A first-principles study of the III-IV-V semiconductor nanosheets.
Alloying the III-V and IV-IV sheets leads to III-IV-V nano-composites, such as the BC2N sheet, having a lower band gap than their parent III-V counterparts while having higher cohesive energies. Unlike the well known BC2N sheet, the formation energy of the III-IV-V sheets with high Z atomic constituents is much low suggesting in favour of their experimental realisation. From first-principles hybrid density functional calculations, we report a family of group III-IV-V nano-sheets that have their electronic band gap lying between 0.13-1.0 eV, which is ideal for device applications. In particular, we compare the electronic, vibrational, mechanical and thermal properties of a set of III-IV-V sheets with their III-V and IV-IV counterparts. The cohesive energies of these III-IV-V sheets are found to be the intermediate of their parent III-V and IV-IV counterparts. The puckered geometry and the presence of heterogeneous bonds may result in low thermal conductivity (due to scattering of low energy phonons at the junction of the IIIV and IVIV chains) of these sheets.


First Report on Stem Cell Transplant From Iraq.
The Iraqi Bone Marrow Transplantation Center is located in the medical city complex of Bab Almuadham in Baghdad, Iraq. It was established on March 11, 2002, and performed its first mini-allotransplant for acute myeloid leukemia on January 24, 2003. Among 16 patients who received hematopoietic stem cell transplant between January 2003 and January 2010, one patient underwent allogeneic bone marrow transplant for acute myeloid leukemia and 15 patients received autologous bone marrow transplant for the following indications: 5 had multiple myeloma, 9 had lymphoma (8 with Hodgkin disease and 1 with non- Hodgkin lymphoma), and 1 had rhabdomyosarcoma. Median age was 34 years (range, 10-56 y), and our patient group included 8 females and 8 males. Of the 16 patients, 12 are still alive. The mortality rate was 25% as measured during our follow-up from 2 to 96 months. Of the 9 patients with lymphoma, 1 died and 2 relapsed after transplant. Therefore, our survival rate in lymphoma was 88%, with progression-free survival in lymphoma ranging from 2 to 66 months (mean survival of 13 mo, mode of 13 mo). For the 5 patients with multiple myeloma who received transplants, 1 died and 2 relapsed, with effective-free survival of 6 to 13 months. Our results show that high-dose chemotherapy followed by autologous stem cell transplant can induce long-term disease control in this cohort of patients with refractory or advanced Hodgkin disease; progression-free survival for our cohort was 50%, with survival comparable to those reported in the literature.


The importance of the supratrochlear foramen of the humerus in humans: an anatomical study.
The supratrochlear foramen (STF) is an important and relatively common anatomic variation in the lower end of the humerus in humans. Its structure has received increased attention in recent years. Anatomical knowledge of STF is useful for anatomists, anthropologists, orthopedic surgeons, and radiologists. This aperture is of great interest to anthropologists who claim it as one of the points in establishing a relationship between humans and lower animals. The goal of this study was to describe the features of STF of the humerus in the Turkish population. All bones were obtained from the Department of Anatomy, Faculty of Medicine and Department of Antrophology, University of Mustafa Kemal, Hatay. A total of 166 dried humeri (83 right side and 83 left side), of which 78 belonged to males and 88 to females, were examined to determine the presence of supratrochlear foramen. Digital vernier calipers were used to measure the maximum width (transverse) and height (vertical) of the STF. Out of 166 bones, the foramen was present in 18 humeri (4 right side and 14 left side), showing the incidence as 10.8% with unpaired humeri. We observed 4 types of shape: oval, round, triangular, and sieve-like. The average diameter of the long (transverse) axis was 5.93±1.68 mm and the short (vertical) axis was 4.06±0.89 mm. Some of the bones showed translucency of the bony septum, found in 17 (20.5%) on both sides of the humeri. There are few studies about STF in the Turkish population. Knowledge of supratrochlear foramen in the distal humerus in humans is important in diagnostic orthopedics, in intramedullary nailing of the humerus, and in possibly increasing the risk of future low-energy fractures. In addition, STF is a radiolucent area in radiographs and may be misinterpreted as an osteolytic or cystic lesion.


Portulene, a new diterpene from Portulaca oleracea L.
Chromatographic fractionation of the chloroform extract of Portulaca oleracea L. growing in Egypt afforded a new clerodene diterpene portulene (1), in addition to the known compounds lupeol (2), beta-sitosterol (3), and daucosterol (4), which were reported for the first time from the title plant. The structures of the isolated compounds were unambiguously established through 1D, 2D, and mass spectral analyses. Co-treatment of CCl(4) hepatic injured rats with 70% alcohol extract of P. oleracea significantly restored the hepatic marker enzymes and total bilirubin to near-normal values, which demonstrated hepatoprotective activity. In addition, the P. oleracea extract showed antibacterial and antifungal activities.


11C-methionine PET for the diagnosis and management of recurrent pituitary adenomas.
The detection of recurrent pituitary adenoma by magnetic resonance imaging (MRI) is rendered uncertain by the tissue remodelling that follows surgery or radiotherapy. We aimed to evaluate the contribution of PET with 11C-methionine (MET-PET) in the detection and management of recurrent pituitary adenoma. Thirty-three patients with pituitary adenoma were evaluated postoperatively by MET-PET, either because of biological evidence of active residual tumour or because of MRI demonstration of non-functional adenoma growth. We studied 24 secreting adenomas and nine non-functional adenomas. In 30 patients, MET-PET detected abnormally hypermetabolic tissue. In 14 out of these, MRI did not differentiate between residual tumour and scar formation. In nine of these 14 cases, major therapeutic decisions were undertaken (radiosurgery and surgery). In another group of 16 patients, both MET-PET and MRI detected abnormal tissue. In one case, neither MRI nor MET-PET detected adenomatous tissue. Finally, abnormal tissue was detected in two patients on MRI solely. In these two cases, failure of MET-PET to reveal the adenoma was attributable to concomitant inhibitory therapy. The sensitivity of MET-PET and MRI varied as a function of the tumour type: all non-functional adenomas were localised by both modalities, while MET-PET detected all adrenocorticotropic hormone-secreting adenomas whereas MRI depicted only one of these eight lesions. Fifteen out of 17 patients treated by radiosurgery showed clinical improvement after treatment. We suggest that MET-PET is a sensitive technique complementary to MRI for the detection of residual or recurrent pituitary adenomas. It should gain a place in the efficient management of these tumours.


Does glucose present in the dialysate limit oxidative stress in patients undergoing regular hemodialysis?
Decreased glucose concentration in the blood causes the inhibition of the hexose monophosphate (HMP) cycle in the erythrocyte. NADPH, which is the source of the reductive equivalents necessary for the reproduction of glutathione (GSH), is not regenerated. The presence of glucose in dialysate should provide the stability of its concentration in the blood of patients undergoing hemodialysis (HD). The aim of the study was to assess the influence of glucose in the dialysate on the intensity of oxidative stress in patients undergoing regular HD. The study comprised 43 patients hemodialyzed with dialysate containing (HD-g(+)) or not containing glucose (HD-g(-)). The concentrations of the products of reaction with thiobarbituric acid-reactive substance (TBARS) and GSH as well as the activity of erythrocyte superoxide dismutase were determined. Glucose concentrations in the blood before and immediately after dialysis were also measured. After flow-through dialysis the glucose concentration in the blood decreases both when dialysate does not contain glucose (4.8 vs. 1.6 mmol/l) and when dialysate contains glucose (6.6 vs. 5.8 mmol/l). HD caused changes in the TBARS concentration: in the HD-g(+) group the concentration decreased after HD, whereas in the HD-g(-) group it increased. In both groups of patients studied the GSH concentration changed after HD; in the HD-g(-) group it decreased and in the HD-g(+) group it increased. The results obtained in the groups of patients examined were confirmed by in vitro studies. The presence of glucose in the dialysate guarantees the normal activity of the HMP cycle, which provides the production of reductive equivalents for the regeneration of reduced GSH - free radicals scavenger - and therefore the limitation of oxidative stress.


Two-dimensional symmetrical radial sub-aperture coherence and the local precision defect elimination method for high-precision beam steering.
Sub-aperture coherence (SAC) is a classical phase control method for high-precision beam steering using liquid crystal optical phased arrays (LCOPA). On this basis, radial sub-aperture coherence (RSAC) and symmetrical radial sub-aperture coherence (SRSAC) were proposed, which guarantee the stability of steering angles when the beam aperture and incident position fluctuate. In this article, the pre-existing one-dimensional SRSAC was firstly extended to a more universal 2D phase generation algorithm. Meanwhile, for the intractable problem of local precision defects caused by the basic two-dimensional variable period grating (2D-VPG) algorithm, we tracked their locations accurately and designed a targeted elimination method carefully. So these remarkable error peaks could be thoroughly removed by using 2D-SRSAC optimized by the local precision defect elimination method. Since then, all the excellent performance of 1D-SRSAC can be perfectly transplanted to 2D, which makes the non-mechanical beam steering technology using LCOPA more mature and competitive in the applications required ultra-high precision.


Circulating endothelial progenitor cells in systemic sclerosis: relation to impaired angiogenesis and cardiovascular manifestations.
Given the essential role of endothelial progenitor cells (EPCs) in endothelial repair and neovascularization, it is likely that insufficient angiogenesis seen in systemic sclerosis (SSc) is related to EPC alterations. The present study was aimed to analyze in SSc the number of circulating EPCs and their contribution into cardiovascular involvement. EPC (CD34+VEGF-R2+ and CD133+VEGF-R2+) circulating levels were evaluated in 40 SSc patients and 24 controls by FACS; their correlations with peripheral vascular manifestations, heart involvement, Framingham risk score, carotid artery disease, endothelial function and morphological signs of microangiopathy were studied. Early stage SSc and high disease activity were accompanied by a rise in circulating EPC levels in association with increased membrane expression of Fas (CD95) that correlated positively with severity of peripheral vascular manifestations. EPC reduction with disease progression was linked with endothelial dysfunction and capillary loss, and showed a strong relation to the development of severe internal organ (predominantly cardiac) involvement and pulmonary hypertension. There was a tendency to decreased EPC levels in SSc pts with low HDL values, but no significant correlations were found between EPCs and Framingham risk factor score, carotid artery IMT and traditional cardiovascular risk factors. In early stage SSc mobilization of EPCs in response to tissue ischemia was preserved, but dropped with disease progression. EPC reduction may contribute to endothelial dysfunction and impaired angiogenesis, leading to the development of severe vascular life-threatening complications of SSc. Traditional cardiovascular risk factors and subclinical atherosclerosis did not influence EPC levels in SSc patients.


