Posttransfusion hepatitis type A.
Hepatitis A virus (HAV) transmission through blood is a rare but potential cause of posttransfusion hepatitis. We can now document such a case supported by laboratory evidence of HAV in the donor blood. A 10-year-old girl manifested icteric hepatitis A 31 days after receiving a single unit of packed RBCs from a donor who subsequently experienced hepatitis A and died in hepatic failure. Hepatitis A virus antigen was detected in the donor's hepatocytes and in plasma obtained from the original donor unit. The density in cesium chloride of the HAV antigenic activity from the liver and plasma ranged from 1.33 to 1.37 g/cu cm, which is similar to that reported for infectious HAV particles. The implicated donor plasma had normal aminotransferase levels and was negative for antibody to HAV. Inoculation of this plasma into a chimpanzee resulted in the development of hepatitis A 23 days later based on the appearance of fecal HAV antigen, hepatitis, and IgM anti-HAV seroconversion. These data clearly document the presence of HAV in the donor sample that produced posttransfusion hepatitis A.


Transmission of brain activity during cognitive task.
The transmission of brain activity during constant attention test was estimated by means of the short-time directed transfer function (SDTF). SDTF is an estimator based on a multivariate autoregressive model. It determines the propagation as a function of time and frequency. For nine healthy subjects the transmission of EEG activity was determined for target and non-target conditions corresponding to pressing of a switch in case of appearance of two identical images or withholding the reaction in case of different images. The involvement of prefrontal and frontal cortex manifested by the propagation from these structures was observed, especially in the early stages of the task. For the target condition there was a burst of propagation from C3 after pressing the switch, which can be interpreted as beta rebound upon completion of motor action. In case of non-target condition the propagation from F8 or Fz to C3 was observed, which can be connected with the active inhibition of motor cortex by right inferior frontal cortex or presupplementary motor area.


Inducing a Net Positive Flow of Water in Functionalized Concentric Carbon Nanotubes Using Rotating Electric Fields.
Electropumping has shown great potential as an effective means of inducing a net positive flow of water in confined channels. In this paper we present the first nonequilibrium molecular dynamics study and continuum based numerical solutions that demonstrate an effective net positive flow between concentric carbon nanotubes (CNT) using electropumping. We apply a spatially uniform rotating electric field that couples to the water's permanent dipole moment. Taking advantage of the coupling between the spin angular momentum and the linear momentum we break the symmetry of the channel radius by functionalizing the inner CNT's outer surface with carboxyl groups to induce a net positive flow. We also show that our results for concentric nanotubes are consistent with our previous work where we demonstrated that an increase in functionalization beyond an optimal point in a single walled carbon nanotube resulted in a decrease in positive net flow. We then numerically solve the coupled hydrodynamic momentum equations to show that the nonequilibrium molecular dynamics results are consistent with the continuum theory.


Management of Flood syndrome: What can we do better?
Approximately 20% of cirrhotic patients with ascites develop umbilical herniation. These patients usually suffer from multisystemic complications of cirrhosis, have a significantly higher risk of infection, and require accurate surveillance- especially in the context of the coronavirus disease 2019 pandemic. The rupture of an umbilical hernia, is an uncommon, life-threatening complication of large-volume ascites and end-stage liver disease resulting in spontaneous paracentesis, also known as Flood syndrome. Flood syndrome remains a challenging condition for clinicians, as recommendations for its management are lacking, and the available evidence for the best treatment approach remains controversial. In this paper, four key questions are addressed regarding the management and prevention of Flood syndrome: (1) Which is the best treatment approach-conservative treatment or urgent surgery? (2) How can we establish the individual risk for herniation and possible hernia rupture in cirrhotic patients? (3) How can we prevent umbilical hernia ruptures? And (4) How can we manage these patients in the conditions created by the coronavirus disease 2019 pandemic?


Consumption of plasma factor VII in a rabbit model of non-overt disseminated intravascular coagulation.
We have recently described an experimental animal model of non-overt disseminated intravascular coagulation (DIC) in the rabbit in which the induction of tissue factor (TF) mRNA and TF antigen expression in peripheral blood leukocytes (PBL) was demonstrated to occur within 2 h of administration of low-dose endotoxin [Hematol. J. 2 (2001) 188]. In the present study, we demonstrate that the leukocyte TF expressed has procoagulant activity leading to a rapid decline in the concentration of factor VII (FVII) in rabbit plasma. Total plasma FVII antigen and FVIIa were quantitated by rabbit FVII-specific immunoassay and FVIIa-specific clotting assays, respectively. Plasma samples from either saline-injected rabbits or rabbits administered a single bolus of 10 microg/kg Salmonella lipopolysaccharide were compared over a 24-h period. Total plasma FVII antigen decreased progressively post-endotoxin injection, reaching 71% of the baseline concentration at 8 h (p<0.001, n=18), and remained low (78%) at 24 h post-injection (p<0.01, n=16), returning to normal by 48 h. Plasma FVIIa levels increased to 120% within 2 h of endotoxin injection, fell to 73% of the baseline concentration at 8 h (p<0.05, n=18) and returned to normal by 24 h post-endotoxin administration. Procoagulant activity of rabbit peripheral blood leukocytes was enhanced at 2 h (p<0.01, n=6) and 4 h (p<0.05, n=6) post-endotoxin injection. The prothrombin time (PT) was increased by <3 s, and thrombin-antithrombin (TAT) complex formation was not significantly increased in the plasma of endotoxin-treated rabbits. No significant changes in total plasma FVII antigen, FVIIa or leukocyte procoagulant activity were observed in rabbits treated with saline. We conclude that the activation of FVII to FVIIa and rapid consumption of total FVII/FVIIa occur very early and likely are integral events linked to the initiation and propagation of non-overt DIC induced by endotoxin.


Obesity: as rural females perceive it.
Out of 318 rural females studied, 17.3% were found to be obese. Most of them are aware of their obese status except for 10.9% who were unaware. Majority of the females considered eating more, childbirth and reduced activity as the possible cause of their obesity and also obesity in other persons. Though 48.1% and 33.6% of the females mentioned dieting and exercise/walking respectively as the method of prevention still 52.5% mentioned that medicine is the only method for prevention of obesity. Regarding remedy of obesity again 48.4% females mentioned medicine as the method.


Preferential potentiation of AMPA-mediated currents in brainstem hypoglossal motoneurons by subchronic exposure of mice expressing the human superoxide dismutase 1 G93A gene mutation to neurotoxicant methylmercury in vivo.
The exact causes of Amyotrophic lateral sclerosis (ALS), a progressive and fatal neurological disorder due to loss of upper and/or lower motoneurons, remain elusive. Gene-environment interactions are believed to be an important factor in the development of ALS. We previously showed that in vivo exposure of mice overexpressing the human superoxide dismutase 1 (hSOD1) gene mutation (hSOD1G93A; G93A), a mouse model for ALS, to environmental neurotoxicant methylmercury (MeHg) accelerated the onset of ALS-like phenotype. Here we examined the time-course of effects of MeHg on AMPA receptor (AMPAR)-mediated currents in hypoglossal motoneurons in brainstem slices prepared from G93A, hSOD1wild-type (hWT) and non-carrier WT mice following in vivo exposure to MeHg. Mice were exposed daily to 3 ppm (approximately 0.7mg/kg/day) MeHg via drinking water beginning at postnatal day 28 (P28) and continued until P47, 64 or 84, then acute brainstem slices were prepared, and spontaneous excitatory postsynaptic currents (sEPSCs) or AMPA-evoked currents were examined using whole cell patch-clamp recording technique. Brainstem slices of untreated littermates were prepared at the same time points to serve as control. MeHg exposure had no significant effect on either sEPSCs or AMPA-evoked currents in slices from hWT or WT mice during any of those exposure time periods under our experimental conditions. MeHg also did not cause any significant effect on sEPSCs or AMPA-currents in G93A hypoglossal motoneurons at P47 and P64. However, at P84, MeHg significantly increased amplitudes of both sEPSCs and AMPA-evoked currents in hypoglossal motineurons from G93A mice (p<0.05), but not the sEPSC frequency, suggesting a postsynaptic action on AMPARs. MeHg exposure did not cause any significant effect on GABAergic spontaneous inhibitory postsynaptic currents (sIPSCs). Therefore, MeHg exposure in vivo caused differential effects on AMPARs in hypoglossal motoneurons from mice with different genetic backgrounds. MeHg appears to preferentially stimulate the AMPAR-mediated currents in G93A hypoglossal motoneurons in an exposure time-dependent manner, which may contribute to the AMPAR-mediated motoneuron excitotoxicity, thereby facilitating development of ALS-like phenotype.


Hairy cells possess more interferon receptors than other lymphoid cell types.
To investigate the possible direct effects of alpha-interferon (IFN-alpha) in hairy cell leukemia, IFN-alpha receptor expression by hairy cells (11 cases) was measured by a radiolabeling technique and compared with that of MOLT-4, chronic lymphocytic leukemia (15 cases), and various other leukemic and normal cell types. Purified peripheral blood and splenic hairy cells showed higher levels of receptor expression (approximately 1,000 +/- 200 binding sites/cell; 11 cases tested) than other normal and leukemic cell types. B cells from normal blood and tonsils showed low levels of receptors (approximately 120 +/- 100 binding sites/cell), while a range of B cell leukemias displayed intermediate levels of expression (100-500 sites/cell). In the 15 cases of chronic lymphocytic leukemia tested, 530 +/- 330 binding sites/cell) were demonstrated, the high standard deviation reflecting the fact that one third of cases had receptor levels comparable with those in hairy cell leukemia. Normal and hairy cell leukemia T cells, red cells, and platelets had no demonstrable IFN-receptors. These findings may be relevant to the efficacy of IFN in hairy cell leukemia.


