An in vitro investigation of the retrograde flow fields of two bileaflet mechanical heart valves.
Fluid stresses occurring in retrograde flow fields during valve closure may play a significant role in thrombogenesis. The squeeze flow and regurgitant jets can cause damage to formed blood elements due to high levels of turbulent shear stress. The aim of this study was to characterize in detail the spatial structure and temporal behavior of the retrograde flow fields of the St. Jude Medical and Medtronic Parallel bileaflet mechanical heart valves. Three-component, coincident laser Doppler anemometry (LDA) velocity measurements were obtained facilitating the determination of the full Reynolds stress tensor and the principal stresses in the valve flow fields. The experiments were performed in the Georgia Tech aortic flow chamber under physiologic pulsatile flow conditions. Data were collected over several hundred cardiac cycles for subsequent phase window averaging and generation of mean velocity and turbulence statistics over 20 ms intervals. A region approximately 8 mm x 10 mm was mapped 1.0 mm upstream of one hinge of each valve with an incremental resolution of 0.13-0.25 mm. Animation of the data allowed the visualization of the flow fields and a quantitative display of mean velocity and turbulent stress values. In the St. Jude Medical squeeze flow, the peak turbulent shear stress was 800 dynes/cm2 and the peak reverse velocity was 0.60 m/s. In the Medtronic Parallel squeeze flow, the peak turbulent shear stress was 1,000 dynes/cm2 and the peak velocity 0.70 m/s. The leakage jet fields of the two valves were very different: in the case of the St. Jude Medical valve, turbulent shear stresses reached 1,800 dynes/cm2 and peak jet velocity was 0.80 m/s; in the case of the Medtronic Parallel valve, turbulent shear stresses reached 3,690 dynes/cm2 and the peak jet velocity was 1.9 m/s. The retrograde flow fields of these two bileaflet mechanical heart valves appear to be design-dependent. The elevated turbulent shear stresses generated by both valve designs may indicate a propensity for blood element damage during the reverse flow phase of the cardiac cycle, but the extent of flow disturbance was twice as high with the Medtronic Parallel than with the St. Jude Medical valve. This research should yield a better understanding of the significance of retrograde flow to the functionality and potential thrombogenicity of bileaflet mechanical heart valves and aid in the development of new designs.


Arterialized capillary blood gases and acid-base studies in normal individuals from 29 days to 24 years of age.
Studies of arterialized capillary blood gases and acid-base values were performed on 712 normal persons who were between the ages of 29 days and 24 years. The results were divided for clinical use into six groups by age; linear regression lines were constructed for better understanding of the development of blood gas levels and the acid-base balance. The blood pH essentially remained unchanged throughout the study period. The oxygen and carbon dioxide pressures, base excess of extracellular fluid, and buffer base and bicarbonate levels are lower in infants than in children and adults; adult values are reached at approximately 7 to 12 years of age. The probable explanation for the lower values in infants is discussed. The effects of crying on the composition of blood gases are mentioned.


Genetic differences in the histochemically defined structure of oligosaccharides in mice.
A wide range of tissues from three interfertile species of mice and an interspecific hybrid was examined with lectins conjugated to peroxidase to localize specifically glycoconjugates containing terminal alpha-N-acetylgalactosamine, alpha-galactose, and alpha-fucose, and the terminal disaccharide galactose-(beta 1----3)-N-acetylgalactosamine. This battery of lectins disclosed marked heterogeneity of glycoconjugates in different histological sites in a given animal and even between cells in a presumably homogeneous cell population within an organ. No variation with any lectin was observed between individuals of two closely related inbred strains of Mus domesticus at any specific histological or cytological site. In contrast, littermates of an outbred strain of Mus castaneus differed in binding of certain lectins at various sites, attesting to a genetic basis for individual variation. Hybrids between castaneus and domesticus mice also showed individual variation. Moreover, extensive differences between the mouse species were demonstrable with every lectin in glycoconjugates of stored secretions, Golgi cisternae, and apical or basolateral plasmalemma in many cell types. Totaling the differences in tabulated staining intensities for each possible species pair gave a measure of the overall extent of difference at 53 histological sites. According to this measure, the three species are about equally divergent from one another. Some differences between species appeared to depend on histological rather than histochemical variation, as, for example, a greater abundance of granular duct cells in the sublingual and submandibular glands in Mus hortulanus. Other differences were apparently derived from pathological change, as exemplified by casts and lymphoid infiltrates in kidney and structurally atypical submandibular gland lobules in Mus castaneus, and possibly by infiltrating cells in intestinal lamina propria and epithelium in Mus castaneus and hortulanus.


Point of care ultrasound 3-point compression vs departmental scanning for lower limb DVT in ambulatory and internal medicine patients.
Point of care ultrasound scanning (POCUS) is safe and effective in positively identifying lower limb DVT in emergency departments globally. In the UK, the requisite knowledge and skills are integrated into the FAMUS and FUSIC curricula. Five FAMUS practitioners of varying experience performed 3-point compression POCUS on medical ambulatory and inpatients. Accuracy and timing of POCUS was compared between practitioners and with subsequent departmental scans. 89% sensitivity and 97% specificity were observed, with little difference between supervisors and candidates. Additionally, a significantly higher proportion of POCUS vs departmental scans (69% vs 7%, p = 0.0001) occurred within 24 hours of request. Minimal experience was required to produce accurate results within ambulatory and internal medicine settings, and significant time savings can be made.


Slow inward current may produce many results attributed to IX1 in cardiac Purkinje fibers.
We have tried to answer two fundamental questions concerning the outward current IX1 of cardiac Purkinje fibers. 1) Is it possible that current changes identified as arising from IX1 in voltage-clamp experiments are actually manifestations of changes in the slow inward current (Isi); and 2) is IX1 in fact required to produce the electrical phenomena attributed to it? Isi behavior and the role of IX1 were explored using computer simulation. The Isi model produced current changes during depolarizations and hyperpolarizations from depolarized resting potentials like those attributed to IX1. It also produced a component of "tail currents" that behaved like IX1. If these current changes were analyzed, assuming that an outward current is responsible, the resulting kinetics and current voltage relation would be very similar to the kinetics and current voltage relation reported for IX1. Using the McAllister, Noble, and Tsien formulation of the Purkinje fiber action potential, we found that IX1 is not essential for repolarization of the reconstructed action potential nor is it needed to reproduce interval duration effects and the effects of applied current in that model. Data suggesting that calcium channel blockers reduce IX1 and that catecholamines increase IX1 may be explained as arising from changes in Isi. Thus many manifestations of IX1 can be explained as arising from unanticipated behavior of Isi, and IX1 does not necessarily play a key role in generating Purkinje fiber electrical activity.


The PPARγ agonist rosiglitazone promotes the induction of brite adipocytes, increasing β-adrenoceptor-mediated mitochondrial function and glucose uptake.
Recruitment and activation of brite (or beige) adipocytes has been advocated as a potential avenue for manipulating whole-body energy expenditure. Despite numerous studies illustrating the differences in gene and protein markers between brown, brite and white adipocytes, there is very little information on the adrenergic regulation and function of these brite adipocytes. We have compared the functional (cyclic AMP accumulation, oxygen consumption rates, mitochondrial function, glucose uptake, extracellular acidification rates, calcium influx) profiles of mouse adipocytes cultured from three contrasting depots, namely interscapular brown adipose tissue, and inguinal or epididymal white adipose tissues, following chronic treatment with the peroxisome proliferator-activated receptor γ (PPARγ) agonist rosiglitazone. Prototypical brown adipocytes readily express β3-adrenoceptors, and β3-adrenoceptor stimulation increases cyclic AMP accumulation, oxygen consumption rates, mitochondrial function, glucose uptake, and extracellular acidification rates. Treatment of brown adipocytes with rosiglitazone increases uncoupling protein 1 (UCP1) levels, and increases β3-adrenoceptor mitochondrial function but does not affect glucose uptake responses. In contrast, inguinal white adipocytes only express UCP1 and β3-adrenoceptors following rosiglitazone treatment, which results in an increase in all β3-adrenoceptor-mediated functions. The effect of rosiglitazone in epididymal white adipocytes, was much lower compared to inguinal white adipocytes. Rosiglitazone also increased α1-adrenoceptor mediated increases in calcium influx and glucose uptake (but not mitochondrial function) in inguinal and epididymal white adipocytes. In conclusion, the PPARγ agonist rosiglitazone promotes the induction and function of brite adipocytes cultured from inguinal and epididymal white adipose depots.


Predicting drug pharmacokinetics and effect in vascularized tumors using computer simulation.
In this paper, we investigate the pharmacokinetics and effect of doxorubicin and cisplatin in vascularized tumors through two-dimensional simulations. We take into account especially vascular and morphological heterogeneity as well as cellular and lesion-level pharmacokinetic determinants like P-glycoprotein (Pgp) efflux and cell density. To do this we construct a multi-compartment PKPD model calibrated from published experimental data and simulate 2-h bolus administrations followed by 18-h drug washout. Our results show that lesion-scale drug and nutrient distribution may significantly impact therapeutic efficacy and should be considered as carefully as genetic determinants modulating, for example, the production of multidrug-resistance protein or topoisomerase II. We visualize and rigorously quantify distributions of nutrient, drug, and resulting cell inhibition. A main result is the existence of significant heterogeneity in all three, yielding poor inhibition in a large fraction of the lesion, and commensurately increased serum drug concentration necessary for an average 50% inhibition throughout the lesion (the IC(50) concentration). For doxorubicin the effect of hypoxia and hypoglycemia ("nutrient effect") is isolated and shown to further increase cell inhibition heterogeneity and double the IC(50), both undesirable. We also show how the therapeutic effectiveness of doxorubicin penetration therapy depends upon other determinants affecting drug distribution, such as cellular efflux and density, offering some insight into the conditions under which otherwise promising therapies may fail and, more importantly, when they will succeed. Cisplatin is used as a contrast to doxorubicin since both published experimental data and our simulations indicate its lesion distribution is more uniform than that of doxorubicin. Because of this some of the complexity in predicting its therapeutic efficacy is mitigated. Using this advantage, we show results suggesting that in vitro monolayer assays using this drug may more accurately predict in vivo performance than for drugs like doxorubicin. The nonlinear interaction among various determinants representing cell and lesion phenotype as well as therapeutic strategies is a unifying theme of our results. Throughout it can be appreciated that macroscopic environmental conditions, notably drug and nutrient distributions, give rise to considerable variation in lesion response, hence clinical resistance. Moreover, the synergy or antagonism of combined therapeutic strategies depends heavily upon this environment.


