Cost-effectiveness of benign Wirsung duct strictures treatment in chronic pancreatitis.
Chronic pancreatitis (CP) is an important problem for modern medicine, the healthcare system (Poland - NFZ) and the national insurance system (Poland - ZUS). The chronic nature of the disease, the lack of targeted treatment and the low mortality rate lead to an accumulation of patients who demand expensive treatment, both conservative and invasive. Rising costs in health care are forcing the need for a more cost-effective method of treatment. The primary aim of this study was to perform a retrospective calculation of costs in both surgical and endoscopic treatment, hospital stay, healthcare, and public insurance of patients suffering from chronic pancreatitis. Parallel quality of life analysis was performed. It was possible to develop a cost-effective therapeutic algorithm for patients with an uncomplicated stricture of Wirsung's duct within the Polish health care system. In Poland, the hospital costs of endoscopic treatment of patients with chronic pancreatitis were higher than those of the surgical treatment group despite both resulting in a similar life quality. From a cost-effectiveness perspective, it was shown that surgical intervention is a more cost-effective therapy than endotherapy. Furthermore, patients with benign stricture of the main pancreatic duct in chronic pancreatitis should not be treated with endotherapy for longer than 12 months.


Facile synthesis of optically pure 1,2-diaryl (and 1-Alkyl-2-aryl) ethyl and propylamines.
A concise high-yielding route to synthetically useful 1,2-diaryl (and 1-alkyl-2-aryl) ethyl and propylamines in high enantiomeric purity is described. The key step of this route is the completely stereoselective addition of lithium (R)-ortho-(p-toluenesulfinyl)benzylic carbanions to (S)-N-p-toluenesulfinylimines, which takes place in very high or quantitative yields. N-Desulfinylation and C-desulfinylation of the resulting adducts can be achieved with no loss of optical purity employing conventional methods (TFA and Raney-Ni, respectively).


Effects of the frequency and duration of cyclic stress on the mechanical properties of cultured collagen fascicles from the rabbit patellar tendon.
The effects of frequency or duration of cyclic stress on the mechanical properties of collagen fascicles were studied by means of in vitro tissue culture experiments. Collagen fascicles of approximately 300 microm in diameter were obtained from rabbit patellar tendons. During culture, cyclic stress having the peak stress of approximately 2 MPa was applied to the fascicles at 1 Hz for 1 hour/day (1 Hz-1 h group), at 1 Hz for 4 hours/day (1 Hz-4 h group), or at 4 Hz for 1 hour/day (4 Hz-1 h group). The frequency of 4 Hz and the duration of 1 hour/day are considered to be similar to those of the in vivo stress applied to fascicles in the intact rabbit patellar tendon. After culture for 1 or 2 weeks, the mechanical properties of the fascicles were determined using a microtensile tester, and were compared to the properties of non-cultured, fresh fascicles (control group) and the fascicles cultured under no load condition (non-loaded group). The tangent modulus and tensile strength of fascicles in the 4 Hz-1 h group were similar to those in the control group; however, the fascicles of the 1 Hz-1 h and 1 Hz-4 h groups had significantly lower values than those of the control group. There was no significant difference in the tensile strength between the 1 Hz-1 h and non-loaded groups, although the strength in the 1 Hz-4 h group was significantly higher than that of the non-loaded group. It was concluded that the frequency and duration of cyclic stress significantly affect the mechanical properties of cultured collagen fascicles. If we apply cyclic stress having the frequency and duration which are experienced in vivo, the biomechanical properties are maintained at control, normal level. Lower frequencies or less cycles of applied force induce adverse effects.


Plasmapheresis in the treatment of tropical malaria.
A case of tropical malaria imported from Kenya was described. Plasmodium falciparum (an etiological agent of this disease) is often drug resistant, therefore pharmacological treatment of the patients was supplemented with plasmapheresis. Full recovery has been achieved. It is suggested that plasmapheresis may be recommended for a complex therapy of severe forms of tropical malaria.


Preclinical evaluation of EPHX2 inhibition as a novel treatment for inflammatory bowel disease.
Epoxyeicosatrienoic acids (EETs) are signaling lipids produced by cytochrome P450 epoxygenation of arachidonic acid, which are metabolized by EPHX2 (epoxide hydrolase 2, alias soluble epoxide hydrolase or sEH). EETs have pleiotropic effects, including anti-inflammatory activity. Using a Connectivity Map (CMAP) approach, we identified an inverse-correlation between an exemplar EPHX2 inhibitor (EPHX2i) compound response and an inflammatory bowel disease patient-derived signature. To validate the gene-disease link, we tested a pre-clinical tool EPHX2i (GSK1910364) in a mouse disease model, where it showed improved outcomes comparable to or better than the positive control Cyclosporin A. Up-regulation of cytoprotective genes and down-regulation of proinflammatory cytokine production were observed in colon samples obtained from EPHX2i-treated mice. Follow-up immunohistochemistry analysis verified the presence of EPHX2 protein in infiltrated immune cells from Crohn's patient tissue biopsies. We further demonstrated that GSK2256294, a clinical EPHX2i, reduced the production of IL2, IL12p70, IL10 and TNFα in both ulcerative colitis and Crohn's disease patient-derived explant cultures. Interestingly, GSK2256294 reduced IL4 and IFNγ in ulcerative colitis, and IL1β in Crohn's disease specifically, suggesting potential differential effects of GSK2256294 in these two diseases. Taken together, these findings suggest a novel therapeutic use of EPHX2 inhibition for IBD.


Recurrent medial ankle instability: the result of distal fibular growth arrest.
Recurrent medial ankle instability is an uncommon clinical entity. A case that resulted from a distal fibular physeal arrest is described. Symptoms resolved after a one-stage fibular lengthening.


[Immunohistochemical study of Ki-67, p53 and Notch1 expressions in prostate cancer of different grades].
To determine the prognostic value of the expression of Ki-67, p53, and Notch1 in the diagnosis of prostate cancer. Surgical and diagnostic materials obtained from patients with benign prostatic hyperplasia, prostate intraepithelial neoplasia, and prostate cancer of different grades underwent studies; a total of 98 patients were examined. Cell antigens were determined using rabbit anti-Ki-67 monoclonal antibodies (Clone SP6), mouse anti-p53 monoclonal antibodies (Clone Y5), and recombinant anti-Notch1 antibodies (Clone EP1238Y). Comparing Ki-67, p53, and Notch1 expression indices revealed statistically significant differences. There was a significant direct correlation between Ki-67 and p53 expression indices and prostate cancer grade groups based on the morphological Gleason grading system (rs=0.736; p<0.001; rs=0.682; p=0.035, respectively) and a strong inverse correlation between Notch1 expression and prostate cancer grade groups (rs= -0.425, p<0.001). Notch1 expression in conjunction with the low proliferative activity of cells and the absence of p53 (Y5) protein may suggest that the mechanism of apoptosis is preserved in tumor cells, which expands indications for medical treatment of prostate cancer.


Integration of dye-sensitized solar cells, thermoelectric modules and electrical storage loop system to constitute a novel photothermoelectric generator.
This study self-develops a novel type of photothermoelectric power generation modules. Dye-sensitized solar cells (DSSCs) serve as the photoelectric conversion system and a copper (Cu) heat-transfer nanofilm coating on both sides of the thermoelectric generator (TEG) acts as a thermoelectric conversion system. Thus module assembly absorbs light and generates electricity by DSSCs, and also recycles waste heat and generates power by the TEG. In addition, a set of pulsating heat pipes (PHP) filled with Cu nanofluid is placed on the cooling side to increase cooling effects and enhance the power generation efficiency. Results show that when the heat source of thermoelectric modules reaches 90 degrees C, TEG power output is increased by 85.7%. Besides, after thermoelectric modules are heated by additional heat source at 80 degrees C, the electrical energy generated by them can let a NiMH cell (1.25 V) be sufficiently charged in about 30 minutes. When photothermoelectric modules is illumined by simulated light, the temperature difference of two sides of TEG can reach 7 degrees C and the thermoelectric conversion efficiency is 2.17%. Furthermore, the power output of the thermoelectric modules is 11.48 mW/cm2, enhancing 1.4 % compared to merely using DSSCs module.


Hypnotic Effect of Red Cabbage (Brassica oleracea) on Pentobarbital-Induced Sleep in Mice.
The present study was performed to investigate the effect of hydroalcoholic extract of red cabbage and its fractions on sleeping behavior in mice. The extract and its fractions were injected to mice and sleep duration as well as sleep latency were recorded. Furthermore, toxicity of the extract was determined both in vivo and in vitro. The extract increased sleep duration at doses of 50-200mg/kg (P < 0.001). This observed hypnotic effect was comparable to that of diazepam (3mg/kg) (P < 0.001 in comparison with control group). Ethyl acetate, n-butanol, and aqueous fractions could increase sleep duration (P < 0.001). The sleep latency was decreased by the extract (P < 0.001) and only ethyl acetate fraction (P < 0.001). LD50 value for red cabbage extract was 2.4g/kg. There was no toxic effect on viability of cultured neuronal cells (PC12). Rotarod test results showed that there were no significant differences between the extract groups and the control group. The results suggest that red cabbage potentiates pentobarbital hypnosis without any toxic effect. The main component(s) responsible for this effect is most likely to be intermediate polar agent(s) such as flavonoids, which are found in ethyl acetate fraction of this plant.


N omega-nitro-L-arginine selectively inhibits vasodilator responses to acetylcholine and bradykinin in cats.
The effects of N omega-nitro-L-arginine (nitroarginine), an inhibitor of endothelium-dependent relaxing factor (EDRF) production, on vascular tone and responses to vasodilator and vasoconstrictor agents were investigated in the hindquarters vascular bed of the cat. Under constant flow conditions, infusion of nitroarginine into the hindquarters vascular bed caused a significant increase in systemic arterial and hindquarters perfusion pressures. During infusion of nitroarginine, hindquarters vasodilator responses to acetylcholine and bradykinin were reduced significantly whereas vasodilator responses to isoproterenol, PGE1, nitroprusside, and 8-bromoguanosine 3',5'-cyclic monophosphate were not altered. Infusion of nitroarginine significantly enhanced vasoconstrictor responses to the thromboxane receptor agonist U 46619 and to phenylephrine. The results of these studies are consistent with the hypotheses that EDRF production may involve the formation of nitric oxide or a nitroso compound from L-arginine, and that EDRF production may play a role in the regulation of vascular tone and in the mediation of responses to the endothelium-dependent vasodilators, acetylcholine and bradykinin, in resistance vessels in the hindquarters. These data support the concept that EDRF is very likely an endogenous nitrovasodilator derived from L-arginine in the hindquarters vascular bed of the cat.