Constraints on the source of short-term motion adaptation in macaque area MT. I. the role of input and intrinsic mechanisms.
Neurons in area MT, a motion-sensitive area of extrastriate cortex, respond to a step of target velocity with a transient-sustained firing pattern. The transition from a high initial firing rate to a lower sustained rate occurs over a time course of 20-80 ms and is considered a form of short-term adaptation. The present paper asks whether adaptation is due to input-specific mechanisms such as short-term synaptic depression or if it results from intrinsic cellular mechanisms such as spike-rate adaptation. We assessed the contribution of input-specific mechanisms by using a condition/test paradigm to measure the spatial scale of adaptation. Conditioning and test stimuli were placed within MT receptive fields but were spatially segregated so that the two stimuli would activate different populations of inputs from the primary visual cortex (V1). Conditioning motion at one visual location caused a reduction of the transient firing to subsequent test motion at a second location. The adaptation field, estimated as the region of visual space where conditioning motion caused adaptation, was always larger than the MT receptive field. Use of the same stimulus configuration while recording from direction-selective neurons in V1 failed to demonstrate either adaptation or the transient-sustained response pattern that is the signature of short-term adaptation in MT. We conclude that the shift from transient to sustained firing in MT cells does not result from an input-specific mechanism applied to inputs from V1 because it operates over a wider range of the visual field than is covered by receptive fields of V1 neurons. We used a direct analysis of MT neuron spike trains for many repetitions of the same motion stimulus to assess the contribution to adaptation of intrinsic cellular mechanisms related to spiking. On a trial-by-trial basis, there was no correlation between number of spikes in the transient interval and the interval immediately after the transient period. This is opposite the prediction that there should be a correlation if spikes cause adaptation directly. Further, the transient was suppressed or extinguished, not delayed, in trials in which the neuron emitted zero spikes during the interval that showed a transient in average firing rate. We conclude that the transition from transient to sustained firing in neurons in area MT is caused by mechanisms that are neither input-specific nor controlled by the spiking of the adapting neuron. We propose that the short-term adaptation observed in area MT emerges from the intracortical circuit within MT.


Possible involvement of adenine nucleotides in sympathetic neuroeffector mechanisms of dog basilar artery.
The transmission mechanism of sympathetic neuroeffector was studied in the isolated dog basilar artery. Electrical transmural stimulation produced an initial contractile response which was followed by a transient relaxation or a late contraction, or both relaxation and contraction. These arteries showed a marked uptake of [3H]norepinephrine ([3H]NE) or [3H]adenosine after incubation with these compounds, and electrical stimulation increased the release of [3H]NE or 3H-purine compounds. After treatment with tetrodotoxin or bretylium or in the sympathetically denervated arteries, the mechanical response to electrical stimulation and the release of 3H-compounds were attenuated; however, the mechanical response was not affected by treatment with reserpine. These results suggest that transmural stimulation releases not only [3H]NE but also 3H-purine compounds predominantly from the sympathetic nerve terminals and produces sympathetic contractile and relaxing responses. Phentolamine enhanced these sympathetic responses and augmented the release of [3H]NE and 3H-purine compounds. Exogenously applied NE produced a slowly developing contractile response and inhibited the release of 3H-purine compounds upon electrical transmural stimulation. Exogenously applied ATP produced responses which were similar in pattern to the sympathetic response and the release of [3H]NE was inhibited. Other adenine nucleotides and adenosine produced only relaxation. Theophylline attenuated the relaxing response to sympathetic nerve stimulation or to exogenously applied nucleotides. These results suggest that ATP or related nucleotides are released, concomitant with NE, from the sympathetic nerve terminals in the dog basilar artery and may act as neurotransmitters and/or modulators on presynaptic and postsynaptic membranes.


The study of depressive disorders using the PSE-ID-CATEGO system.
The PSE-CATEGO-ID system and its approach to the sub-classification of depression is described. The principle of sub-classification partly corresponds to the empirical relationships between symptoms on affective disorder. Comparison of CATEGO and DSM III demonstrates that major differences of classification can arise because of differences of the classificatory algorithm even though similar lists of symptoms are used. Empirical studies of the PSE-CATEGORO-ID system are described and their importance in providing evidence for a rational choice between classificatory system is emphasised.


Active Surveillance for Localized Prostate Cancer: Nationwide Observational Study.
The objective of this study was to investigate nationwide survival outcomes in men with localized prostate cancer managed on active surveillance. A total of 936 men with localized prostate cancer were initiated on active surveillance in Denmark in 2002 to 2012. Kaplan-Meier estimated curative treatment-free, hormonal therapy-free, castration resistant prostate cancer-free and cause specific survival was calculated. Prostate cancer was classified as very low risk in 223 men, low risk in 436, intermediate risk in 259 (87% were at favorable intermediate risk) and high risk in 18. Median followup was 7.5 years (IQR 6.1-9.1). Kaplan-Meier estimated 10-year curative treatment-free survival was 62.8% (95% CI 59.1-66.3), 10-year hormonal therapy-free survival was 92.2% (95% CI 89.2-94.4), 10-year castration resistant prostate cancer-free survival was 97.2% (95% CI 95.3-98.4) and 10-year cause specific survival was 99.6% (95% CI 98.6-99.9). Compared to men with low risk prostate cancer, those with intermediate risk prostate cancer had higher curative treatment-free survival (69% vs 56%, p = 0.008), lower hormonal therapy-free survival (88% vs 95%, p = 0.005) and similar castration resistant prostate cancer-free survival (95% vs 99%, p = 0.17). In this nationwide cohort 10-year cause specific survival was similar to that in prospective active surveillance cohorts. Our study supports the use of active surveillance in men with localized prostate cancer, including men with favorable intermediate risk characteristics.


[Increase in the specific activity of killed influenza vaccines by using polyene antibiotics].
It was shown experimentally that polyenic antibiotics, i. e. amphotericin B and sodium levorin markedly increased the specific immunogenic properties and interferonogenic activity of inactivated influenza virus vaccine prepared with various methods from highly reproductive recombinants. The rate of pneumonia and death from influenza among the vaccinated mice treated with inactivated influenza virus vaccine and one of the polyenic antibiotics was lower than that among the animals treated with the vaccine alone (P less than 0.05). Correlation between the increase in the immunological response, the decrease in the virus reproduction rate in the lungs and addition of the antibiotics into the vaccine was also observed. It is recommended that inactivated influenza virus vaccine be used in conjunction with polyenic antibiotics.


The pallidotomy debate.
It has been suggested that image-guidance and macro-stimulation alone are not sufficiently accurate to result in safe and effective lesion localization in pallidotomy for Parkinson's disease when compared with micro-electrode recording. This review analyses the data in the series published to date, and compares the safety and efficacy of the two techniques, finding no evidence to support this claim. In addition, evidence regarding the necessary accuracy of lesion placement is reviewed.


Prehospital hypocapnia and poor outcome after severe traumatic brain injury.
The Brain Trauma Foundation (BTF) Guidelines for prehospital management of traumatic brain injury (TBI) recommend a goal end-tidal carbon dioxide of 30 mm Hg to 35 mm Hg in patients without signs of herniation. We examined prehospital concordance with BTF Guidelines, selected demographic and physiologic variables and outcomes for 100 consecutive admissions to a well-established Level I regional trauma center. All patients had blunt TBI with Glasgow Coma Score < or = 8 without signs of herniation. All were transported by helicopter by flight paramedics experienced with BTF Guidelines and the continuous wave form capnometer. Patients resumed spontaneous ventilation after intubation. Concordance (prehospital end-tidal carbon dioxide > 29 mm Hg) was achieved in 65 of 100 cases. Mortality was 29% (19 of 65) among those in whom guideline levels were achieved prehospital and 46% (16 of 35) in those in whom guideline levels were not achieved prehospital (odds ratio, 0.49; p = 0.10). The "achieved" group was younger (p = 0.02), with higher calculated probability of survival (p = 0.01). Intracranial pressure was maintained under intensive care within acceptable limits in the hospital in both groups but was significantly higher in the "not achieved" group (p = 0.05). Our data, though not statistically significant, suggest that patients who are harder to keep within the guidelines in the field are more likely to die, because of more severe TBI or complication by other factors such as age or injury severity. Whether increased awareness of this phenomenon can improve outcomes is unknown but suggests an approach to future education and research.


PyADF--a scripting framework for multiscale quantum chemistry.
Applications of quantum chemistry have evolved from single or a few calculations to more complicated workflows, in which a series of interrelated computational tasks is performed. In particular multiscale simulations, which combine different levels of accuracy, typically require a large number of individual calculations that depend on each other. Consequently, there is a need to automate such workflows. For this purpose we have developed PYADF, a scripting framework for quantum chemistry. PYADF handles all steps necessary in a typical workflow in quantum chemistry and is easily extensible due to its object-oriented implementation in the Python programming language. We give an overview of the capabilities of PYADF and illustrate its usefulness in quantum-chemical multiscale simulations with a number of examples taken from recent applications.


Nickel oral hyposensitization in patients with systemic nickel allergy syndrome.
This is the first randomized, double-blind, placebo-controlled trial (EUDRACT No. 2009-013923-43) evaluating nickel oral hyposensitizing treatment (NiOHT) in patients with "systemic nickel allergy syndrome" (SNAS), characterized by Ni-allergic contact dermatitis and systemic reactions after eating Ni-rich food. Adults with positive Ni-patch test, who reported symptoms suggesting SNAS, which improved after Ni-poor diet, and were positive to Ni-oral challenge were eligible. Patients were randomly assigned to three treatments (1.5 μg, 0.3 μg, or 30 ng Ni/week) or placebo for a year, with progressive reintroduction of Ni-rich foods form the 5(th) month. Out of 141 patients randomized, 113 completed the trial. Endpoints were efficacy and tolerability of treatment. During Ni-rich food re-introduction, the 1.5 μg Ni/week group had a mean VAS score significantly higher than placebo (p = 0.044), with significant improvement of gastrointestinal symptoms (p = 0.016;) and significantly fewer rescue medications. Cutaneous manifestations also improved but without reaching statistical significance. After the treatment, oral challenge with higher Ni doses than at baseline were needed to cause symptoms to flare-up in significantly more patients given 1.5 μg Ni/week than placebo (p = 0.05). Patients reported no side-effects. NiOHT is effective in SNAS, in particular on gastrointestinal manifestations, with trend toward improvement of cutaneous symptoms.