Low monocytic HLA-DR expression in critically ill patients of sepsis: An indicator for antimicrobial and/or immunomodulatory intervention.
Sepsis is a result of suppressed host immune response which leads to fatal multi-organ dysfunctionality. Low frequency of active monocytes or reduced expression of human leukocyte antigen (HLA)-DR on monocytes shows the suppressed immune response in sepsis patients. One of the well-studied markers in patients with sepsis is procalcitonin (PCT). The role of monocytic (m) HLA-DR expression has been monitored in sepsis and is being considered a marker of the severity of interim immuno-depression in these patients. The study describes the impact of HLA-DR expression on monocytes quantitatively using flow cytometry. In this prospective study, we quantified monocytes and their HLA-DR expression in 20 patients of sepsis admitted to the Intensive Care Unit (ICU). Serum levels of PCT and interleukin (IL)-6 production were also measured in these patients, and the results were compared with those in healthy controls. Monocyte frequency calculated was higher in sepsis patients as compared to healthy controls, however, HLA-DR expressing monocytes were significantly reduced as was the mean fluorescence intensity (MFI) of HLA-DR. Contrastingly, IL-6 and PCT levels were significantly high in sepsis than controls. The results suggest that low HLA-DR expression, combined with PCT, is a better prognostic parameter in the early phase of sepsis. Poor recovery of mHLA-DR may serve as an early guide for clinicians to assess the prognosis of sepsis patients and consider immunomodulatory therapy in its management.


MWCNTs Alleviated saline-alkali stress by optimizing photosynthesis and sucrose metabolism in rice seedling.
Saline and alkali stress affects the growth and development, survival rate, and final yield of rice, while new nano materials can have a positive effect on rice growth. In order to investing the effects of carboxymethyl multi walled carbon nanotubes (MWCNTs) on the growth and development of rice seedlings under salt alkali stress, rice seedlings were cultured using rice variety "Songjing 3" using nutrient solution water culture method. The effects of MWCNTs on water absorption capacity, leaf photosynthesis, and sucrose metabolism of rice seedlings under 50 mmol/L saline-alkali stress (1NaCl: 9Na2SO4: 9NaHCO3: 1Na2CO3) conditions were investigated. The results showed that MWCNTs can improve the water use ability of roots and leaves, especially the water absorption ability of roots, which provides a guarantee for the improvement of rice biomass and the enhancement of leaf photosynthetic capacity under adverse conditions. After treatment with MWCNTs, the photosynthetic rate (Pn), stomatal conductance (gs), and transpiration rate (Tr) of leaves increased significantly, and the photochemical quenching value (qP), photochemical quantum efficiency value (Fv/Fm), and electron transfer rate value (ETR) of chlorophyll fluorescence parameters increased significantly, which is beneficial to the improvement of the PSII photosynthetic system. MWCNTs treatment promoted the increase of photosynthetic pigment content in leaves under salt and alkali stress, improved the ratio of Chla and Chlb parameters, increased the activities of key photosynthetic enzymes (RUBPCase and PEPCase) in leaves, increased the value of total lutein cycle pool (VAZ), and significantly enhanced the deepoxidation effect of lutein cycle (DEPS), which can effectively alleviate the stomatal and non stomatal constraints on leaf photosynthesis caused by salt and alkali stress. MWCNTs treatment significantly enhanced the activities of sucrose phosphate synthase (SPS) and sucrose synthase (SS) under salt and alkali stress, and decreased the activities of soluble acid invertase (SAInv) and alkaline/neutral invertase (A/N-Inv), indicating that MWCNTs promoted sucrose synthesis while inhibiting sucrose decomposition, thereby promoting sucrose accumulation in rice leaves. This study can provide theoretical and experimental basis for the application of MWCNTs to the production of rice under salt and alkali stress, and can find a new way for rice production in saline and alkaline lands.


Amidative peptide processing and vascular function.
Substance P (SP), an amidated peptide present in many sensory nerves, is known to affect cardiovascular function, and exogenously supplied SP has been shown to activate nitric oxide synthase (NOS) in endothelial cells. We now report that SP-Gly, the glycine-extended biosynthetic precursor of SP (which is enzymatically processed to the mature amidated SP), causes relaxation of rat aortic strips with an efficacy and potency comparable to that of SP itself. Pretreatment of the aortic strips with 4-phenyl-3-butenoic acid (PBA), an irreversible amidating enzyme inactivator, results in marked inhibition of the vasodilation activity induced by SP-Gly but not of that induced by SP itself. Isolated endothelial cell basal NOS activity is also decreased by pretreatment with PBA, with no evidence of cell death or direct action of PBA on NOS activity. Both bifunctional and monofunctional forms of amidating enzymes are present in endothelial cells, as evidenced by affinity chromatography and Western blot analysis. These results provide evidence for a link between amidative peptide processing, NOS activation in endothelial cells, and vasodilation and suggest that a product of amidative processing provides intrinsic basal activation of NOS in endothelial cells.


Carotid intima-media thickness and flow-mediated dilation in obese children with non-alcoholic fatty liver disease.
This study aimed to understand the role of non-alcoholic fatty liver disease (NAFLD) in increasing the risk of atherosclerosis in obese pediatric patients. The study included 109 obese children (age, 9-15 years) and a control group comprising 44 healthy age- and gender-matched children with normal weight. NAFLD was diagnosed using conventional ultrasound (US) examination. Both right carotid intima-media thickness (CIMT) and flow-mediated dilation (FMD) were assessed in addition to anthropometric measures and serum biochemical parameters, including lipid profile and fasting glucose and insulin levels. Homeostatic model assessment of insulin resistance (HOMA-IR) was calculated as a measure of insulin resistance. Mean age and gender distributions were similar in the obese children and control group (p=0.168 and p=0.705, respectively). Median body mass index standard deviation scores of obese children with grade II-III NAFLD were significantly higher than those of obese children without hepatosteatosis (p<0.001). Median total cholesterol levels were similar in all the groups (p=0.263). Low-density lipoprotein cholesterol and triglyceride levels increased and high-density lipoprotein cholesterol levels decreased significantly as the grade of steatosis increased (p<0.001, p<0.05, and p=0.05, respectively). Median alanine aminotransaminase (ALT) and HOMA-IR levels of obese children with grade II-III NAFLD were significantly higher than those of obese children without NAFLD (p=0.01) and obese children with grade I NAFLD (p=0.001). CIMT was significantly correlated with the grade of steatosis (p<0.001) and level of ALT (p=0.005). Linear regression analysis showed that the grade of hepatosteatosis had a significant effect on CIMT. FMD decreased as the grade of hepatosteatosis increased, but it did not reach a significant level. The obese children with hepatosteatosis showed increased CIMT, as indicated by the grade of steatosis, compared with healthy controls and obese children without hepatosteatosis. FMD was not superior to CIMT in predicting the risk of early atherosclerosis.


On combining family-based and population-based case-control data in association studies.
Combining data collected from different sources can potentially enhance statistical efficiency in estimating effects of environmental or genetic factors or gene-environment interactions. However, combining data across studies becomes complicated when data are collected under different study designs, such as family-based and unrelated individual-based case-control design. In this article, we describe likelihood-based approaches that permit the joint estimation of covariate effects on disease risk under study designs that include cases, relatives of cases, and unrelated individuals. Our methods accommodate familial residual correlation and a variety of ascertainment schemes. Extensive simulation experiments demonstrate that the proposed methods for estimation and inference perform well in realistic settings. Efficiencies of different designs are contrasted in the simulation. We applied the methods to data from the Colorectal Cancer Family Registry.


Diode Laser-Assisted Surgical Therapy for Early Treatment of Oral Mucocele in a Newborn Patient: Case Report and Procedures Checklist.
Mucocele (also known as ranula or salivary gland mucous cyst) of the newborn is a lesion present on the intraoral cavity, with the potential to interfere with respiration and feeding. In the present report, a case of mucocele in a 4-month female patient has been described. As conventional surgery can be followed by several complications such as intraoperative bleeding, difficulties in wound healing, and maintenance of sterility during surgery, in the present case, the use of diode laser has been planned. A topic anesthesia with lidocaine gel was performed. A diode laser (810 nm wavelength, continuous wave mode, power output of 3 watt, and 0.4 mm diameter fiber optic) was set for excising the lesion. The tip was directed at an angle of 10 to 15°, moving around the base of the lesion with a circular motion. The procedure was completed in 3 minutes. The patient was visited with a follow-up of 2 weeks and 4 months after excision. The intraoral wound healed without complications, and no signs of infection or mass recurrence were noted. The histopathological examination confirmed the diagnosis of mucocele. On the basis of the results of the present case report, the use of diode laser can be easily performed also in a noncompliant newborn patient for successful excision of mucocele lesions, and checklist of clinical procedures has been described.


Diagnosis and treatment of coronary vulnerable plaques.
Thin-capped fibroatheroma is the morphology that most resembles plaque rupture. Detection of these vulnerable plaques in vivo is essential to being able to study their natural history and evaluate potential treatment modalities and, therefore, may ultimately have an important impact on the prevention of acute myocardial infarction and death. Currently, conventional grayscale intravascular ultrasound, virtual histology and palpography data are being collected with the same catheter during the same pullback. A combination of this catheter with either thermography capability or additional imaging, such as optical coherence tomography or spectroscopy, would be an exciting development. Intravascular magnetic resonance imaging also holds much promise. To date, none of the techniques described above have been sufficiently validated and, most importantly, their predictive value for adverse cardiac events remains elusive. Very rigorous and well-designed studies are compelling for defining the role of each diagnostic modality. Until we are able to detect in vivo vulnerable plaques accurately, no specific treatment is warranted.