[The characteristic of severe acute pancreatitis and the selection of the therapeutic strategy].
To investigate the relationship between the clinical character and therapeutic strategy and prognosis in severe acute pancreatitis. From January 2001 to December 2005, 783 patients with SAP were treated. Therapeutic strategy was selected based on the preliminary scheme for diagnosis and treatment of severe acute pancreatitis by pancreatic surgery society of CMA. All the patients were divided into biliary group and non-biliary group, while 375 patients in biliary group, with 182 patients treated operatively and 193 patients treated nonoperatively; and 408 patients in non-biliary group, with 147 patients treated operatively and 261 patients treated nonoperatively. There were 698 survivals, the overall survival rate was 89.1%. 357 survivals in the biliary SAP group, the survival rate was 95.0%, in which 171 survivals from operation treated cases, with the survival rate of 94.0%, and 186 survivals from non-operation treated cases, with the survival rate of 96.4%; 341 survivals in the non-biliary SAP group, the survival rate was 84.0%, in which 110 survivals from operation treated cases, with the survival rate of 74.8%, and 231 survivals from non-operation treated cases, with the survival rate of 88.5%. 48.3% patients of the survival group had organ dysfunction, and 18.3% patients had multiple organ dysfunctions, while 100% patients of the death group had organ dysfunction, and 97.6% patients had multiple organ dysfunction. Respiratory dysfunction was found to be the most common cause totally followed by nerve system dysfunction and shock, with the rates of 26.3%, 11.7% and 10.3%, respectively. Respiratory dysfunction, renal dysfunction and cardiac dysfunction are most commonly in death group, with the rate of 94.1%, 60.0% and 60.0%, respectively. The rate of fungi infection in the survival group and death group were 8.9% and 37.6%. The rates of alimentary tract fistula in the survival and death group were 0.9% and 14.1%, respectively. The therapy aiming at the cause for biliary SAP and the operation aiming at infected pancreatic necrosis is helpful to improve curative rate; MODS is the main cause of death in severe acute pancreatitis. Respiratory dysfunction, renal dysfunction and cardiac dysfunction are high risk factors.


Oligonucleosome DNA fragmentation of caspase 3 deficient MCF-7 cells in palmitate-induced apoptosis.
Oligonucleosomal fragmentation of nuclear DNA is the late stage hallmark of the apoptotic process. In mammalian apoptotic cells fragmentation is catalyzed by DFF40/ CAD DNase. DFF40/CAD primary activated through site-specific proteolytic cleavage by caspase 3. The absence of caspase 3 in MCF-7 leads to lack of oligonucleosomal DNA fragmentation under numerous apoptotic stimuli. In this study it was shown that palmitate induces apoptotic changes of nuclei and oligonucleosomal DNA fragmentation in casp3 deficient MCF-7. Activation and accumulation of 40-50 kDa DFF40 like DNases in nuclei and cytoplasm of palmitate-treated MCF-7 were detected by SDS-DNA-PAGE assay. Microsomes of apoptotic MCF-7 activate 40-50 kDa nucleases when incubated with human placental chromatin and induce oligonucleosomal fragmentation of chromatin in cell free system. Both DNases activation and chromatin fragmentation are suppressed in presence of caspase 3/7 inhibitor Ac-DEVD-CHO. Microsome associated caspase 7 is suggested to play the principal role in induction of oligonucleosomal DNA fragmentation of casp3 defitient MCF-7.


Local atomic and electronic structure in nanocrystalline Sn-doped anatase TiO2.
Tin-doped anatase TiO(2) nanopowders and nanoceramics with particle sizes between 12 and 30 nm are investigated by X-ray absorption fine-structure (EXAFS) and Mössbauer spectroscopies. Furthermore, ab initio calculations based on the density functional theory are performed to analyze changes in the electronic structure due to Sn doping. The three approaches consistently show that Sn is dissolved on substitutional bulk sites with a slight increase of the bond lengths of the inner coordination shells. The Debye-Waller factors show that the nanocrystallites are highly ordered. There is no indication of defect states or bandgap changes with Sn doping.


Is carbon dioxide a safe and good alternative for diatrizoate meglumine as a contrast in digital subtraction angiography?
Contrast-induced nephropathy is well-known sequelae of iodinated contrast (diatrizoate meglumine). Carbon dioxide (CO(2)) can be used as an alternative contrast agent. The aim of this study was to compare the renal injury and the quality of images of aortogram using iodinated contrast versus CO(2) using digital subtraction angiography (DSA). This prospective randomized study was done in 29 healthy dogs using DSA aortogram. Dogs were randomly assigned to receive iodinated contrast or CO(2). 6-F pigtail catheter was introduced via femoral artery approach to perform aortogram under general anesthesia. Serum creatinine (S.Cr.) and urinary enzymes, namely: N-acetyl D-glucosaminidase (NAG), alanine aminopeptidase (AAP), and gamma glutamyl transferase (GGT), were measured before and 48 hours after aortogram. There was no change in S.Cr. in both the groups. Significantly more enzymuria was seen following iodinated contrast than CO(2). Enzymuria pre and postaortogram following the iodinated contrast was GGT: 14.9 +/- 5.92 vs. 26.2 +/- 15.1 (P = 0.001), NAG: 1.63 +/- 0.90 vs. 3.6 +/- 2.14 (P = 0.0001), and AAP: 1.51 +/- 0.75 vs. 3.38 2.41 (P = 0.001), and in the CO(2) group was GGT: 15.5 +/- 4.9 vs. 21.1 +/- 9.04 (P = 0.02), NAG: 2.12 +/- 1.06 vs. 3.82 3.27 (P = 0.08), and AAP: 1.28 +/- 0.76 vs. 2.51 +/- 1.72 (P = 0.03). More than 50% increase over the preprocedural value was significantly less following CO(2). Images obtained with iodinated contrast were superior to those with CO(2,) however, the quality of image with CO(2) was adequate for delineation of the renal artery and major branches. Both iodinated contrast and CO(2) cause significant enzymuria. More severe enzymuria (>50% increase) was seen significantly less with the use of CO(2). Quality of images is better with iodinated contrast.


Bank Account Ownership and Access Among In-Patients in Psychiatric Care in Berlin, Germany-A Cross-Sectional Patient Survey.
Access to a bank account is critical for overall participation in social life and an indicator for social integration. Worldwide about 1.7 billion people remain with no access to banking facilities as a form of financial exclusion which represents 31% of the world's general population. In contrast, in Western countries like Germany, 99% of the general population use bank accounts. We conducted an exploratory cross-sectional survey on bank account ownership and bank account access among psychiatric in-patients in a psychiatric hospital in Berlin. Out of 540 participants who were reached for an interview, 486 shared information about bank account ownership and 469 on access. Out of 486 participants 49 (10.1%) did not own a bank account. Among the remaining 420 participants owning a bank account, 36 (8.3%) did not have direct access to their bank account, but only, e.g., their legal guardian. Regression results found psychosis, intellectual disabilities, a longer treatment duration, as well as being of male gender and a more instable housing status to be significantly associated with a missing bank account or a missing access to one's bank account. The lack of bank account ownership and access among this population of psychiatric patients is concerning. The interrelationship between factors of financial exclusion and mental health should be further explored in longitudinal studies. More attention is needed to support people with severe mental illness to be able to access resources associated with financial inclusion.


RET proto-oncogene mutations in multiple endocrine neoplasia type 2 and medullary thyroid carcinoma.
Multiple endocrine neoplasia type 2 (MEN-2) is a familial cancer syndrome inherited in an autosomal dominant fashion with age-related penetrance. The main tumour type present in all manifestations of this syndrome. MEN-2A, MEN-2B and familial medullary thyroid carcinoma (FMTC), is medullary thyroid carcinoma (MTC). MTC arises from the parafollicular or C cells of the thyroid. MEN-2A is characterised by the triad of MTC, phaeochromocytoma, and parathyroid hyperplasia. MEN-2B is characterised by features similar to those of MEN-2A, except for the absence of clinically apparent parathyroid hyperplasia, and additional stigmata including a marfanoid habitus, mucosal neuromas and ganglioneuromatosis of the gastrointestinal tract. FMTC families have MTC as their only phenotype. Missense mutations affecting conserved cysteine codons adjacent to the transmembrane domain of the RET proto-oncogene have been identified in the germline DNA of patients with MEN-2A and FMTC. A single mutation at codon 918 in the tyrosine kinase domain of the RET receptor has been associated with the MEN-2B phenotype. In a small number of FMTC families, missense point mutations have also been identified in the intracellular domain of the RET protein. RET mutation analysis of MEN-2 families has allowed the identification of genotype-phenotype correlations. While 25% of all MTCs are hereditary, the great majority of MTCs, 75%, are sporadic. Various somatic RET mutations have been identified in sporadic MTCs. In a small number of hereditary MTCs with germline mutations in RET, an additional somatic missense RET mutation has been identified. The discovery of RET mutations in MEN-2 has made possible accurate DNA-based diagnosis and predictive testing. The clinical significance of somatic RET mutations has yet to be determined.


Three-dimensional histology: new visual approaches to morphological changes during neural regeneration.
Three-dimensional (3D) histology utilizes tissue clearing techniques to turn intact tissues transparent, allowing rapid interrogation of tissue architecture in three dimensions. In this article, we summarized the available tissue clearing methods and classified them according to their physicochemical principles of operation, which provided a framework for one to choose the best techniques for various research settings. Recent attempts in addressing various questions regarding the degenerating and regenerating nervous system have been promising with the use of 3D histological techniques.


[Follow-up of children and young adults with differentiated thyroid cancer treated with radioiodine].
This is a retrospective study carried out in a group of 30 patients with differentiated thyroid cancer (age at diagnosis equal to or less than twenty years old). The aim of the study is to evaluate outcome after 131I therapy. Patients were classified into three groups on the basis of initial surgery, pathology and scintigraphic results: group I (thyroid extent), group II (locoregional extent), and group III (distant metastatic disease). Clinical parameters, 131I scans, serum thyroglobulin determinations and 131I therapeutic administered doses were evaluated in the follow-up. Some other complementary techniques such as chest X-ray and pulmonary function tests are also described. Scintigraphic absence of thyroid tissue has been observed in 83% of the cases; high thyroglobulin level is still detectable in 34% of the patients as a single evidence of disease, and 21% remain without any abnormal clinical, scintigraphic or analytical findings. Total doses administered have increased in groups I, II and III respectively, and have also been inversely proportional to the extension of lymph node surgery. At present, all the patients are alive and in good general condition. According to the results obtained, we conclude that children and young adults with DTC should undergo periodical 131I therapeutic doses in case of positive scans (once total thyroidectomy has been realized, with or without lymph node resection depending on the extension of disease). In our experience, the use of radioiodine is effective and safe in the follow-up of children and youngs with DTC.