Statistical quantification of the effects of viewing distance on texture perception.
In general, viewers are more attracted to local features in images at a shorter viewing distance and to global features in images at a longer viewing distance. However, numerical analysis of the effect of viewing distance on human texture perception and how the perception of global and local changes under certain conditions are still undetermined. In this paper, we present statistical prediction of the relationship between the domination ratio of global and local features and the viewing distances under the control of several factors, using the logistic regression model. We synthesized textures by separately controlling global and local textural features using a texture model based on mathematical morphology, namely the primitive, grain, and point configuration texture model. Visual sensory tests were carried out on 80 subjects during two sets of experiments. The collected data were statistically analyzed using logistic regression and Akaike information criteria. Besides the main factor of viewing distance, the factors including gender, changing the order of viewing positions, and prior knowledge were also shown quantitatively to have significant influence on human texture perception. Our results showed that (1) local features of a texture were more attractive to females than males, (2) the first impression might have affected subsequent decisions in texture perception, and (3) subjects who had prior knowledge (supervised) were more sensitive to the changes in global and local dominance. (4) Regarding the interactions of the factors, prior knowledge reduced the effects of individual differences and perception condition differences on human texture perception. This study is dedicated to the construction of numerical relationships between viewing distance and human texture perception as well as to cognitive investigation of biases in global and local perceptions.


Role of Mycoplasma pneumoniae infection in acute exacerbations of chronic obstructive pulmonary disease.
Eighty per cent of the cases of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) have an infective aetiology, atypical bacteria including Mycoplasma pneumoniae accounting for 5-10 % of these. However, the importance of association of M. pneumoniae with episodes of AECOPD still remains doubtful. The present study was therefore undertaken to delineate the extent of involvement of M. pneumoniae in patients with AECOPD at a referral hospital in Delhi, India. Sputum samples and throat swabs from a total of 100 AECOPD patients attending the Clinical Research Center of Vallabhbhai Patel Chest Institute, Delhi, were collected during a 2-year period (January 2004-June 2006). The samples were investigated for the presence of aerobic bacterial pathogens and M. pneumoniae. Diagnosis of infection with M. pneumoniae was based on culture, serology, direct detection of M. pneumoniae specific antigen and PCR. Bacterial aetiology could be established in 16 of the 100 samples studied. Pseudomonas spp. were recovered from eight cases, Streptococcus pneumoniae from four and Klebsiella spp. from two cases. Acinetobacter sp. and Moraxella catarrhalis were isolated from one case each. Serological evidence of M. pneumoniae infection and/or detection of M. pneumoniae specific antigen were seen in 16 % of the cases. One case with definite evidence of M. pneumoniae infection also had coinfection with Pseudomonas spp. However, no direct evidence of M. pneumoniae infection was found in our study population as defined by culture isolation or PCR. In conclusion, although the serological prevalence of M. pneumoniae infection in our study population was significantly higher than in the control group, there was no direct evidence of it playing a role in AECOPD.


The Importance of DHEA-S Levels in Cushing's Syndrome; Is There a Cut-off Value in the Differential Diagnosis?
The purpose of this study was to determine possible cut-off levels of basal DHEA-S percentile rank in the differential diagnosis of patients with Cushing's syndrome (CS) with ACTH levels in the gray zone and normal DHEA-S levels. In this retrospective study including 623 pathologically confirmed CS, the DHEA-S percentile rank was calculated in 389 patients with DHEA-S levels within reference interval. The patients were classified as group 1 (n=265 Cushing's disease; CD), group 2 (n=104 adrenal CS) and group 3 (n=20 ectopic ACTH syndrome).ROC-curve analyses were used to calculate the optimal cut-off level of DHEA-S percentile rank in the reference interval in the differential diagnosis of CS, and the effectiveness of this cut-off level in the identification of the accurate etiology of CS was assessed in patients who were in gray zone according to their ACTH levels. The DHEA-S percentile rank in the reference interval were significantly lower in group 2 compared to the other two groups (p<0.001), while group 1 and group 3 had similar levels. The optimal cut-off level of DHEA-S percentile rank in the reference interval providing differential diagnosis between group 1 and group 2 was calculated as 19.5th percentile (80.8% sensitivity, 81.5% specificity) and the level demonstrated the accurate etiology in 100% of CD and 76% of adrenal CS patients who were in the gray zone. This study showed that the cut-off value of DHEA-S level less than 20% of the reference interval could be used for differential diagnosis of CD and adrenal CS with high sensitivity and specificity, and it should be taken into the initial evaluation.


Enhanced Soybean Productivity by Inoculation With Indigenous Bradyrhizobium Strains in Agroecological Conditions of Northeast Germany.
Commercial inoculants are often used to inoculate field-grown soybean in Europe. However, nodulation efficiencies in these areas are often low. To enhance biological nitrogen (N) fixation and increase domestic legume production, indigenous strains that are adapted to local conditions could be used to develop more effective inoculants. The objective of this study was to assess the ability of locally isolated Bradyrhizobium strains to enhance soybean productivity in different growing conditions of Northeast Germany. Three indigenous Bradyrhizobium isolates (GMF14, GMM36, and GEM96) were tested in combination with different soybean cultivars of different maturity groups and quality characteristics in one field trial and two greenhouse studies. The results showed a highly significant strain × cultivar interactions on nodulation response. Independent of the Bradyrhizobium strain, inoculated plants in the greenhouse showed higher nodulation, which corresponded with an increased N uptake than that in field conditions. There were significantly higher nodule numbers and nodule dry weights following GMF14 and GMM36 inoculation in well-watered soil, but only minor differences under drought conditions. Inoculation of the soybean cultivar Merlin with the strain GEM96 enhanced nodulation but did not correspond to an increased grain yield under field conditions. USDA110 was consistent in improving the grain yield of soybean cultivars Sultana and Siroca. On the other hand, GMM36 inoculation to Sultana and GEM96 inoculation to Siroca resulted in similar yields. Our results demonstrate that inoculation of locally adapted soybean cultivars with the indigenous isolates improves nodulation and yield attributes. Thus, to attain optimal symbiotic performance, the strains need to be matched with specific cultivars.


May 18F-FAPI PET/CT differentiate Sutures granuloma from metastasis? A case report.
A 35-year-old woman received a surgery of sigmoid colon highly differentiated mucosal adenocarcinoma with greater omentum and peritoneum metastasis.The follow-up contrast-enhanced computed tomography (CT) revealed a new enhanced nodule on the transverse mesocolon about 6 months after surgery. Fluorine-18-fluorodeoxyglucose (18F-FDG) and 18F-fibroblast activation protein inhibitor (FAPI) positron emission tomography (PET)/CT were both performed to evaluate the potential lesions systematically, PET/CT images showed low 18F-FDG activity but very little 18F-FAPI activity in the nodule on the transverse mesocolon. Ultimately, the nodule was pathologically proved to be sutures granuloma. Maybe 18F-FAPI PET/CT is a potential choice to differentiate suture granulomas from metastasis.


Origin and outcome of multiple pregnancies in Bern, Switzerland, 1995-2006 and the current proposal of the Swiss parliament to revise the Swiss law of reproductive medicine: Switzerland quo vadis?
Infertility treatments are a major source of the increase in multiple pregnancies (MPs). The aims of the present study were (1.) to investigate the origin and maternal/neonatal outcomes of MP and (2.) to review the different measures that can be adopted to reduce these serious complications. The study included all women with multiple births between 1 January 1995 and 31 December 2006 at the University Hospital of Bern, Switzerland. The outcomes associated with the various origins of MP (natural conception, ovarian stimulation [OS]--in-vitro fertilisation [IVF-ICSI]) were analysed using a multinomial logistic regression model. An analysis of the Swiss law on reproductive medicine and its current proposed revision, as well as a literature review using Pubmed, was carried out. A total of 592 MP were registered, 91% (n = 537) resulted in live births. There was significantly more neonatal/maternal morbidity in MP after OS compared with natural conception and even with the IVF-ICSI group. With a policy of elective single embryo transfer (eSET), twin rates after IVF-ICSI can be reduced to <5% and triplets to <1%. After OS, more triplets are found and the outcome of MP is worse. MP is known to be associated with morbidity, mortality, and economic and social risks. To counteract these complications (1.) better training for physicians performing OS should be encouraged and (2.) the Swiss law on reproductive medicine needs to be changed, with the introduction of eSET policies. This would lead to a dramatic decrease in neonatal and maternal morbidity/mortality as well as significant cost reductions for the Swiss healthcare system.


Synthetic approaches towards bedaquiline and its derivatives.
Bedaquiline is a diarylquinoline drug that demonstrates potent and selective inhibition of mycobacterial ATP synthase, and is clinically administered for the treatment of multi-drug resistant tuberculosis. Due to its excellent activity and novel mechanism of action, bedaquiline has been the focus of a number of synthetic studies. This review will discuss these synthetic approaches, as well as the synthesis and bioactivity of the numerous derivatives and molecular probes inspired by bedaquiline.


Lack of association between duration of breast-feeding or introduction of cow's milk and development of islet autoimmunity.
The hypothesis that early exposure to cow's milk or lack of breast-feeding predisposes to type 1 diabetes remains controversial. We aimed to determine prospectively the relationship of, first, duration of exclusive breast-feeding and total duration of breast-feeding, and second, introduction of cow's milk protein as infant formula, cow's milk, or dairy products, to the development of islet antibodies in early life. Some 317 children with a first-degree relative with type 1 diabetes were followed prospectively from birth for 29 months (4-73). Mothers kept a home diary and answered infant feeding questionnaires at 6-month intervals. No systematic feeding advice was given. Insulin autoantibodies (normal range <5.5%), anti-GAD antibodies (<5.0 U), and anti-IA2 antibodies (<3.0 U) were measured at 6-month intervals. Cox proportional hazards model of survival analysis detected no significant difference between children who did not develop islet antibodies (225 of 317 [71%]), children with one islet antibody raised once (52 of 317 [16.4%]), children with one antibody raised repeatedly (18 of 317 [5.7%]), or children with two or more antibodies raised (22 of 317 [6.9%]), in terms of duration of exclusive breast-feeding, total duration of breast-feeding, or introduction of cow's milk-based infant formulas, cow's milk, or dairy products (relative risk: 0.91-1.09). Four of the children with two or more islet antibodies developed type 1 diabetes. We conclude that there is no prospective association between duration of breast-feeding or introduction of cow's milk and the development of islet autoimmunity in high-risk children.


