Runoff phosphorus losses as related to phosphorus source, application method, and application rate on a Piedmont soil.
Land application of animal manures and fertilizers has resulted in an increased potential for excessive P losses in runoff to nutrient-sensitive surface waters. The purpose of this research was to measure P losses in runoff from a bare Piedmont soil in the southeastern United States receiving broiler litter or inorganic P fertilizer either incorporated or surface-applied at varying P application rates (inorganic P, 0-110 kg P ha(-1); broiler litter, 0-82 kg P ha(-1)). Rainfall simulation was applied at a rate of 76 mm h(-1). Runoff samples were collected at 5-min intervals for 30 min and analyzed for reactive phosphorus (RP), algal-available phosphorus (AAP), and total phosphorus (TP). Incorporation of both P sources resulted in P losses not significantly different than the unfertilized control at all application rates. Incorporation of broiler litter decreased flow-weighted concentration of RP in runoff by 97% and mass loss of TP in runoff by 88% compared with surface application. Surface application of broiler litter resulted in runoff containing between 2.3 and 21.8 mg RP L(-1) for application rates of 8 to 82 kg P ha(-1), respectively. Mass loss of TP in runoff from surface-applied broiler litter ranged from 1.3 to 8.5 kg P ha(-1) over the same application rates. Flow-weighted concentrations of RP and mass losses of TP in runoff were not related to application rate when inorganic P fertilizer was applied to the soil surface. Results for this study can be used by P loss assessment tools to fine-tune P source, application rate, and application method site factors, and to estimate extreme-case P loss from cropland receiving broiler litter and inorganic P fertilizers.


Effects of dietary arsenic levels on serum parameters and trace mineral retentions in growing and finishing pigs.
This experiment was conducted to investigate the effect of dietary arsenic (As) levels on growth performance, serum biochemistry, and the retention of iron, copper, and zinc in tissues of growing and finishing pigs. Ninety-six crossbred pigs were randomly allotted to four dietary treatments. The corn-soybean basal diets were supplemented with 0, 10, 20, and 30 mg As/kg. Arsenic trioxide was used as the arsenic source. The feeding experiment lasted for 78 d. The results showed that the high arsenic diet decreased average daily gain (ADG) (p<0.05) and increased feed gain ratio (F/G) (p<0.05). Arsenic intake significantly increased (p<0.05) serum gamma-gultamyltransferase (GGT), glutamic-pyruvic transaminase (GPT), and alkaline phosphatase (ALP) activities, and decreased (p<0.05) total protein, urea nitrogen, creatinine, and triglycerides. Glutamic-oxalacetic transaminase (GOT) activity, albumin, and cholesterol were not affected (p>0.05). Arsenic feeding elevated (p<0.05) liver and kidney copper concentration, but reduced (p<0.05) copper concentration in heart, bile, and lymphaden of intestine mesentery. There were increases in iron levels in liver, bile, spleen, thymus, and pancreas in pigs fed the high As diets (p<0.05), but iron contents in kidney, heart, and serum were decreased by the arsenic treatment (p<0.05). Zinc concentrations were increased (p<0.05) in liver, kidney, and thymus of pigs with arsenic treatment, but decreased (p<0.05) in bile and lymphaden of intestine mesentery. This study suggested that high dietary As levels could alter serum biochemical parameters and the retention of copper, iron, and zinc in the viscera of growing and finishing pigs.


Thin layer coulometry based on ion-exchanger membranes for heparin detection in undiluted human blood.
We explore here for the first time a potentially calibration-free methodology for the detection of protamine (and, by titration, heparin) in undiluted human blood in the therapeutic concentration range from 20 to 120 mg L(-1). The use of a thin layer sample (5.8 μL) confined between a tubular protamine selective membrane (inner diameter, 600 μm) and a Ag/AgCl wire (diameter 400 μm) achieves an exhaustive depletion from the sample. Coulometry detection was chosen for the interrogation of the thin layer, employing a double pulse technique with 120 s for each pulse. Protamine calibration curves were recorded at physiological concentrations and in undiluted human blood. A linear relationship was obtained in both cases, but a diminished sensitivity was observed in contact with blood, which is explained with a partial passivation of the inner Ag/AgCl element. Heparin-protamine titrations were performed in undiluted human blood samples, mimicking the final application with patients undergoing critical care. The observed values correlate satisfactorily with those of an alternative technique, so-called flash-chronopotentiometry on planar membranes.


Magnification chromo-colonoscopy.
Chromoscopic colonoscopy using indigo carmine is indispensable for the accurate detection of flat neoplastic lesions. In particular, the dye spray technique facilitates the detection of both flat hyperplastic polyps and highly dysplastic lesions. However, magnification chromo-colonoscopy discriminates adenomas from hyperplastic polyps with greater accuracy than conventional methods by showing distinct and visible pit patterns. A pit pattern represents crypt orifices, which reflect the underlying histological structures and colonoscopists can make histological predictions by observing the pit patterns without obtaining biopsy specimens. The pit patterns are classified as types I, II, IIIL, IIIs, IV and V based on histological characterization of normal mucosa, hyperplastic polyp, polypoid adenoma, flat adenoma, tubulo-villous adenoma and cancerous tissue, respectively. In previous reports, overall accuracy ranged from 80 to 95%. In addition, magnification chromo-colonoscopy is useful for the diagnosis of early cancer associated with substantial invasion of the submucosa, in which type V pits are subclassified as types V-I and V-N. The presence of type V-N pits is significant in correlation to cancer with substantial invasion of the submucosa. Magnification chromo-colonoscopy is useful in clinical decision-making when deciding whether endoscopic resection or bowel resection is the appropriate initial procedure to treat lesions.


2,3'4,4',5-Pentachlorobiphenyl induces hepatocellular carcinoma cell proliferation through pyruvate kinase M2-dependent glycolysis.
Polychlorinated biphenyls (PCBs) are classic persistent organic pollutants (POPs) and are associated with the progression of many cancers, including liver cancer. The present study investigated the effect of 2,3'4,4',5-pentachlorobiphenyl (PCB118) on hepatocellular carcinoma cell proliferation and its underlying mechanisms. The results indicated that PCB118 exposure promotes the proliferation and glycolysis of hepatocellular carcinoma SMMC-7721 cells. Moreover, PCB118 exposure increased the expression level of pyruvate kinase M2 (PKM2) and its nuclear translocation, whereas treatment with PKM2 shRNA suppressed the induction of cell proliferation and glycolysis by PCB118. PCB118 stimulated reactive oxygen species (ROS) production by activating nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. Treatment with the antioxidants N-acetyl-L-cysteine (NAC) and superoxide dismutase (SOD) prevented PCB118-induced effects on PKM2, cell proliferation and glycolysis. Furthermore, we found that PCB118 activated NADPH oxidase through the aryl hydrocarbon receptor (AhR) in SMMC-7721 cells. Consistently, treatment with AhR shRNA suppressed PCB118-induced effects on PKM2, cell proliferation and glycolysis. Overall, these results indicated that PCB118 promotes HCC cell proliferation via PKM2-dependent upregulation of glycolysis, which is mediated by AhR/NADPH oxidase-induced ROS production.


Prevention of perinatal hepatitis B transmission in a health authority area: an audit.
The aim of this audit was to provide baseline measurement of antenatal hepatitis B virus (HBV) screening uptake, coverage of HBV vaccination in infants born to high- and low-risk HBsAg carrier mothers, completion of post-vaccination serological testing, outcome for vaccinated infants, and an assessment of the factors that influenced the effectiveness of the whole programme. Methods included identifying HBV positive pregnancies by laboratory results, and follow up of at-risk infants by a GP survey. Uptake of antenatal HBV screening was 99.9%. Thirty-one HBV positive pregnancies were identified, and twenty-nine infants were followed up. The overall HBV vaccination completion rate was 93%. Fifty per cent of eligible infants were tested for hepatitis carriage, the majority of whom were high-risk infants. None had acquired HBV infection and all had gained adequate immunity. We conclude that, although the local screening programme has been implemented effectively, there is inconsistency in the follow up of infants at high and low risk of acquiring HBV.


Is glycaemia or insulin dose the stronger risk factor for coronary artery disease in type 1 diabetes?
Although coronary artery disease (CAD) is the leading cause of death in type 1 diabetes (T1D), the mechanisms responsible for the greatly increased risk are poorly understood. In particular, the role of glycaemic control is controversial with one study suggesting it predicts CAD mortality but not incidence. In this analysis, of the Pittsburgh Epidemiology of Diabetes Complications study cohort of T1D, we examine whether risk factors differ for CAD morbidity and mortality, with a specific focus on HbA1c and insulin dose. Participants (n=592) were followed for 18 years for incident non-fatal and fatal CAD. Cox stepwise regression was used to determine the independent risk factors for non-fatal and fatal CAD. Mean age and diabetes duration at study baseline were 29 and 20 years, respectively. There were 109 incident non-fatal and 48 fatal CAD events. Baseline HbA(1C) was an independent risk factor for fatal CAD, along with duration of diabetes and albuminuria. In contrast, baseline lower insulin dose was strongly predictive of non-fatal CAD, as was lower renal function, higher diastolic blood pressure, and lipids. HbA(1C) predicts CAD mortality while lower insulin dose and standard CAD risk factors predict CAD morbidity.


Annual deterioration of renal function in hypertensive patients with and without diabetes.
Chronic kidney disease (CKD) complicates hypertension and diabetes. Knowledge of the deterioration rate of CKD may anticipate adjustment of therapies with renal elimination. This study evaluates the rate of annual deterioration of renal function in hypertensive patients either with type 2 diabetes (DM2) or without it (non-DM) followed for 5 years and relates it with blood pressure (BP) and glycemic control. Out of a total of 1924 patients, 1023 patients (594 non-DM and 429 DM2, 53% female, aged 62.1±10.2 years) were evaluated over 5 years for the annual evolution of renal function (estimated glomerular filtration rate [eGFR], Modification of Diet in Renal Disease) ambulatory 24-hour blood pressure and metabolic parameters, corresponding to the analysis of 2378 patient-years. DM2 and non-DM did not differ for age, mean 24-hour BP levels, nighttime BP, albuminuria, and body mass index. DM2 versus non-DM showed a higher (p<0.02) prevalence of stage 3 CKD (24.0% vs 18.0%, eGFR 30-59), stage 4 (5.4% vs 2.7%, eGFR 15-29), and stage 5 (0.8% vs 0.5%, eGFR <15). Average annual decline of eGFR was 3.3±8.2 in DM2 versus 2.4±7.7 in non-DM (p=0.12, nonsignificant). Annual changes of eGFR and of albuminuria correlated (r=0.578, p<0.001). In multivariate analysis, age, nighttime BP, double inhibition of renin angiotensin system, albuminuria, and HbA1c >8.0% in DM2 predicted the decline in eGFR. On average, 16.2% of DM2 and 13.1% of non-DM moved each year toward a more severe stage of CKD. For initial eGFR <90 mL/min/1.73 m2, 26.4% of DM2 and 18.1% of non-DM patients showed a reduction per year >10% from the previous eGFR value (p=0.042). Progressive deterioration of renal function each year is frequent in hypertensive diabetic and non-diabetic patients. Beyond aging, this is particularly dependent on BP control particularly at nighttime, on drug therapy, and on highly abnormal glucose control.