Role of JNK1-dependent Bcl-2 phosphorylation in ceramide-induced macroautophagy.
Macroautophagy is a vacuolar lysosomal catabolic pathway that is stimulated during periods of nutrient starvation to preserve cell integrity. Ceramide is a bioactive sphingolipid associated with a large range of cell processes. Here we show that short-chain ceramides (C(2)-ceramide and C(6)-ceramide) and stimulation of the de novo ceramide synthesis by tamoxifen induce the dissociation of the complex formed between the autophagy protein Beclin 1 and the anti-apoptotic protein Bcl-2. This dissociation is required for macroautophagy to be induced either in response to ceramide or to starvation. Three potential phosphorylation sites, Thr(69), Ser(70), and Ser(87), located in the non-structural N-terminal loop of Bcl-2, play major roles in the dissociation of Bcl-2 from Beclin 1. We further show that activation of c-Jun N-terminal protein kinase 1 by ceramide is required both to phosphorylate Bcl-2 and to stimulate macroautophagy. These findings reveal a new aspect of sphingolipid signaling in up-regulating a major cell process involved in cell adaptation to stress.


CSF monoamine metabolites in child and adult psychiatric patients. A developmental perspective.
Concentrations of acid metabolites of dopamine and serotonin were measured in lumbar CSF of a diagnostically heterogeneous group of 154 psychiatric patients following oral probenecid loading. The patients ranged in age from 2 to 67 years old. No patients had received psychoactive medications for at least two weeks prior to the lumbar puncture. Children had higher mean CSF homovenillic acid (HVA) levels, higher mean CSF HVA-probenecid ratios, higher CSF HVA-log probenecid ratios, and lower mean CSF probenecid levels than adults. Age was negatively correlated with CSF HVA level and with CSF HVA-probenecid ratio. These correlations were more pronounced in male patients than in female patients.


Discrete unified gas kinetic scheme for continuum compressible flows.
In this paper, a discrete unified gas kinetic scheme (DUGKS) is proposed for continuum compressible gas flows based on the total energy kinetic model [Guo et al., Phys. Rev. E 75, 036704 (2007)1539-375510.1103/PhysRevE.75.036704]. The proposed DUGKS can be viewed as a special finite-volume lattice Boltzmann method for the compressible Navier-Stokes equations in the double distribution function formulation, in which the mass and momentum transport are described by the kinetic equation for a density distribution function (g), and the energy transport is described by the other one for an energy distribution function (h). To recover the full compressible Navier-Stokes equations exactly, the corresponding equilibrium distribution functions g^{eq} and h^{eq} are expanded as Hermite polynomials up to third and second orders, respectively. The velocity spaces for the kinetic equations are discretized according to the seventh and fifth Gauss-Hermite quadratures. Consequently, the computational efficiency of the present DUGKS can be much improved in comparison with previous versions using more discrete velocities required by the ninth Gauss-Hermite quadrature.


Cesium could be used as a proxy for potassium in mycorrhizal Medicago truncatula.
Arbuscular mycorrhizal (AM) fungi interact with the roots of most land plants and help them to acquire various mineral resources from the soil, including potassium (K+). However, tracking K+ movement in AM symbiosis remains challenging. Recently, we reported that rubidium can be used as a proxy for K+ in mycorrhizal Medicago truncatula. In the present work, we investigated the possibility of using cesium (Cs+) as another proxy for K+ in AM symbiosis. Plants were placed in growing systems that include a separate compartment only accessible to the AM fungus Rhizophagus irregularis isolate 09 and in which various amounts of cesium chloride (0 mM, 0.5 mM, 1.5 mM, or 3.75 mM) were supplied. Plants were watered with sufficient K+ or K+-free nutrient solutions, and shoot and root biomass, fungal colonization, and K+ and Cs+ concentrations were recorded seven weeks after inoculation. Our results indicate that Cs+ accumulated in plant tissues only when K+ was present in the nutrient solution and when the highest concentration of Cs+ was used in the fungal compartment. Consequently, we conclude that Cs+ could be used as a proxy for K+ in AM symbiosis, but with serious limitations.


Methamphetamine exposures in young children.
Methamphetamine abuse is reaching epidemic proportions. As this occurs, the likelihood of accidental poisoning in children increases. We sought to evaluate the presentation, treatment, and outcome of pediatric methamphetamine exposures reported to the California Poison Control System. This is a retrospective review of California Poison Control System records for methamphetamine exposure from 2000 through 2004. All charts of patients identified as younger than 6 years were reviewed and abstracted. The charts of 47 children younger than 6 years were identified and reviewed. Three were coded as minor effects, 3 as major effects, and 16 as moderate effects. The remainder of the charts were not evaluated because of no effect (n = 6), unrelated or confirmed nonexposure (n = 3), or unable to follow (n = 16). The most common presenting symptom was agitation (82%), whereas seizures were documented in only 2 cases (9%). Tachycardia was common (mean heart rate, 171 beats/min; confidence interval [CI], 154-187), whereas blood pressure (BP) (mean systolic BP, 120 mm Hg; CI, 104-136; and mean diastolic BP, 70 mm Hg; CI, 51-88) and rectal temperature (mean, 37.4 degrees C; CI, 36.9-37.9) were slightly elevated compared with normal values. Creatinine was documented in 6 cases and noted as normal in all (0.3IU/L; CI, 0.2-0.4), whereas creatine kinase was documented in 3 charts and elevated in all (mean 1984 IU/L; range, 212-4942 IU/L). Most cases (55%) received benzodiazepines as treatment, although only 2 received activated charcoal. Symptoms persisted for an average of 22 hours (CI, 16.3-27.2). No deaths were reported. In this series of children, methamphetamine exposure was strongly associated with agitation that was successfully treated with benzodiazepines. Tachycardia was common, although hypertension and hyperthermia were not. Laboratory studies were not routinely recorded. The clinical significance of elevated creatine kinase concentrations recorded in 3 children is unclear.


A population-based study of the fractionation of postlumpectomy breast radiation therapy.
The optimal fractionation schedule of post lumpectomy radiation therapy remains controversial. The objective of this study was to describe the fractionation of post-lumpectomy radiation therapy (RT) in Ontario, before and after the seminal Ontario Clinical Oncology Group (OCOG) trial, which showed the equivalence of 16- and 25-fraction schedules. This was a retrospective cohort study conducted by linking electronic treatment records to a population-based cancer registry. The study population included all patients who underwent lumpectomy for invasive breast cancer in Ontario, Canada, between 1984 and 2008. Over the study period, 41,747 breast cancer patients received post lumpectomy radiation therapy to the breast only. Both 16- and 25-fraction schedules were commonly used throughout the study period. In the early 1980s, shorter fractionation schedules were used in >80% of cases. Between 1985 and 1995, the proportion of patients treated with shorter fractionation decreased to 48%. After completion of the OCOG trial, shorter fractionation schemes were once again widely adopted across Ontario, and are currently used in about 71% of cases; however, large intercenter variations in fractionation persisted. The use of shorter schedules of post lumpectomy RT in Ontario increased after completion of the OCOG trial, but the trial had a less normative effect on practice than expected.


Deletion of endothelial cell-specific liver kinase B1 increases angiogenesis and tumor growth via vascular endothelial growth factor.
Liver kinase B1 (LKB1) is a serine/threonine protein kinase ubiquitously expressed in mammalian cells. It was first identified in Peutz-Jeghers syndrome as a tumor suppressor gene. Whether endothelial LKB1 regulates angiogenesis and tumor growth is unknown. In this study, we generated endothelial cell-specific LKB1-knockout (LKB1endo-/-) mice by crossbreeding vascular endothelial-cadherin-Cre mice with LKB1flox/flox mice. Vascular endothelial growth factor (VEGF) level was highly co-stained in endothelial cells but not in macrophages in LKB1endo-/- mice. Consistently, LKB1endo-/- mouse tissues including the lung, skin, kidney and liver showed increased vascular permeability. Tumors implanted in LKB1endo-/- mice but not macrophage-specific LKB1-knockout mice grew faster and showed enhanced vascular permeability and increased angiogenesis as compared with those implanted in wild-type mice. Injection of VEGF-neutralizing antibody but not the isotype-matched control antibody decreased endothelial-cell angiogenesis and tumor growth in vivo. Furthermore, LKB1 deletion enhanced mouse retinal and cell angiogenesis, and knockdown of VEGF by small-interfering RNA decreased endothelial cell proliferation and migration. Re-expression of LKB1 or knockdown of VEGF receptor 2 decreased the overproliferation and -migration observed in LKB1endo-/- cells. Mechanistically, LKB1 could bind to the VEGF transcription factor, specificity protein 1 (Sp1), which then inhibited the binding of Sp1 to the VEGF promoter to reduce VEGF expression. Endothelial LKB1 may regulate endothelial angiogenesis and tumor growth by modulating Sp1-mediated VEGF expression.


Scaphoid Length Loss Following Nonunion Is Associated with Dorsal Intercalated Segment Instability.
Background Dorsal intercalated segment instability (DISI) in scaphoid nonunions is frequently attributed to fracture location relative to ligamentous attachments onto the scaphoid apex. We hypothesize scaphoid length loss to have a stronger correlation with DISI deformity than fracture location in patients with scaphoid nonunion. Questions/Purposes To investigate the correlation between (1) scaphoid length loss, (2) fracture location relative to the scaphoid apex, and (3) type of nonunion (Herbert classification) and DISI deformity in skeletally mature patients with scaphoid nonunion. Patients and Methods Twenty-seven cases of computed tomography (CT)-confirmed scaphoid nonunion (>6 months) were retrospectively included. Our primary outcome was the degree of DISI as measured by the radiolunate (RL) angle on CT. Scaphoid length loss was expressed as height-to-length (H/L) ratio. Fracture location was classified as proximal or distal to the scaphoid apex. Nonunions were classified as fibrous unions (type D1) or pseudoarthrosis (type D2). The correlation between RL angle, H/L ratio, fracture location, and nonunion type was evaluated. Results H/L ratio was the only factor associated with the degree of DISI as measured by RL angle. As scaphoid length loss increased (increasing H/L ratio), the RL angle increased. There was no significant difference in RL angle between fractures located proximal (30 degrees) or distal (28 degrees) to the scaphoid apex, or type D1 (31 degrees) versus type D2 (28 degrees) nonunions. There was no correlation between patient age, sex, or wrist side affected and RL angle. Conclusions Scaphoid length loss, rather than fracture location, is correlated to the degree of DISI deformity in patients with scaphoid nonunion. This highlights the importance of restoring scaphoid height when planning scaphoid nonunion reconstruction. Level of Evidence Level III, diagnostic study.