Real-life outcomes of COVID-19 vaccination in kidney transplant patients: a single-center experience.
In this study, it was aimed to investigate the clinical (real-life) impact of the vaccination protocol on patients undergoing kidney transplantation during the COVID-19 pandemic. A total of 260 patients who underwent kidney transplantation between June 2012 and May 2022 were retrospectively evaluated. Patients chose vaccination Sinovac-CoronaVac (CoronaVac) and/or BNT162b2 (Biontech), the first vaccine available in the country) in line with the regulations and recommendations of the Ministry of Health. The relationship between vaccination, hospitalization, and mortality in cases diagnosed with COVID-19 was investigated. The prevalence of COVID-19 in patients, the rate of hospital admission, and the mortality of patients before and after the national vaccination program were examined. The study included a total of 260 kidney transplant patients (Female, n = 107 (41%); male, n = 153 (59%). The mean age of patients was 38.42 (11-75). A total of 108 (41.5%) patients were diagnosed with COVID-19. Seven (6.5%) patients died and 221 (85%) patients were vaccinated after the national vaccination program. During the follow-up period, 108 (41.5%) patients were diagnosed with COVID-19. There was no significant difference in terms of hospitalization between two groups. However, there was a significant difference in terms of admission to intensive care unit and mortality (p < 0.001). The majority of cases that died were unvaccinated. However, repeated vaccinations may not adequately protect all transplant recipients. There is a need to develop personalized treatment and prevention strategies in transplantation cases.


Angiotensin II enhances the proliferation of Natural Killer/T-cell lymphoma cells via activating PI3K/Akt signaling pathway.
The present study was to determine the roles of Angiotensin (Ang) II in the growth of lymphoma in nude mice and the proliferation and viability of the human Natural Killer/T (NK/T)-cell lymphoma cell line SNK-6, and the activation of downstream signaling pathway. Lymphoma samples and corresponding normal tissues were obtained from lymphoma patients. Proliferation of SNK-6 cells was detected by CCK8 or MTT assay. The levels of Ang II and its receptor Ang II type 1 receptor (AT1R) were higher in lymphoma tissues than those in control tissues. Ang II increased the lymphoma volume and size in nude mice, the proliferation and viability and the proliferating cell nuclear antigen (PCNA) and Ki67 levels of SNK-6 cells. Losartan, an antagonist of AT1R, reduced lymphoma volume and size in nude mice, and the proliferation and viability and the PCNA and Ki67 levels of SNK-6 cells. The levels of phosphorylated phosphatidylinositol 3-kinase (p-PI3K) and phosphorylated protein kinase B (p-Akt) were increased by Ang II and then reduced by losartan in SNK-6 cells. The proliferation and viability of SNK-6 cells were increased by Ang II, but these increases were inhibited by PI3K inhibitor wortmannin and Akt inhibitor MK2206. The increases of PCNA and Ki67 induced by Ang II were inhibited by wortmannin or MK2206 in SNK-6 cells. These results indicate that Ang II/AT1R is activated in lymphoma, and Ang II promotes the progression of lymphoma in nude mice and the proliferation and viability of SNK-6 cells via activating PI3K/Akt signaling pathway.


Prosthodontics and implants: from xenodontics to biodontics.
To date, the restoration, repair, and replacement of lost and damaged teeth used metals and plastics, nonbiological materials. This type of dentistry has been referred to as "xenodontics." This article discusses the progress in developing a tissue-engineered tooth derived from stem cells. The use of biologically derived replacements for lost and missing teeth is called "biodontics." The technical difficulties that dentists had to overcome historically in restoring, replacing, and repairing lost and damaged teeth are reviewed. The inventiveness and creativity of our professional ancestors in using materials available to restore damaged teeth and to make artificial teeth and denture bases are discussed. This section concludes with the introduction of plastics for both the fabrication of prosthetic teeth and denture bases. The history of root implants is introduced, concluding with the use of titanium. This article concludes by noting that, for the most part, dental schools are just beginning to include implants or computer-aided design (CAD) and computer-aided manufacturing (CAM) into the curriculum and that this process should be accelerated to ensure our graduates are fully prepared to practice efficiently and successfully.


Prestimulus alpha and beta contributions to equiprobable Go/NoGo processing in healthy ageing.
The immediately-prestimulus electroencephalographic (EEG) brain state influences subsequent event-related processing, dynamically impacting event-related potential (ERP) and behavioural outcomes. Both EEG and ERPs are known to undergo age-related change, yet few have investigated the consistency in their dynamic interrelations in the context of ageing. The present investigation assessed the impact of prestimulus alpha and beta brain states in 20 young (18-26 years) and 20 gender-matched healthy older (59-75 years) adults who completed an equiprobable auditory Go/NoGo paradigm. Prestimulus alpha and beta band amplitudes in their prominent band topographies were separately used to derive Go and NoGo ERPs at 10 ascending levels of prestimulus activity, and ERP components were derived for these levels using Principal Components Analysis. Prestimulus alpha directly modulated Go/NoGo P3a amplitudes across the groups, while beta inversely modulated the young (cf. older) adult NoGo N1-1, each supporting and extending limited prior research. Several novel effects were also uncovered, most notably an inverse relationship between prestimulus alpha and reaction time. Prestimulus alpha and beta were confirmed as significant determinants of the processing outcomes in this task, and the complex pattern of results provides a normative map in healthy ageing.


n-Type behavior of graphene supported on Si/SiO(2) substrates.
Results are presented from an experimental and theoretical study of the electronic properties of back-gated graphene field effect transistors (FETs) on Si/SiO(2) substrates. The excess charge on the graphene was observed by sweeping the gate voltage to determine the charge neutrality point in the graphene. Devices exposed to laboratory environment for several days were always found to be initially p-type. After approximately 20 h at 200 degrees C in approximately 5 x 10(-7) Torr vacuum, the FET slowly evolved to n-type behavior with a final excess electron density on the graphene of approximately 4 x 10(12) e/cm(2). This value is in excellent agreement with our theoretical calculations on SiO(2), where we have used molecular dynamics to build the SiO(2) structure and then density functional theory to compute the electronic structure. The essential theoretical result is that the SiO(2) has a significant surface state density just below the conduction band edge that donates electrons to the graphene to balance the chemical potential at the interface. An electrostatic model for the FET is also presented that produces an expression for the gate bias dependence of the carrier density.


Profiles of Motor Laterality in Young Athletes' Performance of Complex Movements: Merging the MOTORLAT and PATHoops Tools.
Laterality is a key aspect of the analysis of basic and specific motor skills. It is relevant to sports because it involves motor laterality profiles beyond left-right preference and spatial orientation of the body. The aim of this study was to obtain the laterality profiles of young athletes, taking into account the synergies between the support and precision functions of limbs and body parts in the performance of complex motor skills. We applied two instruments: (a) MOTORLAT, a motor laterality inventory comprising 30 items of basic, specific, and combined motor skills, and (b) the Precision and Agility Tapping over Hoops (PATHoops) task, in which participants had to perform a path by stepping in each of 14 hoops arranged on the floor, allowing the observation of their feet, left-right preference and spatial orientation. A total of 96 young athletes performed the PATHoops task and the 30 MOTORLAT items, allowing us to obtain data about limb dominance and spatial orientation of the body in the performance of complex motor skills. Laterality profiles were obtained by means of a cluster analysis and a correlational analysis and a contingency analysis were applied between the motor skills and spatial orientation actions performed. The results obtained using MOTORLAT show that the combined motor skills criterion (for example, turning while jumping) differentiates athletes' uses of laterality, showing a clear tendency toward mixed laterality profiles in the performance of complex movements. In the PATHoops task, the best spatial orientation strategy was "same way" (same foot and spatial wing) followed by "opposite way" (opposite foot and spatial wing), in keeping with the research assumption that actions unfolding in a horizontal direction in front of an observer's eyes are common in a variety of sports.


High-performance perovskite-polymer hybrid solar cells via electronic coupling with fullerene monolayers.
A plethora of solution-processed materials have been developed for solar cell applications. Hybrid solar cells based on light absorbing semiconducting polymers infiltrated into mesoporous TiO2 are an interesting concept, but generating charge at the polymer-metal oxide heterojunction is challenging. Metal-organic perovskite absorbers have recently shown remarkable efficiencies but currently lack the range of color tunability of organics. Here, we have combined a fullerene self-assembled monolayer (C60SAM) functionalized mesoporous titania, a perovskite absorber (CH3NH3PbI3-xClx), and a light absorbing polymer hole-conductor, P3HT, to realize a 6.7% efficient hybrid solar cell. We find that photoexcitations in both the perovskite and the polymer undergo very efficient electron transfer to the C60SAM. The C60SAM acts as an electron acceptor but inhibits further electron transfer into the TiO2 mesostructure due to energy level misalignment and poor electronic coupling. Thermalized electrons from the C60SAM are then transported through the perovskite phase. This strategy allows a reduction of energy loss, while still employing a "mesoporous electron acceptor", representing an exciting and versatile route forward for hybrid photovoltaics incorporating light-absorbing polymers. Finally, we show that we can use the C60SAM functionalization of mesoporous TiO2 to achieve an 11.7% perovskite-sensitized solar cell using Spiro-OMeTAD as a transparent hole transporter.


What could health technology assessment learn from living clinical practice guidelines?
A "living" approach to clinical practice guidelines is when the identification, appraisal and synthesis of evidence is maintained and repeated at an agreed frequency, with a clear process for when and how new evidence is to be incorporated. The value of a living approach to guidelines was emphasised during the COVID-19 pandemic when health professionals and policymakers needed to make decisions regarding patient care in the context of a nascent but rapidly evolving evidence base. In this perspective, we draw on our recent experience developing Australian and international living guidelines and reflect on the feasibility of applying living guideline methods and processes to a lifecycle approach to health technology assessment (HTA). We believe the opportunities and challenges of adopting a living approach in HTA fall into five key themes: identification, appraisal and synthesis of evidence; optimising the frequency of updates; embedding ongoing multi-stakeholder engagement; linking the emergence of new evidence to reimbursement; and system capacity to support a living approach. We acknowledge that the suitability of specific living approaches to HTA will be heavily influenced by the type of health technology, its intended use in the health system, local reimbursement pathways, and other policy settings. But we believe that the methods and processes applied successfully to guideline development to manage evidentiary uncertainty could be applied in the context of HTA and reimbursement decision-making to help manage similar sources of uncertainty.


