated the skin. The plate was surgically removed, a relief skin incision was made 6 cm posterior to the skin defect to suture the defected portion without causing tension, and a skin graft was applied to the relief skin incision portion. Two months after the maneuver, the skin graft had been successfully incorporated without infection. Even after the subcutaneous and the cutaneous tissue have completely covered the pinwheel-shaped titanium mini plate, an edge without screw fixation can be easily bent by a hard blow to the overlying scalp. We recommend fixation of pinwheel-shaped titanium plates used in cranioplasty through all screw holes to protect against the plate being bent.


LSD use among Miami's public school students.
This analysis examined LSD use by 492 adolescents in Dade County, Florida public schools in 1992. Significant factors which increase the probability of use include the fact that the adolescents are Euro-American, peers' use of tranquilizers, ready access, and awareness of the risks.


Maternal responses to adolescent positive affect are associated with adolescents' reward neuroanatomy.
The development of reward-based learning and decision-making, and the neural circuitry underlying these processes, appears to be influenced negatively by adverse child-rearing environments characterized by abuse and other forms of maltreatment. No research to-date has investigated whether normative variations in the child-rearing environment have effects on adolescent brain structure. We examined whether normative variations in maternal responses to adolescents' positive affective behavior were associated with morphometric measures of the adolescents' affective neural circuitry, namely the amygdala, orbitofrontal cortex (OFC), and anterior cingulate cortex (ACC). Healthy adolescents (N = 113) participated in laboratory-based interaction tasks with their mothers, and underwent high-resolution (3T) structural magnetic resonance imaging (MRI). The mother-adolescent interactions included a pleasant event-planning interaction (EPI) and a conflictual problem-solving interaction (PSI). Adolescents, whose mothers displayed more punishing responses to their positive affective behavior during both tasks, and only during the PSI, had larger left dorsal ACC and bilateral OFC volumes, respectively. In addition, boys whose mothers evidenced this pattern of behavior during the EPI had larger right amygdala volumes. These results suggest that normative variations in maternal responses to affective behavior are associated with the structural characteristics of adolescents' affective neural circuitry, which may have implications for the development of their social, cognitive and affective functioning.


The Heliothis virescens cadherin protein expressed in Drosophila S2 cells functions as a receptor for Bacillus thuringiensis Cry1A but not Cry1Fa toxins.
Genetic knockout of the BtR4 gene encoding the Heliothis virescens cadherin-like protein (HevCaLP) is linked to resistance against Cry1Ac toxin from Bacillus thuringiensis. However, the functional Cry1Ac receptor role of this protein has not been established. We previously proposed HevCaLP as a shared binding site for B. thuringiensis (Bt) Cry1A and Cry1Fa toxins in the midgut epithelium of H. virescens larvae. Considering that Cry1Ac and Cry1Fa are coexpressed in second-generation transgenic cotton for enhanced control of Heliothine and Spodoptera species, our model suggests the possibility of evolution of cross resistance via alteration of HevCaLP. To test whether HevCaLP is a Cry1Ac and Cry1Fa receptor, HevCaLP was transiently expressed on the surface of Drosophila melanogaster Schneider 2 (S2) cells. Expressed HevCaLP bound [(125)I]Cry1A toxins under native (dot blot) and denaturing (ligand blot) conditions. Affinity pull-down assays demonstrated that Cry1Fa does not bind to HevCaLP expressed in S2 cells or in solubilized brush border membrane proteins. Using a fluorescence-based approach, we tested the ability of expressed HevCaLP to mediate toxicity of Cry1A and Cry1Fa toxins. Cry1A toxins killed S2 cells expressing HevCaLP, whereas Cry1Fa toxin did not. Our results demonstrate that HevCaLP is a functional Cry1A but not Cry1Fa receptor.


Dietary cholesterol is essential to mast cell activation and associated obesity and diabetes in mice.
Mast cell (MC) deficiency in KitW-sh/W-sh mice and inhibition with disodium chromoglycate (DSCG) or ketotifen reduced obesity and diabetes in mice on a high-cholesterol (1.25%) Western diet. Yet, Kit-independent MC-deficient mice and mice treated with DSCG disproved MC function in obesity and diabetes when mice are fed a high-fat diet (HFD) that contains no cholesterol. This study reproduced the obesity and diabetes inhibitory activities of DSCG and ketotifen from mice on a Western diet. Yet, such inhibitory effects were diminished in mice on the HFD. DSCG and ketotifen MC inhibitory activities were recovered from mice on the HFD supplemented with the same amount of cholesterol (1.25%) as that in the Western diet. DSCG and ketotifen effectively blunted the high-cholesterol diet-induced elevations of blood histamine and adipose tissue MC degranulation. Pearson's correlation test demonstrated significant and positive correlations between plasma histamine and total cholesterol or low-density lipoprotein-cholesterol (LDL). In cultured bone marrow-derived MCs, plasma from mice following a Western diet or a cholesterol-supplemented HFD, but not those from HFD-fed mice, induced MC degranulation and the release of β-hexosaminidase, histamine, and serotonin. IgE, LDL, very low-density lipoprotein, and high-density lipoprotein also induced MC activation, which can be inhibited by DSCG and ketotifen depending on the doses and types of MC inhibitors and cholesterol, and also the MC granule molecules of interest. DSCG or ketotifen lost their activities in inhibiting LDL-induced activation of MCs from LDL receptor-deficient mice. These results indicate that dietary cholesterol critically influences the function of mouse MCs.