HIV-1 infection associated with abnormal vaginal flora morphology and bacterial vaginosis.
In-vitro research has suggested that bacterial vaginosis may increase the survival of HIV-1 in the genital tract. Therefore, we investigated the association of HIV-1 infection with vaginal flora abnormalities, including bacterial vaginosis and depletion of lactobacilli, after adjustment for sexual activity and the presence of other sexually transmitted diseases (STDs). During the initial survey round of our community-based trial of STD control for HIV-1 prevention in rural Rakai District, southwestern Uganda, we selected 4718 women aged 15-59 years. They provided interview information, blood for HIV-1 and syphilis serology, urine for detection of Chlamydia trachomatis and Neisseria gonorrhoeae, and two self-administered vaginal swabs for culture of Trichomonas vaginalis and gram-stain detection of vaginal flora, classified by standardised, quantitative, morphological scoring. Scores 0-3 were normal vaginal flora (predominant lactobacilli). Higher scores suggested replacement of lactobacilli by gram-negative, anaerobic microorganisms (4-6 intermediate; 7-8 and 9-10 moderate and severe bacterial vaginosis). HIV-1 frequency was 14.2% among women with normal vaginal flora and 26.7% among those with severe bacterial vaginosis (p < 0.0001). We found an association between bacterial vaginosis and increased HIV-1 infection among younger women, but not among women older than 40 years; the association could not be explained by differences in sexual activity or concurrent infection with other STDs. The frequency of bacterial vaginosis was similar among HIV-1-infected women with symptoms (55.0%) and without symptoms (55.7%). The adjusted odds ratio of HIV-1 infection associated with any vaginal flora abnormality (scores 4-10) was 1.52 (95% CI 1.22-1.90), for moderate bacterial vaginosis (scores 7-8) it was 1.50 (1.18-1.89), and for severe bacterial vaginosis (scores 9-10) it was 2.08 (1.48-2.94). This cross-sectional study cannot show whether disturbed vaginal flora increases susceptibility to HIV-1 infection. Nevertheless, the increased frequency of HIV-1 associated with abnormal flora among younger women, for whom HIV-1 acquisition is likely to be recent, but not among older women, in whom HIV-1 is likely to have been acquired earlier, suggests that loss of lactobacilli or presence of bacterial vaginosis may increase susceptibility to HIV-1 acquisition. If this inference is correct, control of bacterial vaginosis could reduce HIV-1 transmission.


Antibiotic Use Associated with Confirmed Influenza, Pertussis, and Nontyphoidal Salmonella Infections.
Purpose: Antibiotics are not the recommended treatment for uncomplicated influenza or nontyphoidal salmonella infections, whereas they are for current pertussis infection. We investigated adherence to these recommendations in a population of older community-dwelling adults. Methods: Population-based prospective cohort study of Australian adults 45 years of age and older followed by record-linkage to laboratory-confirmed influenza, pertussis, and nontyphoidal salmonella notifications, hospitalization records, and antibiotic dispensing data from January 1, 2009 to December 31, 2015. Proportions of those with infections who were prescribed antibiotics were estimated, and characteristics associated with antibiotic prescribing were examined. Results: There were 1,056 influenza, 151 pertussis, and 334 nontyphoidal salmonella cases in the cohort eligible for analysis. Antibiotics were dispensed in 56.2% (594/1,056) of influenza, 78.8% (119/151) of pertussis, and 39.5% (132/334) of nontyphoidal salmonella cases within the ±10-day window around the infection onset date. The likelihood of antibiotic dispensing did not differ according to most participant characteristics examined, including whether cases had an associated hospitalization, their age, and recorded comorbidities. Macrolides were the predominant class of antibiotics dispensed for pertussis (79%), whereas both beta-lactams (36.3%) and macrolides (35.4%) were used for cases of influenza. There was no dominant antibiotic class dispensed among those with nontyphoidal salmonella. Conclusions: Given concerns regarding increasing antibiotic resistance, the high proportion of adults with influenza and nontyphoidal salmonella cases dispensed antibiotics indicate the need for further strengthening of antimicrobial stewardship by raising education and awareness of guidelines for managing these infections.


A Glance at the Errors of Some Studies on the Health Effects of High Background Natural Radiation Areas.
There is no place on the Earth, the planet we live on, where the natural background radiation level is zero. Since the birth and even in our fetal stage, we have been exposed to different sources of natural radiation. Life, in fact, evolved in a radiation environment that was much more harsh than today. Earth serves as a source of terrestrial radiation. Uranium, thorium, and radium are among the radioactive materials that naturally exist in soil and rock. Moreover, the air, we breathe, contains radon, a colorless, odorless, radioactive gas that is created naturally by the radioactive decay of uranium and radium. The crucial importance of the studies on the health effects of living in areas with high levels of background radiation for understanding the biological impact of exposure to low doses of ionizing radiation is well documented. Despite the undeniable need for accurate information about the health effects of exposure to high levels of background radiation, many published papers suffer from methodological and other common types of errors. In this paper, we review three articles published on high background radiation areas. The first paper has addressed the frequencies of unstable (dicentrics& rings), stable (translocations & inversions), and other types of chromosome aberration in adult men from both high background radiation areas of Kerala and areas with normal background radiation. The second paper has addressed different aspects of the world's high background natural radiation areas. Finally, the third paper has tried to address the role of background radiation on males to females' ratio at birth. The author has mainly referred to the studies performed on the impact of radiation exposures from nuclear testing (worldwide) and Chernobyl fallout (in Europe).The major shortcomings of these three papers, especially methodological errors, which affected the accuracy of their findings and conclusions are discussed.


Union of a chronically infected internally stabilized segmental defect in the rat femur after debridement and application of rhBMP-2 and systemic antibiotic.
The goal of this study was to determine whether recombinant human bone morphogenetic protein-2 (rhBMP-2) would induce new bone formation in an internally stabilized segmental defect with a chronic bacterial infection in the rat femur and whether treatment with systemic antibiotic would enhance this effect. A 6-mm unilateral femoral segmental defect was surgically created in 120 Sprague-Dawley rats, internally stabilized with a polyacetyl plate and 6 Kirschner wires, and contaminated with 10(4) colony-forming units of Staphylococcus aureus. After 2 weeks, all defects were surgically debrided and implanted with 0, 20, or 200 microg of rhBMP-2 in a type 1 bovine collagen sponge. Half of the animals in each treatment group received 4 weeks of systemic antibiotic, and half did not. Animals were euthanized at 4 or 12 weeks after debridement. Bone formation within and adjacent to the defect was assessed using microcomputed tomography, torsional failure testing and undecalcified histology. No substantial callus formed in the infected defects without rhBMP-2. Significantly more mineralized callus was induced with the higher dose of rhBMP-2 than with the lower dose (P = 0.001), with systemic antibiotic therapy than without (P < 0.001), and at 12 weeks after debridement compared with 4 weeks (P < 0.001). Recombinant human bone morphogenetic protein-2 maintained its osteoinductive capability in the presence of a chronic infection, and this property was enhanced by systemic antibiotic. This study presents an intervention that may potentially accelerate fracture healing in the presence of infection and colonized hardware, thereby permitting earlier removal of the hardware, and more timely and effective treatment of infection.


The relation of angiotonin and 1-norepinephrine to essential hypertension as determinded by the reaction of the nailfold capillary bed.
Further evidence has been obtained that L-norepinephrine infusions markedly decreases cutaneous capillary blood flow in the nailfold. Sustained ischemia of the capillary bed occurred prior to the attainment of hypertensive diastolic arterial blood pressure levels. Corroborative evidence of this nailfold capillary ischemia was obtained from the capillary reactive hyperemia that followed the abrupt discontinuance of the L-norepinephrine infusions. The infusion of angiotonin into persons with normal blood pressure did not induce sustained ischemia of the nailfold capillary vessels, even after definite hypertensive diastolic arterial blood pressure levels were attained. Corroboration of the adequacy of nailfold capillary blood flow was obtained by noting the absence of capillary reactive hyperemia following the abrupt cessation of the angiotonin infusions. The nailfold capillary bed in persons with angiotonin-induced hypertension could not be distinguished from that of persons with essential hypertension by direct microscopic examination. During the infusion of angiotonin into subjects with normal cardiovascular systems, the reactivity of the nailfold capillary bed to circulating L-norepinephrine was significantly increased, approaching the levels found in persons with essential hypertension. From the standpoint of its effects upon the nailfold capillary bed, angiotonin, unlike L-norepinephrine, is one substance which possesses the properties required of the hypothetical humoral pressor substance of essential hypertension.


Efficacy of avelumab plus axitinib versus sunitinib by numbers of IMDC risk factors and target tumor sites at baseline in advanced renal cell carcinoma: long-term follow-up results from JAVELIN Renal 101.
In the phase III JAVELIN Renal 101 trial, first-line avelumab + axitinib improved progression-free survival (PFS) and objective response rate versus sunitinib in patients with advanced renal cell carcinoma across all International Metastatic RCC Database Consortium (IMDC) risk groups (favorable, intermediate, and poor); analyses of overall survival (OS) remain immature. Here, we report post hoc analyses of efficacy from the third interim analysis (data cut-off, April 2020) by the numbers of IMDC risk factors and target tumor sites at baseline. Efficacy endpoints assessed were PFS, objective response, and best overall response per investigator assessment (RECIST v1.1) and OS. Best percentage change and percentage change from baseline in target tumor size over time during the study were also assessed. In patients with 0, 1, 2, 3, or 4-6 IMDC risk factors, hazard ratios [HRs; 95% confidence interval (CIs)] for OS with avelumab + axitinib versus sunitinib were 0.660 (0.356-1.223), 0.745 (0.524-1.059), 0.973 (0.668-1.417), 0.718 (0.414-1.248), and 0.443 (0.237-0.829), and HRs (95% CIs) for PFS were 0.706 (0.490-1.016), 0.709 (0.540-0.933), 0.711 (0.527-0.960), 0.501 (0.293-0.854), and 0.395 (0.214-0.727), respectively. In patients with 1, 2, 3, or ≥4 target tumor sites, HRs (95% CIs) for OS with avelumab + axitinib versus sunitinib were 0.912 (0.640-1.299), 0.715 (0.507-1.006), 0.679 (0.442-1.044), and 0.747 (0.346-1.615), and HRs (95% CIs) for PFS were 0.706 (0.548-0.911), 0.552 (0.422-0.723), 0.856 (0.589-1.244), and 0.662 (0.329-1.332), respectively. Across all subgroups, analyses of objective response rate and complete response rate favored avelumab + axitinib versus sunitinib, and a greater proportion of patients treated with avelumab + axitinib had tumor shrinkage. In post hoc analyses, first-line treatment with avelumab + axitinib was generally associated with efficacy benefits versus treatment with sunitinib in patients with advanced renal cell carcinoma across subgroups defined by different numbers of IMDC risk factors or target tumor sites.


