Does significant medical comorbidity negate the benefit of up-front cytoreduction in advanced ovarian cancer?
The objective of the study was to determine if initial surgery (IS) or initial chemotherapy (IC) affects rates of optimal surgery and survival in a population with significant medical comorbidities. Data of all patients with stage III-IV ovarian, peritoneal, and fallopian tube cancers diagnosed from 1995 to 2008 were reviewed. Clinical and pathologic data were abstracted. There were 551 cases for review: 255 (46.3%) received IS, and 296 (53.7%) received IC. Patients who received IC had higher stage (P < 0.001), higher-grade cancers (P < 0.001), higher mean CA-125 (P = 0.015), higher rates of diabetes (P = 0.006), hypertension (P = 0.008), and presurgical embolism (P < 0.022) and were older (P = 0.043). There was no difference with respect to body mass index, albumin, extent of surgery, or intensive care use. Rates of optimal cytoreduction were higher with IC compared with IS (72.7% vs 56.1%, P < 0.001). IS was associated with more blood loss (P = 0.005) and higher rates of postsurgical venous thrombosis (P < 0.001). Optimal cytoreduction predicted survival in both groups. Among optimal patients, IS improved median survival: progression-free survival of 14 months (IS) versus 12 months (IC), P = 0.004; overall survival of 58 months (IS) versus 34 months (IC), P = 0.002. Factors influencing this difference were receipt of IC and history of diabetes; both predictors of mortality: hazard ratios, 1.9 (95% confidence interval, 1.3-2.8; P < 0.001) and 1.8 (95% confidence interval, 1.02-3.1; P = 0.042), respectively. The achievement of optimal cytoreduction continues to be a significant predictor of survival, regardless of treatment approach. Patients selected for IS and in whom optimal cytoreduction was achieved had improvements in both progression-free survival and overall survival. However, the differences could not be explained by surgical effort alone as diabetes was independently associated with mortality.


Electrolyte transport in the renal collecting duct and its regulation by the renin-angiotensin-aldosterone system.
Distal nephron of the kidney plays key roles in fluid volume and electrolyte homeostasis by tightly regulating reabsorption and excretion of Na+, K+, and Cl- Studies to date demonstrate the detailed electrolyte transport mechanisms in principal cells of the cortical collecting duct, and their regulation by renin-angiotensin-aldosterone system (RAAS). In recent years, however, accumulating data indicate that intercalated cells, another cell type that is present in the cortical collecting duct, also play active roles in the regulation of blood pressure. Notably, pendrin in β-intercalated cells not only controls acid/base homeostasis, but is also one of the key components controlling salt and K+ transport in distal nephron. We have recently shown that pendrin is regulated by the co-ordinated action of angiotensin II (AngII) and aldosterone, and at the downstream of AngII, mammalian target of rapamycin (mTOR) signaling regulates pendrin through inhibiting the kinase unc51-like-kinase 1 and promoting dephosphorylation of mineralocorticoid receptor (MR). In this review, we summarize recent advances in the current knowledge on the salt transport mechanisms in the cortical collecting duct, and their regulation by the RAAS.


Momordica charantia reverses type II diabetes in rat.
Diabetes, a disease with abnormal production or use of insulin, is a growing concern that affects many individuals globally. Although many attempts have been made, there is no satisfactory treatment for diabetes. Recently, scientists have been exploring a promising treatment of diabetes involving herbal medicine. In this line, we show that Momordica charantia, a tendril-bearing vine belonging to the Cucurbitaceae family, permanently normalizes blood glucose levels comparable to healthy rats. Most importantly, M. charantia increases the expression of Insulin and Pdx1 genes while lowers the expression Glut2. Moreover, the number and size of the pancreatic islets have remarkably increased in treated animals. Liver ALT, AST, and ALP enzyme activities fell into normal range in treated animals suggesting the protective effect of M. charantia. These data indicate that M. Charantia improves the pancreas function by activating pancreatic beta cells and protecting liver tissue. PRACTICAL APPLICATIONS: Owing to the effectiveness of Momordica Charantia extracts in management of diabetes in STZ-induced diabetic rats, we have intention to evaluate the powder of Charantia to discover novel drug for treating diabetes. It is expected that the results could be translated in clinical trials.


Who are lonely? Loneliness in different age groups (18-81 years old), using two measures of loneliness.
This study asks if the prevalence of loneliness in the population varies depending on the measures used, with special focus on loneliness among the elderly. The study compares loneliness in different age groups between 18 and 81 years old (N = 14,743) using two measures of loneliness: the (indirect) six-item De Jong Gierveld Loneliness Scale and a single-item, direct question about loneliness. Data are from the Norwegian LOGG (Life Course, Generation, and Gender) study. We compare the findings on loneliness according to age, gender, health, and partner status. Overall, the two loneliness measures indicate a similar prevalence of loneliness, but attribute loneliness to somewhat different people. When using a direct measure, loneliness is more prevalent among women; when using the (indirect) De Jong Gierveld Scale, loneliness is more prevalent among men. Also, the association between age and loneliness differed when using the direct and the indirect measure.