WEBnm@: a web application for normal mode analyses of proteins.
Normal mode analysis (NMA) has become the method of choice to investigate the slowest motions in macromolecular systems. NMA is especially useful for large biomolecular assemblies, such as transmembrane channels or virus capsids. NMA relies on the hypothesis that the vibrational normal modes having the lowest frequencies (also named soft modes) describe the largest movements in a protein and are the ones that are functionally relevant. We developed a web-based server to perform normal modes calculations and different types of analyses. Starting from a structure file provided by the user in the PDB format, the server calculates the normal modes and subsequently offers the user a series of automated calculations; normalized squared atomic displacements, vector field representation and animation of the first six vibrational modes. Each analysis is performed independently from the others and results can be visualized using only a web browser. No additional plug-in or software is required. For users who would like to analyze the results with their favorite software, raw results can also be downloaded. The application is available on http://www.bioinfo.no/tools/normalmodes. We present here the underlying theory, the application architecture and an illustration of its features using a large transmembrane protein as an example. We built an efficient and modular web application for normal mode analysis of proteins. Non specialists can easily and rapidly evaluate the degree of flexibility of multi-domain protein assemblies and characterize the large amplitude movements of their domains.


Long-range interactions in neuronal gene expression: evidence from gene targeting in the GABA(A) receptor beta2-alpha6-alpha1-gamma2 subunit gene cluster.
Clustering of GABA(A) receptor alpha1, alpha6, beta2, and gamma2 subunit genes on mouse chromosome 11/human chromosome 5 may have functional significance for coordinating expression patterns, but until now there has been no evidence for cross-talk between the genes. However, altering the structure of the alpha6 gene, specifically expressed in the cerebellum, with neomycin gene insertions in two different experiments unexpectedly reduced the expression of the widespread alpha1 and beta2 genes in the forebrain. There were corresponding reductions in the levels of alpha1 and beta2 subunit proteins and in autoradiographic ligand binding densities to GABA(A) receptors in the forebrain of alpha6-/- mice. The gamma2 mRNA level was not changed, nor were beta3 and delta mRNAs. The data suggest that elements in the neo gene may have an influence over long distances in the GABA(A) subunit gene complex on as yet undefined structures coordinating the expression of the alpha1 and beta2 genes.


Retrospective analysis of absconding behaviour by acute care consumers in one psychiatric hospital campus in Australia.
Absconding is increasingly being recognized as a problem within mental health settings with significant risks for consumers. This study examines absconding behaviours across three acute care wards within an Australian psychiatric hospital campus over a 12-month period. A descriptive statistical analysis determined the rate of absconding from 49 consumers who absconded 64 times. The absconding rate was 13.33% (absconding events), with most absconding events arising from males diagnosed with schizophrenia (57.14%) aged between 20 and 29 years, and with 62.50% of absconding events occurring whilst consumers were on their first 21-day detention order. Nearly half of all absconding events were by consumers who had absconded previously, with the highest proportion of events occurring during nursing handover. A profile of people who abscond, time of day of absconding, legal status and repeated absconding behaviours are described. The emergent profile of consumers who absconded within this study bears some similarities to that described in overseas research, although in this study consumers were slightly older and 25% of absconders were female. Of particular interest are findings that identify the timings of absconding events in relation to a consumer's legal status. Implications for practice, including assessment of risk of absconding and management, are considered.


Quality of life in patients with benign thyroid disorders. A review.
The importance of patient-reported outcomes such as health-related quality of life (HRQL) in clinical research is increasingly acknowledged. In order to yield valid results, the measurement properties of HRQL questionnaires must be thoroughly investigated. One aspect of such a validation process is the demonstration of content validity, i.e. that the questionnaire covers all relevant aspects. We review studies reporting on consequences of thyroid disorders and present the frequency of identified aspects, both overall HRQL issues and classical thyroid symptoms, in order to evaluate which issues are relevant for patients with thyroid diseases. Furthermore, existing questionnaires for thyroid patients are reviewed. A systematic search was performed in the Medline, Cinahl and Psycinfo databases and the reference lists of the relevant articles were hand-searched. Seventy-five relevant studies were identified. According to these studies, patients with untreated thyroid disease suffer from a wide range of symptoms and have major impairment in most areas of HRQL. Furthermore, the studies indicate that impairments in HRQL are also frequent in the long term. Six HRQL questionnaires for thyroid patients were identified. Generally, data supporting the validity of these questionnaires were sparse. According to the available literature, the quality of life of thyroid patients is substantially impaired over a wide range of aspects of HRQL in the untreated phase and continues to be so in many patients also in the long term. Studies systematically exploring the relative importance of these various aspects to thyroid patients are lacking, as is a comprehensive, validated thyroid-specific HRQL questionnaire.


Peak bone mass from longitudinal data: implications for the prevalence, pathophysiology, and diagnosis of osteoporosis.
We estimated peak bone mass (PBM) in 615 women and 527 men aged 16 to 40 years using longitudinal data from the Canadian Multicentre Osteoporosis Study (CaMos). Individual rates of change were averaged to find the mean rate of change for each baseline age. The age range for PBM was defined as the period during which bone mineral density (BMD) was stable. PBM was estimated via hierarchical models, weighted according to 2006 Canadian Census data. Lumbar spine PBM (1.046 ± 0.123 g/cm(2)) occurred at ages 33 to 40 years in women and at 19 to 33 years in men (1.066 ± 0.129 g/cm(2)). Total hip PBM (0.981 ± 0.122 g/cm(2)) occurred at ages 16 to 19 years in women and 19 to 21 years in men (1.093 ± 0.169 g/cm(2)). Analysis of Canadian geographic variation revealed that the levels of PBM and of mean BMD in those over age 65 sometimes were discordant, suggesting that PBM and subsequent rates of bone loss may be subject to different genetic and/or environmental influences. Based on our longitudinally estimated PBM values, the estimated Canadian prevalences of osteoporosis (T-score < -2.5) were 12.0% (L(1)-L(4)) and 9.1% (total hip) in women aged 50 years and older and 2.9% (L(1)-L(4)) and 0.9% (total hip) in men aged 50 years and older. These were higher than prevalences using cross-sectional PBM data. In summary, we found that the age at which PBM is achieved varies by sex and skeletal site, and different reference values for PBM lead to different estimates of the prevalence of osteoporosis. Furthermore, lack of concordance of PBM and BMD over age 65 suggests different determinants of PBM and subsequent bone loss.


A kinetic study of sulphate transport in rat liver mitochondria.
The kinetics of sulphate uptake catalysed by the dicarboxylate carrier were measured. The Km value for sulphate is about 0.3 mM. A completely competitive relation exists between the influxes of sulphate and malonate, whereas the relation between sulphate and phosphate is of the mixed type. The inhibition of sulphate influx by mersalyl and bathophenanthroline is similar to that of malonate influx and different from the inhibition of phosphate influx. It is considered that sulphate and malonate probably bind to the same locus on the carrier, whereas phosphate occupies a different site. The possible implications of this conclusion are discussed.


Cross-cultural differences in maternal evaluation of children's body shapes.
This study investigated cultural variation in mothers' attitudes to children's body shape. One hundred thirty-one mothers from five cultural groups attending a pediatric clinic were approached, and data obtained from 114. Background information was obtained, including weight and height for themselves and their children. Mothers completed the Eating Attitudes Test (EAT-26) and rated drawings of children for attractiveness and health, using Likert scales, scored 1-7. Mothers from the different cultural groups had similar body mass index (BMI) and EAT scores, and their children had similar average body weight. However, UK mothers found slimmer girls attractive compared to mothers from South Asia, the Mediterranean or the Caribbean regions, and sub-Saharan Africa (p < .05). The differences occurred within the mid-range (median scores for all ethnic groups 4-5). South Asian mothers presented to the pediatric clinic with more worries about their children not gaining weight and growth (p < .01). These findings have implications for understanding cultural variation in the acquisition of attitudes to body shape, and these attitudes influence medical help seeking.


Relationships among insulin resistance, type 2 diabetes, essential hypertension, and cardiovascular disease: similarities and differences.
Insulin resistance plays a major role in the pathogenesis and clinical course of patients with type 2 diabetes (2DM) and essential hypertension. However, the syndromes differ in prevalence of insulin resistance, and associated insulin secretory response. Essentially all patients with type 2 diabetes are insulin resistant, whereas only approximately 50% of those with essential hypertension are insulin resistant. Furthermore, 2DM develops when the pancreatic β-cell can no longer maintain the degree of compensatory hyperinsulinemia needed to prevent hyperglycemia. In contrast, the compensatory hyperinsulinemia that prevents most insulin resistant individuals from developing 2DM acts on normally insulin sensitive tissues in a manner that predisposes to the development of essential hypertension. This review will discuss these similarities and differences in some detail, as well as exploring the relationship among insulin resistance and related metabolic abnormalities in the pathogenesis of cardiovascular disease in patients with 2DM and essential hypertension.


CCK-8 infusion increases plasma LMW alkaline phosphatase coincident with enterohepatic circulation of bile acids.
Bile acids may facilitate the release of liver alkaline phosphatase (ALP) from its hydrophobic membrane anchor. The purpose of this study was to determine whether such a facilitatory role could be observed during the enterohepatic circulation of bile acids in dogs. Increased hepatic ALP activity was induced in four dogs by daily injections of 4 mg.kg-1.day-1 of prednisone for 10 days. Intravenous infusions of cholecystokinin octapeptide (CCK-8) were given before treatment and on treatment days 3, 5, 7, and 10 to induce gallbladder emptying and the enterohepatic circulation of bile acids. Blood samples were taken hourly for 4 h before and for 4 h after CCK-8 infusion. These showed that plasma ALP activity increased significantly only after CCK-8 infusion. Gel exclusion chromatography, polyacrylamide gel electrophoresis, and octyl Sepharose phase separation showed that the increased ALP activity was a hydrophilic, low-molecular-weight (LMW) isoform, which is consistent with phospholipase release. Histochemical staining of endogenous ALP activity showed increased ALP activity over sinusoidal surfaces of prednisone-treated dogs. There was also an increased serum-to-tissue ratio of ALP activity in the prednisone-treated dogs, suggestive of increased release of ALP into blood. It was concluded that bile acids probably play a facilitatory role in the enzymatic release of ALP from the sinusoidal surface of hepatocytes, which may be accentuated by the presence of increased amounts of ALP on the sinusoidal surface in some disease states.


Genetic Instability of Influenza pH1N1 Viruses.
Here, we report full-length genome sequences of influenza pH1N1 viruses obtained prior to and after propagation in MDCK cells. Paired comparisons of the genomes showed that each strain acquired 1.0 to 18.8 mutations per genome per replication cycle, which corresponds to 0.5 to 5.8 mutations per virus proteome per replication cycle. Our analysis indicates that pH1N1 viruses accumulated adaptive mutations among others in response to propagation in cell culture. These results could be important for vaccine and drug-sensitivity surveillance studies, as well as for vaccine and antiviral drug development programs where cell cultures are used for influenza propagation.