Role of GacA in virulence of Vibrio vulnificus.
The GacS/GacA two-component signal transduction system regulates virulence, biofilm formation and symbiosis in Vibrio species. The present study investigated this regulatory pathway in Vibrio vulnificus, a human pathogen that causes life-threatening disease associated with the consumption of raw oysters and wound infections. Small non-coding RNAs (csrB1, csrB2, csrB3 and csrC) commonly regulated by the GacS/GacA pathway were decreased (P<0.0003) in a V. vulnificus CMCP6 ΔgacA : : aph mutant compared with the wild-type parent, and expression was restored by complementation of the gacA deletion mutation in trans. Of the 20 genes examined by RT-PCR, significant reductions in the transcript levels of the mutant in comparison with the wild-type strain were observed only for genes related to motility (flaA), stationary phase (rpoS) and protease (vvpE) (P=0.04, 0.01 and 0.002, respectively). Swimming motility, flagellation and opaque colony morphology indicative of capsular polysaccharide (CPS) were unchanged in the mutant, while cytotoxicity, protease activity, CPS phase variation and the ability to acquire iron were decreased compared with the wild-type (P<0.01). The role of gacA in virulence of V. vulnificus was also demonstrated by significant impairment in the ability of the mutant strain to cause either skin (P<0.0005) or systemic infections (P<0.02) in subcutaneously inoculated, non-iron-treated mice. However, the virulence of the mutant was equivalent to that of the wild-type in iron-treated mice, demonstrating that the GacA pathway in V. vulnificus regulates the virulence of this organism in an iron-dependent manner.


Endodontic Retreatment of a Mandibular Second Molar with four Separate Roots: A Case Report.
Aberrations in the root canal anatomy are a commonly occurring phenomenon. Although the mandibular second molar is commonly a bi-rooted tooth with an uncomplicated endodontic anatomy, variations have to be considered every time endodontic therapy is performed. This case report describes the non-surgical endodontic retreatment performed on a mandibular second molar with four seperate roots and canals. ProTaper Universal rotary nickel-titanium instruments (Dentsply Maillefer, Ballaigues, Switzerland) for treatment and retreatment were used to remove the old gutta percha and to clean and shape all root canals, followed by the complete obturation of root canal system. Post-operative CBCT scan was taken to confirm the quality of the performed treatment.


Structure and Function in the Lunge Feeding Apparatus: Mechanical Properties of the Fin Whale Mandible.
The mandibles of rorqual whales are highly modified to support loads associated with lunge-feeding, a dynamic filter feeding mechanism that is characterized by rapid changes in gape angle and acceleration. Although these structures are the largest ossified elements in animals and an important part of the rorqual engulfment apparatus, details of internal structure are limited and no direct measurements of mechanical properties exist. Likewise, the forces that are sustained by the mandibles are unknown. Here we report on the structure and mechanical behavior of the mandible of an adult fin whale. A series of transverse sections were cut at locations along the entire length of a 3.6-m left mandible recovered post-mortem from a 16-m fin whale, and CT scanned to make density maps. Cored samples 6-8 mm in diameter were tested in compression to determine the Young's modulus and strength. In addition, wet density, dry density and mineral density were measured. Dense cortical bone occupies only a relatively narrow peripheral layer while much less dense and oil-filled trabecular bone occupies the rest. Mineral density of both types is strongly correlated with dry density and CT Hounsfield units. Compressive strength is strongly correlated with Young's modulus, while strength and stiffness are both correlated with mineral density. It appears that the superficial compact layer is the main load bearing element, and that the mandible is reinforced against dorso-vental flexion that would occur during the peak loads while feeding. Anat Rec, 300:1953-1962, 2017. © 2017 Wiley Periodicals, Inc.


A phase I study in paediatric patients to evaluate the safety and pharmacokinetics of SPI-77, a liposome encapsulated formulation of cisplatin.
Pre-clinical studies indicate that cisplatin encapsulated in STEALTH((R))liposomes (SPI-77) retains anti-tumour activity, but has a much reduced toxicity, compared to native cisplatin. A phase I study was conducted to determine the toxicity and pharmacokinetics of SPI-77 administered to children with advanced cancer not amenable to other treatment. Paediatric patients were treated at doses ranging from 40 to 320 mg m(-2)by intravenous infusion every 4 weeks. Blood samples taken during, and up to 3 weeks after, administration and plasma and ultrafiltrate were prepared immediately. Urine was collected, when possible, for 3 days after administration. SPI-77 administration was well tolerated with the major toxicity being an infusion reaction which responded to modification of the initial infusion rate of SPI-77. Limited haematological toxicity and no nephrotoxicity were observed. No responses to treatment were seen during the course of this phase I study. Measurement of total plasma platinum showed that cisplatin was retained in the circulation with a half life of up to 134 h, with maximum plasma concentrations approximately 100-fold higher than those reported following comparable doses of cisplatin. Comparison of plasma and whole blood indicated that cisplatin was retained in the liposomes and there was no free platinum measurable in the ultrafiltrate. Urine recovery was less than 4% of the dose administered over 72 h. Results from this phase I study indicate that high doses of liposomal cisplatin can safely be given to patients, but further studies are required to address the issue of reformulation of liposomally bound cisplatin.


Pilot Study: Neurocognitive Disorders and Colonoscopy in Older Adults.
In a preoperative anesthesia setting with integrated neuropsychology for individuals >64 years of age, we completed a pilot study examining the association between neurocognitive disorders with frequency of missed colonoscopies and quality of bowel preparation (prep). Gastroenterologists completed the Boston Bowel Preparation Scale (BBPS) for each patient. Of 47 older adults seen in our service, 68% met criteria for neurocognitive disorders. All individuals failing to attend the colonoscopy procedure had met criteria for major neurocognitive disorder. Poor bowel prep was also identified in 100% of individuals with major neurocognitive disorder and 28% of individuals with mild neurocognitive disorder. Our pilot data suggest that, in high-risk individuals, the presence of neurocognitive disorders is risk factors for missed appointments and inadequate bowel prep. These pilot data provide reference statistics for future intervention protocols.


Influence of third molars in Le Fort 1 osteotomy.
The influence of maxillary third molar (M3) on the outcomes of Le Fort 1 osteotomy is not deeply investigated. To investigate the influence of M3 on Le Fort 1 osteotomies. Tertiary Referral Center, operated by a single surgeon, prospective study. January 2005 to December 2010. Consecutive Le Fort 1 osteotomy patients with both M3. Gender, position, M3 root morphology, and degree of impaction. Time taken after all osteotomy cuts to point of time when maxilla is placed in predetermined plane. A total of 658 M3 in line of cut were studied. Of all M3, 312 were impacted, 28.9% were partially impacted and 23.7% were erupted. Of all the M3, 2.9% had their cuspal tips above the horizontal cut, 13.8% along the line of cut, and in 20.7% below the line but not erupted. Buccoverted tooth took shortest time (7.74 minutes), while palatoversion required more time (8.44 minutes) (P = 0.000). When the cuspal tip of M3 was located above the horizontal line of cut, the mean time required to achieve the planned position was 7 minutes, while the completely erupted teeth took a mean of 8.24 minutes (P = 0.000). When the M3 is placed higher, it takes lesser time to prepare basal bone to receive the maxilla at its predetermined level. Angulation of M3 influences the outcome. Deeply placed M3 reduces the manipulation of the greater pterygoid palatine vessels in the area thereby minimizing the bleeding in the surgical field.


Optimal Thyroid Hormone Replacement.
Hypothyroidism is a common endocrinopathy, and levothyroxine is frequently prescribed. Despite the basic tenets of initiating and adjusting levothyroxine being agreed on, there are many nuances and complexities to consistently maintaining euthyroidism. Understanding the impact of patient weight and residual thyroid function on initial levothyroxine dosage and consideration of age, comorbidities, thyrotropin goal, life stage, and quality of life as levothyroxine is adjusted can be challenging and continually evolving. Because levothyroxine is a lifelong medication, it is important to avoid risks from periods of overtreatment or undertreatment. For the subset of patients not restored to baseline health with levothyroxine, causes arising from all aspects of the patient's life (coexistent medical conditions, stressors, lifestyle, psychosocial factors) should be broadly considered. If such factors do not appear to be contributing, and biochemical euthyroidism has been successfully maintained, there may be benefit to a trial of combination therapy with levothyroxine and liothyronine. This is not supported by the majority of randomized clinical trials, but may be supported by other studies providing lower-quality evidence and by animal studies. Given this discrepancy, it is important that any trial of combination therapy be continued only as long as a patient benefit is being enjoyed. Monitoring for adverse effects, particularly in older or frail individuals, is necessary and combination therapy should not be used during pregnancy. A sustained-release liothyronine preparation has completed phase 1 testing and may soon be available for better designed and powered studies assessing whether combination therapy provides superior therapy for hypothyroidism.


Competition by allelopathy proceeds in traveling waves: colicin-immune strain aids colicin-sensitive strain.
Producing toxic chemicals to suppress both the growth and survivorship of local competitors is called allelopathy; some strains of the bacteria Escherichia coli produce a toxin (named colicin) which may kill colicin-sensitive neighbors while they themselves are immune. In a previous paper, the competitive outcome between colicin-producing and colicin-sensitive strains was shown to differ between a spatially structured and a completely mixed population. In this paper, we analyze the role of a third, "colicin-immune," strain, which does not produce colicin but is immune to it. Without spatial structure, the colicin-immune strain suppresses the colicin-producing strain and enables the colicin-sensitive strain to win. In a spatially structured population, modeled as a reaction-diffusion system, we examine the speed of boundaries between areas dominated by different strains in traveling waves and the events after the collision of two such boundaries. The colicin-immune strain passes through the area dominated by the colicin-sensitive strain and drives the colicin-producing strain to extinction. Subsequently the colicin-sensitive strain occupies the whole population.


The Relationship between Life Stress and Breastfeeding Outcomes among Low-Income Mothers.
Stressful life events during pregnancy negatively affect maternal and infant outcomes including breastfeeding initiation. Their impact on breastfeeding duration is uncertain. Given breastfeeding's important health benefits we analyzed stressful life event types and cessation of any and exclusive breastfeeding by 4 and 13 weeks. Methods. We collected self-administered survey data at 5-7 months postpartum from over 700 primarily urban low-income US mothers. Data covered prepregnancy, prenatal, and postpartum periods including 14 stressful life events (categorized into financial, emotional, partner-associated, traumatic). Analyses included only mothers initiating breastfeeding (n = 341). Logistic regressions controlled for maternal characteristics including a breastfeeding plan. Results. All four stress categories were associated with shorter duration of any and exclusive breastfeeding. In the adjusted models, statistically significant relationships remained for financial stress (4 weeks cessation of any breastfeeding duration) and traumatic stress (13 weeks exclusive breastfeeding cessation). Controlling for stress, a longer breastfeeding plan was significantly associated with a shorter breastfeeding duration (all models) as was depression during pregnancy and current smoking (several models). Conclusions. Among low-income women, impact of stressful life events on cessation of breastfeeding may differ by stress type and interfere with achievement of breastfeeding goal. Among these stressed mothers, breastfeeding may serve as a coping mechanism.