Multi-detector CT angiography for lower gastrointestinal bleeding: Can it select patients for endovascular intervention?
This is a retrospective review of the results at our institution of using multi-detector CT angiography (CTA) to localise lower gastrointestinal (GI) bleeding. We hypothesised that in our patient population: (i) CTA was unlikely to demonstrate bleeding in patients who were haemodynamically stable; (ii) in haemodynamically unstable patients in whom CTA was undertaken, the results could be used to select patients who would benefit from catheter angiography; and (iii) in haemodynamically unstable patients in whom CTA was undertaken, a subgroup of patients could be identified who would benefit from primary surgical treatment, avoiding invasive angiography completely. A retrospective review was conducted of the clinical records of all patients undergoing CTA for lower GI haemorrhage at our institution between 1 January 2005 and 30 June 2007. Out of the 20 patients examined, 10 had positive CTAs demonstrating the bleeding site. Nine were haemodynamically unstable at the time of the study. Four patients with positive CT angiograms were able to be treated directly with surgery and avoided invasive angiography. Ten patients had negative CTAs. Four of these were haemodynamically unstable, six haemodynamically stable. Only one required intervention to secure haemostasis, the rest stopped spontaneously. No haemodynamically stable patient who had a negative CTA required intervention. CTA is a useful non-invasive technique for localising the site of lower GI bleeding. In our patient population, in the absence of haemodynamic instability, the diagnostic yield of CTA was low and bleeding was likely to stop spontaneously. In haemodynamically unstable patients, a positive CTA allowed patients to be triaged to surgery or angiography, whereas there was a strong association between a negative CTA and spontaneous cessation of bleeding.


MALAT1 Promotes the Proliferation and Metastasis of Osteosarcoma Cells By Activating the Rac1/JNK Pathway Via Targeting MiR-509.
Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a long noncoding RNA (lncRNA) that contributes to the initiation and development of many solid tumors, including osteosarcoma (OS). In this study, we showed that MALAT1 was increased in human OS tissues and cell lines. MALAT1 knockdown suppressed OS cell growth and metastasis, induced OS cell apoptosis and delayed tumor growth in an OS xenograft model. We also detected downregulation of microRNA-509 (miR-509), a suppressor of OS growth, in OS tissues and cell lines. Then, we identified that miR-509 is a direct target of MALAT1 and Ras-related C3 botulinum toxin substrate 1 (Rac1) is a direct target of miR-509. MALAT1 may promote OS cell growth through inhibition of miR-509, leading to the activation of Rac1/JNK pathway. Our results suggest a MALAT1/miR-509/Rac1 axis that mediates OS cell proliferation and tumor progression.


Influence of thalassemia on the response to recombinant human erythropoietin in dialysis patients.
Thalassemia is a common genetic disorder among the South Chinese. To see if thalassemia would adversely affect the erythrocyte response to recombinant human erythropoietin (rHuEPO, Epogen) in dialysis patients, the response to rHuEPO in 4 dialysis patients with thalassemic traits (thal-t) was compared with that of 4 control patients who were matched for age, sex, mode of dialysis and baseline hemoglobin levels over a 6-month period. Patients with thal-t showed a reduced erythrocyte response to rHuEPO compared to control dialysis patients as reflected by a reduced reticulocyte index, a slower rise in hemoglobin or hematocrit levels, requirement of a higher cumulated dose of rHuEPO to achieve a target hemoglobin of 10 g/dl and a higher maintenance dose of rHuEPO. A dialysis patient with hemoglobin H disease (HbHD) was also studied. He failed to respond to rHuEPO despite that the dose was increased to 250 U/kg/week. In contrast, his matched control dialysis patient, despite a lower baseline hemoglobin level (6.1 versus 8.8 g/dl), was able to reach a target hemoglobin level of 10 g/dl by 6 weeks and could be maintained at this level with 50 U/kg/week. The patient with HbHD had splenomegaly and a higher baseline serum erythropoietin level, reticulocyte count, serum bilirubin, serum ferritin and serum iron saturation than control patients and patients with thal-t. It was concluded that thal-t reduces the erythrocyte response to rHuEPO in dialysis patients and that in the presence of active hemolysis and enhanced endogenous erythropoietin secretion, dialysis patients with HbHD are resistant to treatment with rHuEPO.


The effect of a low energy diet on the concentration of DDT in the adipose tissue of turkeys.
Turkey hens which had completed a breeding season and contained DDT in their fat were divided into 2 groups of 20 hens each. One group was fed a high wheat control diet throughout a 6 week period while another group was fed a low energy diet for 3 weeks and then the control diet for 3 weeks. Biopsy samples of adipose tissue taken initially and at 3 weeks and carcass adipose tissue samples of 6 weeks were analyzed for DDT and DDE. Total DDT concentration in adipose tissue increased when the hens were fed the low energy diet but decreased again when fed the control diet so that the overall change in DDT concentration over the 6 week period was not different for the two groups. The biopsy technique used in this study was successful in greatly reducing variability and improving precision.


Targeted cytotoxic cells in human peripheral blood lymphocytes.
We have isolated subsets of cells from human PBL and have investigated their abilities to mediate lysis targeted by bispecific antibodies. Targeted cytotoxic cells were divided into two distinct types based on buoyant density. The low buoyant density fraction contained all of the targetable cytotoxic activity in unstimulated PBL, including both T and K cells targeted with anti-CD3 and anti-Fc gamma RIII (CD16) containing bispecific antibodies, respectively. Both types of targetable cytotoxic cells required IL-2 for maintenance of cytotoxic activity, expressed the CD56 (NKH1) marker, and mediated MHC-unrestricted lysis. The targetable T cells in low density PBL were exclusively CD8+ and represented only about 2% of the total PBL. The high buoyant density lymphocytes, depleted of NK cells, had no targetable activity, but were able to generate over several days, targetable T cell activity in the presence of a TCR cross-linking signal plus IL-2. Unlike the low-density cells, the activated high buoyant density effector T cells did not express CD56, consisted of both CD4+ and CD8+ cells, and did not mediate MHC-unrestricted lysis. These cells proliferated more rapidly and generated more total lytic activity than the low-density fraction. Our studies show that targetable cytotoxic activity in human PBL is mediated by several subsets of cells with different activation requirements. Presumably all of these activities could be directed against unwanted cells in clinical or preclinical studies involving targeted cytotoxic cells.


Metabolomic Profiling in Children with Celiac Disease: Beyond the Gluten-Free Diet.
Celiac disease (CD) is included in the group of complex or multifactorial diseases, i.e., those caused by the interaction of genetic and environmental factors. Despite a growing understanding of the pathophysiological mechanisms of the disease, diagnosis is still often delayed and there are no effective biomarkers for early diagnosis. The only current treatment, a gluten-free diet (GFD), can alleviate symptoms and restore intestinal villi, but its cellular effects remain poorly understood. To gain a comprehensive understanding of CD's progression, it is crucial to advance knowledge across various scientific disciplines and explore what transpires after disease onset. Metabolomics studies hold particular significance in unravelling the complexities of multifactorial and multisystemic disorders, where environmental factors play a significant role in disease manifestation and progression. By analyzing metabolites, we can gain insights into the reasons behind CD's occurrence, as well as better comprehend the impact of treatment initiation on patients. In this review, we present a collection of articles that showcase the latest breakthroughs in the field of metabolomics in pediatric CD, with the aim of trying to identify CD biomarkers for both early diagnosis and treatment monitoring. These advancements shed light on the potential of metabolomic analysis in enhancing our understanding of the disease and improving diagnostic and therapeutic strategies. More studies need to be designed to cover metabolic profiles in subjects at risk of developing the disease, as well as those analyzing biomarkers for follow-up treatment with a GFD.


[Unusual displacements of the lower molars].
Two unusual cases of maleruption of mandibular third molars associated with the retention of adjacent teeth and the presence of supernumerary teeth, respectively, are described. Due to the position of the crowns to each other, this phenomenon is termed "kissing teeth" in our clinic.


Dynamics of nonadiabatic chemical reactions.
New methods are proposed to treat nonadiabatic chemical dynamics in realistic large molecular systems by using the Zhu-Nakamura (ZN) theory of curve-crossing problems. They include the incorporation of the ZN formulas into the Herman-Kluk type semiclassical wave packet propagation method and the trajectory surface hopping (TSH) method, formulation of the nonadiabatic transition state theory, and its application to the electron transfer problem. Because the nonadiabatic coupling is a vector in multidimensional space, the one-dimensional ZN theory works all right. Even the classically forbidden transitions can be correctly treated by the ZN formulas. In the case of electron transfer, a new formula that can improve the celebrated Marcus theory in the case of normal regime is obtained so that it can work nicely in the intermediate and strong electronic coupling regimes. All these formulations mentioned above are demonstrated to work well in comparison with the exact quantum mechanical numerical solutions and are expected to be applicable to large systems that cannot be treated quantum mechanically numerically exactly. To take into account another quantum mechanical effect, namely, the tunneling effect, an efficient method to detect caustics from which tunneling trajectories emanate is proposed. All the works reported here are the results of recent activities carried out in the author's research group. Finally, the whole set of ZN formulas is presented in Appendix.