High-Pressure Evolution of Crystal Bonding Structures and Properties of FeOOH.
Recent conflicting reports on the high-pressure structural evolution of iron oxide-hydroxide (FeOOH) offer starkly contrasting scenarios for the hydrogen and oxygen cycles in Earth's interior. Here we explore the crystal structures of FeOOH using an advanced search algorithm combined with first-principles calculations. Our results indicate a phase transition around 70 GPa from the known ε-FeOOH to a new pyrite-type FeOOH (P-FeOOH) phase, and the two phases remain nearly degenerate in an unusually large pressure range. These findings clarify and explain the experimentally observed structural evolution and extensive phase coexistence. Moreover, our structure search identifies a previously unknown monoclinic (M-FeOOH) phase that is energetically close to P-FeOOH at pressures near the core-mantle boundary. We further reveal that the high-pressure FeOOH phases exhibit remarkably distinct sound-velocity profiles, providing key material properties essential to interpreting seismic data and elucidating FeOOH's influence on geophysical and geochemical processes in deep Earth.


Left Ventricular Diastolic Dysfunction in β-Thalassemia Major with Heart Failure.
We studied the clinical, electrocardiographic, echocardiographic, Doppler and T2* cardiac magnetic resonance (CMR) data of all adult β-thalassemia major (β-TM) patients with heart failure (HF) consecutively observed at our referral center of the Sicilian region between 2008 and 2016. There were 16 patients enrolled in the study. Echocardiographic examination showed that only one patient had HF with systolic dysfunction of the left ventricle (HFrEF), whereas the others had HF with preserved systolic function of the left ventricle (HFpEF). Systolic dysfunction of the right ventricle (RV) was observed in 13 cases. Furthermore, 30.0% of the patients presented T2* CMR values consistent with intermediate risk of systolic dysfunction of the left ventricle (LV) due to iron overload, whereas 70.0% had normal values. Typical electrocardiographic abnormalities (wide T wave inversion and low voltages) were observed in 11 out of 16 patients. In conclusion, in the adult β-TM patients with HF recently observed at our center, the predominant form was that with diastolic dysfunction of the LV, and with systolic dysfunction of the RV. Only 30.0% had low values of T2* CMR. Typical electrocardiographic abnormalities were found in 69.0%.


Phenotyping UK Electronic Health Records from 15 Million Individuals for Precision Medicine: The CALIBER Resource.
Electronic health records (EHR) are increasingly being used for observational research at scale. In the UK, we have established the CALIBER research resource which utilizes national primary and hospital EHR data sources and enables researchers to create and validate longitudinal disease phenotypes at scale. In this work, we will describe the core components of the resource and provide results from three exemplar research studies on high-resolution epidemiology, disease risk prediction and subtype discovery which demonstrate both the opportunities and challenges of using EHR for research.


The G protein-coupled taste receptor T1R1/T1R3 regulates mTORC1 and autophagy.
Cells continually assess their energy and nutrient state to maintain growth and survival and engage necessary homeostatic mechanisms. Cell-autonomous responses to the fed state require the surveillance of the availability of amino acids and other nutrients. The mammalian target of rapamycin complex 1 (mTORC1) integrates information on nutrient and amino acid availability to support protein synthesis and cell growth. We identify the G protein-coupled receptor (GPCR) T1R1/T1R3 as a direct sensor of the fed state and amino acid availability. Knocking down this receptor, which is found in most tissues, reduces the ability of amino acids to signal to mTORC1. Interfering with this receptor alters localization of mTORC1, downregulates expression of pathway inhibitors, upregulates key amino acid transporters, blocks translation initiation, and induces autophagy. These findings reveal a mechanism for communicating amino acid availability through a GPCR to mTORC1 in mammals.


[Transjugular intrahepatic portosystemic shunt (TIPS) for the treatment of complications of portal hypertension in patients with liver cirrhosis].
Portal hypertension is a main cause for the development of esophago-gastric varices, ascites and hepatic nephropathy in liver cirrhosis. Reduction of portal pressure by a transjugular intrahepatic portosystemic shunt (TIPS) procedure has been possible for the last decade. The treatment reduces the risk for variceal bleeding, reduces ascites formation and may improve renal function in hepatic nephropathy. Improved survival, however, has not yet been documented. Complications comprise procedure related events (puncture of liver capsule, bleeding, infection, hemolysis with mortality 1-5%), shunt stenosis (30-80% during the first year but reversible), and encephalopathy (30% intermittent, 10% chronic). Indications for the procedure are primarily variceal bleeding resistant to conventional pharmacologic and endoscopic treatment. Absolute and relative contraindications are severe hepatic failure, a history of hepatic encephalopathy, infections, respiratory failure, and non-hepatic renal insufficiency.


Serum TRACP 5b is a useful marker for monitoring alendronate treatment: comparison with other markers of bone turnover.
We studied clinical performance of serum TRACP 5b and other bone turnover markers, including S-CTX, U-DPD, S-PINP, S-BALP, and S-OC, for monitoring alendronate treatment. TRACP 5b had higher clinical sensitivity, area under the ROC curve, and signal-to-noise ratio than the other markers. The purpose of this study was to compare the clinical performance of serum TRACP 5b (S-TRACP5b) with that of other markers of bone turnover in the monitoring of alendronate treatment. This double-blinded study included 148 healthy postmenopausal women that were randomly assigned into two groups: one receiving 5 mg alendronate daily (n=75) and the other receiving placebo (n=73) for 12 months. All individuals in both groups received calcium and vitamin D daily. The bone resorption markers S-TRACP5b, serum C-terminal cross-linked telopeptides of type I collagen (S-CTX), and total urinary deoxypyridinoline (U-DPD), and the serum markers of bone formation procollagen I N-terminal propeptide (S-PINP), bone-specific alkaline phosphatase (S-BALP), and total osteocalcin (S-OC) were assessed at baseline and at 3, 6, and 12 months after initiation of treatment. Lumbar spine BMD (LBMD) was measured at baseline and 12 months. Compared with the placebo group, LBMD increased, and all bone markers decreased significantly more in the alendronate group (p<0.001 for each parameter). The decrease of S-TRACP5b after first 3 months of alendronate treatment correlated significantly with the changes of all other markers except S-OC, the best correlation being with S-CTX (r=0.60, p<0.0001). The changes of LBMD at 12 months only correlated significantly with the changes of S-TRACP5b (r=-0.32, p=0.005) and S-CTX (r=-0.24, p=0.037) at 3 months. Based on clinical sensitivity, receiver operating characteristic (ROC) curves, and signal-to-noise ratio, S-TRACP5b, S-CTX, and S-PINP were the best markers for monitoring alendronate treatment. Clinical sensitivity, area under the ROC curve, and signal-to-noise ratio were higher for S-TRACP5b than for the other markers. These results show that S-TRACP5b, S-CTX, and S-PINP are useful markers for monitoring alendronate treatment.


An integrative taxonomic analysis reveals a new species of lotic Hynobius salamander from Japan.
We examine the phylogenetic structure and morphological differentiation within the Hynobius kimurae-H. boulengeri species complex-a widely-distributed group of stream-breeding hynobiid salamanders, inhabiting montane areas of western, central and eastern parts of Honshu Island, Japan. Phylogenetic relationships were assessed based on analyses of mitochondrial (mtDNA) and nuclear (nuDNA) gene fragments for a total of 51 samples representing 23 localities covering the entire range of the species complex. Morphological study included one-way analysis of variance (ANOVA) and principal components analysis (PCA) analyses of 26 morphometric and six meristic characters for 38 adult specimens of H. kimurae and three adult specimens of H. boulengeri. MtDNA genealogy supported monophyly of the H. kimurae-H. boulengeri complex, which is sister to all other Hynobius except H. retardatus. The complex is subdivided into three major clades, corresponding to the Eastern (Clade I) and Western (Clade II) populations of H. kimurae sensu lato, and to H. boulengeri (Clade III). Monophyly of H. kimurae sensu lato is only moderately supported by mtDNA, while nuDNA suggested that the Western form of H. kimurae is closer to H. boulengeri than to the eastern form. The time of the split of the H. kimurae-H. boulengeri complex is estimated as late Miocene and coincides with intensive crust movement in western Japan. Divergence between Clades I and II took place in early Pliocene and was likely influenced by the uplift of Central Japanese Highlands. All three clades were found to be different in a number of morphological characters, allowing us to describe the eastern form of H. kimurae as a new species, Hynobius fossigenussp. nov.


Typhoid Fever due to Extended Spectrum β-Lactamase-Producing Salmonella enterica Serovar Typhi: A Case Report and Literature Review.
Emergence of cephalosporin-resistant strains of Salmonella enterica serovar Typhi is a cause of concern in the management of enteric fever. Cephalosporin resistance in Salmonella species is mainly due to the production of extended-spectrum β-lactamases (ESBLs). The majority of ESBLs in Salmonella enterica serovar Typhi are derivatives of the TEM, SHV, and CTX-M β-lactamase families. Of these, CTX-M appears to be predominant. This paper discusses the detection and molecular characterization of an ESBL-producing Salmonella enterica serovar Typhi strain isolated from a patient who was admitted to a private hospital in Sri Lanka. The three main types of β-lactamases such as TEM, SHV, and CTX-M were identified in this isolate. This case report from Sri Lanka contributes to the knowledge of the increasingly reported cases of typhoid fever due to Salmonella enterica serovar Typhi resistant to β-lactamase by ESBL production.


Noninvasive assessment of endothelial function and vascular parameters in patients with familial and nonfamilial hypercholesterolemia.
Endothelial dysfunction is one of the markers of atherosclerosis. The aim of the study was to evaluate endothelial function by assessing flow-mediated dilation (FMD) and to measure the parameters of brachial arterial stiffness in patients with familial hypercholesterolemia (FH) and those with high low-density lipoprotein (LDL) cholesterol levels without FH mutations (nonfamilial hypercholesterolemia - non-FH). The study involved 60 patients (mean age, 41.9 ±7.7 y) without documented cardiovascular events and clinical symptoms of cardiovascular diseases: 21 patients with elevated plasma LDL cholesterol levels and genetically confirmed FH, 19 patients with elevated LDL cholesterol levels and without FH mutations, and 20 healthy controls. In each patient, ultrasound imaging was used to assess endothelium-dependent FMD and nitroglycerin-induced endothelium-independent dilation (EID) in the brachial artery. In addition, echo-tracking and photoplethysmography were used to assess the parameters of arterial stiffness. FMD was significantly lower in patients with FH (11.0% ±9.9% vs. 21.0% ±14.3%, P <0.01) and non-FH (14.2% ±10.1% vs. 21.0% ±14.3%, P <0.05) compared with controls. EID and arterial stiffness parameters were similar between the groups. Reduced FMD may suggest endothelial dysfunction. A lack of significant differences in arterial stiffness parameters may indicate that vascular remodeling is not advanced in patients with elevated LDL cholesterol levels. A lack of significant differences in FMD and arterial stiffness between patients with and without FH may indicate that FH mutation itself is not the main determinant of endothelial dysfunction and vascular remodeling in younger patients with hypercholesterolemia.