The Effect of Prophylactic Steroids on Shivering in Adults Undergoing Surgery: A Systematic Review and Meta-analysis of Randomized Controlled Trials.
Shivering is common following anesthesia and surgery. Corticosteroids (steroids) have been tried to reduce the risk of shivering, but the evidence in favor of their use is uncertain. The primary objective of this review was to evaluate the effect of steroids on the risk of perioperative (intra- and postoperative) shivering versus controls (placebo and active controls). Additional objectives were to assess the risk of severity of shivering, patient satisfaction with shivering prophylaxis, quality of recovery (QoR), and the risk of steroid-related adverse effects. PubMed, Embase, Cochrane Central Registry of Trials, Google Scholar, and preprint servers were searched from inception until November 30, 2022. Randomized controlled trials (RCTs) published in the English language were retrieved, provided they reported on shivering either as a primary or secondary outcome following steroid prophylaxis in adult patients undergoing surgery under spinal or general anesthesia. A total of 3148 patients from 25 RCTs were included in the final analysis. The steroids used in the studies were either dexamethasone or hydrocortisone. Dexamethasone was administered intravenously or intrathecally, while hydrocortisone was administered intravenously. Prophylactic administration of steroids reduced the risk of overall shivering (risk ratio [RR], 0.65 [95% confidence interval {CI}, 0.52-0.82]; P = .0002; I2 = 77%) as well as the risk of moderate to severe shivering (RR, 0.49 [95% CI, 0.34-0.71]; P = .0002; I2 = 61%) in comparison to controls. Administration of intravenous dexamethasone (RR, 0.67 [95% CI, 0.52-0.87]; P = .002; I2 = 78%) and hydrocortisone (RR, 0.51 [95% CI, 0.32-0.80]; P = .003; I2 = 58%) were effective in shivering prophylaxis. For intrathecal dexamethasone (RR, 0.84 [95% CI, 0.34-2.08]; P = .7; I2 = 56%), the null hypothesis of no subgroup difference was not rejected ( P = .47), preventing definitive conclusions about the efficacy of this route of administration. The prediction intervals for both overall shivering risk (0.24-1.70) and risk of severity of shivering (0.23-1.0) precluded generalization of results in future studies. Meta-regression analysis was used to further explore heterogeneity. Factors like the dose and timing of administration of steroids or the type of anesthesia were not found to be significant. Patient satisfaction and QoR were higher in the dexamethasone groups versus placebo. No increased risk of adverse events of steroids was noted versus placebo or controls. Prophylactic steroid administration may be beneficial in reducing the risk of perioperative shivering. However, the quality of evidence in favor of steroids is very low. Further well-designed studies are needed for establishing generalization.


Early identification of HIV: empirical support for jail-based screening.
Although routine HIV testing is recommended for jails, little empirical data exist describing newly diagnosed individuals in this setting. Client-level data (CLD) are available on a subset of individuals served in EnhanceLink, for the nine of the 10 sites who enrolled newly diagnosed persons in the client level evaluation. In addition to information about time of diagnosis, we analyzed data on initial CD4 count, use of antiretroviral therapy (ART), and linkage to care post discharge. Baseline data from newly diagnosed persons were compared to data from persons whose diagnoses predated jail admission. CLD were available for 58 newly diagnosed and 708 previously diagnosed individuals enrolled between 9/08 and 3/11. Those newly diagnosed had a significantly younger median age (34 years) when compared to those previously diagnosed (41 years). In the 30 days prior to incarceration, 11% of those newly diagnosed reported injection drug use and 29% reported unprotected anal intercourse. Median CD4 count at diagnosis was 432 cells/mL (range: 22-1,453 cells/mL). A minority (21%, N = 12) of new diagnoses started antiretroviral treatment (ART) before release; 74% have evidence of linkage to community services. Preliminary results from a cross-sectional analysis of this cohort suggest testing in jails finds individuals early on in disease progression. Most HIV(+) detainees did not start ART in jail; therefore screening may not increase pharmacy costs for jails. Detainees newly diagnosed with HIV in jails can be effectively linked to community resources. Jail-based HIV testing should be a cornerstone of "test and treat" strategies.


The effect of social anxiety on the acquisition and extinction of low-cost avoidance.
Excessive avoidance and safety behaviours are a hallmark feature of social anxiety disorder. However, the conditioning and extinction of avoidance behaviour in social anxiety is understudied. Here, we examined the effect of individual differences in social anxiety on low-cost operant avoidance conditioning and extinction in 80 female participants. We employed an avoidance conditioning and extinction paradigm and measured skin conductance response, threat expectancy ratings and avoidance behaviour throughout the task. Findings demonstrated that elevated levels of social anxiety predicted the generalisation of conditioned avoidance responses across to safety cues during avoidance conditioning. When the opportunity to avoid was returned after the threat extinction phase, elevated social anxiety was associated with increased avoidance behaviour to threat cues. The results suggest that compromised extinction of avoidance behaviour is a characteristic of social anxiety and supports the strategy of minimising avoidance and safety behaviours during exposure therapy for the treatment of social anxiety disorder. Future research should utilise the avoidance conditioning and extinction paradigm as a laboratory model for clinical research to investigate how, and under what circumstances, the extinction of avoidance and safety behaviours can be improved for individuals high in social anxiety.


Emergence of protein fold families through rational design.
Diverse proteins with similar structures are grouped into families of homologs and analogs, if their sequence similarity is higher or lower, respectively, than 20%-30%. It was suggested that protein homologs and analogs originate from a common ancestor and diverge in their distinct evolutionary time scales, emerging as a consequence of the physical properties of the protein sequence space. Although a number of studies have determined key signatures of protein family organization, the sequence-structure factors that differentiate the two evolution-related protein families remain unknown. Here, we stipulate that subtle structural changes, which appear due to accumulating mutations in the homologous families, lead to distinct packing of the protein core and, thus, novel compositions of core residues. The latter process leads to the formation of distinct families of homologs. We propose that such differentiation results in the formation of analogous families. To test our postulate, we developed a molecular modeling and design toolkit, Medusa, to computationally design protein sequences that correspond to the same fold family. We find that analogous proteins emerge when a backbone structure deviates only 1-2 angstroms root-mean-square deviation from the original structure. For close homologs, core residues are highly conserved. However, when the overall sequence similarity drops to approximately 25%-30%, the composition of core residues starts to diverge, thereby forming novel families of protein homologs. This direct observation of the formation of protein homologs within a specific fold family supports our hypothesis. The conservation of amino acids in designed sequences recapitulates that of the naturally occurring sequences, thereby validating our computational design methodology.


Detecting the misuse of 7-oxo-DHEA by means of carbon isotope ratio mass spectrometry in doping control analysis.
The misuse of 7-oxo-DHEA (3β-hydroxyandrost-5-ene-7,17-dione) is prohibited according to the World Anti-Doping Agency (WADA) code. Nevertheless, it is easily available as a dietary supplement and from black market sources. In two recent doping control samples, significant amounts of its main metabolite 7β-OH-DHEA were identified, necessitating further investigations. As both 7-oxo-DHEA and 7β-OH-DHEA are endogenously produced steroids and no concentration thresholds applicable to routine doping controls exist, the development and validation of a carbon isotope ratio (CIR) mass spectrometry method ha been desirable. Excretion studies encompassing 7-oxo-DHEA, 7-oxo-DHEA-acetate, and in-house deuterated 7-oxo-DHEA were conducted and evaluated with regard to urinary CIR and potential new metabolites of 7-oxo-DHEA. Numerous urinary metabolites were identified, some of which have not been reported before, while others corroborate earlier findings on the metabolism of 7-oxo-DHEA. The CIRs of both 7-oxo-DHEA and 7β-OH-DHEA were significantly influenced for more than 50 h after a single oral dose of 100 mg, and a novel metabolite (5α-androstane-3β,7β-diol-17-one) was found to prolong this detection time window by approximately 25 h. Applying the validated method to routine doping control specimens presenting atypically high urinary 7β-OH-DHEA levels clearly demonstrated the exogenous origin of 7-oxo-DHEA and 7β-OH-DHEA. As established for other endogenously produced steroids such as testosterone, the CIR allows for a clear differentiation between endo- and exogenous sources of 7-oxo-DHEA and 7β-OH-DHEA. The novel metabolites detected after administration may help to improve the detection of 7-oxo-DHEA misuse and simplify its detection in doping control specimens.


Review of Testicular Tumor: Diagnostic Approach and Management Outcome in Africa.
Testicular cancer is a common malignancy in young males with higher incidence in developed nations but with the lowest incidence in Africa (0.3-0.6/100 000). Ironically, the global testicular cancer mortality rate has shown a reverse trend to its incidence with higher rates in low- and middle-income countries (0.5 per 100 000) than in high-income countries. Data from GLOBOCAN 2008 have shown relatively high mortality rates in sub-Saharan countries like Mali, Ethiopia, Niger and Malawi. The prognosis of testicular tumor is good with remarkable chemosensitivity to cisplatin-based regimen. Early diagnosis, careful staging and a multidisciplinary management approach is crucial to achieve this optimal result. These results are achievable in the sub-Saharan region if the relevant resources are appropriated for cancer care and clinical guidelines are formulated in a regional context.


Whole-Lesion Histogram Analysis of the Apparent Diffusion Coefficient as a Quantitative Imaging Biomarker for Assessing the Level of Tumor-Infiltrating Lymphocytes: Value in Molecular Subtypes of Breast Cancer.
To assess whether apparent diffusion coefficient (ADC) metrics can be used to assess tumor-infiltrating lymphocyte (TIL) levels in breast cancer, particularly in the molecular subtypes of breast cancer. In total, 114 patients with breast cancer met the inclusion criteria (mean age: 52 years; range: 29-85 years) and underwent multi-parametric breast magnetic resonance imaging (MRI). The patients were imaged by diffusion-weighted (DW)-MRI (1.5 T) using a single-shot spin-echo echo-planar imaging sequence. Two readers independently drew a region of interest (ROI) on the ADC maps of the whole tumor. The mean ADC and histogram parameters (10th, 25th, 50th, 75th, and 90th percentiles of ADC, skewness, entropy, and kurtosis) were used as features to analyze associations with the TIL levels in breast cancer. Additionally, the correlation between the ADC values and Ki-67 expression were analyzed. Continuous variables were compared with Student's t-test or Mann-Whitney U test if the variables were not normally distributed. Categorical variables were compared using Pearson's chi-square test or Fisher's exact test. Associations between TIL levels and imaging features were evaluated by the Mann-Whitney U and Kruskal-Wallis tests. A statistically significant difference existed in the 10th and 25th percentile ADC values between the low and high TIL groups in breast cancer (P=0.012 and 0.027). For the luminal subtype of breast cancer, the 10th percentile ADC value was significantly lower in the low TIL group (P=0.041); for the non-luminal subtype of breast cancer, the kurtosis was significantly lower in the low TIL group (P=0.023). The Ki-67 index showed statistical significance for evaluating the TIL levels in breast cancer (P=0.007). Additionally, the skewness was significantly higher for samples with high Ki-67 levels in breast cancer (P=0.029). Our findings suggest that whole-lesion ADC histogram parameters can be used as surrogate biomarkers to evaluate TIL levels in molecular subtypes of breast cancer.