Prostate Focused Ultrasound Therapy.
The tremendous progress in engineering and computing power coupled with ultrasound transducer technology and imaging modalities over the past 20 years have encouraged a revival of clinical interest in ultrasound therapy, mainly in High-Intensity Focused Ultrasound (HIFU). So far, the most extensive results from HIFU obtained in urology involve transrectal prostate ablation, which appears to be an effective therapeutic alternative for patients with malignant prostate tumors. Prostate cancer (PCa) is one of the most frequently diagnosed cancers in men. Several treatment options with different therapeutic approaches exist, including HIFU for localized PCa that has been in use for over 15 years. Since the early 2000s, two systems have been marketed for this application, and other devices are currently in clinical trials. HIFU treatment can be used either alone or in combination with (before- or after-) external beam radiotherapy (EBRT) (before or after HIFU) and can be repeated multiple times. HIFU treatment is performed under real-time monitoring with ultrasound or guided by MRI. Two indications are validated today: Primary care treatment and EBRT failure. The results of HIFU for primary care treatment are similar to standard conformal EBRT, even though no randomized comparative studies have been performed and no 10-year follow up data is yet available for HIFU. Salvage HIFU after EBRT failure is increasing with oncological outcomes, similar to those achieved with surgery but with the advantage of fewer adverse effects. HIFU is an evolving technology perfectly adapted for focal treatment. Thus, HIFU focal therapy is another pathway that must be explored when considering the accuracy and reliability for PCa mapping techniques. HIFU would be particularly suited for such a therapy since it is clear that HIFU outcomes and toxicity are relative to the volume of prostate treated.


Comparative metabolism of tritiated water by macropodid marsupials.
The total body-water content (TBW) and rate of water turnover were measured usingtritiated water in five species of macropodod marsupials (kangaroos), which ranged in weight from 1 to 50 kg. Animals fitted with rumen cannulas were used to estimate the time required for tritiated water to equilibrate within the body of large kangaroos. In hydrated kangaroos this was 6 h, during the time 2.7% of the injected tritiated waterwas lost from the body. During dehydration, the equilibrium time was extended to 10h. Values up to 78% of body weight were found for TBW in the larger species of kangaroo, and these values were similiar to those found for other ruminantlike mammals, particularly those with a low body-fat content. The smaller macropodids had a TBW (about 60% of body weight) similiar to that of most laboratory mammals. The rates of waterturnover of the macropodids were related to body weights by the expression 1/day = 0.09kg-0.80. Macropodid marsupials have a daily water usage shich is about two-thirds ofthat found for eitherians and this may be related to the lower metabolic rate of marsupials.


Age-dependent sparing of visual function after bilateral lesions of primary visual cortex.
Bilateral lesions of primary visual cortex (PVC) sustained early in life induce the visual system to undergo structural and functional reorganization and produce modified neuronal networks capable of mediating visual abilities that would be impaired if the lesions occurred in adulthood. Reorganization after early lesion is also accompanied by degeneration of the lateral geniculate nucleus of the thalamus, and 90% of beta retinal ganglion cells die via retrograde degeneration. It is unclear whether the high potential of the system to reorganize after early lesion could overcome the effects of beta retinal ganglion cell death. Visual acuity, which depends on an intact beta-cell array, was impaired in cats that underwent PVC lesions on postnatal day 1 and indicated that neuroplastic potential was insufficient to overcome early lesion-induced maladaptive plasticity. Animals with lesions made at 1 month of age, a stage accompanied by high levels of neuroplastic potential but no death of beta cells, achieved acuity measures equivalent to intact animals. The authors conclude that visual signals are rerouted to subserve functionality when the lesion is made at 1 month of age, but not at 1 day of age.


A model for multitalker speech perception.
A listener's ability to understand a target speaker in the presence of one or more simultaneous competing speakers is subject to two types of masking: energetic and informational. Energetic masking takes place when target and interfering signals overlap in time and frequency resulting in portions of target becoming inaudible. Informational masking occurs when the listener is unable to distinguish target and interference, while both are audible. A computational model of multitalker speech perception is presented to account for both types of masking. Human perception in the presence of energetic masking is modeled using a speech recognizer that treats the masked time-frequency units of target as missing data. The effects of informational masking are modeled as errors in target segregation by a speech separation system. On a systematic evaluation, the performance of the proposed model is in broad agreement with the results of a recent perceptual study.


Parotid Duct Repair with Intubation Tube: Technical Note.
The parotid duct can be damaged in traumatic injuries and surgical interventions. Early diagnosis and treatment of a duct injury is of great importance because complications such as sialocele and salivary gland fistula may develop if the duct is not surgically repaired. We think the cuff of an intubation tube is an ideal material in parotid duct repair, because of its technical characteristics, easiness of availability, and low-cost. In this paper, we described the use of the cuff cannula of an intubation tube for the diagnosis and treatment of parotid duct laceration, as a low-cost and easy to access material readily available in every operating room.


Evaluation of Clinicopathological and Risk Factors for Nonmalignant H. Pylori Associated Gastroduodenal Disorders in Iraqi Patients.
To determine the risk factors associated with H. pylori infection and possible correlation with clinicopathological parameters. Gastroduodenal biopsies were examined by rapid urease test and Gram staining. Cag A cytotoxin was detected by in situ hybridization. Risk of H. pylori acquisition reported as following: Males have 1.38 fold, rural residents have 0.63 fold, Nonsmokers have 0.39 fold, mild smokers have 18 fold, and moderate smokers have 1.4 fold while heavy smokers have 1 fold. A person who's in contact with animals has 1.52 fold risks. Illiterates and patients with primary education have 5.36 & 3 fold risk respectively. Patients under proton pump inhibitor (PPI) therapy have 1.02 fold. Patients under NSAID therapy have 3.48 fold while nonalcoholic Patients have 0.75 fold. Patients using tap water have 0.45 fold risk. H. pylori infection positively correlated with age, weight loss, and heartburn. H. pylori inversely correlated with endoscopic diagnosis, Cag A positivity, and education level. Cag A positivity correlated with animal contact and NSAID usage. Several life style factors, education, animal contact, using of PPI, and NSAIDs increase the risk of H. pylori infection. Weight loss and heartburn cardinal signs for H. pylori infection. Endoscopic diagnosis and clinicopathological parameters not strictly associated with Cag A positivity.


Singular evanescent wave resonances in moving media.
Resonators fold the path of light by reflections leading to a phase balance and thus constructive addition of propagating waves. However, amplitude decrease of these waves due to incomplete reflection or material absorption leads to a finite quality factor of all resonances. Here we report on our discovery that evanescent waves can lead to a perfect phase and amplitude balance causing an ideal Fabry-Perot resonance condition in spite of material absorption and non-ideal reflectivities. This counterintuitive resonance occurs if and only if the metallic Fabry-Perot plates are in relative motion to each other separated by a critical distance. We show that the energy needed to approach the resonance arises from the conversion of the mechanical energy of motion to electromagnetic energy. The phenomenon is similar to lasing where the losses in the cavity resonance are exactly compensated by optical gain media instead of mechanical motion. Nonlinearities and non-localities in material response will inevitably curtail any singularities however we show the giant enhancement in non-equilibrium phenomena due to such resonances in moving media.


Teaching with audiovisual recordings of consultations.
The experience gained from two years' teaching with audiovisual recordings of consultations of both undergraduates and postgraduates is presented. Some basic teaching rules are suggested and further applications of the technique are discussed.


Persistent narrowing of nuclear-spin fluctuations in InAs quantum dots using laser excitation.
We demonstrate the suppression of nuclear-spin fluctuations in an InAs quantum dot and measure the timescales of the spin narrowing effect. By initializing for tens of milliseconds with two continuous wave diode lasers, fluctuations of the nuclear spins are suppressed via the hole-assisted dynamic nuclear polarization feedback mechanism. The fluctuation narrowed state persists in the dark (absent light illumination) for well over 1 s even in the presence of a varying electron charge and spin polarization. Enhancement of the electron spin coherence time (T2*) is directly measured using coherent dark state spectroscopy. By separating the calming of the nuclear spins in time from the spin qubit operations, this method is much simpler than the spin echo coherence recovery or dynamic decoupling schemes.


Minute chromatin bodies in a murine in vitro cell line.
A murine anaplastic sarcoma and an in vitro cell line established from it were studied by the TG banding technique. The neoplasm originated in a BALB/c mouse inoculated with human tumor cells. Microchromatin bodies were found in 100% of the karyotypes in the original tumor and in the 120 in vitro passages. A long marker chromosome, also observed in all metaphases, was interpreted as a translocation in tandem of a No. 16 chromosome into a No. 1; this involved loss of the centromeric part of chromosome No. 1.


Effect of piceatannol against malignant melanoma in vivo and in vitro.
To study the antitumor effect of piceatannol (PIC) on malignant melanoma in vitro and in vivo. B16F10 cells were cultured in vitro and treated with gradient concentrations of PIC. Cell viability was detected with methyl thiazolyl tetrazolium (MTT) assay; matrix metalloproteinase (MMP)-2, MMP-9, vascular endothelial growth factor (VEGF), spleen tyrosine kinase (Syk), and p-Syk were detected with Western blot; migration ability was detected with wound healing assay; invasion ability was detected with Transwell assay. Syk expression was suppressed through RNA interference for the detection of the possible mechanism of PIC in melanoma. An in vivo study was established by creating B16F10-bearing mice with intraperitoneal injection of PIC. The cell viability of B16F10 decreased with increasing PIC concentration. The results of the Transwell assay showed that invasion ability decreased with increasing PIC concentration, and healing time was prolonged at increased PIC concentration in the wound healing assay. Western blot results showed that PIC mainly inhibited the phosphorylation of Syk and inhibited the expression of MMP-2, MMP-9, and VEGF. RNA interference pointed out that blocking the expression of Syk can reveal the same inhibition effect on B16F10 cells as PIC. In vivo study revealed that different concentrations of PIC cangreatly inhibit melanoma progression. PIC might block the progression of malignant melanoma by inhibiting spleen tyrosine kinase.


The Proteome of the Red Blood Cell: An Auspicious Source of New Insights into Membrane-Centered Regulation of Homeostasis.
During the past decade, the hand-in-hand development of biotechnology and bioinformatics has enabled a view of the function of the red blood cell that surpasses the supply of oxygen and removal of carbon dioxide. Comparative proteomic inventories have yielded new clues to the processes that regulate membrane-cytoskeleton interactions in health and disease, and to the ways by which red blood cells communicate with their environment. In addition, proteomic data have revealed the possibility that many, hitherto unsuspected, metabolic processes are active in the red blood cell cytoplasm. Recent metabolomic studies have confirmed and expanded this notion. Taken together, the presently available data point towards the red blood cell membrane as the hub at which all regulatory processes come together. Thus, alterations in the association of regulatory proteins with the cell membrane may be a sine qua non for the functional relevance of any postulated molecular mechanism. From this perspective, comparative proteomics centered on the red blood cell membrane constitute a powerful tool for the identification and elucidation of the physiologically and pathologically relevant pathways that regulate red blood cell homeostasis. Additionally, this perspective provides a focus for the interpretation of metabolomic studies, especially in the development of biomarkers in the blood.