Novel FDG-PET findings in anti-NMDA receptor encephalitis: a case based report.
The clinical manifestation and nuclear imaging findings in a 15-year-old boy with anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis are described in this case report. The previously healthy patient presented with new onset hallucinations, seizure, and within a week, his mental status rapidly deteriorated to nonverbal with oro-lingual-facial dyskinesias. An extensive laboratory work-up for encephalopathy was negative. Repeated brain magnetic resonance imaging (MRI) studies were normal. On day 26 of admission, nuclear imaging using fluorodeoxyglucose positron emission tomography (FDG-PET) showed global hypometobolism with a prominent focally intense hypermetabolic lesion in the right cerebellar cortex. Diagnosis of anti-NMDAR encephalitis was confirmed with quantitative serology. The patient showed clinical signs of improvement after 2 courses of intravenous immunoglobulin therapy over 4 weeks. On day 46, repeat brain FDG-PET showed overall improvement but in contrast to the previous, the right cerebellar cortex showed focal hypometabolism. This is the first reported case of such findings using FDG-PET in anti-NMDAR encephalitis.


Life expectancy among HIV-positive patients in Rwanda: a retrospective observational cohort study.
Rwanda has achieved substantial progress in scaling up of antiretroviral therapy. We aimed to assess the effect of increased access to antiretroviral therapy on life expectancy among HIV-positive patients in two distinct periods of lower and higher antiretroviral therapy coverage (1997-2007 and 2008-11). In a retrospective observational cohort study, we collected clinical and demographic data for all HIV-positive patients enrolled in care at 110 health facilities across all five provinces of Rwanda. We included patients aged 15 years or older with a known enrolment date between 1997 and 2014. We constructed abridged life tables from age-specific mortality rates and life expectancy stratified by sex, CD4 cell count, and WHO disease stage at enrolment in care and initiation of antiretroviral therapy. We included 72,061 patients in this study, contributing 213,983 person-years of follow-up. The crude mortality rate was 33·4 deaths per 1000 person-years (95% CI 32·7-34·2). Life expectancy for the overall cohort was 25·6 additional years (95% CI 25·1-26·1) at 20 years of age and 23·3 additional years (95% CI 22·9-23·7) at 35 years of age. Life expectancy at 20 years of age in the period of 1997-2007 was 20·4 additional years (95% CI 19·5-21·3); for the period of 2008-11, life expectancy had increased to 25·6 additional years (95% CI 24·8-26·4). Individuals enrolling in care with CD4 cell counts of 500 cells per μL or more, and with WHO disease stage I, had the highest life expectancies. This study adds to the growing body of evidence showing the benefit to HIV-positive patients of early enrolment in care and initiation of antiretroviral therapy. Bill & Melinda Gates Foundation.


Transcriptional regulation of tropoelastin expression in rat lung fibroblasts: changes with age and hyperoxia.
Elastic fibers are thought to provide structural support for secondary septa as the lung undergoes the transition from the saccular to the alveolar stage. The synthesis of the soluble precursor of elastin, tropoelastin, occurs during a finite developmental period. We have investigated the developmental regulation of tropoelastin gene transcription and mRNA expression in fetal and postnatal rat lung fibroblasts and have assessed the changes in tropoelastin gene expression caused by hyperoxic exposure during secondary septal development. With the use of an RT-PCR assay and intron-specific primers to detect heterogeneous nuclear RNA (hnRNA) and intron-spanning primers to detect mRNA in freshly isolated rat lung fibroblasts, tropoelastin gene expression was found to be upregulated late in gestation. From days 18 to 21 of gestation, there was a 4.5-fold increase in tropoelastin hnRNA (P < 0.0001) and a 6-fold increase in mRNA (P = 0.002). After birth, tropoelastin expression was downregulated. Signals decreased from fetal day 21 to postnatal day 2 for both tropoelastin hnRNA (P = 0. 021) and mRNA (P = 0.043). Tropoelastin hnRNA decreased further from days 2 to 6 (P = 0.04). Both tropoelastin hnRNA and mRNA were again upregulated during alveolarization from days 9 to 11, indicating that, once upregulated, transcription of the tropoelastin gene is not constant but varies with fetal and postnatal age. Exposure to >95% oxygen, when initiated on postnatal day 2 or 3 and continued until day 11, significantly diminished the developmental increase in tropoelastin hnRNA (P < 0.005) and mRNA (P < 0.05) normally seen on days 9-11, indicating that the postnatal upregulation of tropoelastin gene expression is inhibited by hyperoxic exposure in the early postnatal period.


Morphological Reconstruction Improves Microvessel Mapping in Super-Resolution Ultrasound.
Generation of super-resolution (SR) ultrasound (US) images, created from the successive localization of individual microbubbles in the circulation, has enabled the visualization of microvascular structure and flow at a level of detail that was not possible previously. Despite rapid progress, tradeoffs between spatial and temporal resolution may challenge the translation of this promising technology to the clinic. To temper these tradeoffs, we propose a method based on morphological image reconstruction. This method can extract from ultrafast contrast-enhanced US (CEUS) images hundreds of microbubble peaks per image (312-by-180 pixels) with intensity values varying by an order of magnitude. Specifically, it offers a fourfold increase in the number of peaks detected per frame, requires on the order of 100 ms for processing, and is robust to additive electronic noise (down to 3.6-dB CNR in CEUS images). By integrating this method to an SR framework, we demonstrate a sixfold improvement in spatial resolution, when compared with CEUS, in imaging chicken embryo microvessels. This method that is computationally efficient and, thus, scalable to large data sets may augment the abilities of SR-US in imaging microvascular structure and function.


Characterization of the Stat5 protease.
Immature myeloid cells have been shown to transduce signals through a carboxyl-terminally truncated isoform of Stat5. This functionally distinct signal transducer and activator of transcription isoform is generated through a unique protein-processing event. Evaluation of numerous cell lines has determined that there is a direct correlation between the expression of truncated Stat5 and protease activity. Moreover, protease activity is found only in the myeloid and not in lymphoid progenitors. To further characterize the protease small quantities have been purified to near homogeneity. Studies on this purified material indicate that the protease has an apparent molecular mass of approximately 25 kDa and is active over a wide range of pH values. The protease will also cleave both activated (i.e. tyrosine-phosphorylated) and inactivate Stat5. Although this activity is sensitive to phenylmethylsulfonyl fluoride, it is notably not sensitive to several other serine protease inhibitors. Additional studies have led to the identification of the unique site where the protease cleaves Stat5. Mutagenesis of this site renders Stat5 resistant to cleavage. Consistent with the model that Stat5 cleavage is important for early myeloid development, introduction of a "non-cleavable" isoform of Stat5 into FDC-P1 cells (a myeloid progenitor line) leads to significant phenotypic changes.


Outcome of thyroid function in Graves' patients treated with radioiodine: role of thyroid-stimulating and thyrotropin-blocking antibodies and of radioiodine-induced thyroid damage.
We investigated the interrelationship and the influence of thyroid-stimulating antibodies (TSAb), TSH-blocking antibodies (TSHBAb), and of radioiodine (131I)-induced thyroid damage in the early (within 1 yr) outcome of thyroid function in hyperthyroid patients with Graves' disease (GD) treated with 131I. TSAb, TSHBAb, and ultrasound thyroid volume (as an index of thyroid damage) were simultaneously measured before and at 1, 3, 6, and 12 months after 131I in 31 GD patients. One year after radioiodine, 9.7% of patients were hyperthyroid (Hyper-group), requiring methimazole; 12.9% were euthyroid (Eu-group); and 77.4% were hypothyroid (Hypo-group). Pretreatment thyroid volume in the Eu-group and Hyper-group was significantly greater (P = 0.009) than in the Hypo-group. Pre-131I TSAb levels were higher in the Hyper-group vs. the Hypo-group (P = 0.01) or the Eu-group (P = 0.03). A significant post-131I increase in TSAb levels occurred in 66% of patients developing hypothyroidism but not in those remaining hyperthyroid. After 131I, TSHBAb appeared in 7 patients, in all but one associated with high levels of TSAb. One year after radioiodine: 1) the mean percent reduction in thyroid volume was greater in the Hypo-group (80.7%) or the Eu-group (83.5%) than in the Hyper-group (35.7%) (P = 0.007 and 0.0033 respectively); 2) hypothyroid patients had smaller (P = 0.0058) post-131I thyroids than hyperthyroid patients; and 3) TSAb were still elevated in 75% hypothyroid patients, but all of them had a thyroid volume < or = 8 mL, indicating major postradioiodine gland damage. 1) the early outcome of thyroid function after 131I for GD is mainly related to pretreatment thyroid volume and to the degree of its reduction after therapy; 2) high TSAb levels before 131I are associated with a relative resistance to therapy; 3) a postradioiodine increase in TSAb levels is related to the development of hypothyroidism; and 4) the concomitant appearance of TSHBAb and disappearance of TSAb are not frequent after 131I and play a role in the development of early postradioiodine hypothyroidism only in a minority of patients.


The effect of recipient-specific surgical issues on outcome of liver transplantation in biliary atresia.
Biliary atresia (BA), the most common reason for orthotopic liver transplantation (OLT) in children, is often accompanied by unique and challenging anatomical variations. This study examines the effect of surgical-specific issues related to the presence of complex vascular anatomic variants on the outcome of OLT for BA. The study group comprised 944 patients who were enrolled in the Studies of Pediatric Liver Transplantation (SPLIT) registry and underwent OLT for BA over an 11-year period. 63 (6.7%) patients met the study definition of complex vascular anomalies (CVA). Patient survival, but not graft survival, was significantly lower in the CVA group, (83 vs. 93 % at 1-year post-OLT). The CVA group had a significantly higher incidence of all reoperations, total biliary tract complications, biliary leaks and bowel perforation. The most frequent cause of death was infection, and death from bacterial infection was more common in the CVA group. Pretransplant portal vein thrombosis and a preduodenal portal vein were significant predictors of patient survival but not graft survival. This study demonstrates that surgical and technical factors have an effect on the outcome of BA patients undergoing OLT. However, OLT in these complex patients is technically achievable with an acceptable patient and graft survival.