Does depth of squat-stand maneuver affect estimates of dynamic cerebral autoregulation?
Repeated squat-stand maneuvers (SSM) are an effective way of measuring dynamic cerebral autoregulation (dCA), but the depth of SSM required to improve dCA estimations has never been studied. We compared beat-to-beat cerebral hemodynamic parameters between maximal depth SSM (SSMD ) and a shallower alternative (SSMS ) in two age groups (younger [20-34 years] vs. older [50-71 years]) at a frequency of 0.05 Hz. Cerebral blood flow velocity, continuous blood pressure (BP) and end-tidal CO2 (EtCO2 ) were measured using transcranial Doppler ultrasound, the Finometer device, and capnography, respectively. Coherence (at 0.05 Hz) was significantly higher in both SSM recordings compared to spontaneous BP oscillations at baseline standing (BS ). Median (IQR) autoregulation index (ARI) was reduced during SSMD (4.46 [4.03-5.22], p < .01) compared to SSMS (5.96 [5.40-6.69]) and BS (6.03 [5.20-6.49], p < .01) with similar relative differences also observed for phase (at 0.05 Hz). End-tidal CO2 was increased in SSMD (38.3 ± 3.7 mmHg, p < .01) compared to both SSMS (36.6 ± 3.6 mmHg) and BS (35.5 ± 3.2 mmHg). The older group demonstrated significantly lower ARI and phase estimates during SSM and found SSMS more effortful than SSMD . In conclusion, both SSMD and SSMS are effective at estimating dCA, and dCA appears to be less efficient during maximal depth SSM compared to baseline rest or a shallower alternative.


Staff attitudes to an ultrasound-guided peripheral nerve block room for orthopaedic patients.
Ultrasound-guided peripheral nerve blocks have well recognised benefits in orthopaedic patients. Some hospitals, to maximise these benefits, establish dedicated "block rooms" to deliver this service. Orthopaedic surgery makes up a large proportion of our hospitals work load, and many of these patients would benefit from ultrasound-guided peripheral nerve blocks. We analysed the attitudes of key staff in our hospital towards the establishment of a block room. Sixty questionnaires were distributed and 47 (78%) were completed. Orthopaedic surgeons (n = 6) were concerned ultrasound-guided peripheral nerve blocks would delay theatre lists (83%), and cause patients pain (67%) and increased anxiety (67%). Anaesthetists (n = 10) and Nurses (n = 30) were concerned there was insufficient experience in their departments to deliver this service (80% and 77%, respectively). However, 91% of all staff believed funding should be available for a block room. Our survey has identified areas of concern, and deficiencies that we must address before proceeding with the development of such a service.


Fibrinogen as a risk factor for coronary heart disease and mortality in middle-aged men and women. The Scottish Heart Health Study.
Fibrinogen was measured in 5095 men and 4860 men aged 40-59 in a random population sample from 25 districts of Scotland recruited during 1984-87: the Scottish Heart Health Study. Fibrinogen was then related to the chance of fatal and non-fatal coronary events and death from any cause during a subsequent follow-up period of around 8 years. Fibrinogen was measured by the Clauss assay. The effect of fibrinogen on coronary heart disease and death was assessed through age-adjusted means and Cox proportional hazards regression models, accounting for age, cotinine (a measure of tobacco smoke inhalation) and 11 other major coronary risk factors. Fibrinogen was found to be an important risk factor for coronary heart disease in men and women, with and without pre-existing coronary heart disease. There appears to be a threshold effect, with those in the highest fifth of the distribution having a much increased risk. Estimated age-adjusted hazard ratios by sex and pre-existing coronary heart disease group for the highest to lowest fifth of fibrinogen range between 1.93 and 4.86. Fibrinogen is also important as a risk factor for coronary death and all-causes mortality, with a similar threshold effect. Comparing the two extreme fifths, the hazard ratios for coronary death are 3.01 and 3.42, and for all-cause mortality are 2.59 and 2.20, for men and women respectively. Adjustment for cotinine reduces the hazard ratios, but further adjustment for the other 11 risk factors has little effect for coronary heart disease events. After full adjustment there is a remaining significant (P < 0.05) hazard ratio for coronary death and death from any cause and for a coronary heart disease event for those free of coronary heart disease at baseline, amongst men, comparing the highest to the lowest fifth. Fibrinogen is a strong predictor of coronary heart disease, fatal or non-fatal, new or recurrent, and of death from an unspecified cause, for both men and women. Its effect is only partially attributable to other coronary risk factors, the most important of which is smoking.