Relationship between separation anxiety and panic and agoraphobic disorders.
The paper addresses several issues pertinent to the characteristics and treatment of separation anxiety in children and adults. The rationale for separating separation anxiety from other childhood anxiety conditions rests on clinical observations of its relationship to panic disorder and its response to drug treatment. The psychopharmacological treatment of separation anxiety is reviewed, with special emphasis on the use of tricyclic antidepressants. The literature relevant to a possible association between separation anxiety and adult panic disorder is presented. The prevalence of separation anxiety disorder in adult outpatients with panic disorder is discussed. Data are presented to address the issue of treatment response in adult panic disorders with and without separation anxiety.


Subendothelial matrix of cultured endothelial cells contains fully processed high molecular weight von Willebrand factor.
Von Willebrand factor (vWf) is an adhesive glycoprotein composed of identical subunits linked by disulfide bonds to form multimers of varying sizes. VWf is found in platelets and plasma, where it functions in the adhesion of platelets to exposed subendothelium. Subendothelial matrix contains vWf, but the multimeric composition of matrix vWf, its binding site in matrix, and the mechanism by which it is delivered to matrix are unknown. Using human umbilical vein endothelial cell (HUVE) cultures, we have partially characterized subendothelial matrix vWf. Matrix from HUVE was solubilized in sodium dodecyl sulfate and electrophoresed on 1.25% agarose gels. The extracted vWf was composed of extremely high molecular weight (HMW) multimers of vWf not normally found in plasma. The vWf content of HUVE supernatant, extract, and matrix was quantitated and characterized by radioimmunoassay, agarose gel electrophoresis, and densitometry. The matrix-bound or -associated vWf represented 4% to 18% of total HUVE vWf. Western blot analysis of matrix vWf after reduction showed a subunit species of 220 kd. Long-term incubation of HUVE with phorbol 12-myristate 13-acetate (PMA), a compound that causes release of HMW vWf from Weibel-Palade bodies in HUVE, resulted in a marked decrease in matrix vWf (0.2% to 1% of the total vWf). The multimeric pattern of the remaining matrix vWf continued to show predominantly HMW multimers.(ABSTRACT TRUNCATED AT 250 WORDS)


[Surgery in utero on a two-headed monster. The value of echography].
A binovular triplet pregnancy with a normal fetus and bicephalic monster was diagnosed by ultrasound after 19 weeks of amenorrhoea. After selective amniocentesis and genetic studies the diagnosis led us to kill the double monster in utero by injecting hypertonic saline into its aorta. The healthy twin went on growing normally in the following weeks. Premature vaginal delivery resulted in the expulsion of a macerated double monster and the birth of a baby weighing 1,650 g in blood health. This case history leads us to discuss the value of ultrasound in multiple pregnancies and the ability to carry out intra-uterine procedures in these special cases.


Scanning electron microscopic preliminary study of the efficacy of SmearClear and EDTA for smear layer removal after root canal instrumentation in permanent teeth.
This study aimed to evaluate the efficacy of SmearClear (SybronEndo, Orange, CA) and EDTA for smear layer removal from root canals of permanent teeth after instrumentation. Thirty extracted human permanent teeth (n = 10) were randomly assigned to the following groups: group 1 = 14.3% EDTA, group 2 = SmearClear, and group 3 = no smear layer removal procedure was undertaken (control). The specimens were submitted to scanning electron microscopy analysis. Magnifications of 200x and 750x were used to evaluate cleaning at the apical, middle, and cervical thirds according to a three-point scoring system. Data were analyzed statistically by the Mann-Whitney U test (5% significance level). Groups 1 and 2 differed significantly from group 3 (p < 0.01). However, there was no statistically significant difference (p > 0.05) between groups 1 and 2. In conclusion, SmearClear was able to remove the smear layer from the root canals of permanent teeth similarly as 14.3% EDTA, suggesting that both solutions may be indicated for such purpose.


Generic maximum-valence model for fluid polyamorphism.
Recently, a maximal-valence model has been proposed to model a liquid-liquid phase transition induced by polymerization in sulfur. In this paper we present a simple generic model to describe liquid polyamorphism in single-component fluids using a maximum-valence approach for any arbitrary coordination number. The model contains three types of interactions: (i) atoms attract each other by van der Waals forces that generate a liquid-gas transition at low pressures, (ii) atoms may form covalent bonds that induce association, and (iii) additional repulsive forces between atoms with maximal valence and atoms with any valence. This additional repulsion generates liquid-liquid phase separation and the region of the negative heat expansion coefficient (density anomaly) on a P-T phase diagram. We show the existence of liquid-liquid phase transitions for dimerization, polymerization, gelation, and network formation for corresponding coordination numbers z=1,2,...,6 and discuss the limits of this generic model for producing fluid polyamorphism.


Quantitative analyses of postembryonic hair cell addition in the otolithic endorgans of the inner ear of the European hake, Merluccius merluccius (Gadiformes, Teleostei).
Bony fishes add sensory hair cells to the saccule and lagena of the ear for at least several years after hatching. However, it is not known whether hair cell proliferation occurs for the whole lifetime of an animal, whether proliferation occurs in all endorgans of the ear, or whether the rate of proliferation is the same in all of the endorgans. To obtain answers to these questions, the extent of postembryonic hair-cell proliferation was determined in the saccule, lagena, and utricle of the ear in the European hake, Merluccius merluccius, for fish ranging from 7 to 75 cm in total length (6 months to 9 years of age). Results demonstrated that hair-cell addition continued throughout this period in all three otic endorgans, although endorgan size was proportionally greatest in smaller animals. Of the three endorgans, cell addition was greatest in the saccule. Moreover, far more cells were added to the caudal end of the saccule than to the rostral end. Each saccule of the largest hake had over 900,000 hair cells. It is estimated that each saccule adds approximately 110,000 new hair cells each year (or 302 cells/day) over the life span of the fish studied. A significant number of small ciliary bundles, thought to represent newly proliferated hair cells, was found throughout each endorgan, and the number of such bundles declined as the rate of hair cell proliferation decreased. The results demonstrate that extensive proliferation occurs in all three otolithic endorgans of the ears in a fish and that such proliferation continues for virtually the whole life of the animal. The functional significance of this addition is not known.


Mesenchymal Stem Cell-Derived Extracellular Vesicles: A Novel Cell-Free Therapy for Sepsis.
Sepsis remains a serious and life-threatening disease with high morbidity and mortality. Due to the unique immunomodulatory, anti-inflammatory, anti-apoptotic, anti-microbial, anti-oxidative, and reparative properties, mesenchymal stem cells (MSCs) have been extensively used in preclinical and clinical trials for diverse diseases and have shown great therapeutic potential in sepsis. However, concerns remain regarding whether MSCs can become tumorigenic or have other side effects. Extracellular vesicles (EVs) are a heterogeneous group of membrane-enclosed particles released from almost any cell and perform an important role in intercellular communication. Recently, it has emerged that EVs derived from MSCs (MSC-EVs) appear to exert a therapeutic benefit similar to MSCs in protecting against sepsis-induced organ dysfunction by delivering a cargo that includes RNAs and proteins to target cells. More importantly, compared to their parent cells, MSC-EVs have a superior safety profile, can be safely stored without losing function, and possess other advantages. Hence, MSC-EVs may be used as a novel alternative to MSC-based therapy in sepsis. Here, we summarize the properties and applications of MSC-EVs in sepsis.


Hydrogen-Bonding-Assisted Substituent Engineering for Modulating Magnetic Spin Couplings and Switching in m-Phenylene Nitroxide Diradicals.
Rational modification of the coupler for the theoretical design of molecular magnets has attracted extensive interest. Substituent insertion is a widely used strategy for adjusting molecular properties, but its effect and modulation on magnetic spin couplings have been less investigated. In this work, we predict the magnetic properties of the design m-phenylene nitroxide (NO) diradicals regulated by introducing substituents. The calculated results for those two pairs of diradicals indicate that the signs of their magnetic coupling constants J do not change, but the magnitudes remarkably change after substituent regulation in the range from 253 to 730 cm-1. Such noticeable magnetic changes induced by introducing subsituents are mainly attributed to different electronic effects of substituents, assisted by the proximity of two NO groups, good planarity, conjugation, and an intramolecular hydrogen bond. In particular, the insertion of intramolecular H-bonds not only indicates an electronic effect but also has greatly changed the spin density distribution. Further aromaticity of the coupler ring, spin densities, and molecular orbitals and energetics was evaluated to gain a better understanding of magnetic regulation. Interestingly, further protonation of some substituents (e.g., -NO2 and -CO2) can noticeably turn the spin coupling from ferromagnetic to antiferromagnetic, showing manipulable magnetic switching. This work provides a promising strategy based on substituent engineering for magnetic spin coupling modulation, not only turning the coupling magnitude but also enabling the magnetic switching, thus providing insights into molecular magnetic manipulation for spintronics applications.


Is there a third-line therapy for metastatic colorectal cancer?
Selection of third-line treatment in metastatic colorectal cancer depends on the agents that have been used in prior therapy. A principle in treatment is to use all five of the active drugs in this setting (5-fluorouracil [5-FU], oxaliplatin, irinotecan, cetuximab, and bevacizumab) during the patient's overall treatment course for metastatic disease because cumulative use of available active drugs appears to increase overall survival. Currently, 5-FU/leucovorin (5-FU/LV)/oxaliplatin (FOLFOX) or 5-FU/LV plus irinotecan (FOLFIRI) can be considered standard therapy in first-line treatment, with cross-over irinotecan or oxaliplatin-containing regimens as a component of several possible second-line regimens. On this scenario, third-line treatment can include the combination of irinotecan with cetuximab or bevacizumab or both or the use of cetuximab and bevacizumab in combination. Data from randomized trials on third-line treatment are needed.