[Epizootiological characteristics of clonorchiasis foci in the Amur River ecosystem in the Jewish autonomic region].
Malacofaunal and ichthyoparasitological studies were conducted in the floodplain-river ecosystem in the middle course of the Amur River. The studies covered its channels and tributaries, such as Big and Small Bira, Bidzhan, In, and Vertoprashikha Rivers, in the Birobidzhan, Leninskoye, and Smidovich districts of the Jewish Autonomic Region in the second half of August 2011. It was established that there were biotopes of the mollusk Parafossalurus manchouricus, the first intermediate host of Clonorchis sinensis, in the exosystems of the In, Bira, and Bidzhan Rivers. Sporadic P. manchouricus specimens were found in the Bidzhan channel in the vicinity of its estuary and on the flooded bank of the In River. The bay of the Bira River (the town of Birobidzhan) exhibited a biotope of P. manchouricus with a mollusk population density of 180 to 300 specimens/m2. Seven of 16 examined fish species showed metacercariae of Clonorchis. Among them there were not only Cyprinidae, but also representatives of other families and orders. The two-year-olds of orca-skripuns (Pseudobagrus fulvidraco), orca-whips (Tachysyrus ussuriensis), and Brazhnikov's orsas (Liocassis braschnikowi) were infected with C. sinensis metacercariae. Clonorchis metacercariae were first detected in Amur sleepers (Percottus glehni). This fish species has not been heretofore recorded as the second intermediate host ofC. sinensis. The highest invasion extent for C. sinensis metacercariae was revealed in Amur bitterlings (Rhodeus sericeus) born during the current year. In the biotopes ofdifferent water reservoirs, it changed from 10.0 to 48.0%. In 4 of 6 water reservoirs, Amur bitterlings were found to have larvae of this species of trematodes. The invasion rates were in the range from 1 to 4 metacercariae per fish. Only in individual cases, they were as great as 28 parasitic larvae per fish.


Two step micro-rheological behavior in a viscoelastic fluid.
We perform micro-rheological experiments with a colloidal bead driven through a viscoelastic worm-like micellar fluid and observe two distinctive shear thinning regimes, each of them displaying a Newtonian-like plateau. The shear thinning behavior at larger velocities is in qualitative agreement with macroscopic rheological experiments. The second process, observed at Weissenberg numbers as small as a few percent, appears to have no analog in macro-rheological findings. A simple model introduced earlier captured the observed behavior and implied that the two shear thinning processes correspond to two different length scales in the fluid. This model also reproduces oscillations, which have been observed in this system previously. While the system under macro-shear seems to be near equilibrium for shear rates in the regime of the intermediate Newtonian-like plateau, the one under micro-shear is thus still far from it. The analysis suggests the existence of a length scale of a few micrometres, the nature of which remains elusive.


Optimization of Product Design Mode of Art Industry Based on Multiterminal Selection Algorithm of Internet of Things.
This article has first presented an overview and a brief design to the system, and then analyzed the system design goal and design principle. The role of the resource representation model in the Internet of Things is more important than the significance of the database schema for the web information system. In the current "vertical" application model, the device resources of the perception layer and the application entities of the business layer are in a tightly coupled relationship. In the process of system operation, it changes flexibly as the situation changes. This article will combine the characteristics of resources in the Internet of Things, from the perspectives of resources and services, and refer to the basic structure of the traditional Internet resource reference model OWL-S to appropriately expand and tailor it, and describe the relationship between Internet of Things device resources and application services. Therefore, the resource representation model oriented to the Internet of Things service in this article is proposed and simulated and verified. To a certain extent, this model can provide support for the unified description of IoT resources and services, so as to better adapt to the development needs of diversified IoT services. Based on the application and service in the Internet of Things environment restricted by time and space correlation and limited resources, the article discusses and proposes a multiterminal selection algorithm for Internet of Things business, and converts it into a mathematical combination optimization problem. Based on the ant colony optimization algorithm, a solution is given, which can realize the optimization of equipment combination scheme under resource-constrained conditions to maximize the total benefit value of the service, and can effectively improve the utilization rate of terminal resources. In the research on the analysis of the development strategy of China's industrial design industry in the era of intelligent interconnection, the analysis of the development strategy of the industrial design industry in the era of intelligent interconnection through analysis tools of industrial strategy reveals the new trend of industrial design in the era of intelligent interconnection. The analysis and formulation of industrial strategy are complicated, and it is a systematic project involving all aspects. The rational use of corresponding strategic analysis tools can further enhance the scientificity and rationality of industrial design strategy.


Molecular properties of aqueous solutions: a focus on the collective dynamics of hydration water.
When a solute is dissolved in water, their mutual interactions determine the molecular properties of the solute on one hand, and the structure and dynamics of the surrounding water particles (the so-called hydration water) on the other. The very existence of soft matter and its peculiar properties are largely due to the wide variety of possible water-solute interactions. In this context, water is not an inert medium but rather an active component, and hydration water plays a crucial role in determining the structure, stability, dynamics, and function of matter. This review focuses on the collective dynamics of hydration water in terms of retardation with respect to the bulk, and of the number of molecules whose dynamics is perturbed. Since water environments are in a dynamic equilibrium, with molecules continuously exchanging from around the solute towards the bulk and vice versa, we examine the ability of different techniques to measure the water dynamics on the basis of the explored time scales and exchange rates. Special emphasis is given to the collective dynamics probed by extended depolarized light scattering and we discuss whether and to what extent the results obtained in aqueous solutions of small molecules can be extrapolated to the case of large biomacromolecules. In fact, recent experiments performed on solutions of increasing complexity clearly indicate that a reductionist approach is not adequate to describe their collective dynamics. We conclude this review by presenting current ideas that are being developed to describe the dynamics of water interacting with macromolecules.


Leukocyte procoagulant activity in man: an in vitro correlate of delayed-type hypersensitivity.
Human mononuclear leukocytes generate cell-bound procoagulant activity (LPCA) after incubation with an antigen (mumps or tuberculin) to which the donor was previously sensitized. An inhibitor of coagulation appears to be liberated into the extracellular culture fluid during incubation of leukocytes with the sensitizing antigen. Removal of this activity before measuring LPCA resulted in a reliable test that correlated directly with delayed skin reactivity. The assay was particularly sensitive in that cells from weakly sensitized donors who reacted only to high doses of tuberculin (100 TU) in the delayed skin tests produced detectable LPCA in vitro. By contrast cells from weakly sensitized donors did not react to PPD in the lymphocyte blast transformation test or the direct macrophage migration inhibition factor test. The LPCA assay correlated closely with the blast transformation and MIF tests in which cells were used from more strongly sensitized donors who reacted in skin tests with lower doses of tuberculin (1 or 10 TU). The assays were antigen-specific in that cells from donors sensitive to mumps antigen but not to tuberculin reacted only to mumps antigen in vitro. The assay was extremely reproducible; cells from individual donors reacted to the same extent over a period of 8 mo). We propose that the assay system reported here represents an improved method for the measurement of cell-mediated immunity in vitro because it requires fewer donor cells, is technically simpler, and is more sensitive than previously described methods.


A Ca2+-dependent protein kinase activity associated with serotonin binding protein.
The endogenous phosphorylation of serotonin binding protein (SBP), a soluble protein found in central and peripheral serotonergic neurons, inhibits the binding of 5-hydroxytryptamine (5-HT, serotonin). A protein kinase activity that copurifies with SBP (SBP-kinase) was partially characterized and compared with calcium/calmodulin-dependent protein kinase II (CAM-PK II). SBP itself is not the enzyme since heating destroyed the protein kinase activity without affecting the capacity of the protein to bind [3H]5-HT. SBP-kinase and CAM-PK II kinase shared the following characteristics: (1) size of the subunits; (2) autophosphorylation in a Ca2+-dependent manner; and (3) affinity for Ca2+. In addition, both forms of protein kinase phosphorylated microtubule-associated proteins well and did not phosphorylate myosin, phosphorylase b, and casein. Phorbol esters or diacylglycerol had no effect on either of the protein kinases. However, substantial differences between SBP-kinase and CAM-PK II were observed: (1) CAM enhanced CAM-PK II activity, but had no effect on SBP-kinase; (2) synapsin I was an excellent substrate for CAM-PK II, but not for SBP-kinase; (3) 5-HT inhibited both the autophosphorylation of SBP-kinase and the phosphorylation of SBP, but had no effect on CAM-PK II. These data indicate that SBP-kinase is different from CAM-PK II. Phosphopeptide maps of SBP and SBP-kinase generated by digestion with S. aureus V8 protease are consistent with the conclusion that these proteins are distinct molecular entities. It is suggested that phosphorylation of SBP may regulate the transport of 5-HT within neurons.


Three new species of Holoscolex (Clitellata, Glossoscolecidae) from the Gurupi Biological Reserve, last forest remnant of the Belém Endemism Area, Eastern Amazon.
We describe three new species of the earthworm genus Holoscolex from the Gurupi Biological Reserve in Maranhão state, Brazil. The Reserve, with the Indigenous Territories Awá, Caru, Alto Turiaçu and Alto Rio Guamá represent the last continuous forest remnants of the Belém Endemism Area, the most deforested and threatened area of Brazilian Amazonia. Holoscolex dossantosi sp. nov. has tubercula pubertatis looking like double bands, Holoscolex alatus sp. nov. presents alate tubercula pubertatis, and Holoscolex fernandoi sp. nov. has testis sacs and several intraclitellar atrial glands associated with genital markings between XIX and XXII. The presence of these unusual characters in Holoscolex fernandoi sp. nov. suggests that this species could be an evolutionary transitional stage linking Eudrilidae and more recent Glossoscolecidae genera.


Organic Acids from Roselle (Hibiscus sabdariffa L.)-A Brief Review of Its Pharmacological Effects.
Roselle (Hibiscus sabdariffa L.), also known as jamaica in Spanish, is a perennial plant that grows in tropical and subtropical regions, including China, Egypt, Indonesia, Mexico, Nigeria, Thailand, and Saudi Arabia. It has a long history of uses, mainly focused on culinary, botanical, floral, cosmetic, and medicinal uses. The latter being of great impact due to the diuretic, choleretic, analgesic, antitussive, antihypertensive, antimicrobial, immunomodulatory, hepatoprotective, antioxidant, and anti-cancer effects. These therapeutic properties have been attributed to the bioactive compounds of the plant, mainly phenolic acids, flavonoids, anthocyanins, and organic acids (citric, hydroxycitric, hibiscus, tartaric, malic, and ascorbic). Most literature reviews and meta-analyses on the therapeutic potential of Hibiscus sabdariffa L. (Hs) compounds have not adequately addressed the contributions of its organic acids present in the Hs extracts. This review compiles information from published research (in vitro, in vivo, and clinical studies) on demonstrated pharmacological properties of organic acids found in Hs. The intent is to encourage and aid researchers to expand their studies on the pharmacologic and therapeutic effects of Hs to include assessments of the organic acid components.