Mussel-inspired chemistry for robust and surface-modifiable multilayer films.
In this article, we report a bioinspired approach to preparing stable, functional multilayer films by the integration of mussel-inspired catechol oxidative chemistry into a layer-by-layer (LbL) assembly. A polyanion of poly(acrylic acid-g-dopamine) (PAA-dopamine) bearing catechol groups, a mussel adhesive protein-mimetic polymer, was synthesized as the building block for LbL assembly with poly(allylamine hydrochloride) (PAH). The oxidization of the incorporated catechol group under mild oxidative condition yields o-quinone, which exhibits high reactivity with amine and catechol, thus endowing the chemical covalence and retaining the assembled morphology of multilayer films. The cross-linked films showed excellent stability even in extremely acidic, basic, and highly concentrated aqueous salt solutions. The efficient chemical cross-linking allows for the production of intact free-standing films without using a sacrificial layer. Moreover, thiol-modified multilayer films with good stability were exploited by a combination of thiols-catechol addition and then oxidative cross-linking. The outstanding stability under harsh conditions and the facile functionalization of the PAA-dopamine/PAH multilayer films make them attractive for barriers, separation, and biomedical devices.


Endoscopic implant evaluation and capsulotomy.
Clinical use of breast endoscopy was begun 5 years ago for the purpose of internal endoscopic capsulotomy. This limited role for the endoscope has been entirely displaced by its use for inspection of implants for leaks or rupture. The materials and equipment are readily available, the proper techniques are safe for patient and implant, the method is easily learned, and the evaluation has been reliable. This report describes our first 50 breast endoscopies and details the technique and the means of learning it. The accuracy is far superior to that of mammogram or ultrasound, and to date, there have been no infections or damaged implants from the technique as described.


Chemokines and their receptors in allergic disease.
Mechanisms of chemoattraction underlie the spatial organization of the cells of the immune system under basal conditions and the localization of these cells to sites of inflammation. The chemokines, a family of around 50 small proteins, play a major role in these processes. Leukocytes are equipped with cell-surface sensors for chemokines. There are 19 such receptors that are differentially expressed on leukocytes: the repertoire of receptor expression depending on the type of leukocyte and its stage in maturation. From observations in animal models, clinical studies, in vitro cell biology, and molecular analysis, a working hypothesis has been established to explain the cellular interactions underlying allergic responses and the chemokines-chemokine receptors involved. Chemokines signal through G protein-coupled receptors that are used typically for sensory functions (eg, detection of olfactory signals in the nose). This type of receptor can be blocked selectively by small-molecule antagonists. This provides the opportunity for the development of therapeutic compounds designed to suppress the recruitment of particular leukocyte types in allergic reactions.


A novel contactless technique to measure water waves using a single photon avalanche diode detector array.
Commonly deployed measurement systems for water waves are intrusive and measure a limited number of parameters. This results in difficulties in inferring detailed sea state information while additionally subjecting the system to environmental loading. Optical techniques offer a non-intrusive alternative, yet documented systems suffer a range of problems related to usability and performance. Here, we present experimental data obtained from a 256 × 256 Single Photon Avalanche Diode (SPAD) detector array used to measure water waves in a laboratory facility. 12 regular wave conditions are used to assess performance. Picosecond resolution time-of-flight measurements are obtained, without the use of dye, over an area of the water surface and processed to provide surface elevation data. The SPAD detector array is installed 0.487 m above the water surface and synchronized with a pulsed laser source with a wavelength of 532 nm and mean power <1 mW. Through analysis of the experimental results, and with the aid of an optical model, we demonstrate good performance up to a limiting steepness value, ka, of 0.11. Through this preliminary proof-of-concept study, we highlight the capability for SPAD-based systems to measure water waves within a given field-of-view simultaneously, while raising potential solutions for improving performance.


Effects of Different Vitamin D Supplementation Schemes in Post-Menopausal Women: A Monocentric Open-Label Randomized Study.
The improvement of muscular strength is a well-known extra-skeletal effect of Vitamin D. The aim of the study was to evaluate the effectiveness of the calcifediol supplementation compared to various cholecalciferol administration schedules in increasing 25(OH)D serum levels and improving muscular function. 107 post-menopausal women with hypovitaminosis D were assigned to receive Vitamin D supplementation according to four different regimens: colecalciferol single, monthly, or weekly oral dose and calcifediol weekly oral dose. Serum levels of 25(OH)D and muscular function of lower limbs (Sit-to-Stand test and Timed-Up-and-Go test) were evaluated at baseline and during 6 months follow-up. Calcifediol and weekly cholecalciferol induced a greater and faster increase of serum 25(OH)D, compared to monthly or single-dose cholecalciferol administration. The 25(OH)D increase was associated with an improvement of muscle function of lower limbs. The larger increase of serum 25(OH)D observed with calcifediol and with weekly cholecalciferol was associated with a concomitant greater improvement of muscle strength. Supplementation with calcifediol is more effective and faster compared to cholecalciferol in increasing 25(OH)D serum levels and is associated with a greater improvement of muscular function, thus representing a therapeutic alternative for treatment of hypovitaminosis D.


Hirshfeld-based intrinsic polarizability density representations as a tool to analyze molecular polarizability.
In this work, a general scheme to visualize polarizability density distributions is proposed and implemented in a Hirshfeld-based partitioning scheme. This allows us to obtain easy-to-interpret pictorial representations of both total and intrinsic polarizabilities where each point of the density is formed by the contribution of any atom or group of atoms in the molecule. In addition, the procedure used here permits the possibility of removing the size dependence of the electric-dipole polarizability. Such a development opens new horizons in exploring new applications for the analysis of the molecular polarizability tensor. For instance, this visualization shows which atoms or regions are more polarizable distinguishing, moreover, the fine structure of atoms affected by the vicinity, and might extend the dipole polarizability as a tool for aromaticity studies in polycyclic aromatic hydrocarbons. Additionally, this approach can serve us to assess the methods performance in describing the interaction of electric fields with a molecule and local electron correlation effects in intrinsic polarizabilities.