Safety and tolerability of new-generation anti-obesity medications: a narrative review.
The prevalence of obesity and associated comorbidities is rising. Despite their weight-loss efficacy, new generation anti-obesity medications are only prescribed to a minority of adults with obesity, possibly, which in part may be due to safety concerns. This review presents detailed safety profiles for orlistat, phentermine/topiramate, lorcaserin, naltrexone/bupropion and liraglutide 3.0 mg, and discusses the associated risk-benefit profiles. Two anti-obesity medications presented safety issues that warranted further discussion; phentermine/topiramate (fetal toxicity) and liraglutide 3.0 mg (risk of gallstone disease and mild, acute pancreatitis), whereas the adverse events associated with orlistat, lorcaserin, and naltrexone/bupropion were mostly transient tolerability issues. The difficulties surrounding the objective determination of risk-benefit for anti-obesity medications is discussed. The need for more long-term data, thorough patient assessment, individualization of pharmacological interventions and adherence to stopping rules to maximize risk-benefit are highlighted. Overall, the majority of new generation anti-obesity medications present encouraging tolerability profiles; however, in some cases a lack of long-term clinical trials confounds the accurate determination of risk-benefit.


Identification and composition of the streptococcal and enterococcal flora of tonsils, intestines and faeces of pigs.
Streptococcus suis was the most frequent Streptococcus spp. in pig tonsils, followed by the beta-haemolytic porcine 'equisimilis' ecovar of Strep. dysgalactiae. The intestinal streptococcal flora was composed of Strep. bovis, Strep. hyointestinalis and Strep. suis. Many of these intestinal Strep. suis belonged to a beta-glucuronidase-negative biotype which is infrequent in lesions. Nearly half of the strains presumptively identified as Strep. alactolyticus produced acid from lactose. This species was not found in tonsils and intestines but was about equally prevalent as Strep. hyointestinalis in pig faeces and rectal swabs. Other streptococci were rare in this material. Enterococci were much less frequently identified than streptococci in tonsils and faeces. In intestinal samples Enterococcus faecalis, Ent. faecium, Ent. hirae and Ent. cecorum were most frequently found. In faeces Ent. faecium was the most prevalent enterococcus. The characteristics of the less well known species Strep. alactolyticus and Strep. hyointestinalis are described in detail, and guidelines for their differentiation from Strep. bovis and Strep. suis given.


The Development of Predictive Gender Processing Strategies During Noun Phrase Decoding: An Eye-Tracking Study With German 5- to 10-Year-Old Children.
Many models of language comprehension assume that listeners predict the continuation of an incoming linguistic stimulus immediately after its onset, based on only partial linguistic and contextual information. Their related developmental models try to determine which cues (e.g., semantic or morphosyntactic) trigger such prediction, and to which extent, during different periods of language acquisition. One morphosyntactic cue utilized predictively in many languages, inter alia German, is grammatical gender. However, studies of the developmental trajectories of the acquisition of predictive gender processing in German remain a few. This study attempts to shed light on such processing strategies used in noun phrase decoding among children acquiring German as their first language by examining their eye movements during a language-picture matching task (N = 78, 5-10 years old). Its aim was to confirm whether the eye movements indicated the presence of age-specific differences in the processing of a gender cue, provided either in isolation or in combination with a semantic cue. The results revealed that German children made use of predictive gender processing strategies from the age of 5 years onward; however, the pace of online gender processing, as well as confidence in the predicted continuation, increased up to the age of 10 years. Predictive processing of gender cues plays a role in German language comprehension even in children younger than 8 years.


Negative Effects of Chronic Rapamycin Treatment on Behavior in a Mouse Model of Fragile X Syndrome.
Fragile X syndrome (FXS), the most common form of inherited intellectual disability, is also highly associated with autism spectrum disorders (ASD). It is caused by expansion of a CGG repeat sequence on the X chromosome resulting in silencing of the FMR1 gene. This is modeled in the mouse by deletion of Fmr1 (Fmr1 KO). Fmr1 KO mice recapitulate many of the behavioral features of the disorder including seizure susceptibility, hyperactivity, impaired social behavior, sleep problems, and learning and memory deficits. The mammalian target of rapamycin pathway (mTORC1) is upregulated in Fmr1 KO mice and is thought to be important for the pathogenesis of this disorder. We treated Fmr1 KO mice chronically with an mTORC1 inhibitor, rapamycin, to determine if rapamycin treatment could reverse behavioral phenotypes. We performed open field, zero maze, social behavior, sleep, passive avoidance, and audiogenic seizure testing. We found that pS6 was upregulated in Fmr1 KO mice and normalized by rapamycin treatment, but, except for an anxiogenic effect, it did not reverse any of the behavioral phenotypes examined. In fact, rapamycin treatment had an adverse effect on sleep and social behavior in both control and Fmr1 KO mice. These results suggest that targeting the mTOR pathway in FXS is not a good treatment strategy and that other pathways should be considered.


Impact of Supplemental Material Use on Student Metacognitive Monitoring and Calibration.
Objective. To determine whether third year Doctor of Pharmacy students' self-reported use of optional supplemental material impacted their ability to accurately predict their performance on a low-stakes assessment.Methods. An instructor created optional supplemental material in the form of an online quiz. Students were asked to report whether they used the supplemental material and to predict and postdict their performance on an in-class assessment. The relative accuracy of the predictions and postdictions as well as the assessment grades and overall course grades were compared between students who reported using the supplemental material and those who reported not using the supplemental material.Results. More than half of the students (60%) reported using the supplemental material. Most students underpredicted their performance on the in-class assessment, but there was no difference in the accuracy of predictions based on supplemental material use or non-use (-1.2 vs -1.0) or on the postdictions (-1.3 vs. -1.0). Students who reported using the supplemental material performed better on both the low-stakes assessment (7.7 vs 7.2 out of 10) and overall in the course (87.0% vs 84.9%).Conclusion. Pharmacy students' self-reported use of optional supplemental material does not appear to impact their ability to accurately predict their performance on a low-stakes assessment.


Comprehensive review of the evidence regarding the effectiveness of community-based primary health care in improving maternal, neonatal and child health: 7. shared characteristics of projects with evidence of long-term mortality impact.
There is limited evidence about the long-term effectiveness of integrated community-based primary health care (CBPHC) in improving maternal, neonatal and child health. However, the interventions implemented and the approaches used by projects with such evidence can provide guidance for ending preventable child and maternal deaths by the year 2030. A database of 700 assessments of the effectiveness of CBPHC in improving maternal, neonatal and child health has been assembled, as described elsewhere in this series. A search was undertaken of these assessments of research studies, field project and programs (hereafter referred to as projects) with more than a single intervention that had evidence of mortality impact for a period of at least 10 years. Four projects qualified for this analysis: the Matlab Maternal Child Health and Family Planning (MCH-FP) P in Bangladesh; the Hôpital Albert Schweitzer in Deschapelles, Haiti; the Comprehensive Rural Health Project (CRHP) in Jamkhed, India; and the Society for Education, Action and Research in Community Health (SEARCH) in Gadchiroli, India. These four projects have all been operating for more than 30 years, and they all have demonstrated reductions in infant mortality, 1- to 4-year mortality, or under-5 mortality for at least 10 years. They share a number of characteristics. Among the most notable of these are: they provide comprehensive maternal, child health and family planning services, they have strong community-based programs that utilize community health workers who maintain regular contact with all households, they have develop strong collaborations with the communities they serve, and they all have strong referral capabilities and provide first-level hospital care. The shared features of these projects provide guidance for how health systems around the world might improve their effectiveness in improving maternal, neonatal and child health. Strengthening these features will contribute to achieving the goal of ending preventable child and maternal deaths by the year 2030.


Laparoscopic application of PGE2 to re-establish oviducal patency and fertility in infertile mares: a preliminary study.
Mares are occasionally encountered that consistently fail to conceive when inseminated, naturally or artificially, with fertile stallion semen in the absence of any identifiable pathology of either the structure or function of their reproductive tract. Temporary blockage of the oviducts by accumulations of naturally occurring oviducal masses may be preventing oviducal transport of the embryo to the uterus. Mares, with known reproductive histories, that had exhibited inexplicable failure of conception were treated by laparoscopically guided administration of PGE2-laced triacetin gel directly onto the surface of their oviducts. Fifteen mares age 10-21 years that had exhibited inexplicable failure of conception during 1-4 years were treated, of which 14 (93%) conceived within the same or subsequent breeding season. The high success rate of this treatment supports the tentative diagnosis of oviducal obstruction in these mares and indicates that blockage of the mare's oviducts may occur in the form of a moveable accumulation of debris rather than from permanent fibrous adhesions resulting from salpingitis. This laparoscopic application of PGE2 to the oviducts constitutes a sound and practical method of restoring fertility in mares suffering oviducal obstruction and further studies involving the procedure are warranted.


Ultrasound screening for congenital dysplasia of the hip in newborns: its value.
Three hundred seven newborns were examined clinically and by ultrasound for congenital dysplasia of the hip (CDH). The purpose of the study was to determine the prevalence of sonographic abnormalities and to discover if sonography could be helpful in detecting cases of CDH that would be missed by clinical diagnosis alone. Eighty-two hips (13.4%) had ultrasound abnormalities despite a normal clinical examination. Of these, three developed definite hip dysplasia. The remaining 79 hips became clinically and sonographically normal within 12 weeks. Ultrasound visualized and recorded the dislocation-reposition maneuver of three other hips that were clinically dislocatable at birth. Dislocation occurred in a craniodorsal direction.


Integrative comparative analysis of avian chromosome evolution by in-silico mapping of the gene ontology of homologous synteny blocks and evolutionary breakpoint regions.
Avian chromosomes undergo more intra- than interchromosomal rearrangements, which either induce or are associated with genome variations among birds. Evolving from a common ancestor with a karyotype not dissimilar from modern chicken, two evolutionary elements characterize evolutionary change: homologous synteny blocks (HSBs) constitute common conserved parts at the sequence level, while evolutionary breakpoint regions (EBRs) occur between HSBs, defining the points where rearrangement occurred. Understanding the link between the structural organization and functionality of HSBs and EBRs provides insight into the mechanistic basis of chromosomal change. Previously, we identified gene ontology (GO) terms associated with both; however, here we revisit our analyses in light of newly developed bioinformatic algorithms and the chicken genome assembly galGal6. We aligned genomes available for six birds and one lizard species, identifying 630 HSBs and 19 EBRs. We demonstrate that HSBs hold vast functionality expressed by GO terms that have been largely conserved through evolution. Particularly, we found that genes within microchromosomal HSBs had specific functionalities relevant to neurons, RNA, cellular transport and embryonic development, and other associations. Our findings suggest that microchromosomes may have conserved throughout evolution due to the specificity of GO terms within their HSBs. The detected EBRs included those found in the genome of the anole lizard, meaning they were shared by all saurian descendants, with others being unique to avian lineages. Our estimate of gene richness in HSBs supported the fact that microchromosomes contain twice as many genes as macrochromosomes.