Apolipoprotein B is highly associated with the risk of coronary heart disease as estimated by the Framingham risk score in healthy Korean men.
The aim of this study was to examine the association between serum apolipoprotein B (apoB) and the risk of coronary heart disease (CHD) using Framingham risk score (FRS) in healthy Korean men. A total of 13,523 men without medication history of diabetes and hypertension were enrolled in this study. The FRS is based on six coronary risk factors. FRS ≥ 10% was defined as more-than-a-moderate risk group and FRS ≥ 20% as high risk group, respectively. The logistic regression analyses were conducted. When quartile 1 (Q1) set as a reference, in unadjusted analyses, the Q2, Q3, Q4 of apoB level had increased odds ratio (OR) for the risk of CHD in both more-than-a-moderate risk and high risk group, respectively. After adjusting for confounding variables, multivariable-adjusted logistic regression analyses showed a strong relationship between the quartiles of apoB level and more-than-a-moderate risk and high risk group, respectively. These associations were attenuated, but still remained statistically significant. ApoB is found to be independently related to the risk of CHD using FRS in healthy Korean men, and the link between apoB and the risk of CHD is dose-dependent.


Receptor-mediated mitogenic signals and lung cancer.
Most lung cancers are simultaneously stimulated by several autocrine and paracrine growth factors. Diseases resulting in excessive production of these factors and/or changes in the receptors, second messengers, or genes comprising their signal transduction pathways can thus result in the stimulation of continuous cell proliferation characteristic of cancer. Some carcinogenic N-nitrosamines mimic the stimulatory effect of cell-type-specific growth factors by binding to their receptors, and in this way mediate their selective carcinogenic effects. In this review I discuss the significance of receptor-mediated mitogenic signal transduction pathways for the initiation and progression of lung cancer, and describe novel lung cancer therapeutics that target components of these pathways.


Spatial and temporal dynamics of the colonization of Pinus radiata by Fusarium circinatum, of conidiophora development in the pith and of traumatic resin duct formation.
· Fusarium circinatum causes pitch canker disease in a wide range of pine trees, including Pinus radiata, with devastating economic consequences. · To assess the spatial and temporal dynamics of growth of this pathogen in radiata pine, we examined the process of infection using both real-time PCR to quantify fungal biomass inside the plant host, and confocal microscopy using a green fluorescent protein (GFP)-tagged strain of F. circinatum. · Pathogen growth exhibited three distinct phases: an initial exponential increase in fungal biomass, concomitant with pathogen colonization of the cortex and phloem; a slowdown in fungal growth coincident with sporulating hyphae deep within the host; and stabilization of the fungal biomass when the first wilting symptoms appeared. The number of resin ducts in the xylem was found to increase in response to infection and the fungus grew inside both constitutive and traumatic resin ducts. · These results indicate that conidiation may contribute to the spatial or temporal dissemination of the pathogen. Moreover, the present findings raise the intriguing possibility that the generation of traumatic resin ducts may be of more benefit to the fungus than to the plant.


Spinal Cord Subependymoma Surgery : A Multi-Institutional Experience.
A spinal cord subependymoma is an uncommon, indolent, benign spinal cord tumor. It is radiologically similar to a spinal cord ependymoma, but surgical findings and outcomes differ. Gross total resection of the tumor is not always feasible. The present study was done to determine the clinical, radiological and pathological characteristics of spinal cord subependymomas. We retrospectively reviewed the medical records of ten spinal cord subependymoma patients (M : F=4 : 6; median 38 years; range, 21-77) from four institutions. The most common symptoms were sensory changes and/or pain in eight patients, followed by motor weakness in six. The median duration of symptoms was 9.5 months. Preoperative radiological diagnosis was ependymoma in seven and astrocytoma in three. The tumors were located eccentrically in six and were not enhanced in six. Gross total resection of the tumor was achieved in five patients, whereas subtotal or partial resection was inevitable in the other five patients due to a poor dissection plane. Adjuvant radiotherapy was performed in two patients. Neurological deterioration occurred in two patients; transient weakness in one after subtotal resection and permanent weakness after gross total resection in the other. Recurrence or regrowth of the tumor was not observed during the median 31.5 months follow-up period (range, 8-89). Spinal cord subependymoma should be considered when the tumor is located eccentrically and is not dissected easily from the spinal cord. Considering the rather indolent nature of spinal cord subependymomas, subtotal removal without the risk of neurological deficit is another option.


Packing DNA into chromosomes.
Electron microscopy of HeLa metaphase nucleoids (i.e. whole metaphase cells exposed to 2 M salt and non-ionic detergent) spread by the Kleinschmidt technique, reveals a variety of protein-depleted structures (spreads) derived from chromosomes. Spreads vary in size and shape. At one extreme are oval structures with one or more cores surrounded by a network of supercoiled fibres. These fibres are probably arranged as loops and we estimate that 600-1000 may emerge from a single, large core region. At the other extreme are chromosome-shaped spreads with an elongated core which takes the form of a multifibred axis. At intervals groups of lateral fibres appear to emerge from each axis to produce the network. Spreads intermediate between these extremes occur in which axial fibres can be resolved in only part of the elongated core. Similar structures are observed in chromosomes deproteinized and spread after isolation by a procedure which preserves high molecular weight DNA. The appearance of chromosomes isolated by the Wray-Stubblefield hexylene glycol procedure agrees in general with previous findings of others, except that in some more extended spreads axial fibres are visible. We believe our observations are consistent with the idea that the chromonema of each metaphase chromatid contains regions of multistranded DNA. We do not propose, however, that the chromatid is functionally multineme, but rather that axial fibre folding either within or between chromomere regions contributes to packing of DNA in the metaphase chromosome. These regions of constraint re also postulated as the locations of emergence of lateral loops. In spread preparations the axial fibres are seen clearly only when chromatids have been elongated beyond the contracted metaphase length. Elongation would be produced both by relaxation of chromosomal coils (gyres) and by extension of the chromonema upon deproteinization and spreading. Whereas in deproteinized nucleoids the long axis is liable to elongate, fragment or collapse, the chromomena of Wray-Stubblefield chromosomes is locked at the metaphase (gyred) length and axial fibres are generally not visible. We propose that the assembly of the complex DNA axis of the metaphase chromosome from its extended interphase counterpart plays a major part in increasing the DNA packing ratio in the mitotic cell.


Dynamic filling parameters in patients with atrial fibrillation: differentiating rhythm induced from ventilation-induced variations in pulse pressure.
In patients with sinus rhythm, the magnitude of mechanical ventilation (MV)-induced changes in pulse pressure (PP) is known to predict the effect of fluid loading on cardiac output. This approach, however, is not applicable in patients with atrial fibrillation (AF). We propose a method to isolate this effect of MV from the rhythm-induced chaotic changes in PP in patients with AF. In 10 patients undergoing pulmonary vein ablation for treatment of AF under general anesthesia, ECG and PP waveforms were analyzed during apnea (T1) and during MV at tidal volumes of 8 ml/kg (T2) and 12 ml/kg (T3), respectively. In a first step, three mathematical models were compared in their ability to predict individual PP at T1. The best-fitting model was then selected as the reference to quantify the effects of MV on PP in these patients. A local polynomial regression model based on two preceding RR intervals (LOC2) was found to be superior over the quadratic models to predict PP. LOC2 was therefore selected to quantify variations in PP induced by MV. During T2 and T3, magnitude of PP deviations was related with the amplitude of tidal volume [mean bias error (SD) of -5 (6) and -8 (7) mmHg for T2 and T3, respectively; P = 0.003 repeated-measures ANOVA]. We conclude that LOC2 most accurately predicted rhythm-induced variations in PP. MV-induced deviations in PP can be quantified and may therefore provide a method to study cardiopulmonary interactions in the presence of arrhythmia.


Characterization of polar-flagellar-length mutants in Vibrio alginolyticus.
Vibrio alginolyticus has two types of flagella, polar (Pof) and lateral (Laf). From a Laf-defective mutant (Pof+Laf-), polar-flagellar-length mutants which have short Pof and long Pof were isolated. The mean lengths of the helical axis in wild-type, short and long Pof were 220.127.116.11 μm, 184.108.40.206 μm and 126.96.36.199 μm, respectively. The swimming speeds of the short- and long-Pof mutants were slower than that of the wild-type strain. The relationship between swimming speed and flagellar length in a population of mutant cells was examined. In the short-Pof mutant, the decrease of swimming speed seemed to be derived from the decrease in flagellar length. In the long-Pof mutant, there was almost no correlation between swimming speed and flagellar length, and the slow swimming was explained by the helical shape of the flagella, whose pitch and radius were 1.4 μm and 0.062 μm, respectively, whereas those of the wild-type flagella were 1.5 μm and 0.16 μm. The relative amounts of the various molecular components of the long Pof were different from those of the wild-type or the short Pof. This seems to be the reason for the difference in flagellar shape and length, though the mutation may be pleiotropic and affect flagellar function or regulation.


[Contractile apparatus organization of cardiomyocytes upon their cultivation in collagen gels].
Cardiomyocytes are known to change their morphology and reorganize the contractile apparatus upon their culturing in 2D culture systems. Therefore, the monolayer cardiomyocyte cultures appear to be a poor model for studying of the biologically important processes in the heart. Present study relates to the searching for the most optimal culture conditions allowing cardiomyocytes to maintein their typical morphology and the native state of contractile apparatus. In this study, we investigated organization of the contractile apparatus of cardiomyocytes when cultured in 3D collagen gels of different density. It has been shown that cardiomyocytes preserve the initial organization of their contractile apparatus during prolonged cultivation in collagen gels at a concentration of 1 mg/ml, whereas partial reorganization of their contractile apparatus is observed at a concentration of 0.5 and 1.5 mg/ml. Thus, cardiomyocytes placed in 3D collagen gels with a protein concentration of 1 mg/ml could be considered as a culture be model which approximates to the natural conditions.