[Laryngeal function preservated surgery for piriform sinus carcinoma with paraglottic space involvement].
To investigate the feasibility and results of laryngeal functional preservation surgery for piriform sinus carcinoma with paraglottic space involvement. Fourteen cases of piriform sinus carcinoma with paraglottic space involvement were reviewed. Laryngoplasty was performed after tumor was resected, bilater al selective neck dissections were performed at the same stage. Postoperative chemoradiotherapy was applied to 11 patients while the other 3 patients did not receive chemotherapy nor radiotherapy. The follow-up time ranged from 6 months to 5 years, and the mean follow-up time was three and a half years. Twelve cases healed primarily while 2 cases experienced delayed heal because of pharyngeal fistula. Postoperative swallow bucking occurred in all patients, the longest gastric feeding time was 2 months. For the patients underwent postoperative chemoradiotherapy, the tumor did not recur in ten cases during the 3 years follow-up, while recurred in another case and the patient died without further treatment. Among those 3 cases without postoperative radiotherapy or chemotherapy, the tumor recurred in 2 cases during the following 6 months and chemoradiotherapy was applied, no recurrence presented in one patient, another one lost of follow-up. For the patient with recurred tumor 8 months after surgery, total laryngectomy was employed with postoperative chemoradiotherapy, the case died of tumor recurrence one and half year after the first surgery. The 3-year survival rate was 78.6%. For the vocal cord at lesion side, the mobility was noticeable in 6 patients, and visible anatomic landmark was lost in the other 8 patients. Laryngeal function preservated surgery could be performed in selected cases of piriform sinus carcinoma with para-glottic space involvement in order to achieve better clinical results and quality of life.


Safety and efficacy of concurrent interstitial radiation and hyperthermia in the treatment of progressive malignant brain tumors.
High activity 125I brachytherapy has efficacy in selected recurrent malignant brain tumors, but limited efficacy and risk of radiation necrosis have prompted investigation of additional adjunctive therapies. This study aims to assess the toxicity of interstitial conductive hyperthermia used concurrently with 125I brachytherapy for the treatment of recurrent brain malignancies. Twelve patients with recurrent malignant brain tumors were implanted using afterloading catheters intended to deliver 50 Gy at the isodose line encompassing the enhancing tumor with a 5-mm margin and heated to 41.5 degrees C for 48 h. The average implant volume was 18 cc with 5.3 catheters containing 9.4 sources with a total activity of 265 mCi. Serious toxicities included 8 motor deficits, 2 mood alterations, 4 seizures and 2 catheter wound cerebrospinal fluid leaks. Median survival was 10.35 months with the best responses being 6 with stable disease and 2 with partial responses. Reoperation rate for radiation necrosis was 33%. Concurrent conductive thermoradiotherapy is feasible but is associated with serious toxicity. There is no suggestion of improved survival with thermoradiotherapy over brachytherapy alone. Given the degree of toxicity observed, alternative approaches to improving local control of these tumors are being explored.


Influence of bronchial diameter change on the airflow dynamics based on a pressure-controlled ventilation system.
Bronchial diameter is a key parameter that affects the respiratory treatment of mechanically ventilated patients. In this paper, to reveal the influence of bronchial diameter on the airflow dynamics of pressure-controlled mechanically ventilated patients, a new respiratory system model is presented that combines multigeneration airways with lungs. Furthermore, experiments and simulation studies to verify the model are performed. Finally, through the simulation study, it can be determined that in airway generations 2 to 7, when the diameter is reduced to half of the original value, the maximum air pressure (maximum air pressure in lungs) decreases by nearly 16%, the maximum flow decreases by nearly 30%, and the total airway pressure loss (sum of each generation pressure drop) is more than 5 times the original value. Moreover, in airway generations 8 to 16, with increasing diameter, the maximum air pressure, maximum flow, and total airway pressure loss remain almost constant. When the diameter is reduced to half of the original value, the maximum air pressure decreases by 3%, the maximum flow decreases by nearly 5%, and the total airway pressure loss increases by 200%. The study creates a foundation for improvement in respiratory disease diagnosis and treatment.


Carcinoma of the female reproductive organs. Value of cross-sectional imaging.
Cross-sectional imaging techniques i.e., computed tomography (CT) and magnetic resonance imaging (MRI), play an integral role in the evaluation of patients with carcinoma of the female reproductive system. Neither CT nor MRI, however, are tissue-specific, and benign and malignant disease cannot be differentiated using these techniques alone. Therefore, the diagnosis is clinical and is based on history, physical examination, and histology. After the diagnosis has been made, CT and MRI are recommended for noninvasive evaluation of tumor extent, often helping in designing optimal therapy, thus facilitating more effective treatment and ultimately influencing patient prognosis. In evaluating tumors of the uterus, including endometrial and cervical carcinomas, CT is limited to the evaluation of more extensive disease. It is believed that the value of CT rises proportionately to the size and extent of disease. Its major limitation is suboptimal tissue contrast resolution, making differentiation between a small tumor and the surrounding normal tissue difficult. MRI renders excellent soft tissue contrast, allowing direct tumor visualization and assessment of tumor volume, depth of penetration, and extension to adjacent tissues. Assessment of these parameters is crucial in deciding on the choice of therapy, whether surgery, radiation, chemotherapy, or their combination. The initial management of ovarian cancer usually includes surgical staging with tumor debulking. CT remains the primary staging technique; its value resides primarily in identification of tumor metastases and in patient follow-up. Despite progress in the use of CT and MRI, second-look laparotomy for ovarian cancer has not been superseded. Technical advances in radiologic cross-sectional imaging have significantly improved the accuracy of noninvasive tumor staging. Although there are still limitations to these techniques, additional technical improvement and better tissue characterization are imminent.


A DNA Crosslinker Collects Mitotic Chromosomes.
Incorporating each set of daughter chromosomes into a single nucleus at the end of mitosis is essential for genome stability. In a recent Cell paper, Samwer et al. (2017) show that by non-covalently crosslinking DNA, BAF promotes chromosome coalescence, preventing nuclear membranes from enwrapping individual chromosomes to form micronuclei.


Proliferation and differentiation characteristics of normal human squamous mucosal cells of the upper aerodigestive tract.
Normal human squamous mucosal cells of the soft palate, buccal surface, epiglottis, hypopharynx, floor of the mouth, and tongue were cultured in vitro in serum-free medium. In medium MCDB 153 containing epidermal growth factor, insulin, bovine pituitary extract, and 0.1 or 2.0 mmol/L Ca++, squamous mucosal cells double every 24 hours. These cells then can be induced to arrest their proliferation reversibly by treatment with transforming growth factor-beta or ethionine, and they can irreversibly growth-arrest during senescence or when cultured in growth factor-deficient medium containing 2 mmol/L Ca++. The latter medium also induces differentiation, as does culture of cells in serum-containing medium. Serum-containing medium furthermore promotes extensive cell stratification and the formation of multilayered squamous mucosal tissue specimens that can be removed intact by Dispase treatment. These specimens represent potential autogenous mucosal grafts that can be used in patients who require reconstructive surgery of the oral cavity and oropharynx. Normal human squamous mucosal cells therefore closely resemble keratinocytes derived from the epidermis in the mechanisms that regulate proliferation and differentiation. This model cell system should facilitate future studies on upper aerodigestive tract squamous mucosal cell physiology and pathophysiology.


Middle segment-preserving pancreatectomy for metachronous intraductal papillary mucinous neoplasm after pancreatoduodenectomy: a case report.
Total pancreatectomy has occasionally been performed to treat patients with multiple lesions (such as intraductal papillary mucinous neoplasm (IPMN)) or patients who have undergone repeated pancreatic resection. However, deficiencies of the exocrine and endocrine functions worsen patients' quality of life. Recently, there have been several case reports citing middle segment-preserving pancreatectomy (MSPP) as a safe procedure and beneficial with respect to preservation of the exocrine and endocrine functions. We herein report the case of a patient who underwent MSPP for repeat pancreatectomy for IPMN and in whom a favorable outcome was achieved. The patient, a 70-year-old man, was diagnosed with branch duct-type IPMN (BD-IPMN) with worrisome features in the pancreatic head and a single cyst in the pancreatic tail, during a preoperative examination of early gastric cancer. Pancreatoduodenectomy was performed for BD-IPMN in the pancreatic head and gastric cancer. A histopathological examination showed an intraductal papillary mucinous adenoma (IPMA) with mild-moderate atypia. During the follow-up, the size of the cystic lesion in the pancreatic tail and the diameter of the main pancreatic duct were gradually increasing. Therefore, at 2 years and 6 months after surgery, distal pancreatectomy with preservation of the spleen (namely MSPP) was performed. The pancreatic resection margin was histologically negative. The length and volume of the remnant pancreas were approximately 6 cm and 10 ml, respectively. A histopathological examination showed an IPMA. The patient had no diarrhea or weight loss without digestive enzymes and maintained favorable glucose tolerance without oral hypoglycemic agents or insulin. He has showed no evidence of new lesions in the remnant pancreas at 3 years of follow-up after the last surgery.


Prenatal development of intrafetal and maternal-fetal synchrony.
Fetal and maternal data were monitored serially at 6 gestational ages from 20 to 38 weeks in 195 Peruvian fetuses. Digitized data included fetal heart rate and motor activity, as well as maternal heart rate and electrodermal conductance. Time series analysis evaluated the development of synchrony in 2 streams of fetal functioning and between mothers and fetuses. Intrafetal synchrony between heart rate and motor activity developed in an orderly fashion, with peak cross-correlation approaching an asymptote at 5 s at 28 weeks. Synchrony was not observed between fetal heart rate and maternal measures. Fetal motor activity exhibited synchrony with both maternal electrodermal and heart rate activity. Implications for revealing fundamental properties of neural development prior to birth are discussed.