Salt dependency of chromaffin granule aggregation by annexin II tetramer.
Annexin II tetramer (AIIt) is a Ca2+ and phospholipid binding protein that has been shown to reconstitute secretion in permeabilized adrenal medulla cells. In the present study, we have characterized the interactions of AIIt with biological membranes using isolated adrenal medulla secretory granules as a model system. Without added salt, maximal binding of AIIt to chromaffin granules occurred in the absence of AIIt-dependent chromaffin granule aggregation, whereas increasing the osmolality of the reaction mixture with sucrose did not activate AIIt-dependent chromaffin granule aggregation. As the KCl or potassium glutamate concentration of the reaction mixture was increased to between 30 and 50 mM salt, AIIt-dependent chromaffin granule aggregation increased to a maximum, while AIIt binding to chromaffin granules decreased. As the salt concentration was increased from 50 to 150 mM, both AIIt-dependent chromaffin granule aggregation and the binding of AIIt to chromaffin granules were decreased. Furthermore, at optimal salt concentration, KCl and potassium glutamate activated AIIt-dependent aggregation of chromaffin granules to maximum values of about 210% and 195% of control, respectively, whereas potassium phosphate supported AIIt-dependent aggregation of chromaffin granules to only 120% of control. The concentration of AIIt for half-maximal binding to chromaffin granules without added salt or at 50 mM KCl was 0.163 +/- 0.007 (mean +/- SD, n = 3) or 0.173 +/- 0.034 microM AIIt (mean +/- SD, n = 3), respectively, and binding of AIIt to chromaffin granules was not measurable at 150 mM KCl. In contrast, at 50 mM KCl, half-maximal AIIt-dependent chromaffin granule aggregation required 0.171 +/- 0.001 microM AIIt (mean +/- SD, n = 3) and was not measurable without added salt or in the presence of 150 mM KCl. Without added salt, at 50 mM KCl, or at 150 mM KCl, the Ca2+ concentrations for half-maximal aggregation of chromaffin granules and the maximal extent of chromaffin granule aggregation (Amax) were pCa2+ = 3.79 +/- 0.062 (mean +/- SD, n = 3) and Amax = 127% of control, pCa2+ = 6.07 +/- 0.021 (mean +/- SD, n = 3) and Amax = 185% of control, or pCa2+ 4.41 +/- 0.07 (mean +/- SD, n = 3) and Amax = 156% of control, respectively. The stimulation of chromaffin granule aggregation activity and the chromaffin granule binding activity of AIIt was reversible by removal of Ca2+. These results suggest that both ionic strength and salt composition modulate both AIIt-dependent chromaffin granule aggregation and binding to the membranes of these secretory granules.


Gene Editing of Human Hematopoietic Stem and Progenitor Cells: Promise and Potential Hurdles.
Hematopoietic stem and progenitor cells (HSPCs) have great therapeutic potential because of their ability to both self-renew and differentiate. It has been proposed that, given their unique properties, a small number of genetically modified HSPCs could accomplish lifelong, corrective reconstitution of the entire hematopoietic system in patients with various hematologic disorders. Scientists have demonstrated that gene addition therapies-targeted to HSPCs and using integrating retroviral vectors-possess clear clinical benefits in multiple diseases, among them immunodeficiencies, storage disorders, and hemoglobinopathies. Scientists attempting to develop clinically relevant gene therapy protocols have, however, encountered a number of unexpected hurdles because of their incomplete knowledge of target cells, genomic control, and gene transfer technologies. Targeted gene-editing technologies using engineered nucleases such as ZFN, TALEN, and/or CRISPR/Cas9 RGEN show great clinical promise, allowing for the site-specific correction of disease-causing mutations-a process with important applications in autosomal dominant or dominant-negative genetic disorders. The relative simplicity of the CRISPR/Cas9 system, in particular, has sparked an exponential increase in the scientific community's interest in and use of these gene-editing technologies. In this minireview, we discuss the specific applications of gene-editing technologies in human HSPCs, as informed by prior experience with gene addition strategies. HSPCs are desirable but challenging targets; the specific mechanisms these cells evolved to protect themselves from DNA damage render them potentially more susceptible to oncogenesis, especially given their ability to self-renew and their long-term proliferative potential. We further review scientists' experience with gene-editing technologies to date, focusing on strategies to move these techniques toward implementation in safe and effective clinical trials.


A gene expression analysis in rat kidney following high and low salt intake.
The effects of salt intake on renal regulation have been investigated for decades. To find new pathways and to demonstrate the utility of oligonucleotide expression arrays, we studied whole kidneys. Eight Sprague-Dawley rats were divided into two groups. One group received a 6% salt (by weight) diet, while the other group received a 0.3%, otherwise identical, salt diet for 7 days. The rats were sacrificed after 7 days and the left kidney was subjected to RNA extraction. Oligonucleotide expression arrays (Affymetrix) were used to determine downregulation and upregulation, comparing high with low salt intake. Four rats from each group were studied separately. The experiments were reproducible. Thirty genes were downregulated with the high-salt diet, while 35 genes were upregulated. The renin gene, beta-2 glycoprotein-1, retinol binding protein, annexin VI, and the PTP2C protein tyrosine phosphatase were among the downregulated genes. The angiotensin II receptor type 1B receptor, HMG-CoA reductase, B7 antigen, and the rat calcium channel beta subunit III were among the upregulated genes. Differentially regulated were the p55 subunit (upregulated) and the p50 subunit (downregulated) of the phosphatidyl inositol 3-kinase enzyme complex. We verified our results by selecting a high-salt downregulated gene (renin) and an upregulated gene (B7 antigen) and subjecting these genes to real-time polymerase chain reaction. The results were consistent. Oligonucleotide expression arrays can detect novel genes encoding for proteins not generally associated with responses to varied salt intake. Experiments of this nature have substantial limitations and require detailed verification. However, overall, the utility is promising.


Diagnostic value of endoscopic ultrasonography-guided fine-needle aspiration cytology of mediastinal masses in patients with intrapulmonary lesions and nondiagnostic bronchoscopy.
Several procedures are available for the cytopathological diagnosis of mediastinal lesions. The purpose of this study was to evaluate the diagnostic value of endoscopic ultrasonography (EUS)-guided fine-needle aspiration (FNA) in patients with mediastinal mass lesions/lymph node enlargement. All patients had intrapulmonary lesions on chest X ray and/or CT scan, and inconclusive findings by endobronchial forceps biopsy and/or brush cytology. EUS-guided FNA was performed in 16 patients using a modified oblique forward-viewing gastroscope with an electronic multielement curved linear ultrasound transducer. After the region of interest was localized, a 22-gauge Vilmann-Hancke needle was introduced via the 2-mm biopsy channel. The cytological diagnosis of EUS-guided FNA was conclusive for cancer in 9 patients and in the other 7 patients the aspirated samples revealed a benign lesion. In 10 patients the final diagnosis was cancer, thus EUS-guided FNA was diagnostic for malignancy in all but 1 of the lesions (sensitivity 90.0%). In 1 patient epitheloid cell granuloma was detected by cytological examination of the FNA. Following tuberculostatic treatment the lesions disappeared completely on CT scan and EUS. The overall accuracy in this study amounted to 93.7%. From this and other studies discussed, it is assumed that the procedure is an accurate and safe technique to examine nodular lesions suggestive of metastatic lymph node involvement.


Fabrication of a highly efficient core-mode blocker using a femtosecond laser ablation technique.
We present a method for the fabrication of a highly efficient core-mode blocker based on a laser micromachining technique. The process for the fabrication is as follows. A micron-sized crater is made by irradiation of an ultra-short pulse laser on the end face of a single-mode fiber, and then a defect that acts as a core-mode blocker is formed by splicing the cratered fiber with a normal fiber. The attenuation of the core mode was adjustable up to 25 dB according to the initial crater size and the splicing condition. An all-fiber acousto-optic tunable bandpass filter built with the core-mode blocker is also demonstrated, which exhibits a low insertion loss of 1.8 dB with non-resonance light suppression greater than 23 dB.


Apoptotic signaling induced by immunomodulatory thalidomide analogs in human multiple myeloma cells: therapeutic implications.
Thalidomide (Thal) achieves responses even in the setting of refractory multiple myeloma (MM). Although increased angiogenesis in MM bone marrow and the antiangiogenic effect of Thal formed the empiric basis for its use in MM, we have shown that Thal and its immunomodulatory analogs (IMiDs) directly induce apoptosis or growth arrest of MM cells, alter adhesion of MM cells to bone marrow stromal cells, inhibit the production of cytokines (interleukin-6 and vascular endothelial growth factor) in bone marrow, and stimulate natural killer cell anti-MM immunity. In the present study, we demonstrate that the IMiDs trigger activation of caspase-8, enhance MM cell sensitivity to Fas-induced apoptosis, and down-regulate nuclear factor (NF)-kappa B activity as well as expression of cellular inhibitor of apoptosis protein-2 and FLICE inhibitory protein. IMiDs also block the stimulatory effect of insulinlike growth factor-1 on NF-kappa B activity and potentiate the activity of TNF-related apoptosis-inducing ligand (TRAIL/Apo2L), dexamethasone, and proteasome inhibitor (PS-341) therapy. These studies both delineate the mechanism of action of IMiDs against MM cells in vitro and form the basis for clinical trials of these agents, alone and coupled with conventional and other novel therapies, to improve outcome in MM.


Real-time visualization of chromatin modification in isolated nuclei.
Chromatin modification is traditionally assessed in biochemical assays that provide average measurements of static events given that the analysis requires components from many cells. Microscopy can visualize single cells, but the cell body and organelles can hamper staining and visualization of the nucleus. Normally, chromatin is visualized by immunostaining a fixed sample or by expressing exogenous fluorescently tagged proteins in a live cell. Alternative microscopy tools to observe changes of endogenous chromatin in real-time are needed. Here, we isolated transcriptionally competent nuclei from cells and used antibody staining without fixation to visualize changes in endogenous chromatin. This method allows the real-time addition of drugs and fluorescent probes to one or more nuclei while under microscopy observation. A high-resolution map of 11 endogenous nuclear markers of the histone code, transcription machinery and architecture was obtained in transcriptionally active nuclei by performing confocal and structured illumination microscopy. We detected changes in chromatin modification and localization at the single-nucleus level after inhibition of histone deacetylation. Applications in the study of RNA transcription, viral protein function and nuclear architecture are presented. This article has an associated First Person interview with the first author of the paper.