Characterization of inhibitory circuits in the malformed hippocampus of Lis1 mutant mice.
Heterozygous mutation or deletion of a lissencephaly gene (Lis1) in humans is associated with a severe disruption of cortical and hippocampal lamination, cognitive deficit, and severe seizures. Mice with one null allele of Lis1 (Lis1(+/-) mice) exhibit significant brain malformations and slowed migration of interneuron precursors. Although hyperexcitability was demonstrated in dysplastic hippocampal slices from Lis1(+/-) mice, little is known about synaptic function in these animals. Here we analyzed GABA-mediated synaptic inhibition. We recorded isolated whole cell inhibitory postsynaptic currents (IPSCs) on visually identified pyramidal neurons in disorganized CA1 regions of hippocampal slices prepared from Lis1(+/-) mice. We observed a 32% increase in spontaneous IPSC frequency in Lis1(+/-) mice compared with normotopic CA1 pyramidal neurons in age-matched controls. This increase was not associated with a change in spontaneous IPSC decay or miniature IPSC frequency. Mean IPSC amplitude was increased, and event histograms indicated a greater number of large (>125 pA) events. Tonic inhibition, response to paired-pulse stimulation and evoked IPSC decay kinetics were not altered. Consistent with increased synaptic inhibition, Lis1(+/-) interneurons also exhibited more spontaneous firing in cell-attached recordings and increased excitation as measured by voltage-clamp recording of spontaneous excitatory postsynaptic currents (EPSCs) onto interneurons. Our results reveal a significant alteration in the function of inhibitory circuits within the malformed Lis1(+/-) hippocampus. Given that precisely coordinated GABAergic activity is vital to generation of oscillatory activity and place field precision in hippocampus, these alterations in synaptic inhibition may contribute to seizures and altered cognitive function in type I Lissencephaly.


Systematic prioritization of functional hotspot in RIG-1 domains using pattern based conventional molecular dynamic simulation.
Retinoic acid inducible gene 1 (RIG-1), multi-domain protein has a role-play in detecting viral nucleic acids and stimulates the antiviral response. Dysfunction of this protein due to mutations makes the route vulnerable to viral diseases. Identification of functional hotspots that maintains conformational stability in RIG-1 domains. In this study, we employed a systematic in silico strategy on RIG-1 protein to understand the mechanism of structural changes upon mutation. We computationally investigated the protein sequence signature for all the three domains of RIG-1 protein that encloses the mutation within the motif. Further, we carried out a structural comparison between RIG-1 domains with their respective distant orthologs which revealed the minimal number of interactions required to maintain its structural fold. This intra-protein network paved the way to infer hotspot residues crucial for the maintenance of the structural architecture and folding pattern. Our analysis revealed about 40 hotspot residues that determine the folding pattern of the RIG-1 domains. Also, conventional molecular dynamic simulation coupled with essential dynamics provides conformational transitions of hot spot residues among native and mutant structures. Structural variations owing to hotspot residues in mutants again confirm the significance of these residues in structural characterization of RIG-1 domains. We believe our results will help the researchers to better comprehend towards regulatory regions and target-binding sites for therapeutic design within the pattern recognition receptor proteins. Our protocol employed in this work describes a novel approach in identifying signature residues that would provide structural insights in protein folding.


Filtration recovery of extracellular DNA from environmental water samples.
qPCR methods are able to analyze DNA from microbes within hours of collecting water samples, providing the promptest notification and public awareness possible when unsafe pathogenic levels are reached. Health risk, however, may be overestimated by the presence of extracellular DNA (eDNA) that is corecovered by the filtration procedure which is the most commonly used method to concentrate target microbes from environmental waters. Using C. parvum 18S rRNA gene fragment as a representative of eDNA, we examined the impact of filters (types and pore sizes) and physiochemical properties of surface water samples on the recovery of spiked DNA. Our results indicated that binding affinities of various filter membranes were quantifiably different for eDNA fragments with the polycarbonate (PC) binding the least and mixed cellulose acetate and cellulose nitrate (MCE) binding the most as evidenced by up to 16% recovery of the spiked plasmid DNA with a pore size of 0.2 μm. Water quality parameters also had a distinct influence on the recovery of eDNA which was enhanced by the presence of high total suspended solid (TSS) concentrations and reduced pH. At pH 5.5, with 150 mg/L of clay, DNA recovery was increased to as much as 18%. By shielding the negative charge, thus increasing the interaction of DNA and colloids, the increase of Na(+) and Ca(2+) concentrations resulted in more DNA binding and consequently more recovery from environmental water samples. Therefore, in addition to analytical uncertainties, potential differences in qPCR data from filtered waters characterized with low pH and high TSS and ionic strength should be considered in pollution assessments.


Benefit of single-leaf resection for horizontal meniscus tear.
When treating a horizontal meniscus tear, the surgeon must decide whether to resect one or both leaves of the tear. We asked whether there is a biomechanical advantage to sparing one leaf when performing a partial meniscectomy for horizontal meniscus tear. We used pressure-sensitive film to measure the contact area, mean pressure, and peak pressure on the lateral tibial plateau of cadaveric sheep knees loaded to 2x body weight. For tears restricted to the posterior third, single-leaf resection decreased contact area by 40% compared with the intact case. Sparing one leaf was beneficial because resection of the second leaf reduced contact area an additional 15%. Similarly, mean pressure was increased 24% for single-leaf resection and an additional 27% for double-leaf resection. Peak pressure showed no differences with single- and double-leaf resections. For tears that span the entire meniscus, single-leaf resection reduced contact area by 59%, increased mean pressure by 55%, and increased peak pressure by 19%. Double-leaf resection in this situation did not change these values substantially, suggesting sparing one leaf offers no benefit over resecting both leaves with extensive horizontal meniscus tears.


The Set1 N-terminal domain and Swd2 interact with RNA polymerase II CTD to recruit COMPASS.
Methylation of histone H3 lysine 4 (H3K4) by Set1/COMPASS occurs co-transcriptionally, and is important for gene regulation. Set1/COMPASS associates with the RNA polymerase II C-terminal domain (CTD) to establish proper levels and distribution of H3K4 methylations. However, details of CTD association remain unclear. Here we report that the Set1 N-terminal region and the COMPASS subunit Swd2, which interact with each other, are both needed for efficient CTD binding in Saccharomyces cerevisiae. Moreover, a single point mutation in Swd2 that affects its interaction with Set1 also impairs COMPASS recruitment to chromatin and H3K4 methylation. A CTD interaction domain (CID) from the protein Nrd1 can partially substitute for the Set1 N-terminal region to restore CTD interactions and histone methylation. However, even when Set1/COMPASS is recruited via the Nrd1 CID, histone H2B ubiquitylation is still required for efficient H3K4 methylation, indicating that H2Bub acts after the initial recruitment of COMPASS to chromatin.


[The role of psychotherapy in managing panic disorder].
This general presentation reviews briefly the various psychotherapies proposed for panic attacks and agoraphobia treatment. Cognitive-behaviour therapy (CBT) is the only validated therapy. Behavioural model of agoraphobia and cognitive model of panic attacks are detailed. The main techniques are described. The results of controlled studies and meta-analyses demonstrate that CBT represents an alternative to anxiolytics and antidepressants. CBT is a brief form of therapy (10-20 sessions) which has been compared with waiting list, placebo, relaxation, antidepressants, anxiolytics or supportive therapy. Four meta-analyses agree on that in vivo exposure is a core element of the treatment of panic attacks and agoraphobia. They demonstrate also that agoraphobia is more difficult to treat than panic attacks in which placebo effect is quite powerful. Cognitive therapy centered on panic attacks demonstrated a significant effectiveness in controlled studies. CBT facilitates benzodiazepines withdrawal. Combination of in vivo exposure with high doses of benzodiazepines is counter-productive in the long term. Controlled studies are favorable to the combination of CBT with imipramine, SSRI (paroxetine, fluvoxamine) or buspirone. But the positive effects of these combinations are only found in the short term. CBT possesses the advantage of stable long term effects.


A pilot study: Validity and reliability of the CSEP-PATH PASB-Q and a new leisure time physical activity questionnaire to assess physical activity and sedentary behaviours.
The purpose of this study was to evaluate the accuracy of 2 newly developed physical activity questionnaires: the Canadian Society for Exercise Physiology (CSEP) Physical Activity and Sedentary Behaviour Questionnaire (PASB-Q) and a newly modified Leisure-Time Physical Activity Questionnaire (mLTPA-Q). These questionnaires were compared with objective measurements of physical activity and fitness (accelerometry and physiological assessments) in 35 adults, before and after a week of daily living activity. Objectively measured moderate- to vigorous-intensity aerobic physical activity (MVPA) was moderately correlated with the PASB-Q's physical activity vital sign (PAVS) (r = 0.50, p = 0.004) and the mLTPA-Q (r = 0.56, p = 0.001). Bland-Altman plots suggest minimal bias from self-reported to objective measures of MVPA. The ability of PAVS to accurately distinguish who does and does not achieve Canadian physical activity guidelines was 83% and 60%, respectively, compared with 82% and 73% of the mLTPA-Q. Self-reported sedentary time was greatly underestimated in the PASB-Q compared with the objective measure (6.4 ± 3.5 vs 12.2 ± 1.2 h/day). The results of this study suggest the PASB-Q and mLTPA-Q are valid and reliable measures of adult physical activity and provide reasonable indication of those individuals who meet physical activity guidelines. Future questionnaire development should take into account the underestimation of time spent engaging in sedentary activities.


A 15-year exercise program for rheumatoid vasculitis.
A rare case of rheumatoid vasculitis and responses to a 15-year supervised exercise program. This patient presented with significant impairment in mobility and physical work capacity. His exercise tolerance improved considerably and he benefited emotionally.


Genomic landscape of human diversity across Madagascar.
Although situated ∼400 km from the east coast of Africa, Madagascar exhibits cultural, linguistic, and genetic traits from both Southeast Asia and Eastern Africa. The settlement history remains contentious; we therefore used a grid-based approach to sample at high resolution the genomic diversity (including maternal lineages, paternal lineages, and genome-wide data) across 257 villages and 2,704 Malagasy individuals. We find a common Bantu and Austronesian descent for all Malagasy individuals with a limited paternal contribution from Europe and the Middle East. Admixture and demographic growth happened recently, suggesting a rapid settlement of Madagascar during the last millennium. However, the distribution of African and Asian ancestry across the island reveals that the admixture was sex biased and happened heterogeneously across Madagascar, suggesting independent colonization of Madagascar from Africa and Asia rather than settlement by an already admixed population. In addition, there are geographic influences on the present genomic diversity, independent of the admixture, showing that a few centuries is sufficient to produce detectable genetic structure in human populations.