Glial cell loss, proliferation and replacement in the contused murine spinal cord.
Studies in the rat have shown that contusive spinal cord injury (SCI) results in devastating pathology, including significant loss of mature oligodendrocytes and astrocytes even in spared white matter. Subsequently, there is increased proliferation of endogenous NG2(+) cells, postulated to contribute to replacement of mature glia chronically, which is important for functional recovery. Studies of mechanisms that stimulate endogenous progenitor cells would be facilitated by using mouse models with naturally occurring and genetically engineered mutations. To determine whether the murine response is similar to that in the rat, we performed contusive SCI on adult female C57Bl/6 mice at the T8-9 level. Animals received bromodeoxyuridine injections in the first week following injury and were killed at 1, 3, 4, 7 or 28 days postinjury (DPI). The overall loss of macroglia and the temporal-spatial response of NG2(+) cells after SCI in the (C57Bl/6) mouse was very similar to that in the (Sprague-Dawley) rat. By 24 h after SCI nearly half of the macroglia in spared ventral white matter had been lost. Cell proliferation was increased at 1-7 DPI, peaking at 3-4 DPI. Dividing cells included NG2(+) cells and Cd11b(+) macrophages and microglia. Furthermore, cells dividing in the first week expressed markers of mature glia at 28 DPI. The similarities in endogenous progenitor cell response to SCI in the mouse and rat suggest that this is a fundamental injury response, and that transgenic mouse models may be used to further probe how this cellular response to SCI might be enhanced to improve recovery after SCI.


Electroencephalography (EEG) Reveals Increased Frontal Activity in Social Presence.
It remains an unsolved conundrum how social presence affects the neural processes involved in adaptive situation-specific decision-making mechanisms. To investigate this question, brain potential changes via electroencephalography (EEG) and skin conductance responses (SCR) were taken within this study, while participants were exposed to pre-rated pleasant, neutral, and unpleasant pictures, which they had to rate in terms of their perceived arousal. Crucially, they had to-in respective runs-do this alone and in the presence of a significant other. Contrasting respective event-related potentials (ERPs) revealed significantly more negative going potentials peaking at 708 ms post stimulus onset at mid-frontal electrode locations (around FPz and AFz), when participants were exposed to neutral pictures while in the presence of a significant other. SCR results demonstrate higher states of arousal in the presence of a significant other regardless of picture emotion category. Self-reported arousal turned out to be highest in response to neutral pictures within the significant other condition, whereas in the alone condition in response to the pleasant pictures. In light of existing literature on social aspects and the anterior cingulate cortex (ACC), the ERP finding in the significant other condition, while rating emotionally neutral pictures, is interpreted as reflecting heightened ACC activation, which is supported by electrode locations showing significant brain activity differences as well as by source localization results. Neutral pictures are inherently ambiguous, and the current results indicate the presence of another person to change the way one processes, perceives, and acts on them. This is in support for theories proposing the ACC to be part of a larger signal-specification network that gauges relevant stimuli for adequate execution of control.


Structural and Biophysical Characterization of Rab5a from Leishmania Donovani.
Leishmania donovani possess two isoforms of Rab5 (Rab5a and Rab5b), which are involved in fluid phase and receptor-mediated endocytosis, respectively. We have characterized the solution structure and dynamics of a stabilized truncated LdRab5a mutant. For the purpose of NMR structure determination, protein stability was enhanced by systematically introducing various deletions and mutations. Deletion of hypervariable C-terminal and the 20 residues LdRab5a specific insert slightly enhanced the stability, which was further improved by C107S mutation. The final construct, truncated LdRab5a with C107S mutation, was found to be stable for longer durations at higher concentration, with an increase in melting temperature by 10°C. Solution structure of truncated LdRab5a shows the characteristic GTPase fold having nucleotide and effector binding sites. Orientation of switch I and switch II regions match well with that of guanosine 5'-(β, γ-imido)triphosphate (GppNHp)-bound human Rab5a, indicating that the truncated LdRab5a attains the canonical GTP bound state. However, the backbone dynamics of the P-loop, switch I, and switch II regions were slower than that observed for guanosine 5'-(β, γ-imido)triphosphate (GMPPNP)-bound H-Ras. This dynamic profile may further complement the residue-specific complementarity in determining the specificity of interaction with the effectors. In parallel, biophysical investigations revealed the urea induced unfolding of truncated LdRab5a to be a four-state process that involved two intermediates, I1 and I2. The maximal 4,4'-dianilino-1,1'-binaphthyl-5,5'-disulfonic acid (Bis-ANS) binding was observed for I2 state, which was inferred to have molten globule like characteristics. Overall, the strategy presented would have significant impact for studying other Rab and small GTPase proteins by NMR spectroscopy.


A molecular chaperone breaks the catalytic cycle that generates toxic Aβ oligomers.
Alzheimer's disease is an increasingly prevalent neurodegenerative disorder whose pathogenesis has been associated with aggregation of the amyloid-β peptide (Aβ42). Recent studies have revealed that once Aβ42 fibrils are generated, their surfaces effectively catalyze the formation of neurotoxic oligomers. Here we show that a molecular chaperone, a human Brichos domain, can specifically inhibit this catalytic cycle and limit human Aβ42 toxicity. We demonstrate in vitro that Brichos achieves this inhibition by binding to the surfaces of fibrils, thereby redirecting the aggregation reaction to a pathway that involves minimal formation of toxic oligomeric intermediates. We verify that this mechanism occurs in living mouse brain tissue by cytotoxicity and electrophysiology experiments. These results reveal that molecular chaperones can help maintain protein homeostasis by selectively suppressing critical microscopic steps within the complex reaction pathways responsible for the toxic effects of protein misfolding and aggregation.


Killing the messenger: antisense DNA and siRNA.
Among the technologies available for gene knockdown RNase H-dependent antisense oligonucleotides and RNAi are very popular. Both offer specificity and efficient knockdown of the genes; both are useful tools to study gene functions. Antisense and RNAi methods share many practical problems such as site selection, toxicity at high concentration, and the difficulty of transfection in certain cell types. We will focus in this review on the most important issues in the development of both methods and their possible use in gene-silencing therapy.


Gel purification of gDNA for next-generation sequencing applications.
We demonstrate that gDNA can be conveniently and efficiently isolated and purified using standard agarose gel electrophoresis, band excision and gel purification. This method yields a substantial amount at microgram levels of gDNA per gel cleanup with high purity. An RNase A treatment step can be omitted. The quality of gDNA is suitable for next-generation sequencing, resulting in >10 Mb reads and high-quality read data (Phred score >28 up to 100 of 150 base reads). Furthermore, the gDNA can be kept intact in a gel slice for several days. This method has been tested for dictyostelids, bacteria and plants.


Visualizing dynamic interaction between calmodulin and calmodulin-related kinases via a monitoring method in live mammalian cells.
A new visualizing method was developed for monitoring protein-protein (P-P) interactions in live mammalian cells. P-P interactions are visualized by directing localization of a bait protein to endosomes. This method is sufficiently robust to analyze signal-dependent P-P interactions such as calcium-dependent protein interactions. We visualized interactions between activated calmodulin and calmodulin-binding proteins, and observed oscillatory interactions via time-lapse imaging. In addition, this new method can simultaneously monitor multiple P-P interactions in a single live cell, which allows comparison of interactions between several prey proteins and a single bait protein. We observed that CaMKK1 and CaMKIIalpha bind calmodulin with distinct binding affinities in live cell, which indicates that calcium signaling is fine-tuned by distinct activation patterns of CaM kinases. This method will enable investigation of cellular processes based on dynamic P-P interactions.


Early, transient depletion of plasmacytoid dendritic cells ameliorates autoimmunity in a lupus model.
Plasmacytoid dendritic cells (pDCs) have long been implicated in the pathogenesis of lupus. However, this conclusion has been largely based on a correlative link between the copious production of IFN-α/β by pDCs and the IFN-α/β "signature" often seen in human lupus patients. The specific contribution of pDCs to disease in vivo has not been investigated in detail. For this reason, we generated a strain of BXSB lupus-prone mice in which pDCs can be selectively depleted in vivo. Early, transient ablation of pDCs before disease initiation resulted in reduced splenomegaly and lymphadenopathy, impaired expansion and activation of T and B cells, reduced antibodies against nuclear autoantigens and improved kidney pathology. Amelioration of pathology coincided with decreased transcription of IFN-α/β-induced genes in tissues. PDC depletion had an immediate impact on the activation of immune cells, and importantly, the beneficial effects on pathology were sustained even though pDCs later recovered, indicating an early pDC contribution to disease. Together, our findings demonstrate a critical function for pDCs during the IFN-α/β-dependent initiation of autoimmune lupus and point to pDCs as an attractive therapeutic target for the treatment of SLE.


Green tea extract protects endothelial progenitor cells from oxidative insult through reduction of intracellular reactive oxygen species activity.
Many studies have reported that tea consumption decreases cardiovascular risk, but the mechanisms remain unclear. Green tea is known to have potent antioxidant and free radical scavenging activities. This study aimed to investigate whether green tea extract (GTE) can protect endothelial progenitors cells (EPCs) against oxidative stress through antioxidant mechanisms. Mononuclear cells (MNCs) were isolated from peripheral blood by density gradient centrifugation with Ficoll. The cells were then plated on fibronectin-coated culture dishes. After 7 days of culture, EPCs were characterized as adherent cells double positive for DiI-ac-LDL uptake and lectin binding. EPCs were further identified by assessing the expression of CD34/45, CD133, and KDR. EPCs were then treated with hydrogen peroxide (H2O2) at doses of 50, 100, 200 µM and incubated with or without GTE (25 µg/ml). The intracellular reactive oxygen species (ROS) levels were detected by flow cytometry using a 2',7'-dichlorofluorescein diacetate (DCF-DA) fluorescent probe. GTE ameliorated the cell viability of EPCs induced by H2O2 at doses of 50, 100, 200 µM for about 25.47, 22.52, and 11.96% higher than controls, respectively. GTE also decreased the intracellular ROS levels of EPCs induced by H2O2 at doses of 50, 100, 200 µM for about 84.24, 92.27, and 93.72% compared to controls, respectively. GTE improves cell viability by reducing the intracellular ROS accumulation in H2O2-induced EPCs.