Does Online Search Behavior Coincide with Candida auris Cases? An Exploratory Study.
Candida auris is an emerging multidrug resistant infectious yeast which is challenging to eradicate and despite available laboratory methods is still difficult to identify especially in less developed countries. To limit the rapid spread of C. auris, quick and accurate detection is essential. From the perspective of disease surveillance, additional methods of tracking this yeast are needed. In order to increase global preparedness, we explored the use of online search behavior to monitor the recent global spread of C. auris. We used Google Trends to assess online search behavior on C. auris from January 2016 until August 2018. Weekly Google Trends results were counted as hits and compared to confirmed C. auris cases obtained via publications and a global expert network of key opinion leaders. A total of 44 countries generated a hit, of which 30% (13/44) were confirmed known cases, 34% (15/44) were missed known cases, 34% (15/44) were hits for unknown cases, and 2% (1/44) were confirmed unknown cases. Conclusions: Google Trends searches is rapidly able to provide information on countries with an increased search interest in C. auris. However, Google Trends search results do not generally coincide with C. auris cases or clusters. This study did show that using Google Trends provides both insight into the known and highlights the unknown, providing potential for surveillance and tracking and hence aid in taking timely precautionary measures.


Automatic indicator dilution curve extraction in dynamic-contrast enhanced imaging using spectral clustering.
Indicator dilution theory provides a framework for the measurement of several cardiovascular parameters. Recently, dynamic imaging and contrast agents have been proposed to apply the method in a minimally invasive way. However, the use of contrast-enhanced sequences requires the definition of regions of interest (ROIs) in the dynamic image series; a time-consuming and operator dependent task, commonly performed manually. In this work, we propose a method for the automatic extraction of indicator dilution curves, exploiting the time domain correlation between pixels belonging to the same region. Individual time intensity curves were projected into a low dimensional subspace using principal component analysis; subsequently, clustering was performed to identify the different ROIs. The method was assessed on clinically available DCE-MRI and DCE-US recordings, comparing the derived IDCs with those obtained manually. The robustness to noise of the proposed approach was shown on simulated data. The tracer kinetic parameters derived on real images were in agreement with those obtained from manual annotation. The presented method is a clinically useful preprocessing step prior to further ROI-based cardiac quantifications.


The CLK family kinases, CLK1 and CLK2, phosphorylate and activate the tyrosine phosphatase, PTP-1B.
The protein-tyrosine phosphatase PTP-1B is an important regulator of intracellular protein tyrosine phosphorylation, and is itself regulated by phosphorylation. We report that PTP-1B and its yeast analog, YPTP, are phosphorylated and activated by members of the CLK family of dual specificity kinases. CLK1 and CLK2 phosphorylation of PTP-1B in vitro activated the phosphatase activity approximately 3-5-fold using either p-nitrophenol phosphate, or tyrosine-phosphorylated myelin basic protein as substrates. Co-expression of CLK1 or CLK2 with PTP-1B in HEK 293 cells led to a 2-fold stimulation of phosphatase activity in vivo. Phosphorylation of PTP-1B at Ser(50) by CLK1 or CLK2 is responsible for its enzymatic activation. These findings suggest that phosphorylation at Ser(50) by serine threonine kinases may regulate the activation of PTP-1B in vivo. We also show that CLK1 and CLK2 phosphorylate and activate the S. cerevisiae PTP-1B family member, YPTP1. CLK1 phosphorylation of YPTP1 led to a 3-fold stimulation of phosphatase activity in vitro. We demonstrate that CLK phosphorylation of Ser(83) on YPTP1 is responsible for the activation of this enzyme. These findings demonstrate that the CLK kinases activate PTP-1B family members, and this phosphatase may be an important cellular target for CLK action.


An update on the systemic therapy of malignant salivary gland cancers: role of chemotherapy and molecular targeted agents.
Salivary gland cancers are a rare malignancy accounting for less than 1% of all cancers and 3-6% of cancers of the head and neck region. The classification of salivary gland tumors is traditionally based on morphology and the different subtypes exhibit various clinical behaviors. The low grade and biologically indolent cell types include the adenoid cystic, acinic cell and adenocarcinoma while the salivary duct, squamous and mucoepidermoid are more active and high grade. The initial management of salivary gland malignancies is to assess resectability and possible adjuvant radiation therapy. Those with locoregional recurrence or metastatic disease are treated with systemic therapy. Numerous studies with small sample sizes have assessed the activity of different cytotoxic agents. Both single agent and combination chemotherapy have been used for the treatment of this disease. For these agents, the response rates are generally modest with objective response rates ranging from 15-50%. Duration of response is typically cited in the range of 6-9 months. Clinicopathological data have demonstrated correlations between poor clinical outcomes and the expression of molecular markers such as mutated p53 protein and vascular endothelial growth factor (VEGF) in salivary gland cancers. Recent studies have also evaluated the epidermal growth factor receptor family including erbB1/EGFR and erbB2/HER2 as potential therapeutic targets. While the prognostic significance of EGFR overexpression has not been well defined, overexpression of the HER2 oncoprotein has been associated with biological aggressiveness and poor prognosis in most series. Given the suboptimal response rates, duration of response, and toxicity of conventional chemotherapy, a better understanding of the biology of salivary gland malignancies will lead to improved prognostication and treatment. With the emergence of molecular targeted therapy, these tumors become an optimal candidate for trials of investigational drugs and established drugs for new indications.


Characterization of Vibrio viscosus and Vibrio wodanis isolated at different geographical locations: a proposal for reclassification of Vibrio viscosus as Moritella viscosa comb. nov.
Vibrio viscosus and Vibrio wodanis are recently described species of psychrotropic bacteria that have been found associated with a disease called 'winter ulcer', affecting salmonid fish reared in saline water in Norway, Iceland and recently in Scotland. V. viscosus and V. wodanis strains initially isolated from fish in Iceland and Norway were subjected to characterization using biochemical tests, SDS-PAGE of whole-cell proteins and a novel DNA fingerprinting method, amplified fragment length polymorphism (AFLP). The V. viscosus strains isolated from diseased fish grouped into homogeneous subgroups according to geographical origin and challenge experiments revealed that representatives of these groups are virulent. The results revealed that the V. wodanis strains are heterogeneous genotypically and phenotypically. Sequencing of almost complete 16S rRNA genes of V. viscosus and V. wodanis revealed that V. viscosus showed a 99.1% sequence similarity to Moritella marina and V. wodanis showed a 98.8% sequence similarity to Vibrio logei CIP 103204. A reclassification of Vibrio viscosus as Moritella viscosa comb. nov. is proposed.


MAD Bayes for Tumor Heterogeneity - Feature Allocation with Exponential Family Sampling.
We propose small-variance asymptotic approximations for inference on tumor heterogeneity (TH) using next-generation sequencing data. Understanding TH is an important and open research problem in biology. The lack of appropriate statistical inference is a critical gap in existing methods that the proposed approach aims to fill. We build on a hierarchical model with an exponential family likelihood and a feature allocation prior. The proposed implementation of posterior inference generalizes similar small-variance approximations proposed by Kulis and Jordan (2012) and Broderick et.al (2012b) for inference with Dirichlet process mixture and Indian buffet process prior models under normal sampling. We show that the new algorithm can successfully recover latent structures of different haplotypes and subclones and is magnitudes faster than available Markov chain Monte Carlo samplers. The latter are practically infeasible for high-dimensional genomics data. The proposed approach is scalable, easy to implement and benefits from the exibility of Bayesian nonparametric models. More importantly, it provides a useful tool for applied scientists to estimate cell subtypes in tumor samples. R code is available on http://www.ma.utexas.edu/users/yxu/.


Optimal design of porous structures for the fastest liquid absorption.
Porous materials engineered for rapid liquid absorption are useful in many applications, including oil recovery, spacecraft life-support systems, moisture management fabrics, medical wound dressings, and microfluidic devices. Dynamic absorption in capillary tubes and porous media is driven by the capillary pressure, which is inversely proportional to the pore size. On the other hand, the permeability of porous materials scales with the square of the pore size. The dynamic competition between these two superimposed mechanisms for liquid absorption through a heterogeneous porous structure may lead to an overall minimum absorption time. In this work, we explore liquid absorption in two different heterogeneous porous structures [three-dimensional (3D) circular tubes and porous layers], which are composed of two sections with variations in radius/porosity and height. The absorption time to fill the voids of porous constructs is expressed as a function of radius/porosity and height of local sections, and the absorption process does not follow the classic Washburn's law. Under given height and void volume, these two-section structures with a negative gradient of radius/porosity against the absorption direction are shown to have faster absorption rates than control samples with uniform radius/porosity. In particular, optimal structural parameters, including radius/porosity and height, are found that account for the minimum absorption time. The liquid absorption in the optimized porous structure is up to 38% faster than in a control sample. The results obtained can be used a priori for the design of porous structures with excellent liquid management property in various fields.


Adiponectin and negative mood in healthy premenopausal and postmenopausal women.
Negative mood and stress are associated with cardiovascular and metabolic disease. There are likely many physiological mechanisms underlying the poor health outcomes. The relationship of psychological states (negative mood, life stress, and stress-responsive hormones) and adiponectin, an adipokine that promotes insulin sensitivity, was investigated in two separate studies. The two groups of participants included 52 healthy, premenopausal women, and 63 postmenopausal women with a range of stress levels. The relationship between adiponectin and psychological state (perceived stress and negative mood) was examined cross-sectionally in both groups of participants, but also prospectively (1 year later) in the group of postmenopausal women. In premenopausal women, negative mood and nocturnal urinary epinephrine were significantly related to adiponectin, independent of BMI. In postmenopausal women, negative mood was not associated with adiponectin cross-sectionally, but negative mood was a significant predictor for lower levels of adiponectin 1 year later, independent of initial adiponectin concentrations and changes in body mass index. Lastly, having a depressive disorder was related to lower adiponectin. As adiponectin levels are associated with insulin resistance, obesity, and diabetes mellitus, these findings suggest there may be an adiponectin-mediated pathway explaining in part how negative mood affects metabolic health. Mechanistic studies are needed to explore this potential relationship further.