Community health workers: challenges and vulnerabilities of Accredited Social Health Activists working in conflict-affected settings in the state of Assam, India.
It is well acknowledged that India's community health workers known as Accredited Social Health Activists (ASHA) are the bedrock of its health system. Many ASHAs are currently working in fragile and conflict-affected settings. No efforts have yet been made to understand the challenges and vulnerabilities of these female workers. This paper seeks to address this gap by bringing attention to the situation of ASHAs working in the fragile and conflict settings and how conflict impacts them and their work. Qualitative fieldwork was undertaken in four conflict-affected villages in two conflict-affected districts -Kokrajhar and Karbi Anglong of Assam state situated in the North-East region of India. Detailed account of four ASHAs serving roughly 4000 people is presented. Data transliterated into English were analysed by authors by developing a codebook using grounded theory and thematic organisation of codes. ASHAs reported facing challenges in ensuring access to health services during and immediately after outbreaks of conflict. They experienced difficulty in arranging transport and breakdown of services at remote health facilities. Their physical safety and security were at risk during episodes of conflict. ASHAs reported hostile attitudes of the communities they served due to the breakdown of social relations, trauma due to displacement, and loss of family members, particularly their husbands. Conflict must be recognised as an important context within which community health workers operate, with greater policy focus and research devoted to understanding and addressing the barriers they face as workers and as persons affected by conflict.


Genetic investigation of sudden unexpected death in epilepsy cohort by panel target resequencing.
Sudden unexpected death in epilepsy (SUDEP) is defined as the abrupt, no traumatic, witnessed or unwitnessed death, occurring in benign circumstances, in an individual with epilepsy, with or without evidence for a seizure and excluding documented status epilepticus (seizure duration ≥ 30 min or seizures without recovery), and in which postmortem examination does not reveal a cause of death. Although the physiopathological mechanisms that underlie SUDEP remain to be clarified, the genetic background has been described to play a role in this disorder. Pathogenic variants in genes associated with epilepsy and encoding cardiac ion channels could explain the SUDEP phenotype. To test this we use the next-generation sequencing technology to sequence a cohort of SUDEP cases and its translation into clinical and forensic fields. A panel target resequencing was used to study 14 SUDEP cases from both postmortem (2 cases) and from living patients (12 cases). Genes already associated with SUDEP and also candidate genes had been investigated. Overall, 24 rare genetic variants were identified in 13 SUDEP cases. Four cases showed rare variants with complete segregation in the SCN1A, FBN1, HCN1, SCN4A, and EFHC1 genes, and one case with a rare variant in KCNQ1 gene showed incomplete pattern of inheritance. In four cases, rare variants were detected in CACNA1A, SCN11A and SCN10A, and KCNQ1 genes, but familial segregation was not possible due to lack of DNA from relatives. Finally, in the four remaining cases, the rare variants did not segregate in the family. This study confirms the link between epilepsy, sudden death, and cardiac disease. In addition, we identified new potential candidate genes for SUDEP: FBN1, HCN1, SCN4A, EFHC1, CACNA1A, SCN11A, and SCN10A. Further confirmation in larger cohorts will be necessary especially if genetic screening for SUDEP is applied to forensic and clinical medicine. Nevertheless, this study supports the emerging concept of a genetically determined cardiocerebral channelopathy.


Strategy updating rules and strategy distributions in dynamical multiagent systems.
In the evolutionary version of the minority game, agents update their strategies (gene value p) in order to improve their performance. Motivated by the recent intriguing results obtained for prize-to-fine ratios, which are smaller than unity, we explore the system's dynamics with a strategy updating rule of the form p-->p+/-delta(p) (0<or=p<or=1). We find that the strategy distribution depends strongly on the values of the prize-to-fine ratio R, the length scale delta(p), and the type of boundary condition used. We show that these parameters determine the amplitude and the frequency of the temporal oscillations observed in the gene space. These regular oscillations are shown to be the main factors which determine the strategy distribution of the population. In addition, we find that the agents characterized by p=1/2 (a coin-tossing strategy) have the best chances of survival at asymptotically long times, regardless of the value of delta(p) and the boundary conditions used.


MERTK Mediates Intrinsic and Adaptive Resistance to AXL-targeting Agents.
The TAM (TYRO3, AXL, MERTK) family receptor tyrosine kinases (RTK) play an important role in promoting growth, survival, and metastatic spread of several tumor types. AXL and MERTK are overexpressed in head and neck squamous cell carcinoma (HNSCC), triple-negative breast cancer (TNBC), and non-small cell lung cancer (NSCLC), malignancies that are highly metastatic and lethal. AXL is the most well-characterized TAM receptor and mediates resistance to both conventional and targeted cancer therapies. AXL is highly expressed in aggressive tumor types, and patients with cancer are currently being enrolled in clinical trials testing AXL inhibitors. In this study, we analyzed the effects of AXL inhibition using a small-molecule AXL inhibitor, a monoclonal antibody (mAb), and siRNA in HNSCC, TNBC, and NSCLC preclinical models. Anti-AXL-targeting strategies had limited efficacy across these different models that, our data suggest, could be attributed to upregulation of MERTK. MERTK expression was increased in cell lines and patient-derived xenografts treated with AXL inhibitors and inhibition of MERTK sensitized HNSCC, TNBC, and NSCLC preclinical models to AXL inhibition. Dual targeting of AXL and MERTK led to a more potent blockade of downstream signaling, synergistic inhibition of tumor cell expansion in culture, and reduced tumor growth in vivo Furthermore, ectopic overexpression of MERTK in AXL inhibitor-sensitive models resulted in resistance to AXL-targeting strategies. These observations suggest that therapeutic strategies cotargeting both AXL and MERTK could be highly beneficial in a variety of tumor types where both receptors are expressed, leading to improved survival for patients with lethal malignancies. Mol Cancer Ther; 17(11); 2297-308. ©2018 AACR.


AFM analysis of DNA-protamine complexes bound to mica.
A novel method for reconstituting sperm chromatin was used to investigate how protamine 1 condenses DNA. Complexes formed in vitro using linearized plasmid DNA were imaged and measured by atomic force microscopy (AFM). The structures formed were found to be highly dependent on the sample preparation method used for reconstitution. Interstrand, side-by-side fasiculation of DNA and toroidal-like structures only 1-2 DNA diameters thick were observed for complexes formed in solution following direct mixing of the DNA and protamine. Large chromatin aggregates were also observed on the mica. However, if the DNA was first allowed to attach to the mica prior to addition of the protamine, well-defined toroidal complexes were formed without any observed DNA fasiculation or aggregate formation. The diameter of the toroids measured 30.6-50.2 nm (mean 39.4 nm). The dimensions of these structures indicate that the condensed DNA is stacked vertically by four to five turns, with each coil containing as little as 360-370 bp of 'B'-form DNA. This approach for preparing and imaging DNA-protamine complexes permits the analysis of intermediate structures 'trapped' on the mica as partially formed toruses of nucleoprotamine.


Clustering and longitudinal change in SARS-CoV-2 seroprevalence in school children in the canton of Zurich, Switzerland: prospective cohort study of 55 schools.
To examine longitudinal changes in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroprevalence and to determine the clustering of children who were seropositive within school classes in the canton of Zurich, Switzerland from June to November 2020. Prospective cohort study. Switzerland had one of the highest second waves of the SARS-CoV-2 pandemic in Europe in autumn 2020. Keeping schools open provided a moderate to high exposure environment to study SARS-CoV-2 infections. Children from randomly selected schools and classes, stratified by district, were invited for serological testing of SARS-CoV-2. Parents completed questionnaires on sociodemographic and health related questions. 275 classes in 55 schools; 2603 children participated in June-July 2020 and 2552 in October-November 2020 (age range 6-16 years). Serology of SARS-CoV-2 in June-July and October-November 2020, clustering of children who were seropositive within classes, and symptoms in children. In June-July, 74 of 2496 children with serological results were seropositive; in October-November, the number had increased to 173 of 2503. Overall SARS-CoV-2 seroprevalence was 2.4% (95% credible interval 1.4% to 3.6%) in the summer and 4.5% (3.2% to 6.0%) in late autumn in children who were not previously seropositive, leading to an estimated 7.8% (6.2% to 9.5%) of children who were ever seropositive. Seroprevalence varied across districts (in the autumn, 1.7-15.0%). No significant differences were found among lower, middle, and upper school levels (children aged 6-9 years, 9-13 years, and 12-16 years, respectively). Among the 2223 children who had serology tests at both testing rounds, 28/70 (40%) who were previously seropositive became seronegative, and 109/2153 (5%) who were previously seronegative became seropositive. Symptoms were reported for 22% of children who were seronegative and 29% of children who were newly seropositive since the summer. Between July and November 2020, the ratio of children diagnosed with SARS-CoV-2 infection to those who were seropositive was 1 to 8. At least one child who was newly seropositive was detected in 47 of 55 schools and in 90 of 275 classes. Among 130 classes with a high participation rate, no children who were seropositive were found in 73 (56%) classes, one or two children were seropositive in 50 (38%) classes, and at least three children were seropositive in 7 (5%) classes. Class level explained 24% and school level 8% of variance in seropositivity in the multilevel logistic regression models. With schools open since August 2020 and some preventive measures in place, clustering of children who were seropositive occurred in only a few classes despite an increase in overall seroprevalence during a period of moderate to high transmission of SARS-CoV-2 in the community. Uncertainty remains as to whether these findings will change with the new variants of SARS-CoV-2 and dynamic levels of community transmission. NCT04448717.


Epidermal growth factor-mediated apoptosis of MDA-MB-468 human breast cancer cells.
MDA-MB-468 human breast cancer cells lack estrogen receptors, overexpress epidermal growth factor (EGF) receptors, and are growth inhibited by EGF. We show that treatment of MDA-MB-468 cells with EGF leads to inhibition of cell proliferation, fragmentation of DNA into nucleosomal oligomers, and the development of apoptotic morphology. This treatment is associated with increased expression of c-myc, c-fos, jun family members, and transforming growth factor beta 1 mRNA and with partial proteolytic cleavage of poly(ADP-ribose) polymerase and lamin B. The observation that EGF can mediate apoptosis in EGF receptor-overexpressing cells has important implications for clinical efforts directed at the EGF receptor.