Comprehensive Thermodynamic Profiling for the Binding of a G-Quadruplex Selective Indoloquinoline.
Binding of a positively charged indoloquinoline derivative to a G-quadruplex formed by the G-rich promoter element of the c-MYC oncogene was subjected to a rigorous isothermal calorimetric analysis. Binding of the indoloquinoline is primarily enthalpy-driven but is also promoted by a favorable entropy term. Both binding enthalpy ΔH° and binding entropy ΔS° exhibit a noticeable temperature dependence with almost complete enthalpy-entropy compensation as a result of a negative change in heat capacity ΔCp°. Salt-dependent polyelectrolyte effects only moderately contribute to the overall free energy of association. More details on the binding process are revealed in an attempt to dissect the total free energy into individual contributory terms. Accordingly, specific intermolecular interactions between the indoloquinoline ligand and G-quadruplex substantially contribute in addition to hydrophobic effects in promoting the association. Comparing thermodynamic profiles for various quadruplex ligands indicates different energetic patterns that may aid in the rational design of more efficient quadruplex binding ligands in the future.


Detection of sebaceous gland hyperplasia with dermoscopy and reflectance confocal microscopy.
Sebaceous gland hyperplasia (SGH) is a benign cutaneous proliferation of the sebaceous glands that are mostly present on the face or the neck of older adults. They typically appear as single or multiple soft umbilicated papules; however, in challenging cases, it can be difficult to distinguish them from trichoepitheliomas, base cell carcinomas, or other tumors. Although pathological results have diagnostic value, the significance of non-invasive examinations in diagnosis and differential diagnosis is also worth exploring. This study aimed to describe the dermoscopic and reflectance confocal microscopy (RCM) features of SGH. A total of 31 patients diagnosed with SGH, according to clinical and histopathological standards, were examined using dermoscopy and RCM between March 2018 and January 2022. Dermoscopically, lesions revealed a yellowish-red background and a faint-yellow background in 25 (80.65%) and six cases (19.35%), respectively. White-yellowish lobulated structures in the center of the lesion were present in 31 patients (100%) and umbilications in 19 patients (61.29%). Crown vessels at the periphery of the lesions were observed in 11 patients (35.48%), whereas irregular linear vessels were observed on the surface of the lesions in 18 patients (58.06%). Under RCM, all lesions presented a honeycomb pattern in the epidermis and the typical morulae-shaped sebaceous lobules in the dermis. A dilated follicular infundibulum was observed in 15 patients (48.39%) and dilated vessels in 26 patients (83.87%). Dermoscopy and RCM enabled us to describe the imaging features of SGH. Combining these two useful tools provides a non-invasive basis for accurate clinical diagnosis.


Assessment of Morphological Variations of the Coronoid Process, Condyle, and Sigmoid Notch as an Adjunct in Personal Identification Using Orthopantomograms Among the North Indian Population.
The aim of this study is to assess morphological variations of the coronoid process, condyle, and sigmoid notch as an adjunct in personal identification using orthopantomograms among the North Indian population. The study sample (n=240) was distributed into four age groups: Group I: 30 males and 30 females aged 10-19 years, Group II: 30 males and 30 females aged 20-29 years, Group III: 30 males and 30 females aged 30-39 years, and Group IV: 30 males and 30 females aged 40-59 years. All were subjected to panoramic radiographs. The different morphological forms of the coronoid process, condyle, and sigmoid notch were evaluated. The results showed that across all age groups, angular condyles were the most common kind of condyle in males, followed by round and convex types. The present study found that the coronoid process typically takes on a triangle shape across all ages and sexes. Additionally, the vast majority of cases were triangular on both sides, and this was true across both sexes. It was found in this study that the sigmoid notch most commonly took the form of a larger notch, followed by a rounder notch. Using panoramic photos to portray the different morphologies of the coronoid process, condyle, and sigmoid notch can be a much simpler and faster method of identifying an individual, especially in the event of a mass disaster, so long as antemortem data are kept. The method of radiographic identification of individuals has recently gained prominence due to its efficacy. Radiographs like these can be invaluable in forensic dentistry, where they can help unearth previously hidden evidence if premortem records are retained. As a potential approach for individual identification among our population, panoramic radiographs were used to investigate the varying morphological forms of the coronoid process, condyle, and sigmoid notch.


Motor vehicle operation in the setting of multiple sclerosis with myelopathy: assessment, adaptive equipment, counseling, and cessation of driving.
Many individuals with multiple sclerosis are safe drivers; others self-regulate their driving or cease driving altogether because of their own safety concerns. When patients are unsafe to drive and have poor insight into their condition, they may ignore a provider's repeated communication to stop driving. Addressing this issue when a person is initially diagnosed with multiple sclerosis and continuing the discussion over time when assessing other activities of daily living may ease the process of driving cessation. Referral for a driving evaluation may be appropriate, in conjunction with referrals to a social worker for mobility counseling and to a psychologist for grief and loss issues associated with driving cessation. When repeated recommendations to stop driving are ignored, notifying the appropriate government agencies should be considered.


[Effects of sulfur on transformation of selenium in soil and uptake of selenium in rape].
The high-quality, high-yield rape (Brassica napus L. cv. Xiangnongyou 571) was chosen as the experimental material to undergo seedling stage soil cultivation and solution cultivation. This study was aimed to investigate the effects of sulfur (S) on the fraction and species of amend selenium (Se) in soil by applying S fertilizer, and to reveal the mechanism through which S controls the Se uptake of rape. The results showed that applications of both Se at 5 mg.kg-1 and S at 150 mg.kg-1 could provide some boost to rape growth, however such boost was unremarkable; S application could significantly reduce Se content in shoots and roots by as much as 64. 0% and 39. 1% , respectively; S application could significantly decrease the pH value and increase the organic matter content by as much as 0. 65 units and 1.76 g.kg-1 , respectively; S application could significantly decrease soluble Se and Fe/Mn oxide-bound Se, and significantly increase organic matter-bound Se, however, there was no remarkable effect on exchangeable and residual Se. S could significantly decrease the content of Se(IV) in the soluble Se and significantly increase the content of Se(IV) in the exchangeable Se, with remarkable decrease in Se(VI) content in both fractions, and no remarkable effect on Se(II). S had a profound effect on the uptake of Se by rape seedlings when Se( IV) and Se( VI) were applied. The Se contents in shoot and root of the Se( VI)-treated rape were 7.3 and 3.2 times respectively as high as that of the Se( IV)-treated rape, while with a S rate of 2 mmolL-1, their Se contents were lower than 32.6% and 8.7% of that of the Se(IV)-treated rape. In conclusion, in addition to improving crop growth, appropriate amount of S fertilizer could also reduce soil pH and increase organic content, causing available Se in soil to be Fe/Mn oxide-bound and organic matter-bound, and retarding its transformation to Se( VI), thus reducing Se uptake by rape. This has significant value for regulation of Se content in crops from Se-rich regions, ensuring food quality and safety, benefiting the long-term use of soil Se resources and regional economic development.


Targeting the epigenome in malignant pleural mesothelioma.
Malignant pleural mesotheliomas (MPM) are notoriously refractory to conventional treatment modalities. Recent insights regarding epigenetic alterations in MPM provide the preclinical rationale for the evaluation of novel combinatorial regimens targeting the epigenome in these neoplasms.


Acoustic imaging in application to reconstruction of rough rigid surface with airborne ultrasound waves.
Accurate reconstruction of the surface roughness is of high importance to various areas of science and engineering. One important application of this technology is for remote monitoring of open channel flows through observing its dynamic surface roughness. In this paper a novel airborne acoustic method of roughness reconstruction is proposed and tested with a static rigid rough surface. This method is based on the acoustic holography principle and Kirchhoff approximation which make use of acoustic pressure data collected at multiple receiver points spread along an arch. The Tikhonov regularisation and generalised cross validation technique are used to solve the underdetermined system of equations for the acoustic pressures. The experimental data are collected above a roughness created with a 3D printer. For the given surface, it is shown that the proposed method works well with the various number of receiver positions. In this paper, the tested ratios between the number of surface points at which the surface elevation can be reconstructed and number of receiver positions are 2.5, 5, and 7.5. It is shown that, in a region comparable with the projected size of the main directivity lobe, the method is able to reconstruct the spatial spectrum density of the actual surface elevation with the accuracy of 20%.


Thermal Expansion Anomaly in TTB Ferroelectrics: The Interplay between Framework Structure and Electric Polarization.
Tetragonal tungsten bronze (TTB) makes up a large family of functional materials with fascinating dielectric, piezoelectric, or ferroelectric properties. Understanding the thermal expansion mechanisms associated with their physical properties is important for their practical applications as well as theoretical investigations. Fortunately, the appearance of anomalous thermal expansion in functional materials offers a chance to capture the physics behind them. Herein, we report an investigation of the thermal expansion anomalies in TTBs that are related to ferroelectric transitions and summarize recent progress in this field. The special role of Pb(2+) cation is elucidated. The interplay between the thermal expansion anomaly, electric polarization, and framework structure provides new insight into the structure-property relationships in functional materials.


Impact of early palliative care on overall survival of patients with metastatic upper gastrointestinal cancers treated with first-line chemotherapy: a randomised phase III trial.
Palliative care (PC) has usually been offered at the end-of-life stage, although the WHO recommends providing PC as early as possible in the course of the disease. A recent study has shown that early PC (EPC) provides a more meaningful effect on quality of life and, surprisingly, on overall survival (OS) than standard treatment for patients with metastatic lung cancer. Whether EPC benefits also apply to patients with metastatic upper gastrointestinal (GI) cancers is unknown. EPIC is a randomised phase III trial comparing EPC plus standard oncologic care versus standard oncologic care in patients with metastatic upper GI cancers. Its primary objective is to evaluate the efficacy of EPC in terms of OS. Its secondary objectives are to assess the effects of EPC on patient-reported outcomes (quality of life, depression and anxiety) and the effect of EPC on the number of patients receiving chemotherapy in their last 30 days of life. Assuming an exponential distribution of survival time, 381 deaths are required to ensure an 80% power for an absolute difference of 10% in 1 year OS rates (40% vs 50.3%, HR=0.75; log rank test two-sided alpha=5%), leading to a planned sample size of 480 patients enrolled over 3 years and a final analysis at 4 years. The main analysis will be performed on the intent-to-treat dataset. This study was approved by the 'Comité de Protection des Personnes Nord-Ouest I' (4 April 2016), complies with the Helsinki declaration and French laws and regulations and follows the International Conference on Harmonisation E6 (R1) Guideline for Good Clinical Practice. The trial results, even if they are inconclusive, will be presented at international oncology congresses and published in peer-reviewed journals. EudraCT: 2015-A01943-46; Pre-results. NCT02853474.