Transgene-induced gene silencing is not affected by a change in ploidy level.
Whole genome duplication, which results in polyploidy, is a common feature of plant populations and a recurring event in the evolution of flowering plants. Polyploidy can result in changes to gene expression and epigenetic instability. Several epigenetic phenomena, occurring at the transcriptional or post-transcriptional level, have been documented in allopolyploids (polyploids derived from species hybrids) of Arabidopsis thaliana, yet findings in autopolyploids (polyploids derived from the duplication of the genome of a single species) are limited. Here, we tested the hypothesis that an increase in ploidy enhances transgene-induced post-transcriptional gene silencing using autopolyploids of A. thaliana. Diploid and tetraploid individuals of four independent homozygous transgenic lines of A. thaliana transformed with chalcone synthase (CHS) inverted repeat (hairpin) constructs were generated. For each line diploids and tetraploids were compared for efficiency in post-transcriptional silencing of the endogenous CHS gene. The four lines differed substantially in their silencing efficiency. Yet, diploid and tetraploid plants derived from these plants and containing therefore identical transgene insertions showed no difference in the efficiency silencing CHS as assayed by visual scoring, anthocyanin assays and quantification of CHS mRNA. Our results in A. thaliana indicated that there is no effect of ploidy level on transgene-induced post-transcriptional gene silencing. Our findings that post-transcriptional mechanisms were equally effective in diploids and tetraploids supports the use of transgene-driven post-transcriptional gene silencing as a useful mechanism to modify gene expression in polyploid species.


Patient-reported Outcomes and Revision Rates at a Mean Follow-up of 10 Years After Lumbar Total Disc Replacement.
Prospective observational cohort study. The aim of this study was to determine the long-term clinical results and prosthesis survival in patients treated with lumbar total disc replacement (TDR). Fusion has become the current standard surgical treatment for lumbar degenerative disease. TDR is an alternative treatment that seeks to avoid fusion-related adverse events, specifically adjacent segment disease. Sixty-eight consecutive patients treated with TDR from 2003 to 2008 were invited to follow-up and complete a Visual Analog Scale (VAS) for back and leg pain, the Dallas Pain Questionnaire (DPQ), and the Short Form-36. These surveys were also administered to the subjects before their index TDRs. Data on reoperation were collected from the patients' medical records. Fifty-seven (84%) patients were available for follow-up at a mean 10.6 years post-operatively (range 8.1-12.6 years). There was a significant improvement from preop to latest follow-up in VAS (6.8 vs. 3.2, P < 0.000) and DPQ (63.2 vs. 45.6, P = 0.000) in the entire cohort. Nineteen patients (33%) had a revision fusion surgery after their index TDR. Patients who had revision surgery had statistically significant worse outcome scores at last follow-up than patients who had no revision. Thirty patients (52.6%) would choose the same treatment again if they were faced with the same problem. This study demonstrated significant improvement in long-term clinical outcomes, similar to previously published studies, and two-thirds of the discus prostheses were still functioning at follow-up. However, there is still a lack of well-designed long-term studies, thus requiring further investigation. 3.


Web-based survey of fertility issues in young women with breast cancer.
Young women with breast cancer often seek advice about whether treatment will affect their fertility. We sought to gain a better understanding of women's attitudes about fertility and how these concerns affect decision making. We developed a survey about fertility issues for young women with a history of early-stage breast cancer. The survey was e-mailed to all registered Young Survival Coalition survivor members (N = 1,702). E-mail reminders were used. Six hundred fifty-seven eligible respondents completed the survey. Mean age at breast cancer diagnosis was 32.9 years; mean current age was 35.8 years. Ninety percent of women were white; 62% were married; 76% were college graduates. Stages at diagnosis were as follows: 0, 10%; I, 27%; II, 47%; III, 13%. Sixty-two percent of women were within 2 years of diagnosis. Fifty-seven percent recalled substantial concern at diagnosis about becoming infertile with treatment. In multivariate logistic regression, greater concern about infertility was associated with wish for children/more children (odds ratio [OR], 120; P < .0001), number of prior pregnancies (OR, 0.78; P = .01), and prior difficulty conceiving (OR, 1.86; P = .08). Twenty-nine percent of women reported that infertility concerns influenced treatment decisions. Seventy-two percent of women reported discussing fertility concerns with their doctors; 51% felt their concerns were addressed adequately. Women seemed to overestimate their risk of becoming postmenopausal with treatment. Fertility after treatment is a major concern for young women with breast cancer. There is a need to communicate with and educate young patients regarding fertility issues at diagnosis and a need for future research directed at preserving fertility for young breast cancer survivors.


[Haemophilus influenzae in respiratory pathology in adults].
Fifty patients were diagnosed bronchopulmonary Haemophilus infections, because of the production of a purulent sputum, containing at least 10(8) Haemophilus influenzae per ml. Among them were 36 males (average 52 years old) and 14 females (average 58 years old). There was a high percentage (64%) of smokers (over 30 packs/year) within this population, which also included heavy drinkers. The top incidence occurred in winter and spring. Most cases were related to an acute infection in a chronic bronchitis (26 cases). The other cases included 6 cancers, 6 sequelae of tuberculosis, 4 bronchiectasis, 4 asthma, and only 3 pulmonary consolidations. There usually was a low grade fever (only 8 cases reached or went beyond 38 degrees, while in 29 cases the body temperature kept below 38 degrees). The return to a normal temperature was obtained after 4 to 10 days of ampicillin therapy, with no fatal case within this series. The 50 strains were studied by the microbiology laboratory. The minimum inhibitory concentrations showed an elective response to ampicillin and erythromycin, and a less dramatic response to chloramphenicol and tetracyclin. Some strains were proved resistant (MIC over 4 micrograms per ml) to cefoxitin and cefamandole.


Assessing Social Functioning During COVID-19 and Beyond: Tools and Considerations for Nursing Home Staff.
Social functioning is defined as how a person operates in their unique social environment (ie, engagement in activities, connectedness with others, and contributions to social roles). Healthy social functioning is important for nursing home residents as they are at increased risk for loneliness and isolation. Social functioning has long been an underacknowledged aspect of nursing home residents' health, but now, with the COVID-19 pandemic, residents' risk for decreased social functioning is increased. Several reliable and well-validated tools are available to supplement routine care planning and delivery and track and improve changes in social functioning over time. The overarching aim of this article is to provide resources and recommendations for interdisciplinary team assessment related to social functioning for nursing home residents. We describe 2 domains of social functioning measures, care-planning measures and outcome measures, and provide recommendations for how to integrate said measures into practice. Healthy social functioning is needed to maintain nursing home residents' well-being and quality of life. Measures and recommendations outlined in this article can be used by nursing home staff to understand residents' social preferences and address social functioning during COVID-19 and beyond.


Designing a risk communication strategy for health hazards posed by traditional slaughter of goats in Tshwane, South Africa.
In African societies, traditional slaughter is linked to celebrations like weddings or births, as well as funerals and ancestor veneration. Participants in traditional slaughter of goats are at risk of exposure to hazards during slaughter, food preparation and consumption of goat meat. For risk mitigation strategies to be implemented, identification of the population at risk is required. This study is based on the premise that the demographic profile of people involved in traditional slaughter of goats is important for risk communication. Both structured and informal interviews were recorded and analysed using a thematic analysis. A total of 105 people were interviewed at taxi ranks in Tshwane, Gauteng. Of these, 48 were women and 57 men. The median age of women and men was 40.6 years and 44.3 years, respectively. The majority of respondents (61.9%, n = 65) interviewed were from the Gauteng Province. Sixty percent (n = 63) of respondents had a secondary education, whilst less than 4.81% (n = 5) of respondents had no formal education. This study demonstrated that interviewing commuters at taxi ranks gave access to a cross section of gender, age, language and origin. It was found that both genders were involved in traditional slaughter of goats. Risk communication strategies should thus target women as well as men. Communication strategies to mitigate the risks of traditional slaughter of goats should take into consideration the dynamic nature of demographic and cultural norms. In light of the wide demographic profile of the respondents, it was concluded that it should be possible to use taxi ranks for successful dissemination of food safety and occupational health risk mitigation messages.


Charge-to-alanine mutagenesis of the adeno-associated virus type 2 Rep78/68 proteins yields temperature-sensitive and magnesium-dependent variants.
The adeno-associated virus type 2 (AAV) replication (Rep) proteins Rep78 and 68 (Rep78/68) exhibit a number of biochemical activities required for AAV replication, including specific binding to a 22-bp region of the terminal repeat, site-specific endonuclease activity, and helicase activity. Individual and clusters of charged amino acids were converted to alanines in an effort to generate a collection of conditionally defective Rep78/68 proteins. Rep78 variants were expressed in human 293 cells and analyzed for their ability to mediate replication of recombinant AAV vectors at various temperatures. The biochemical activities of Rep variants were further characterized in vitro by using Rep68 His-tagged proteins purified from bacteria. The results of these analyses identified a temperature-sensitive (ts) Rep protein (D40,42,44A-78) that exhibited a delayed replication phenotype at 32 degrees C, which exceeded wild-type activity by 48 h. Replication activity was reduced by more than threefold at 37 degrees C and was undetectable at 39 degrees C. Stability of the Rep78 protein paralleled replication levels at each temperature, further supporting a ts phenotype. Replication differences resulted in a 3-log-unit difference in virus yields between the permissive and nonpermissive temperatures (2.2 x 10(6) and 3 x 10(3), respectively), demonstrating that this is a relatively tight mutant. In addition to the ts Rep mutant, we identified a nonconditional mutant with a reduced ability to support viral replication in vivo. Additional characterization of this mutant demonstrated an Mg(2+)-dependent phenotype that was specific to Rep endonuclease activity and did not affect helicase activity. The two mutants described here are unique, in that Rep ts mutants have not previously been described and the D412A Rep mutant represents the first mutant in which the helicase and endonuclease functions can be distinguished biochemically. Further understanding of these mutants should facilitate our understanding of AAV replication and integration, as well as provide novel strategies for production of viral vectors.