Plasma chromogranin A response to octreotide test: prognostic value for clinical outcome in endocrine digestive tumors.
Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) expressing somatostatin receptors may be treated with somatostatin analogs (SSAs). Selection criteria are a positive Octreoscan or a >50% hormone level decrease after octreotide subcutaneous (s.c.) injection (octreotide test) (OT). Plasma chromogranin A (CgA) is the best general GEP-NET marker, but data on CgA response to OT are scanty. Thus, we evaluated whether plasma CgA response to OT could predict the clinical response to SSAs. At diagnosis, 38 GEP-NET patients received octreotide 200 microg s.c., with plasma CgA determination at 0, 3, and 6 h. Long-term SSA treatment was then given by monitoring symptomatic, biochemical, and objective responses, and survival. Basal plasma CgA levels were significantly higher in patients with functioning than non-functioning tumors (median (range): 220 (18-2,230) vs. 46 (25-8,610) U/l, P=0.03) and in those with than without metastases (171 (18-8,610) vs. 43 (28-220) U/l, P=0.04). CgA levels significantly correlated with WHO classification, clinical TNM staging, and Ki-67 proliferative index. After OT, CgA levels decreased from 146 (18-8,610) to 61 (10-8,535) U/l (basal and nadir values), P<0.001. In patients responsive to OT, a successful objective response occurred in 21/31 patients (68%). Successful symptomatic response occurred in 13/18 patients (72%), biochemical response in 25/31 (81%), and objective response in 21/31 (68%). In the remaining seven unresponsive cases, with CgA decrement <30%, disease progressed to death in six (86%). Median survival from enrollment was 48 months (6-138) in responsive and 6 (6-30) in unresponsive patients (P=0.0005). In GEP-NETs, plasma CgA is a reliable marker, and a >30% decrease after OT has a relevant prognostic meaning allowing the identification of the subgroup of patients most likely to be responsive to chronic SSAs.


Voltage-dependent Ca2+ channels are involved in regulation of steroid synthesis by bovine but not rat fasciculata cells.
Bovine but not rat fasciculata cells show a concentration-dependent stimulation of the production of corticosteroids by addition of external Ca2+ to the incubation medium. Both cell types respond to ACTH in a concentration-dependent manner. Increasing concentrations of K+ (0-20 mM) cause increased production of corticosteroids and accelerated influx of Ca2+ in bovine fasciculata cells but no change in either of these two parameters in rat fasciculata cells. Two inhibitors of Ca2+ channels (nifedipine and PY108-068) inhibit both the production of steroids by unstimulated bovine cells and the stimulation produced by three agents (ACTH, (Bu)2 cAMP, and K+). Half-maximal inhibition of these responses was produced in each case by submicromolar or low micromolar concentrations of the inhibitors. These inhibitors are without effect in rat fasciculata cells. One Ca2(+)-channel agonist (BAY K8644) stimulated synthesis of steroids by bovine cells and potentiated the response to ACTH. The agonist acts in the low micromolar range but was without effect on rat cells or on the responses of steroid synthesis by these cells to either ACTH or dibutyryl cAMP. Moreover, bovine fasciculata cells show specific binding sites for [+]PN 200-110, a specific ligand for 1,4-dihydropyridine receptors associated with voltage-dependent Ca2+ channels [dissociation constant (Kd), 14.3 nM; maximum number of binding sites (Bmax), 0.52 pmol/10(6) cells]. Rat cells show no specific binding of PN 200-110. We conclude that bovine fasciculata cells possess voltage-dependent Ca2+ channels which are involved in the regulation of steroid synthesis in these cells and that rat fasciculata cells are without such channels.


Protective effect of endogenous PPARgamma against acute gastric mucosal lesions associated with ischemia-reperfusion.
Acute gastric mucosal lesions (AGMLs) are an important cause of gastrointestinal bleeding. Herein, we demonstrate that peroxisome proliferator-activated receptor-gamma (PPARgamma), a member of a nuclear receptor family, functions as an endogenous anti-inflammatory pathway in a murine model of AGML induced by ischemia-reperfusion (I/R). Treatment with specific PPARgamma ligands such as BRL-49653, pioglitazone, or troglitazone was examined in a model of AGML induced by I/R. PPARgamma-deficient and wild-type mice were also examined for their response to I/R in stomach. Specific PPARgamma ligands exhibited dramatic and rapid protection against AGML formation associated with I/R in mice in a dose-dependent manner. In contrast, the AGML induced by I/R in PPARgamma-deficient mice was more severe than that observed in wild-type mice. Administration of the PPARgamma ligand significantly inhibited the upregulation of TNF-alpha, ICAM-1, inducible nitric oxide synthase, apoptosis, and nitrotyrosine formation induced by I/R in the stomach. These data indicate that an endogenous pathway associated with PPARgamma plays an important role in the pathogenesis of I/R-associated injury in the stomach.


Genotype in the 24-kDa subunit gene (NDUFV2) of mitochondrial complex I and susceptibility to Parkinson disease.
We analyzed the gene encoding the 24-kDa subunit of mitochondrial complex I, which has been implicated in the pathogenesis of Parkinson disease (PD). We set out to identify a polymorphism in the 24-kDa subunit gene (NDUFV2) in patients with PD and determine whether genetic polymorphism of this gene is associated with a higher risk of PD. The subjects comprised 126 patients with PD, and the control group comprised 113 unrelated individuals without neurodegenerative disorders. A novel polymorphism (Ala29Val) in the mitochondrial targeting sequence of NDUFV2 was found in patients with PD. The distribution of the three genotypes was significantly different between the two groups (chi 2 = 7.53, df = 2, P = 0.023). The frequency of homozygotes for the mutation was significantly higher in PD patients (23.8%) than in control subjects (11.5%, Fisher's exact test, P = 0.0099 < 0.01). The risk of developing PD associated with homozygosity for this mutation was calculated as 2.40 (95% CI: 1.18-4.88). NDUFV2 constitutes one genetic risk factor for PD, and the mutation may well be a cause of complex I deficiency in this disease.


Conformational properties of the pentapeptide fragment [32-36] of the thymic hormone thymopoietin.
The conformational energy for the pentapeptide Arg-Lys-Asp-Val-Tyr (TP5) is calculated using empirical potential functions. Calculation of the local interactions for each independent residue gives a local energy term for which the probabilities as a function of phi, psi are plotted on Ramachandran-type maps. The interaction energy between residues is calculated only for these points in the maps with maximum probability. The most probable conformation for TP5 is found to have an extended backbone arrangement having the Arg and Tyr sidechains folded over the backbone. 13C n.m.r. spin lattice relaxation time measurements show no increase in T1 of the alpha-carbons at the first and terminal amino acids. The increase in T1 along the sidechain as found for Lys does not occur for Arg and Tyr. These signs of reduced mobility are consistent with a set of folded conformations in which the Arg and Tyr sidechains have hindered internal rotations. The vicinal NH-C alpha H couplings agree well with those calculated for the most probable conformer. This is not so for the C alpha H-C beta H couplings. These data are consistent with previous n.m.r. and structure activity studies.


Influence of temperature and cocaine on responses of the isolated mouse vas deferens to adrenergic amines.
Lowering the bath temperature from 37 degrees C to 20 degrees C resulted in supersensitivity of the isolated mouse was deferens to norepinephrine. Dose-response curves to norepinephrine were shifted to the left along the log dose axis (enhanced potency) and the maximum degree of contraction that could be elicited was increased. The effect of cocaine on norepinephrine effects was qualitatively the same as hypothermia. Both treatments enhanced the potencies of other alpha receptor agonists that are substrates for the adrenergic neuronal membrane uptake mechanism. Neither treatment enhanced the potency of methoxamine, which is not taken up by adrenergic neurons, but hypothermia increased the methoxamine-induced maximum contractile height. Uptake of 14C-norepinephrine by the vas deferens was abolished by cocaine and low temperature. The data suggest that enhanced potency of adrenergic amines by hypothermia results from an inhibition of uptake by adrenergic neurons. Increased height of maximum contraction at low temperature may be partly due to decreased neuronal uptake, but other mechanisms are also likely to be involved in this effect.


Reactivity and effectiveness of traditional and novel ligands for multi-micronutrient fertilization in a calcareous soil.
This study compares the effectiveness of multi-micronutrient formulations containing iron (Fe), manganese (Mn), and zinc (Zn) with traditional (EDTA, DTPA, HEEDTA, and EDDHAm) or novel chelates (o,p-EDDHA, S,S-EDDS, and IDHA) and natural complexing agents (gluconate and lignosulfonate). The stability and reactivity of the formulations were studied on batch experiments with calcareous soil and by speciation modeling. Formulations containing traditional ligands maintained higher Mn but lower Zn concentration in soil solution than the novel ligands. The gluconate and lignosulfonate maintained low concentrations of both Mn and Zn in soil solution. Selected formulations were applied into calcareous soil and their efficacy was evaluated in a pot experiment with soybean. The formulation containing DTPA led to the highest Zn concentration in plants, as well as the formulation containing S,S-EDDS in the short-term, which correlated with its biodegradability. The application of traditional or novel ligands in formulations did not result in sufficient plant Mn concentrations, which was related to the low Mn stability observed for all formulations under moderate oxidation conditions. The results highlight the need to consider the effect of metals and ligands interactions in multi-nutrient fertilization and the potential of S,S-EDDS to be used for Zn fertilization. Furthermore, it is necessary to explore new sources of Mn fertilization for calcareous soils that have greater stability and efficiency, or instead to use foliar fertilization.


Internal mammary lymph node siliconoma in absence of prosthesis rupture: a case series that raises concern for potential risk of overdiagnosis.
Silicon migration after rupture is an adverse event of breast implant, whose risk increases with the aging of prosthesis. The exact prevalence of this complication remains unclear and reported data are inconsistent. In addition, microscopic diffusion of silicone gel through intact implant, known as gel bleeding, might verify thus complicating diagnosis. Although high cohesive gel has reduced the occurrence of gel bleeding, this phenomenon is still possible and its occurrence rate remains underestimated. If silicon droplets migrate in locoregional lymph node, a swelling that mimics recurrence can arise. Therefore, a risk of overdiagnosis is possible when clinicians rely only on imaging techniques. The aim of this study is to evaluate the actual prevalence of metastasis in internal mammary lymph node (IMLN) in presence of PET positive uptake and no prosthesis rupture. We retrospectively evaluated our patient's records and selected those with intact breast implants and suspected relapse in IMLN that underwent biopsy, either surgical or imaging guided. All patients performed PET/CT scan showing pathological uptake in IMLNs. A breast magnetic resonance (MRI) or ultrasound (US) imaging confirmed a suspicious adenopathy and excluded prosthesis rupture. From 2015 to 2019 a total of nine patients underwent biopsy of the IMLN and only six of them met inclusion criteria. Four biopsies were CT-guided, two were surgical. Three patients (50%) were diagnosed with breast cancer relapse while two (33.3%) were found with siliconoma and one (16.7%) was inflammatory. Siliconoma can occur even without evidence of capsule rupture, challenging the clinicians and leading to a risk of relapse over diagnosis. Echographic, MRI and nuclear medicine imaging criteria may be not sufficient in differential diagnosis. To overcome the issue, we suggest introducing into the clinical practice the biopsy of suspicious enlarged IMLN with minimally invasive technique.