French patients on daily hemodialysis: clinical characteristics and treatment trajectories.
Increasing the weekly frequency of hemodialysis sessions has positive effects, on the control of several biological data of patients. However, knowledge about Daily HemoDialysis (DHD) practices is limited in France. The aim of the present study was to describe the characteristics and treatment trajectories of all French patients undergoing DHD. All patients older than 18 years who started DHD between 2003 and 2012 in France were included and followed until December 31, 2013. The patients' demographic and clinical characteristics and treatment modalities were extracted from the French Renal Epidemiological and Information Network (REIN) registry. During the inclusion period, 753 patients started DHD in France. Based on their median age (64 years), patients were classified in two groups: "old" group (≥64 years) and "young" group (<64 years). Patients in the old group had more comorbidities than in the young group: 48 % had diabetes (vs 29 % in the young group), 17 % an active malignancy (vs 10 %) and 80 % ≥1 cardiovascular disease (vs 41 %). Concerning patients' treatment trajectories, 496 (66 %) patients started with another dialysis before switching to DHD and 257 (34 %) directly with DHD. At the end of the follow-up, 69 % of patients in the old group were dead (27.4 % in the young group) and kidney transplantation was more frequent in the young group (30.4 % vs 0.5 %). In France, DHD is proposed not only to young in rather good clinical conditions and waiting for kidney transplantation, but also to old and frail patients with higher mortality.


The influence of non-radioactive iodine (127I) on the outcome of radioiodine (131I) therapy in patients with Graves' disease and toxic nodular goitre.
The aim of the study was to achieve an effective target dose in the thyroid by increasing the effective half-life (Teff) of (131)I by use of iodide ((127)I) two days after (131)I therapy in patients with hyperthyroidism with low Teff. The study was carried out in two groups. Group A - 41 patients, and Group B - 14 patients, all the patients were with hyperthyroidism with Teff less than 3 days qualified for (131)I therapy. Only group A patients received 600 μg of iodide a day for 3 days, two days after (131)I therapy. Radioiodine uptake (RAIU) after 24 and 48 hours, thyroid scintiscan and ultrasonography were done before and after 12 months of (131)I therapy. In group A a significant increase was seen in the Teff (5 days on average) resulting in an increase in the energy target dose by 28% and 37%, in patients with Graves' disease (GD) and toxic nodular goitre (TNG), respectively. After one year of therapy 50% of GD and 93% of TNG patients achieved euthyroidism; 28% of GD and 3% of TNG patients were in hypothyroidism. In Group B, all the patients had radioiodine treatment failure and received a second therapeutic dose of (131)I. Administration of (127)I after (131)I treatment can lead to an increase in its effective half-life. This will also increase the absorbed energy dose in thyroid tissue, thereby improving therapeutic outcome without administration of a higher or second dose of (131)I. This may minimize whole-body exposure to radiation and reduces the cost of treatment.


Statistical significance of normalized global alignment.
The comparison of homologous proteins from different species is a first step toward a function assignment and a reconstruction of the species evolution. Though local alignment is mostly used for this purpose, global alignment is important for constructing multiple alignments or phylogenetic trees. However, statistical significance of global alignments is not completely clear, lacking a specific statistical model to describe alignments or depending on computationally expensive methods like Z-score. Recently we presented a normalized global alignment, defined as the best compromise between global alignment cost and length, and showed that this new technique led to better classification results than Z-score at a much lower computational cost. However, it is necessary to analyze the statistical significance of the normalized global alignment in order to be considered a completely functional algorithm for protein alignment. Experiments with unrelated proteins extracted from the SCOP ASTRAL database showed that normalized global alignment scores can be fitted to a log-normal distribution. This fact, obtained without any theoretical support, can be used to derive statistical significance of normalized global alignments. Results are summarized in a table with fitted parameters for different scoring schemes.


Genetics of glycopeptide resistance in enterococci.
Glycopeptide resistance in enterococci is phenotypically and genotypically heterogeneous. The genes responsible for inducible resistance to high levels of vancomycin and teicoplanin (VanA phenotype) are carried by the 10,851-bp Tn1546 transposon. Transposition of Tn1546 into self-transferable plasmids and subsequent transfer by conjugation appears to be responsible for the dissemination of this type of resistance. Nine polypeptides are encoded by Tn1546 that belong to five functional groups: transposition functions (ORF1 and ORF2), regulation of resistance gene expression (VanR and VanS), synthesis of depsipeptide D-Ala-D-lactate (VanH and VanA), hydrolysis of D-Ala-D-Ala-containing peptidoglycan precursors (VanX and VanY), and low-level teicoplanin resistance (VanZ). VanB-type resistance (various levels of resistance to vancomycin and susceptibility to teicoplanin) is also due to production of D-Ala-D-Lac. The VanB ligase of VanB-type strains is structurally and functionally similar to VanA. The vanB gene was found on composite transposon Tn1547, which, in turn, was part of larger conjugative chromosomally located elements (90 to 250 kb). In contrast to acquired VanA- and VanB-type resistance, VanC-type resistance (low level of resistance to vancomycin and susceptibility to teicoplanin) is an intrinsic property of motile enterococci. Resistance in these species is due to synthesis of dipeptide D-Ala-D-Ser by VanC ligases leading to production of cell wall precursors with reduced vancomycin affinity.


A rhythmic modulatory gating system in the stomatogastric nervous system of Homarus gammarus. II. Modulatory control of the pyloric CPG.
1. In the European rock lobster, Homarus gammarus, two bilaterally symmetrical pairs of commissural neurons, P and commissural pyloric (CP), evoke excitatory postsynaptic potentials in the neurons of the pyloric motor network. The present paper shows that the two commissural neurons also exert a modulatory control over the pyloric network. 2. The P and CP neurons were active during ongoing pyloric rhythms. Ongoing pyloric activity was terminated when the neurons were hyperpolarized to inhibit their firing. 3. When the pyloric network was quiescent, depolarizing either the P or CP neuron induced a robust pyloric rhythm. 4. We studied the actions of the P and CP neurons on individual pyloric neurons isolated in situ from network interactions by a photoinactivation techniques. The P neuron induced oscillatory properties in the pacemaker pyloric dilator (PD) neurons and the motor neuron, ventricular dilator (VD), whereas the CP neuron induced rhythmogenic properties in all the network neurons but VD. Together, the P-CP neurons modulated the entire pyloric network. The modulatory effects of the P-CP neurons did not outlast the duration of their discharge. 5. The P and CP neurons also controlled the firing frequency of all the pyloric neurons. They may, in addition, control phasing of the constrictor neurons discharges, but this effect was state-dependent and occurred only when the pyloric central pattern generator was functioning weakly. Their role in providing flexibility to the network operation appeared relatively limited. 6. We conclude that the P and CP neurons are good candidates for insuring long-term maintenance of pyloric network activity patterns.


Quantitative Targeted Absolute Proteomics (QTAP)-based Pharmacoproteomics: The Importance of International Collaboration.
Proteins such as membrane transporters, enzymes, receptors and channels play key roles in drug absorption, distribution, metabolism, and elimination, and also influence efficacy and the likelihood of adverse reactions. Therefore, if we can quantify the activities of these molecules, it may be possible to predict the behavior of candidate drugs in humans in disease states; such methodology would be extremely helpful for efficient drug development. We have developed an in silico method to select appropriate peptides within amino acid sequences in order to quantify targeted proteins by LC-MS/MS in selected reaction monitoring (SRM) mode. We have applied this method for the quantification of functional proteins in order to validate various in vitro and in vivo models. We found fairly good correlation between protein amounts and the enzymatic activities of microsomal cytochrome P450 (CYP) isoforms and uridine 5'-diphospho-glucuronosyltransferase (UGT) in human liver, as well as between protein amounts and the transport activities of multiple transporters in human lung cells. These results suggest that protein quantification can be useful in predicting activity. We have applied this approach to evaluate the usefulness and limitations of an immortalized human brain capillary endothelial cell line (D3 cells) and a P-glycoprotein humanized (hMDR1) mouse model by comparing the amounts of functional proteins in the models with those in isolated capillaries from human brain. In order to obtain sufficient human tissue specimens for further studies leading to clinical applications, we believe that international collaboration will be crucial.


Randomised clinical trial: reducing the intake of dietary FODMAPs of breastfeeding mothers is associated with a greater improvement of the symptoms of infantile colic than for a typical diet.
Therapeutic diets for infantile colic lack evidence. In breastfed infants, avoiding "windy" foods by the breastfeeding mother is common. To examine the effects of a maternal low-FODMAP (Fermentable, Oligosaccharides, Disaccharides, Monosaccharides, And Polyols) diet compared to a typical-Australian diet on infant crying-fussing durations of infants with colic in a randomised, double-blind, crossover feeding study. Between 2014 and 2016 exclusively breastfed infants aged ≤9 weeks meeting Wessel criteria for colic were recruited. Mothers were provided a 10-day low-FODMAP or typical-Australian diet, then alternated without washout. Infants without colic (controls) were observed prospectively and mothers remained on habitual diet. Infant crying-fussing durations were captured using a Barr Diary. Measures of maternal psychological status and samples of breast milk and infant faeces were collected. Mean crying-fussing durations were 91 min/d in seven controls compared with 269 min/d in 13 colicky infants (P < 0.0001), which fell by median 32% during the low-FODMAP diet compared with 20% during the typical-Australian diet (P = 0.03), confirmed by a two-way mixed-model analyses-of-variance (ƞp 2 = 0.719; P = 0.049) with no order effect. In breast milk, lactose concentrations remained stable and other known dietary FODMAPs were not detected. Changes in infant faecal calprotectin were similar between diets and groups, and faecal pH did not change. Median maternal anxiety and stress fell with the typical-Australian diet (P < 0.01), but remained stable on the low-FODMAP diet. Maternal low-FODMAP diet was associated with enhanced reduction in crying-fussing durations of infants with colic. This was not related to changes in maternal psychological status, gross changes in breast milk or infant faeces. Mechanisms require elucidation. Trial Registration Australian New Zealand Clinical Trials Registry (ANZCTR): 12616000512426 - anzctr.org.au.