Variable in Vivo and in Vitro Biological Effects of Cerium Oxide Nanoparticle Formulations.
Cerium oxide nanoparticles (CeNPs) exhibit redox capacity in vitro with efficacy in in vivo disease models of oxidative stress. Here we compare, in parallel, three CeNP formulations with distinct chemical stabilizers and size. In vitro assays revealed antioxidant activity from all the CeNPs, but when administered to mice with a reactive oxygen species (ROS) mediated model of multiple sclerosis, only custom-synthesized Cerion NRx (CNRx) citrate-EDTA stabilized CeNPs provided protection against disease. Detectable levels of ceria and reduced ROS levels in the brains of CNRx CeNP-treated mice imply that these CeNPs' unique properties influence tissue distribution and subsequent biological activity, suggesting why differing CeNP formulations yield different in vivo effects in various models. Further, the variation in in vivo vs in vitro results with these CeNP formulations highlights the necessity for in vivo studies that confirm whether the inherent catalytic activity of CeNPs is maintained after transport and distribution within intact biological systems.


Paraesophageal Hernia: To Mesh or Not to Mesh? The Controversy Continues.
Introduction: Paraesophageal hernias represent 5%-10% of all primary hiatal hernias and are becoming increasingly more common with the aging of the population. Surgical treatment includes closure of the wide hiatal gap. Achieving tension-free closure is difficult, and several studies have reported lower recurrence rates with the use of mesh reinforcement. The use of this technique, however, is controversial. Objective and Materials and Methods: Narrative revision of the literature revising: (1) evidence-based surgery and clinical studies, (2) what the experts say (Delphi), (3) complications of mesh, and (4) long-term results of laparoscopic treatment impact on the quality of life. Results: Consensus about the type of mesh continues to be elusive, and we clearly need a higher level of evidence to address the controversy. Conclusion: Mesh reinforcement can effectively reduce the hernia recurrence rate. Mesh-associated complications are few, but because they are serious, most experts recommend mesh use only in specific circumstances, particularly those in relation to the size of the hiatal defect and the quality of the crura.


Divergent signaling pathways regulate IL-12 production induced by different species of Lactobacilli in human dendritic cells.
Recent studies have indicated that different strains of Lactobacilli differ in their ability to regulate IL-12 production by dendritic cells (DCs), as some strains are stronger inducer of IL-12 while other are not and can even inhibit IL-12 production stimulated by IL-12-inducer Lactobacilli. In this report we demonstrate that Lactobacillus reuteri 5289, as previously described for other strains of L. reuteri, can inhibit DC production of IL-12 induced by Lactobacilllus acidophilus NCFM. Remarkably, L. reuteri 5289 was able to inhibit IL-12 production induced not only by Lactobacilli, as so far reported, but also by bacteria of different genera, including pathogens. We investigated in human DCs the signal transduction pathways involved in the inhibition of IL-12 production induced by L. reuteri 5289, showing that this potential anti-inflammatory activity, which is also accompanied by an elevated IL-10 production, is associated to a prolonged phosphorilation of ERK1/2 MAP kinase pathway. Improved understanding of the immune regulatory mechanisms exerted by Lactobacilli is crucial for a more precise employment of these commensal bacteria as probiotics in human immune-mediated pathologies, such as allergies or inflammatory bowel diseases.


Effects of T'ai Chi on Serotonin, Nicotine Dependency, Depression, and Anger in Hospitalized Alcohol-Dependent Patients.
The aim of this study was to investigate the effects of t'ai chi on blood serotonin levels, nicotine dependence, depression, and anger in hospitalized alcohol-dependent patients. This study followed an experimental and nonequivalent control group in a non-synchronized design. It was performed in a hospital located in Young Ju city, Korea, from April to August 2013. Thirty-eight patients who were hospitalized with alcohol dependence were included. They were randomly divided into an experimental and a control group, with 19 patients in each group. Patients in the experimental group practiced the 24-posture yang style t'ai chi for 50 min three times per week for 8 weeks as part of the routine hospital rehabilitation program, and those in the control group followed only the routine hospital rehabilitation program. The effect of treatment was measured using blood serotonin levels and a questionnaire on nicotine dependence, depression, and anger. Both measurements were performed before and after 8 weeks of intervention. Data were analyzed using the t-test, chi-square test, and paired t-tests. The experimental group showed a significantly increased blood serotonin level (p = 0.001) and significantly reduced nicotine dependence, depression, and anger (p = 0.001) than the control group did after 8 weeks of treatment. T'ai chi was shown to be an effective nursing intervention in hospitalized alcohol-dependent patients.


Alternative pathways of carbon dioxide fixation: insights into the early evolution of life?
The fixation of inorganic carbon into organic material (autotrophy) is a prerequisite for life and sets the starting point of biological evolution. In the extant biosphere the reductive pentose phosphate (Calvin-Benson) cycle is the predominant mechanism by which many prokaryotes and all plants fix CO(2) into biomass. However, the fact that five alternative autotrophic pathways exist in prokaryotes is often neglected. This bias may lead to serious misjudgments in models of the global carbon cycle, in hypotheses on the evolution of metabolism, and in interpretations of geological records. Here, I review these alternative pathways that differ fundamentally from the Calvin-Benson cycle. Revealingly, these five alternative pathways pivot on acetyl-coenzyme A, the turntable of metabolism, demanding a gluconeogenic pathway starting from acetyl-coenzyme A and CO(2). It appears that the formation of an activated acetic acid from inorganic carbon represents the initial step toward metabolism. Consequently, biosyntheses likely started from activated acetic acid and gluconeogenesis preceded glycolysis.


Bacteriophage Delivery by Nebulization and Efficacy Against Phenotypically Diverse Pseudomonas aeruginosa from Cystic Fibrosis Patients.
The rise in antibiotic-resistant Pseudomonas aeruginosa and the considerable difficulty in eradicating it from patients has re-motivated the study of bacteriophages as a therapeutic option. For this to be effective, host range and viability following nebulization need to be assessed. Host-range has not previously been assessed for the Liverpool Epidemic Strain (LES) isolates that are the most common cystic fibrosis-related clone of P. aeruginosa in the UK. Nebulization studies have not previously been linked to clinically relevant phages. 84 phenotypically variable isolates of the LES were tested for susceptibility to seven bacteriophages known to have activity against P. aeruginosa. Five of the phages were from the Eliava Institute (IBMV) and 2 were isolated in this study. The viability of the two bacteriophages with the largest host ranges was characterized further to determine their ability to be nebulized and delivered to the lower airways. Phages were nebulized into a cascade impactor and the phage concentration was measured. The bacteriophages tested killed between 66%-98% of the 84 Liverpool Epidemic Strain isolates. Two isolates were multi phage resistant, but were sensitive to most first line anti-Pseudomonal antibiotics. The amount of viable bacteriophages contained in particles that are likely to reach the lower airways (<4.7 μm) was 1% for the Omron and 12% AeroEclipse nebulizer. Individual P. aeruginosa bacteriophages can lyse up to 98% of 84 phenotypically diverse LES strains. High titers of phages can be effectively nebulized.


Pharmacologic pain treatment in a multidisciplinary pain center: do patients adhere to the prescription of the physician?
Medication nonadherence is a frequent problem in chronic conditions. In chronic noncancer pain, medication is often used as an important cornerstone of the treatment. Studies on medication nonadherence in this population, however, are scarce. The aim of this study was to determine the prevalence of medication underuse and overuse nonadherence in a large sample of chronic pain patients treated in a multidisciplinary pain center. Second, an extensive list of demographic, disease-related, treatment-related and health behavior-related factors was included to compare these factors between adherent, overusers, and underusers, respectively. Self-report was used to measure medication adherence. Forty-eight percent of the patients were nonadherent, with 34% of them showing underuse and 14% overuse of the prescribed medication. Multivariable analyses showed a significant association between younger age and medication nonadherence (both underuse and overuse). Furthermore, underuse was significantly associated with self-medication. Overuse was associated with current smoking, opioid prescription, and more medication intake moments. We can conclude that medication nonadherence, especially underuse of medication, occurs frequently among patients with chronic nonmalignant pain. Prospective research is needed to learn about the impact of medication overuse or underuse on clinical outcomes. Future research should examine underuse and overuse as different types of nonadherence as different factors might predict this behavior.


Psoralen mapping reveals a bacterial genome supercoiling landscape dominated by transcription.
DNA supercoiling is a key regulator of all DNA metabolic processes including replication, transcription, and recombination, yet a reliable genomic assay for supercoiling is lacking. Here, we present a robust and flexible method (Psora-seq) to measure whole-genome supercoiling at high resolution. Using this tool in Escherichia coli, we observe a supercoiling landscape that is well correlated to transcription. Supercoiling twin-domains generated by RNA polymerase complexes span 25 kb in each direction - an order of magnitude farther than previous measurements in any organism. Thus, ribosomal and many other highly expressed genes strongly affect the topology of about 40 neighboring genes each, creating highly integrated gene circuits. Genomic patterns of supercoiling revealed by Psora-seq could be aptly predicted from modeling based on gene expression levels alone, indicating that transcription is the major determinant of chromosome supercoiling. Large-scale supercoiling patterns were highly symmetrical between left and right chromosome arms (replichores), indicating that DNA replication also strongly influences supercoiling. Skew in the axis of symmetry from the natural ori-ter axis supports previous indications that the rightward replication fork is delayed several minutes after initiation. Implications of supercoiling on DNA replication and chromosome domain structure are discussed.


Diminished sympathetic silent period in spontaneously hypertensive rats.
To determine if elevated sympathetic activity occurs in spontaneously hypertension, the silent period induced in splanchnic nerves following electrical stimulation of dorsal medullary sympathoexcitatory sites was compared in anesthetized normotensive Wistar Kyoto rats (WKYs) and Okamoto spontaneously hypertensive rats (SHRs). The strength of silent periods was defined as the degree of inhibition of responses to testing stimuli delivered at various latencies following conditioning trains, and it was assumed to be inversely related to the level of sympathetic activity. Weanling SHRs exhibited weaker silent periods than weanling WKYs although, at that age, the arterial pressures of the strains were not significantly different. Silent periods were also weaker in adult SHRs than in adult WKYs. This difference persisted after arterial pressures, which fell under anesthesia, were raised by phenylephrine infusions to the respective "normal" levels in each strain. These results support the hypothesis that elevated sympathetic activity exists during both the development and maintenance of spontaneous hypertension in rats.