Correlation Among Y-Balance Test-Lower Quarter Composite Scores, Hip Musculoskeletal Characteristics, and Pitching Kinematics in NCAA Division I Baseball Pitchers.
Context: Numerous studies have reported kinematic data on baseball pitchers using three-dimensional (3D) motion analysis, but no studies to date have correlated this data with clinical outcome measures. Objective: To examine the relationship among Y-Balance Test-Lower Quarter (YBT-LQ) composite scores, musculoskeletal characteristics of the hip, and pitching kinematics in National Collegiate Athletic Association (NCAA) Division I baseball pitchers. Design: Cross-sectional. Setting: 3D motion analysis laboratory. Participants: Nineteen healthy male college baseball pitchers. Main Outcome Measures: Internal and external hip passive range of motion, hip abduction strength, YBT-LQ composite scores, and kinematic variables of the pitching motion. Results: Stride length demonstrated a moderate positive correlation with dominant limb YBT-LQ composite score (r = .524, P = .02) and nondominant limb YBT-LQ composite score (r = .550, P = .01), and a weak positive correlation with normalized time to maximal humerus velocity (r = .458, P = .04). Stride length had a moderate negative correlation with normalized time to maximal thorax velocity (r = -.522, P = .02) and dominant hip total rotational motion (TRM; r = -.660, P = .002), and had a strong negative correlation with normalized time from stride foot contact to maximal knee flexion (r = -.722, P < .001). Dominant limb YBT-LQ composite score had a weak negative correlation with hip abduction strength difference (r = -.459, P = .04) and normalized time to maximal thorax velocity (r = -.468, P = .04). Nondominant limb YBT-LQ composite score demonstrated a weak negative correlation with normalized time to maximal thorax velocity (r = -.450, P = .05) and had a moderate negative correlation with dominant hip TRM (r = -.668, P = .001). There were no other significant relationships between the remaining variables. Conclusions: YBT-LQ is a clinical measure that can be used to correlate with hip musculoskeletal characteristics and pitching kinematics in NCAA Division I pitchers.


Fully Optical Modulation of the Two-Dimensional Electron Gas at the γ-Al2O3/SrTiO3 Interface.
Two-dimensional electron gas (2DEG) formed at the heterointerface between two oxide insulators hosts plenty of emergent phenomena and provides new opportunities for electronics and photoelectronics. However, despite being long sought after, on-demand properties controlled through a fully optical illumination remain far from being explored. Herein, a giant tunability of the 2DEG at the interface of γ-Al2O3/SrTiO3 through a fully optical gating is discovered. Specifically, photon-generated carriers lead to a delicate tunability of the carrier density and the underlying electronic structure, which is accompanied by the remarkable Lifshitz transition. Moreover, the 2DEG can be optically tuned to possess a maximum Rashba spin-orbit coupling, particularly at the crossing region of the sub-bands with different symmetries. First-principles calculations essentially well explain the optical modulation of γ-Al2O3/SrTiO3. Our fully optical gating opens a new pathway for manipulating emergent properties of the 2DEGs and is promising for on-demand photoelectric devices.


Interactions of erythropoietin, granulocyte colony-stimulating factor, stem cell factor, and interleukin-11 on murine hematopoiesis during simultaneous administration.
We investigated how in vivo effects of single hematopoietic cytokines change if given in combination for a prolonged time. Mice were treated with every combination of recombinant human (rh) erythropoietin (EPO), rh granulocyte colony-stimulating factor (G-CSF), recombinant rat (rr) stem cell factor (SCF), and rh interleukin (IL)-11 by continuous infusion over 7 days (full factorial design with three dose levels for each cytokine). Burst-forming unit-erythroid (BFU-E), colony-forming unit-erythroid (CFU-E), and colony-forming unit-granulocyte-macrophage (CFU-GM) were determined in bone marrow and spleen, reticulocytes, hematocrit, granulocytes, and thrombocytes in the peripheral blood. An analysis of variance (ANOVA) and multiple comparison of means was used to evaluate the data. For several cell types, cytokine effects superimposed in an additive way if combined. However, in a large number of circumstances, nonadditive pairwise interactions were found. They differed in type and magnitude involving high-dose saturation, high-dose antagonistic effects, and even effect reversals (qualitative interactions). Hence, in general, it was not possible to foresee the combination effects on the basis of existing knowledge of single effects. On the other hand, the cytokine network was robust and no system hazards were observed under multiple cytokine combinations. The results illustrate that the cytokine network has nonlinear dynamic properties in vivo with dose-response characteristics of one cytokine being continuously modified by other cytokines.


Quality of Conduct and Reporting of Propensity Score Methods in Studies Investigating the Effectiveness of Antimicrobial Therapy.
Propensity score methods are becoming increasingly popular in infectious disease medicine to correct for confounding in observational studies. However, applying and reporting propensity score techniques correctly requires substantial knowledge of these methods. The quality of conduct and reporting of propensity score methods in studies investigating the effectiveness of antimicrobial therapy is yet undetermined. A systematic review was performed to provide an overview of studies (2005-2020) on the effectiveness of antimicrobial therapy that used propensity score methods. A quality assessment tool and a standardized quality score were developed to evaluate a subset of studies in which antibacterial therapy was investigated in detail. The scale of this standardized score ranges between 0 (lowest quality) and 100 (excellent). A total of 437 studies were included. The absolute number of studies that investigated the effectiveness of antimicrobial therapy and that used propensity score methods increased 15-fold between the periods 2005-2009 and 2015-2019. Propensity score matching was the most frequently applied technique (65%), followed by propensity score-adjusted multivariable regression (25%). A subset of 108 studies was evaluated in detail. The median standardized quality score per year ranged between 53 and 61 (overall range: 33-88) and remained constant over the years. The quality of conduct and reporting of propensity score methods in research on the effectiveness of antimicrobial therapy needs substantial improvement. The quality assessment instrument that was developed in this study may serve to help investigators improve the conduct and reporting of propensity score methods.


Removing the cloak of invisibility: phenotyping the mouse.
If you study a human disease, it is likely that you have tried to generate a mouse model. Sometimes, these models are excellent; others are disappointing. Or, so we think. How often does our mouse mutant not model the human disease because of limitations in how we may look at it? In any living organism, many factors work together to produce the phenotype. Here, new phenotyping paradigms for assessing mouse biology and physiology are described and proposed. Advances in mouse phenotype assessments have paralleled human clinical diagnostics. The future brings a multitude of mouse strains that might be exposed to a variety of conditions. To assess health will require the ability to perform a broad-based phenotype assessment of every animal until we can understand how the perturbation of one system affects others.


Guidelines for meetings.
The major purpose of a meeting is to make decisions. The most basic and important elements of conducting a meeting, preparing motions for consideration, and recording the decisions are presented. The use of the guidelines for more or less formal meetings is discussed.


Low-Energy Electron-Induced Strand Breaks in Telomere-Derived DNA Sequences-Influence of DNA Sequence and Topology.
During cancer radiation therapy high-energy radiation is used to reduce tumour tissue. The irradiation produces a shower of secondary low-energy (<20 eV) electrons, which are able to damage DNA very efficiently by dissociative electron attachment. Recently, it was suggested that low-energy electron-induced DNA strand breaks strongly depend on the specific DNA sequence with a high sensitivity of G-rich sequences. Here, we use DNA origami platforms to expose G-rich telomere sequences to low-energy (8.8 eV) electrons to determine absolute cross sections for strand breakage and to study the influence of sequence modifications and topology of telomeric DNA on the strand breakage. We find that the telomeric DNA 5'-(TTA GGG)2 is more sensitive to low-energy electrons than an intermixed sequence 5'-(TGT GTG A)2 confirming the unique electronic properties resulting from G-stacking. With increasing length of the oligonucleotide (i.e., going from 5'-(GGG ATT)2 to 5'-(GGG ATT)4 ), both the variety of topology and the electron-induced strand break cross sections increase. Addition of K+ ions decreases the strand break cross section for all sequences that are able to fold G-quadruplexes or G-intermediates, whereas the strand break cross section for the intermixed sequence remains unchanged. These results indicate that telomeric DNA is rather sensitive towards low-energy electron-induced strand breakage suggesting significant telomere shortening that can also occur during cancer radiation therapy.


Vasoactive intestinal peptide-receptor imaging for the localization of intestinal adenocarcinomas and endocrine tumors.
Intestinal adenocarcinomas and various endocrine tumors express large numbers of high-affinity receptors for vasoactive intestinal peptide (VIP). We have evaluated the usefulness of scanning with VIP labeled with iodine-123 for tumor localization in patients with gastrointestinal tumors. Radioiodinated VIP was purified by high-pressure liquid chromatography and administered as a single intravenous bolus injection (300 pmol [1 microgram]). Scanning with radiolabeled VIP was compared with computed tomography and scanning with somatostatin analogues in 79 patients with colorectal cancer, pancreatic carcinoma, gastric cancer, carcinoid tumor, or insulinoma. Visualization of gastrointestinal tumors and metastases was obtained with radiolabeled VIP. Binding of the labeled peptide by primary tumors and metastases was visible shortly after the injection and was still demonstrable at 24 hours. In patients with colorectal adenocarcinomas, primary or recurrent tumors were visualized in 10 of 10, liver metastases in 15 of 18, lung metastases in 2 of 3, and lymph-node metastases in 4 of 4. Primary pancreatic adenocarcinomas were visualized by imaging in 10 of 12 patients, and liver metastases were seen in 7 of 7. Primary or recurrent gastric adenocarcinomas were visualized in 5 of 5 patients, and liver metastases were seen in 2 of 2 patients. VIP scans were positive in 9 of 10 patients with carcinoid tumors and in 4 of 4 patients with insulinomas. Some tumors with positive VIP scans were also visualized with somatostatin analogues (4 of 17 colorectal adenocarcinomas, 8 of 9 carcinoids, and 2 of 2 insulinomas). In vitro binding studies confirmed the presence of VIP receptors on gastrointestinal tumors. Scanning with radiolabeled VIP can visualize intestinal tumors and metastases that express receptors for VIP.