Aphanomyces invadans and ulcerative mycosis in estuarine and freshwater fish in Florida.
In the spring of 1998, the Florida Fish and Wildlife Research Institute received numerous reports of lesioned or ulcerated fish primarily from the St. Lucie Estuary on the southeast coast of Florida, an area known since the late 1970s for lesions of the ulcerative mycosis (UM) type. From these and archived reports, as well as others received from different areas of Florida, we documented that diseased specimens had randomly distributed skin ulcers (usually reddened or hemorrhagic) with raised irregular margins and, in some cases, deeply penetrating hyphae in the surrounding muscle tissue. Since 1998, 256 fish (comprising 18 species) with ulcerative lesions (from 15 different locations) were confirmed with hyphae in fresh squash preparation or by histological evaluation. Squash preparations revealed nonseptate, sparsely branching, thick-walled hyphae; histological sections revealed mycotic granulomas in the dermis that occasionally penetrated into the skeletal muscle. These pathological characteristics were consistent with UM caused by the oomycete Aphanomyces invadans in Southeast Asia, Japan, Australia, and the United States. For specific identification, six isolates from ulcerated fish were cultured and prepared for molecular characterization using established diagnostic methods. Ribosomal RNA gene sequence analysis identified three isolates as Aphanomyces invadans, one as the oomycete Achlya bisexualis, and two as the ascomycete Phialemonium dimorphosporum. A more extensive survey of 67 ulcerated skin samples from fish collected between 1998 and 2003 was performed using a polymerase chain reaction assay specific for Aphanomyces invadans. Of these, 26 (38.8%) samples from seven fish species and nine collection locations were positive. Confirmation of UM associated with Aphanomyces invadans represents new host records in Florida for the sheepshead Archosargus probatocephalus, striped mullet Mugil cephalus, white mullet Mugil curema, silver perch Bairdiella chrysoura, black drum Pogonias cromis, largemouth bass Micropterus salmoides, and American shad Alosa sapidissima.


Research advances in myocardial injury caused by COVID-19.
Coronavirus disease 2019 (COVID-19) caused a large-scale infection in China at the end of 2019. The virus, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has the characteristics of strong transmission capacity, diverse clinical manifestations, long incubation period, strong infection in incubation period, etc. With the increase of the number of cases and the continuous improvement of clinical data, we found that patients with COVID-19 have myocardial injury besides typical respiratory system manifestations. According to published data, we summarized the clinical manifestations of myocardial injury in COVID-19 patients, and discussed the probable injury mechanism, treatment methods and future research directions.


Are sluggish cognitive tempo symptoms associated with executive functioning in preschoolers?
The aim of this study is to investigate whether sluggish cognitive tempo (SCT) symptoms are associated with neurocognitive task performance and ratings of real-world executive functioning (EF) in preschoolers at risk for attention-deficit/hyperactivity disorder (ADHD). The associations between parent- and teacher-rated SCT symptoms and neuropsychological task performance and ratings of EF in 61 4-year-old preschool children (51 boys, 10 girls) with self-regulation difficulties were examined, with regression analyses controlling for the effects of ADHD inattention symptoms. In the study sample, higher teacher-rated SCT symptoms are significantly associated with poorer performance on tasks of visual-perceptual abilities, auditory and visual attention, sustained and selective attention, inhibitory control, pre-numerical/numerical concepts, and slower processing speed, but SCT symptoms are not significantly associated with working memory, attention shifting or cognitive flexibility when controlling for ADHD inattention. Higher parent-rated SCT symptoms are significantly associated with visual-perceptual abilities. ADHD inattention symptoms are more strongly associated than SCT with daily life EF ratings; neither parent- nor teacher-rated SCT symptoms are significantly associated with daily life ratings of inhibition, working memory, or planning/organization after controlling for ADHD inattention. This study suggests that SCT symptoms contribute to EF deficits at least on neurocognitive tasks assessing visual-perceptual/spatial abilities, attention to detail and processing speed, as observed in this sample of young children at risk for ADHD, and may be an important intervention target.


Bromocryptine in levodopa response-losing parkinsonism. A double blind study.
23 patients with advanced Parkinson's disease were allocated in a double-blind study of bromocryptine. These patients had an insufficient or deteriorating response to levodopa treatment. The dosages of levodopa were optimal and stabilized 3 months prior to and during this 5-month study. The addition of bromocryptine in high doses (average daily dose 71 mg) induced a significant improvement in the total score of the Webster and the NUDS scales. The global assessment, both by the investigator and by the patients, also showed significant improvement. The efficacy of bromocryptine in these type of parkinsonian patients in a double-blind trial has not yet been established. The conclusion of this trial is that bromocryptine significantly increases the therapeutic effectiveness in these poorly levodopa responding parkinsonian patients.


Real-world evidence from users of a behavioral digital therapeutic for chronic insomnia.
There have been many research trials of various digital therapeutics, but few real world evaluations of their efficacy. This type of data, however, can provide a more rounded understanding of their impact, utility, reach, and adoption. Findings presented here focus on outcome and patient engagement data of SHUTi (Sleep Health Using the Internet), a digital therapeutic delivering Cognitive Behavioral Therapy for insomnia (CBT-I), in a large real-world dataset of adults with insomnia. 7216 adults who purchased access to SHUTi between December 2015 and February 2019 are included in the analysis. The Insomnia Severity Index (ISI) was administered at the beginning of each of six treatment Cores of the intervention. Users entered sleep diaries between Cores to track changes in sleep over time and obtain tailored sleep recommendations. Number of Cores completed and sleep diaries entered indicate program usage. Users showed a reduction in mean ISI scores and a corresponding increase in effect size at the start of each subsequent Core (compared to Core 1) (range: d = 0.3-1.9). Effect sizes at the last Core relative to the first were moderate-to-large for diary-derived sleep onset latency and wake after sleep onset. A reduction in number of medicated nights was also found, with those with severe insomnia showing the largest reduction from last-to-first week of treatment (d = 0.3). At the last Core, 61% met criteria for meaningful treatment response (reduction of >7 points on ISI) and 40% met criteria for remission (ISI<8). Engagement was comparable to SHUTi research trials. Consistent with controlled trials, real-world data suggest that digital therapeutics can result in relatively high levels of engagement and clinically meaningful sleep improvements.


Dietary hepatic cholesterol elevation: effects on coxsackievirus B infection and inflammation.
Mice made hypercholesterolemic (HC) by diet are highly susceptible to coxsackievirus (CV) B5, whereas normal adult animals remain resistant. In attempting to define those dietary-induced physiological changes which contribute to altered resistance, a strong association between accumulation of intrahepatic cholesterol and increased CV B5-induced mortality was demonstrated, with maximum susceptibility to CV coinciding with a 2.5-fold increase in the ratio of hepatic cholesterol to protein. This metabolic imbalance was associated with a lower clearance rate of CV from the blood and liver of C57BL/6 mice, although virus-specific neutralizing antibody production was unaltered. In addition to CV, HC mice were more susceptible to an intravenous inoculation of Listeria monocytogenes in comparison to controls. The macrophage stimulant Corynebacterium parvum failed to increase resistance of HC mice to a high dose of CV B4 and L. monocytogenes and failed to induce the hepatomegaly, splenomegaly, and cellular infiltrate seen in the liver and spleen of normal animals. Furthermore, the peritoneal monocytic infiltrate induced by thioglycolate in normal animals was absent in HC mice. Results from these experiments suggest that decreased resistance to CV in the HC host is attributed to a defect in the nonspecific immune responses of macrophages and monocytes which are of primary importance in resistance to this virus and other infectious agents.


[Production of potato cybrids without using genetic selection markers of the parental material: Solanum tuberosum L. plants (cv. Svitanok Kyivsky) with S. pinnatisectum Dun. plastids].
Interspecific cybrid plants of potato were created using the cell technology that does not require the presence of any genetic selectable markers in the parental material. Cybrid production was based on double inactivation of S. pinnatisectum Dun. protoplasts, served as the donors of organelles (by gamma-irradiation for the nuclei inactivation and by chemical mutagenesis for the efficient induction of chlDNA mutations), and the transfer of mutant plastids into S. tuberosum L. by protoplast fusion. Selection of cell colonies for streptomycin resistance was performed to identify the cybrid clones with mutant donor-type plastids. Restriction analysis of organelle DNA, chromosome counting, and isoenzyme analysis of the cybrids revealed the presence of nuclear material of S. tuberosum L. (cv. Svitanok kyivsky) and plastids from wild tuber-bearing S. pinnatisectum Dun. These plants enable the study of traits encoded by organelle DNA and to broaden the cytoplasmic diversity of cultivated potato.


[Evaluation and results of the gliding nail in the elderly patient].
Evaluation of the gliding nail in the elderly patient with unstable fracture of the proximal femur. Primary aims of the study were the description of surgical procedure, the specific complications, postoperative pain, recovered mobility and social status after nailing procedure. The observation period of this prospective non-randomized observational cohort study was from 10/97 to 07/00. 121 patients (90 female, 31 male) with unstable femoral fracture were included. Data evaluation included type of fracture, surgical data, procedure specific complications and pre and post surgical development (pain, mobility and social status). The evaluation of the outcome was performed at least 3 months (median 10.4 months) after surgical intervention by telephone-interview. A subgroup of 20 patients was re-examined. 24 A1-, 65 A2-, 16 A3-, 11 subtrochanteric and 5 other fractures were stabilized with a gliding nail. The mean time of surgery was 77 minutes. In 15 out of 121 patients complications lead to a second surgical intervention. In the follow-up examination we were able to obtain following findings: 33.9 % vs. 56.2 % (preoperative) of patients were self-contained. The need for professional care was unchanged. 23.5 % vs. 58.7 % (preoperative) showed unlimited mobility. 20.3 % vs. 12.8 % complained light or moderate pain. According to our experience the gliding nail is a safe and minimal invasive system with a low complication rate. In consideration of patient based outcome the gliding nail shows good results compared to other treatment options. For the given reasons the authors prefer the gliding nail as treatment of choice for proximal femoral fractures.


The ecotoxicity of chlorate to aquatic organisms: a critical review.
In order to assess the risk posed by chlorate in aquatic ecosystems, data on the effects of chlorate on aquatic organisms (microorganisms, algae, invertebrates, and fish) and mesocosm studies have been collated and critically reviewed. The geometric mean E(L)C50 values for both freshwater and marine species were (as ClO3-): microorganisms, 38,583 mg.liter-1; microalgae, 563 mg.liter-1; invertebrates, 2442 mg.liter-1; fish, 3815 mg.liter-1. Marine macro red algae were insensitive to chlorate, whereas marine macro brown algae (e.g., Fucus sp.) appeared to be exceptionally sensitive to chlorate, adverse long-term effects having been reported at concentrations as low as 0.015 mg ClO3-.liter-1. Evidence for the mechanism by which chlorate is thought to be particularly toxic to these species is also reviewed. It is concluded that, based on the species reported, chlorate is nontoxic (acute toxicity > 100 mg.liter-1) to most of the freshwater and marine species examined. However, chlorate is highly toxic (acute toxicity < 0.1 mg.liter-1) to certain macro brown algal species. For macro brown algae, the NOEC after 6 months was reported to be approximately 0.005 mg ClO3-.liter-1. It is also concluded that an improved understanding of the actual mode of action of chlorate in sensitive species is desirable. Together with further information on the environmental fate of chlorate, this will improve the risk assessment for chlorate in the aquatic environment.