Expression of Ki-67 and cytokeratin 20 in hyperplastic polyps of the colorectum.
To study the expression of Ki-67 and cytokeratin 20 (CK20) in a group of hyperplastic polyps (including a group with "atypical" features) with the aim of determining whether upper crypt Ki-67 staining and lower crypt CK20 staining correlated with these atypical features, as assessed by light microscopy. Fifty seven formalin fixed, paraffin wax embedded hyperplastic colorectal polyps from 53 patients were selected on histological grounds; these comprised 26 typical polyps and 31 with atypical features, which included nuclear hyperchromatism, basal crowding, and increased mitotic activity. These polyps were examined using a standard immunohistochemical method with antibodies against CK20 and Ki-67. Comparisons were made with normal mucosa, adenomatous polyps, and carcinomas. Of the 26 typical polyps, 17 showed the usual pattern of lower crypt Ki-67 and upper crypt CK20 staining; one with upper crypt Ki-67 staining but normal surface CK20 staining; seven with Ki-67 confined to the lower half of crypts but with scattered lower crypt CK20; and one with both upper crypt Ki-67 staining, together with scattered CK20 basal staining. Of the 31 polyps with atypical features, 11 showed the usual staining pattern of lower crypt Ki-67 staining and surface staining with CK20; two showed Ki-67 staining extending into the upper half of crypts, but with a normal surface staining with CK20; 14 showed Ki-67 confined to the lower half of crypts, but scattered lower crypt staining with CK20; and four showed upper crypt Ki-67 staining together with scattered CK20 lower crypt staining. The normal pattern of lower crypt Ki-67 and upper crypt CK20 was seen in 28 of the 57 hyperplastic polyps and, in general, this corresponded with standard light microscopic appearances. Twenty one of the 57 polyps showed lower crypt mosaic CK20 staining, which in general corresponded with basal abnormalities on light microscopy, although seven specimens had normal appearances. Two smaller subsets emerged, one showing upper crypt Ki-67 staining in the presence of normal CK20 expression (three cases) and another in which a combination of lower crypt CK20 and upper crypt Ki-67 expression was seen (five cases). This last pattern was similar to that of neoplastic polyps and raises the possibility that a subgroup of hyperplastic polyps exists that may be a variant with malignant potential. Further studies with markers of mismatch repair genes and K-ras mutations may help to clarify this issue.


Characterisation of capn1, capn2-like, capn3 and capn11 genes in Atlantic halibut (Hippoglossus hippoglossus L.): Transcriptional regulation across tissues and in skeletal muscle at distinct nutritional states.
The typical calpain proteases are a subset of a wider superfamily and regulate a broad spectrum of physiological processes. Here we characterised Atlantic halibut complete-coding orthologues of calpain-1, calpain-2-like, "muscle-specific" calpain-3, plus calpain-11, a recently recognised vertebrate-wide family member. Phylogenetic analysis established the relationship of each sequence within a comprehensive framework of vertebrate calpains, including teleost paralogues. This approach provided significant insight into the evolution of teleost calpains. For example, teleost sequences considered calpain-2 orthologues formed a monophyletic clade external to sister clades for tetrapod calpain-2 and vertebrate calpain-8. Thus, teleost "calpain-2" is likely not directly orthologous to tetrapod calpain-2 and represents a calpain-2-like protein. The characteristic domain structure of typical calpains was observed in each halibut sequence, although calpain-3, as for other teleosts, retained only one (IS2) of three further domains found in human calpain-3 (NS, IS1 and IS2). Transcripts for capn1, capn2-like and capn11 were widely detected across eleven halibut tissues, whereas capn3 was detected in striated muscles, spleen and ovary, but absent or relatively less abundant in other tissues. We assessed the transcript expression of each calpain gene in fast-twitch skeletal muscle where nutritional state was altered with 60days feed restriction, followed by 60days satiation refeeding. Measured by quantitative real-time PCR, capn1 transcript levels were highest during maximal fasting and then steadily decreased with refeeding, where muscle was in net positive protein balance. Conversely capn2-like showed little response, whereas capn3 and capn11 transcript levels were lowest at maximal fasting before being strongly constitutively upregulated with subsequent refeeding. Halibut capn3 transcript abundance was on average 6.5, 23.7 and 5.9 fold greater than capn1, capn2-like and capn11 respectively in skeletal muscle across nutritional states. In turn, transcript levels of capn1 and capn11 were invariably higher than capn2-like, but were dependent on nutritional state compared to each other. The differential regulation of these genes in response to nutritional status suggests distinct roles for typical calpain family members in regulating the balance between catabolism and growth in teleost skeletal muscle.


Lack of prognostic relevance of Her-2/neu, topoisomerase IIα and EGFR in advanced ovarian carcinoma.
Patients with advanced ovarian cancer (FIGO stage III) have a poor clinical prognosis. However, these patients show distinct differences in their survival time, possibly due to differing responses to chemotherapy and differing tumor biology. In contrast to histological subtype, grading and staging, which are known to affect a patient's prognosis, the impact of the human epidermal growth factor receptor 2 (Her-2/neu), topoisomerase IIα and epidermal growth factor receptor (EGFR) on survival remain inconclusive. Therefore, the aim of this study was to assess their impact on survival in a group of advanced ovarian cancer patients. Tissue microarrays were constructed from specimens of 243 patients. Gene copy and chromosome numbers were evaluated by fluorescence in situ hybridization (FISH) and protein expression by immunohistochemistry (IHC). Scoring for the latter was calculated by considering the percentage of positive tumor cells and the relative staining intensity. FISH results were evaluated by previously published recommendations and correlated with overall survival. Using IHC, 1.6% of the cases that were tested for Her-2/neu and topoisomerase IIα were strongly positive, and 12.3% were positive for EGFR. Using FISH, 4.4% amplifications and 2.1% polysomies for Her-2/neu were identified; topoisomerase IIα showed 2.2% amplifications, 0.4% deletions and 3.5% polysomies. We observed 10.8% high polysomies, but no amplification for EGFR. None of the results obtained by IHC or FISH correlated with overall survival. In general, Her-2/neu, topoisomerase IIα and EGFR may be prognostic factors in ovarian carcinomas. However, within this group of FIGO stage III patients, differences in gene aberration or protein expression were not able to predict differences in survival.


Clinical Spectrum and Trajectory of Innovative Therapeutic Interventions for Insomnia: A Perspective.
Increasing incidences of insomnia in adults, as well as the aging population, have been reported for their negative impact on the quality of life. Insomnia episodes may be associated with neurocognitive, musculoskeletal, cardiovascular, gastrointestinal, renal, hepatic, and metabolic disorders. Epidemiological evidence also revealed the association of insomnia with oncologic and asthmatic complications, which has been indicated as bidirectional. Two therapeutic approaches including cognitive behavioral therapy (CBT) and drugs-based therapies are being practiced for a long time. However, the adverse events associated with drugs limit their wide and long-term application. Further, Traditional Chinese medicine, acupressure, and pulsed magnetic field therapy may also provide therapeutic relief. Notably, the recently introduced cryotherapy has been demonstrated as a potential candidate for insomnia which could reduce pain, by suppressing oxidative stress and inflammation. It seems that the synergistic therapeutic approach of cryotherapy and the above-mentioned approaches might offer promising prospects to further improve efficacy and safety. Considering these facts, this perspective presents a comprehensive summary of recent advances in pathological aetiologies of insomnia including COVID-19, and its therapeutic management with a greater emphasis on cryotherapy.


Social networks and future direction for obesity research: A scoping review.
Despite significant efforts to decrease obesity rates, the prevalence of obesity continues to increase in the United States. Obesity risk behaviors including physical inactivity, unhealthy eating, and sleep deprivation are intertwined during daily life and are difficult to improve in the current social environment. Studies show that social networks-the thick webs of social relations and interactions-influence various health outcomes, such as HIV risk behaviors, alcohol consumption, smoking, depression, and cardiovascular mortality; however, there is limited information on the influences of social networks on obesity and obesity risk behaviors. Given the complexities of the biobehavioral pathology of obesity and the lack of clear evidence of effectiveness and sustainability of existing interventions that are usually focused on an individual approach, targeting change in an individual's health behaviors or attitude may not take sociocontextual factors into account; there is a pressing need for a new perspective on this problem. In this review, we evaluate the literature on social networks as a potential approach for obesity prevention and treatment (i.e., how social networks affect various health outcomes), present two major social network data analyses (i.e., egocentric and sociometric analysis), and discuss implications and the future direction for obesity research using social networks.


Nutritive Value of Sorghum Dried Distillers Grains with Solubles and its Effect on Performance in Geese.
The study was conducted to determine the chemical composition and nutritive value of sorghum dried distillers grains with solubles (sDDGS) and its effect as a feed supplement on the performance of geese. Experiment 1 showed that the gross energy, crude protein, ether extract, crude fiber, calcium, phosphorus, and amino acid content values of sDDGS were 17.87 MJ/kg and 15.48, 4.26, 31.46, 0.17, 0.25, and 0.06-3.18% [dry matter basis (DM)], respectively. Experiment 2 used fasting-force feeding to measure the true metabolizable energy of sDDGS (11.38 MJ/kg DM) and true total tract digestibility of amino acids (43.16-80.92% DM) in geese. Experiment 3 examined the effectiveness of sDDGS as a feed supplement for geese. Three hundred and fifteen 35-day-old male Sichuan white geese with an initial average bodyweight of 1,732 g were randomly allocated to five treatments. Geese in each treatment group were fed one of five experimental diets (control diet alone, or supplemented with 4, 8, 12, or 16% sDDGS) until 70 days of age. Inclusion of sDDGS in the diet did not affect daily average weight gain (P>0.05). Birds fed diets containing up to 8% sDDGS had higher average feed intake (P<0.05) than geese fed the control diet, and the feed/gain ratio in geese fed diets containing 16% sDDGS was higher (P<0.05) than in the control and the 4% sDDGS group. The yields of breast meat, leg meat, subcutaneous fat and skin, and abdominal fat were not affected (P>0.05) bydietary sDDGS levels. Generally, sDDGS is a potentially valuable feedstuff for geese, but it should be supplemented with a high-energy or protein-rich ingredient. To improve growth performance and carcass yield, up to 12% sDDGS can be included in diets from 35 to 70 days of age.


[Epidemiologic and prognostic aspects of nosocomial bacteremia in the intensive care unit].
The nosocomial bacteremia (NB) are frequent and associated to a high mortality and morbidity with extension of stay in the intensive care unit (ICU). The aim of this study is to evaluate epidemiological aspect and prognosis of NB. It is a retrospective study about 872 patients hospitalized in our unit during 2 years. The diagnosis of the NB is based on two positive hemocultures with 24 hours of interval in the patients who are hospitalized more than 48 hours. The incidence of the bacteremia represents 6.6% (n = 58). The portal of entry is noticed in 55% of the cases (n = 32). The most frequent origin is respiratory infection 24% (n = 14), whereas bacteremia after catheter colonization represents 3.4% (n = 2). Gram Positive cocci were incriminated in more than 53% of the cases (n = 39). Staphylococcus aureus was the first causal germ (n = 28) whereas the Pseudomonas is the most frequent of the gram negative bacilli that represent 41% of the isolate germs (n = 31). The sensitibility of this germ to ceftazidim and imipenen was respectively 18% and 19%. The rate of the resistant Staphylococcus to meticilline was 38%. The whole mortality represented 28% (n = 16) that 7% (n = 14) of the cases were directly in relationship with the septic shock. Among prognostic factors evaluated, only septic shock and multivisceral failures are correlated to mortality. NB mortality is not negligible in ICU. Staphylococcus and Pseudomonas are the most frequent germs. Limitation of invasive acts, rigorous antibiotherapy management and observance of hygienic measures will significantly reduce incidence of NB.


Characterizing homogeneous chemistry using well-mixed microeddies.
Well-mixed reaction volumes are often sought in engineered microchemical devices and can be an important feature of naturally occurring physicochemical processes such as pitting corrosion. Steady streaming eddies can serve as well-mixed, easily controlled microliter chemical reactors for characterizing homogeneous chemical reactions. Here, steady streaming eddies are produced by oscillating a liquid-filled cuvette around a stationary cylindrical electrode (radius 406 microm, length 1.6 cm) at audible frequencies (75 Hz). Oxidant (ferricyanide) electrochemically dosed at small rates (<or=30 nmol/s) from the cylindrical electrode accumulates to millimolar concentrations within the closed streamlines of each eddy, where it mixes and reacts with an antioxidant (vitamin C) present in the bulk solution. The composition in the eddy is controlled by varying the oxidant dosing rate and the bulk antioxidant concentration (<or=10 mM), as well as the cuvette oscillation amplitude. A simple algebraic mole balance is combined with Raman spectroscopy measurements of oxidant concentration in the eddy and bulk to determine the reaction rate law and homogeneous rate constant (45 +/- 9 M(-1) s(-1)) for the antioxidant properties of vitamin C against ferricyanide. Numerical solutions to the full Navier-Stokes equations and species continuity equations illustrate the distribution of species during the reaction and general limitations to the assumption of a well-mixed eddy.


Concise synthesis of (+)-allo-kainic acid via MgI2-mediated tandem aziridine ring opening-formal [3 + 2] cycloaddition.
3-Methyl vinyl aziridine undergoes a mild MgI2-promoted S(N)2' ring opening and concomitant cyclization with fumarate Michael acceptors to give trisubstituted pyrrolidines. The process is efficient and highly diastereoselective. This methodology has been applied to a concise asymmetric synthesis of (+)-allo-kainic acid.


In vivo creep behavior of the normal and degenerated porcine intervertebral disk: a preliminary report.
The viscoelastic properties of normal and surgically altered lumbar intervertebral disks from eight immature swine were examined in vivo. Rheological models were used to mathematically characterize the compressive creep-relation behavior of the disks before and after alteration by either chemonucleolysis [chymopapain (Chymodyactin) injection] or denucleation. In the normal disks, a significant modulating effect of respiration was observed that tended to increase the creep deformation response in comparison to that observed during similar in vitro and in situ studies. These results suggest that, in terms of assessing the absolute magnitude of the viscoelastic properties of lumbar disks, the influence of normal physiological function on adjacent vertebrae and surrounding tissues cannot be neglected. Preliminary results obtained from the experimentally altered disks indicated that partial denucleation primarily affected the initial stiffness behavior of the disk (24% decrease in elastic modulus), whereas chemonucleolysis caused changes in both the time-dependent (15% increase in creep rate) and instantaneous (23% decrease in elastic modulus) properties of the disk. Both partial denucleation and acute chemonucleolysis produced biomechanical changes that were comparable to grade II or slightly degenerative, age-related changes found in human lumbar intervertebral disks.


Key features and context-dependence of fishery-induced trophic cascades.
Trophic cascades triggered by fishing have profound implications for marine ecosystems and the socioeconomic systems that depend on them. With the number of reported cases quickly growing, key features and commonalities have emerged. Fishery-induced trophic cascades often display differential response times and nonlinear trajectories among trophic levels and can be accompanied by shifts in alternative states. Furthermore, their magnitude appears to be context dependent, varying as a function of species diversity, regional oceanography, local physical disturbance, habitat complexity, and the nature of the fishery itself. To conserve and manage exploited marine ecosystems, there is a pressing need for an improved understanding of the conditions that promote or inhibit the cascading consequences of fishing. Future research should investigate how the trophic effects of fishing interact with other human disturbances, identify strongly interacting species and ecosystem features that confer resilience to exploitation, determine ranges of predator depletion that elicit trophic cascades, pinpoint antecedents that signal ecosystem state shifts, and quantify variation in trophic rates across oceanographic conditions. This information will advance predictive models designed to forecast the trophic effects of fishing and will allow managers to better anticipate and avoid fishery-induced trophic cascades.


Breast is best for GPs--or is it? Breastfeeding attitudes and practice of general practitioners in the Mid-West of Ireland.
In light of the 1994 National Breastfeeding Policy and the 1999 Mid-Western Health Board (MWHB) Breastfeeding Strategy, a telephone survey of 164 General Practitioners (GPs) in the Mid-West was performed to ascertain their attitudes and practice in relation to breastfeeding. 95% believe breastfeeding promotion is part of their role and almost 40% consider GPs influential in the decision to breastfeed. Less than 10% have formal breastfeeding training, while 1/3 would be interested in formal training. 80% promote breastfeeding, and 90% are confident to deal with breastfeeding problems. Those with formal training reported higher promotion and confidence rates, and scored higher on management scenarios, GPs in the Mid-West of Ireland have positive attitudes towards breastfeeding. Training in relation to breastfeeding appears lacking, however. Formal training appears to confer advantage, and if, made accessible to interested GPs has the potential to positively influence breastfeeding rates.


Rapid identification and discrimination of methicillin-resistant Staphylococcus aureus strains via matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.
Methicillin-resistant Staphylococcus aureus (MRSA) is one of major clinical pathogens responsible for both hospital- and community-acquired infections worldwide. A delay in targeted antibiotic treatment contributes to longer hospitalization stay, higher costs, and increasing in-hospital mortality. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) has been integrated into the routine workflow for microbial identification over the past decade, and it has also shown promising functions in the detection of bacterial resistance. Therefore, we describe a rapid MALDI-TOF MS-based methodology for MRSA screening with machine-learning algorithms. A total of 452 clinical S. aureus isolates were included in this study, of which 194 were MRSA and 258 were methicillin-sensitive S. aureus (MSSA). The mass-to-charge ratio (m/z) features from MRSA and MSSA strains were binned and selected through Lasso regression. These features were then used to train a non-linear support vector machine (SVM) with radial basis function (RBF) kernels to evaluate the discrimination performance. The classifiers' accuracy, sensitivity, specificity, and the area under the receiver operating characteristic (ROC) curve (AUC) were evaluated and compared with those from the random forest (RF) model. A total of 2601 unique spectral peaks of all isolates were identified and 38 m/z features were selected for the classifying model. The AUCs of the non-linear RBF-SVM model and the RF model were 0.89 and 0.87, respectively, and the accuracy ranged between 0.86 (RBF-SVM) and 0.82 (RF). Our study demonstrates that MALDI-TOF MS coupled with machine-learning algorithms could be used to develop a rapid and easy-to-use method to discriminate MRSA from MSSA. Considering that this method is easy to implement in routine microbiology laboratories, it suggests a cost-effective and time-efficient alternative to conventional resistance detection in the future to improve clinical treatment.


Effect of tone-based sound stimulation on balance performance of normal subjects: preliminary investigation.
Sound is known to affect the human brain, hence sound or music therapy is sometimes used to improve a subject's physicaland mental health. In this study, the effects sound stimulation has on balance were investigated by means of computerizeddynamic posturography tests performed with eyes closed on an unstable surface using a CAPS® system, exceeding theInternational Society for Posture and Gait Research (ISPGR) recommended metrological performance standards. Subjectswere tested without listening to any music (baseline), listening to "pure music", and listening to the same music with differenttones embedded into it (one for each key). We found that different subjects react differently to different tones. Music alonedid not have a statistically significant effect on balance compared to the baseline, but the "best" tone significantly improvedbalance compared to the baseline or the "pure music" conditions. Furthermore, the "worst" tone reduced the balancecompared to "pure music", but the reduction was not statistically significant relative to the baseline. The results thereforeindicate that, at least relative to balance performance, the tone-based sound stimulation we investigated is effective andinherently safe, but that tone selection depends on the individual subject.


Divergent DNA methylation patterns associated with abiotic stress in Hevea brasiliensis.
Cytosine methylation is a fundamental epigenetic mechanism for gene-expression regulation and development in plants. Here, we report for the first time the identification of DNA methylation patterns and their putative relationship with abiotic stress in the tree crop Hevea brasiliensis (source of 99% of natural rubber in the world). Regulatory sequences of four major genes involved in the mevalonate pathway (rubber biosynthesis pathway) and one general defense-related gene of three high-yielding popular rubber clones grown at two different agroclimatic conditions were analyzed for the presence of methylation. We found several significant variations in the methylation pattern at core DNA binding motifs within all the five genes. Several consistent clone-specific and location-specific methylation patterns were identified. The differences in methylation pattern observed at certain pivotal cis-regulatory sites indicate the direct impact of stress on the genome and support the hypothesis of site-specific stress-induced DNA methylation. It is assumed that some of the methylation patterns observed may be involved in the stress-responsive mechanism in plants by which they adapt to extreme conditions. The study also provide clues towards the existence of highly divergent phenotypic characters among Hevea clones despite their very similar genetic make-up. Altogether, the observations from this study prove beyond doubt that there exist epigenetic variations in Hevea and environmental factors play a significant role in the induction of site-specific epigenetic mutations in its genome.


Calcium sparks.
The calcium ion (Ca(2+)) is the simplest and most versatile intracellular messenger known. The discovery of Ca(2+) sparks and a related family of elementary Ca(2+) signaling events has revealed fundamental principles of the Ca(2+) signaling system. A newly appreciated "digital" subsystem consisting of brief, high Ca(2+) concentration over short distances (nanometers to microns) comingles with an "analog" global Ca(2+) signaling subsystem. Over the past 15 years, much has been learned about the theoretical and practical aspects of spark formation and detection. The quest for the spark mechanisms [the activation, coordination, and termination of Ca(2+) release units (CRUs)] has met unexpected challenges, however, and raised vexing questions about CRU operation in situ. Ample evidence shows that Ca(2+) sparks catalyze many high-threshold Ca(2+) processes involved in cardiac and skeletal muscle excitation-contraction coupling, vascular tone regulation, membrane excitability, and neuronal secretion. Investigation of Ca(2+) sparks in diseases has also begun to provide novel insights into hypertension, cardiac arrhythmias, heart failure, and muscular dystrophy. An emerging view is that spatially and temporally patterned activation of the digital subsystem confers on intracellular Ca(2+) signaling an exquisite architecture in space, time, and intensity, which underpins signaling efficiency, stability, specificity, and diversity. These recent advances in "sparkology" thus promise to unify the simplicity and complexity of Ca(2+) signaling in biology.