Power Doppler sonography of cervical lymph nodes in patients with head and neck cancer.
The purpose of this preliminary study was to evaluate the usefulness of power Doppler sonography in differentiating metastatic from nonmetastatic cervical lymph nodes in patients with cancer. Histologically proved metastatic (n = 71) and nonmetastatic (n = 220) lymph nodes were examined with power Doppler sonography in 77 patients with head and neck cancer. Power Doppler sonography was assessed for its ability to differentiate metastatic from nonmetastatic lymph nodes. Power Doppler sonography showed characteristic features of parenchymal blood flow signal in 59 (83%) of the 71 metastatic lymph nodes. By contrast, only four (2%) of the 220 nonmetastatic nodes showed these power Doppler signals. In addition, power Doppler sonography showed high levels of sensitivity (83%) and specificity (98%) in depicting metastatic lymph nodes, which were superior to the values (66% sensitivity and 92% specificity) obtained by applying size criteria (transverse to longitudinal ratio). However, a combination of the two criteria (parenchymal color signal and transverse to longitudinal ratio) improved diagnostic accuracy to 92% sensitivity and 100% specificity. Our preliminary findings suggest that the power Doppler criteria of no hilar flow, peripheral parenchymal nodal flow, and a transverse to longitudinal ratio of more than 0.65 together constitute a powerful tool for depicting metastatic lymph nodes in patients with cancer.


The impact of motives for Facebook use on Facebook addiction among ordinary users in Jordan.
Facebook has become the most popular social networking site with more than 2.07 billion monthly active users. However, this popularity has its pains too reflected by some addictive behavior among its users. Although researchers have recently started to examine the factors that influence Facebook addiction, little research examined the links between motives for Facebook use and Facebook addiction. These studies mainly concentrate on students too. Also, little research has explored this issue among general public in general and among people in Jordan in particular. This study therefore examined the impact of motives for Facebook use on Facebook addiction among ordinary users in Jordan. A sample of 397 ordinary users is employed to achieve the study objective. Results showed that 38.5% of the participants were addicted to Facebook. Facebook addiction was significantly associated with six motives, namely exhibitionism and companionship, entertainment, escapism and passing time, social curiosity, relationships formation and relationships maintenance. Among these six motives, escapism and passing time, exhibitionism and companionship, and relationships maintenance were the strong predictors of Facebook addiction.


Role of magnesium in carbon partitioning and alleviating photooxidative damage.
Magnesium (Mg) deficiency exerts a major influence on the partitioning of dry matter and carbohydrates between shoots and roots. One of the very early reactions of plants to Mg deficiency stress is the marked increase in the shoot-to-root dry weight ratio, which is associated with a massive accumulation of carbohydrates in source leaves, especially of sucrose and starch. These higher concentrations of carbohydrates in Mg-deficient leaves together with the accompanying increase in shoot-to-root dry weight ratio are indicative of a severe impairment in phloem export of photoassimilates from source leaves. Studies with common bean and sugar beet plants have shown that Mg plays a fundamental role in phloem loading of sucrose. At a very early stage of Mg deficiency, phloem export of sucrose is severely impaired, an effect that occurs before any noticeable changes in shoot growth, Chl concentration or photosynthetic activity. These findings suggest that accumulation of carbohydrates in Mg-deficient leaves is caused directly by Mg deficiency stress and not as a consequence of reduced sink activity. The role of Mg in the phloem-loading process seems to be specific; resupplying Mg for 12 or 24 h to Mg-deficient plants resulted in a very rapid recovery of sucrose export. It appears that the massive accumulation of carbohydrates and related impairment in photosynthetic CO2 fixation in Mg-deficient leaves cause an over-reduction in the photosynthetic electron transport chain that potentiates the generation of highly reactive O2 species (ROS). Plants respond to Mg deficiency stress by marked increases in antioxidative capacity of leaves, especially under high light intensity, suggesting that ROS generation is stimulated by Mg deficiency in chloroplasts. Accordingly, it has been found that Mg-deficient plants are very susceptible to high light intensity. Exposure of Mg-deficient plants to high light intensity rapidly induced leaf chlorosis and necrosis, an outcome that was effectively delayed by partial shading of the leaf blade, although the Mg concentrations in different parts of the leaf blade were unaffected by shading. The results indicate that photooxidative damage contributes to development of leaf chlorosis under Mg deficiency, suggesting that plants under high-light conditions have a higher physiological requirement for Mg. Maintenance of a high Mg nutritional status of plants is, thus, essential in the avoidance of ROS generation, which occurs at the expense of inhibited phloem export of sugars and impairment of CO2 fixation, particularly under high-light conditions.


Conservative surgery and irradiation (QUART) in the treatment of 243 stage I-II breast cancer patients.
From 1980 to 1987, 243 evaluable patients with pT1, pT2 (less than 3 centimeters in diameter), N0, M0, invasive breast cancer were treated with "quadrantectomy" with axillary dissection followed by electron beam radiation therapy (QUART) at the St. Bortolo Hospital, Vicenza. Stage II patients received adjuvant chemotherapy (CMF) if preperimenopausal or hormonotherapy (tamoxifen) if postmenopausal. The median follow-up was 54 months (26 to 116 months). The 4.5-year overall survival (OS) and disease-free survival (DFS) were respectively 91% and 85%; the 10-year actuarially estimated OS and DFS was 77%. Thirty-three patients relapsed, 11 of whom had local recurrence, and 23 developed distant metastases. A significantly longer OS and DFS were observed in stage I versus stage II (p = 0.0008) and in pT1 versus pT2 (p = 0.001) tumors. No difference was found regarding menopausal status and histotype. The local control of disease was very high (95.5%), with a significantly higher local recurrence rate in premenopausal women compared to postmenopausal (10/117 versus 1/126; p = 0.009). Tumor size did not influence the frequency of local recurrence. No major complications occurred but a significantly higher rate of reversible radiation-pneumonitis occurred in patients treated with higher energies of electrons (17 to 20 MeV) compared with lower (6 to 13 MeV) (33/177 versus 7/66; p less than 0.05). Cosmetic results were judged as excellent in 20%, satisfactory in 68%, unsatisfactory in 6% and not evaluable in 6% of cases. We conclude first, that small pT2 breast carcinomas may also be safely treated with QUART, second, that the electron beam is a radiotherapeutic technique able to produce a good cosmetic result and to assure a satisfactory local control and, finally, that the use of tamoxifen in postmenopausal stage II breast carcinomas is safe and easy to combine with radiotherapy in the conservative management of early breast cancer due to the lower toxic effects, compared to those observed in premenopausal women treated with chemotherapy.


Independent deletions of a pathogen-resistance gene in Brassica and Arabidopsis.
Plant disease resistance (R) genes confer race-specific resistance to pathogens and are genetically defined on the basis of intra-specific functional polymorphism. Little is known about the evolutionary mechanisms that generate this polymorphism. Most R loci examined to date contain alternate alleles and/or linked homologs even in disease-susceptible plant genotypes. In contrast, the resistance to Pseudomonas syringae pathovar maculicola (RPM1) bacterial resistance gene is completely absent (rpm1-null) in 5/5 Arabidopsis thaliana accessions that lack RPM1 function. The rpm1-null locus contains a 98-bp segment of unknown origin in place of the RPM1 gene. We undertook comparative mapping of RPM1 and flanking genes in Brassica napus to determine the ancestral state of the RPM1 locus. We cloned two B. napus RPM1 homologs encoding hypothetical proteins with approximately 81% amino acid identity to Arabidopsis RPM1. Collinearity of genes flanking RPM1 is conserved between B. napus and Arabidopsis. Surprisingly, we found four additional B. napus loci in which the flanking marker synteny is maintained but RPM1 is absent. These B. napus rpm1-null loci have no detectable nucleotide similarity to the Arabidopsis rpm1-null allele. We conclude that RPM1 evolved before the divergence of the Brassicaceae and has been deleted independently in the Brassica and Arabidopsis lineages. These results suggest that functional polymorphism at R gene loci can arise from gene deletions.


Vaccine Effectiveness Against SARS-CoV-2 Related Hospitalizations in People who had Experienced Homelessness or Incarceration - Findings from the Minnesota EHR Consortium.
COVID-19 disproportionately affects people experiencing homelessness or incarceration. While homelessness or incarceration alone may not impact vaccine effectiveness, medical comorbidities along with social conditions associated with homelessness or incarceration may impact estimated vaccine effectiveness. COVID-19 vaccines reduce rates of hospitalization and death; vaccine effectiveness (VE) against severe outcomes in people experiencing homelessness or incarceration is unknown. We conducted a retrospective, observational cohort study evaluating COVID-19 vaccine VE against SARS-CoV-2 related hospitalization (positive SARS-CoV-2 molecular test same week or within 3 weeks prior to hospital admission) among patients who had experienced homelessness or incarceration. We utilized data from 8 health systems in the Minnesota Electronic Health Record Consortium linked to data from Minnesota's immunization information system, Homeless Management Information System, and Department of Corrections. We included patients 18 years and older with a history of experiencing homelessness or incarceration. VE and 95% Confidence Intervals (CI) against SARS-CoV-2 hospitalization were estimated for primary series and one booster dose from Cox proportional hazard models as 100*(1-Hazard Ratio) during August 26, 2021, through October 8, 2022 adjusting for patient age, sex, comorbid medical conditions, and race/ethnicity. We included 80,051 individuals who had experienced homelessness or incarceration. Adjusted VE was 52% (95% CI, 41-60%) among those 22 weeks or more since their primary series, 66% (95% CI, 53-75%) among those less than 22 weeks since their primary series, and 69% (95% CI: 60-76%) among those with one booster. VE estimates were consistently lower during the Omicron predominance period compared with the combined Omicron and Delta periods. Despite higher exposure risk, COVID-19 vaccines provided good effectiveness against SARS-CoV-2 related hospitalizations in persons who have experienced homelessness or incarceration.