Gas-phase chemistry of actinides ions: new insights into the reaction of UO+ and UO2+ with water.
The ability of uranium monoxide cations, UO+ and UO2+, to activate the O-H bond of H2O was studied by using two different approaches of the density functional theory. First, relativistic small-core pseudopotentials were used together with B3LYP hybrid functional. In addition, frozen-core PW91-PW91 calculations were performed within the ZORA approximation. A close description of the reaction mechanisms leading to two different reaction products is presented, including all the involved minima and transition states. Different possible spin states were considered as well as the effect of spin-orbit interactions on the transition state barrier heights. The nature of the chemical bonding of the key minima and transition states was studied by using topological methodologies (ELF, AIM). The obtained results are compared with experimental data, as well as with previous studies on the reaction of the bare uranium cations with water, to analyze the influence of the oxo-ligand in reactivity.


Detoxification, Apoptosis, and Immune Transcriptomic Responses of the Gill Tissue of Bay Scallop Following Exposure to the Algicide Thiazolidinedione 49.
Thiazolidinedione 49 (TD49), a newly synthesized algicide, shows strong toxicity at low concentrations of 0.1-2.0 μM. However, its potential effects on non-target species at the transcript level were not investigated. Differentially expressed genes (DEGs) in the gills of the bay scallop, Argopecten irradians, were accessed after treatment with 0.68 μM TD49 for up to 48 h. Following exposure, it was observed that 5214 genes were upregulated and 3497 were downregulated. Functional enrichment analysis revealed that the apoptosis pathway was activated. The extrinsic apoptosis pathway was activated and the survival factors related pathway was suppressed. Furthermore, gene expressions related to ATP-binding cassette, nuclear factor erythroid 2-related factor, B cell lymphoma-2 family protein, glutathione reductase, glutathione peroxidase, catalase, NADPH2:quinone reductase, and superoxide dismutase were decreased. Conversely, gene expressions related to FAS-associated death domain protein, glutathione S-transferase, caspase 6, 8, cytochrome P450 1A1, and 2C8 were increased. These results comprehensively demonstrated the toxicity of the novel algicide TD49, and should draw the attention of researchers to the importance of analyzing the potential impact of chemical compounds as algicides to control the proliferation of harmful algae, due to the secondary pollution caused by their application.


The Effect of GHR/exon-3 Polymorphism and Serum GH, IGF-1 and IGFBP-3 Levels in Diabetes and Coronary Heart Disease.
The present study investigated the effects of growth hormone (GH), insulin-like growth factor-1 (IGF-1), insulin-like growth factor binding protein-3 (IGFBP-3) and GH-receptor (GHR)/exon-3 polymorphism on diabetes mellitus (DM) and coronary heart disease (CHD) patients. Ninety patients with CHD, 90 patients with DM and 96 controls were included in this study. The GH, IGF-1 and IGFBP-3 serum levels were measured with enzyme-linked immunosorbent assay. GHR/exon-3 variants were determined by multiplex-polymerase chain reaction. The frequency of all alleles and genotypes in all study groups were distributed according to the Hardy-Weinberg equilibrium. In addition, any association between GHR/exon-3 variants and the presence of risk factors were detected. The blood levels of GH, IGF-1 and IGFBP-3 were not distributed according to GHR/exon-3 variants. However, in the DM group, higher levels of IGF-1 and lower levels of GH and IGFBP-3, and in CHD group lower levels of IGF-1, GH and IGFBP-3 were observed. The order of GH levels were DM<CHD< Controls; IGF-1 levels were CHD<Controls<DM and IGFBP-3 levels were CHD<DM<Controls. No direct effect of GHR/exon-3 polymorphism was observed in DM or CHD patients. However GH, IGF-1, IGFBP-3 and insulin were thought to act together to establish body homeostasis in patients with DM and CHD.


AVPR2 gene and weight changes during triathlons.
The arginine vasopressin receptor 2 (AVPR2) plays an important antidiuretic role in regulating water balance to maintain osmotic equilibrium. The aim of this study was to determine if there were any associations between single nucleotide polymorphisms (SNPs), within the AVPR2 gene, and changes in serum sodium concentrations and/or body weight (BW) in Ironman triathletes. Caucasian male triathletes who completed either the 2000, 2001 or 2006 South African Ironman Triathlons were genotyped (n=570) for at least one SNP. Pre- and post-race serum [Na+] (pre n=514; post n=423) and BWs (pre n=556; post n=552) were measured. Triathletes were divided into 3 groups according to their relative BW loss during the triathlon (BW loss of 0-3, 3-5 and >5%). There was a significant linear trend (p=0.010, x2=6.7) for the distribution of minor haplotypes GCT, GTC and GCC across the 3 BW loss groups. The >5% group had the highest percentage (4.7%) of triathletes with minor haplotypes followed by the 3-5% (3.6%) and 3-0% (0%) groups. In conclusion, the minor haplotype constructs of AVPR2 SNPs were associated with larger BW losses during the Ironman Triathlons. This finding supports a possible genetic contribution to BW loss during endurance exercise events acting through the argine vasopression system.


[Acute inter-hemispheric subdural hematoma].
Interhemispheric subdural hematoma in adults is a rare complication of head injury with no more than 100 cases reported since 1940. The classical presentation of this disorder is a contralateral monoparesis of the leg or a hemiparesis more pronounced in the leg. We report three cases of interhemispheric subdural hematoma following closed head injuries and the review of the literature with an analysis and of the therapeutic possibilities. Conservative management under close supervision may be a proper attitude in those patients without alterations of consciousness. Surgical treatment is necessary in patients with progressive deterioration.


Knowledge, Decision-Making and Acceptance of Human Papilloma Virus Vaccination among Parents of Primary School Students in Kota Bharu, Kelantan, Malaysia
Background: The incidence of cervical cancer in younger women remains high. This is worrisome as it affects future generations. Therefore Malaysia implements human papilloma virus (HPV) vaccination as a national vaccination program. Parents play an important role in determining the success of this HPV vaccination program among schoolaged girls by their compliance. Objective: To assess parental knowledge, decision-making and acceptance of HPV vaccination. Methods: This cross sectional study was conducted among 280 randomly selected parents of primary school students aged 11 in Kota Bharu using a pre-validated self-administered questionnaire to assess knowledge and decision-making with regard to HPV vaccination. Results: Most parents (62%) were shown to have poor knowledge while most decision-making was shared. Age of respondents (adjusted odds ratio 'AOR'= 1.09; 95% confidence interval 'CI'= 1.04-1.14; p <0.001) and good knowledge of HPV vaccination (AOR= 16.32; 95% CI= 7.32-36.4; p <0.001) were significantly associated with HPV vaccine acceptance. Conclusion: The majority of parents exhibited poor knowledge which may affect their decision-making and uptake of HPV vaccination among their children. This highlights the need to better educate parents on HPV vaccination.


Developmental changes in morphometry of the small intestine and jejunal sucrase activity during the first nine weeks of postnatal growth in pigs.
The objective of this study was to investigate the development of small intestinal size and digestive capacity of the jejunum in growing pigs. The weight, length, surface area, and mucosa weight of the small intestine were measured when pigs were 1, 3, 5, and 9 wk of age. Sucrase and alkaline phosphatase (ALP) activities of the jejunal brush-border membrane, prepared by differential centrifugation and Mg2+ precipitation, were determined at the respective postnatal stages. Body weights increased 7-fold from 2.7 kg at 1 wk to 23.32 kg at 9 wk postnatal. Body weight gains were greater (P < 0.05) from wk 3 to 5 than from wk 1 to 3. Weights of the small intestine and of the intestinal mucosa increased faster (P < 0.05) from 3 to 5 wk than from 1 to 3 wk; the slowest increase occurred from 5 to 9 wk. Weights of the duodenum, jejunum, and ileum, and mucosa from the respective sections increased (P < 0.05) as pigs grew from 3 to 9 wk. Mucosa weight relative to the weight of the section was greater (P < 0.05) for the duodenum and jejunum than for the ileum at 9 wk of age. Between the ages of 3 and 9 wk, the increase in mucosa weight was highest for the jejunum followed by the duodenum and the ileum. The increase was greatest for the duodenum followed by the jejunum and the ileum when mucosal weight was expressed per unit of appropriate intestinal section weight. There was a 55-fold increase in jejunal sucrase activity from 1 to 9 wk; the greatest rate of increase occurred between 5 and 9 wk. Total jejunal ALP activities in pigs at 9 wk was greater (P < 0.05) than at 5 wk, which in turn was greater than at 1 wk of age. In summary, increases in BW during the first 9 wk of postnatal growth in pigs are accompanied by significant developmental changes in digestive capacity including intestinal weights, length, and area as well as jejunal brush-border sucrase and ALP activities.


Groundwater contamination downstream of a contaminant penetration site. I. Extension-expansion of the contaminant plume.
This study concerns the possible use of boundary layer (BL) approach for the analysis and evaluation of contaminant transport in groundwater due to contaminant penetration into the groundwater aquifer through a site of limited size. The contaminant penetration may occur through either the upper (surface) or lower (bedrock) boundary of the aquifer. Two general cases of contaminant penetration mechanisms are considered: (1) the contaminant is transferred through an interface between a contaminating and freshwater fluid phases, and (2) the contaminant arrives at groundwater by leakage and percolation. For the purpose of BL evaluation the contaminant plume is divided into three different sections: (1) the penetration section, (2) the extension-expansion section, and (3) the spearhead section. In each section a different BL method approach yields simple analytical expressions for the description of the contaminant plume migration and contaminant transport. Previous studies of the BL method can be directly applied to the evaluation of contaminant transport at the contaminant penetration section. The present study extends those studies and concerns the contaminant transport in the two other sections, which are located downstream of the penetration section. This study shows that the contaminant concentration profiles in sections 2 and 3 incorporate two BLs: (1) an inner BL adjacent to the aquifer bottom or surface boundary, and (2) an outer BL, which develops above or below the inner one. The method developed in the present study has been applied to practical issues concerning salinity penetration into groundwater in south central Kansas.