FIM-Minimum Data Set Motor Item Bank: Short Forms Development and Precision Comparison in Veterans.
To improve the practical use of the short forms (SFs) developed from the item bank, we compared the measurement precision of the 4- and 8-item SFs generated from a motor item bank composed of the FIM and the Minimum Data Set (MDS). The FIM-MDS motor item bank allowed scores generated from different instruments to be co-calibrated. The 4- and 8-item SFs were developed based on Rasch analysis procedures. This article compared person strata, ceiling/floor effects, and test SE plots for each administration form and examined 95% confidence interval error bands of anchored person measures with the corresponding SFs. We used 0.3 SE as a criterion to reflect a reliability level of .90. Veterans' inpatient rehabilitation facilities and community living centers. Veterans (N=2500) who had both FIM and the MDS data within 6 days during 2008 through 2010. Not applicable. Four- and 8-item SFs of FIM, MDS, and FIM-MDS motor item bank. Six SFs were generated with 4 and 8 items across a range of difficulty levels from the FIM-MDS motor item bank. The three 8-item SFs all had higher correlations with the item bank (r=.82-.95), higher person strata, and less test error than the corresponding 4-item SFs (r=.80-.90). The three 4-item SFs did not meet the criteria of SE <0.3 for any theta values. Eight-item SFs could improve clinical use of the item bank composed of existing instruments across the continuum of care in veterans. We also found that the number of items, not test specificity, determines the precision of the instrument.


Recognition of spectrally degraded phonemes by younger, middle-aged, and older normal-hearing listeners.
The effects of spectral degradation on vowel and consonant recognition abilities were measured in young, middle-aged, and older normal-hearing (NH) listeners. Noise-band vocoding techniques were used to manipulate the number of spectral channels and frequency-to-place alignment, thereby simulating cochlear implant (CI) processing. A brief cognitive test battery was also administered. The performance of younger NH listeners exceeded that of the middle-aged and older listeners, when stimuli were severely distorted (spectrally shifted); the older listeners performed only slightly worse than the middle-aged listeners. Significant intragroup variability was present in the middle-aged and older groups. A hierarchical multiple-regression analysis including data from all three age groups suggested that age was the primary factor related to shifted vowel recognition performance, but verbal memory abilities also contributed significantly to performance. A second regression analysis (within the middle-aged and older groups alone) revealed that verbal memory and speed of processing abilities were better predictors of performance than age alone. The overall results from the current investigation suggested that both chronological age and cognitive capacities contributed to the ability to recognize spectrally degraded phonemes. Such findings have important implications for the counseling and rehabilitation of adult CI recipients.


Immunolocalization and adenoviral vector-mediated manganese superoxide dismutase gene transfer to experimental oral tumors.
The anti-oxidant enzyme system protects cellular macromolecules against damage from reactive oxygen species. One component of this system, manganese superoxide dismutase (MnSOD), has also been shown to display tumor suppressor gene-like activity. The purpose of this study was to examine changes in MnSOD expression during hamster cheek pouch carcinogenesis, and the effects of MnSOD overexpression using an adenoviral vector. Tumor induction was carried out using 7,12-dimethylbenz[alpha]anthracene. Animals were killed at periodic intervals, and cheek pouch tissues were excised and examined for MnSOD expression by immunohistochemistry and digital image analysis. We observed a reduction in MnSOD expression as early as 2 weeks after the start of carcinogen application. Low MnSOD expression persisted until the end of the 23-week experimental period. Solid hamster cheek pouch carcinoma xenografts were then established in nude mice. An adenoviral vector encoding the human MnSOD gene was delivered to the xenografts by direct injection. We observed high, immediate expression of MnSOD in the xenografts that persisted for 10 days following cessation of viral construct delivery. Delivery of the MnSOD construct resulted in a maximal 50% reduction in tumor growth compared with untreated controls. Our results suggest that MnSOD may be a tumor suppressor gene in the hamster cheek pouch model system.


Comparison of lumbar and shunt cerebrospinal fluid specimens for cytologic detection of leptomeningeal disease in pediatric patients with brain tumors.
Leptomeningeal disease (LMD) significantly affects the prognosis and treatment of pediatric patients with primary CNS tumors. Cytologic examination of lumbar CSF is routinely used to detect LMD. To determine whether examination of CSF obtained from ventricular shunt taps is a more sensitive method of detecting LMD in these patients, we designed a prospective study to compare the findings of cytologic examinations of CSF obtained from concurrent lumbar and ventriculoperitoneal (VP) shunt taps. As a part of diagnostic staging, follow-up testing, or both, 52 consecutive patients underwent concurrent lumbar and shunt taps on 90 separate occasions, ranging from the time of diagnosis to treatment follow-up. CSF from both sites was examined cytologically for malignant cells. The median age of the 28 males and 24 females was 7.5 years (range, 0.6 to 21.4 years). The primary CNS tumors included medulloblastoma (n = 29), astrocytoma (n = 10), ependymoma (n = 5), germinoma (n = 3), atypical teratoid rhabdoid tumor (n = 2), choroid plexus carcinoma (n = 2), and pineoblastoma (n = 1). Each site yielded a median CSF volume of 1.0 mL. Fourteen of 90 paired CSF test results were discordant: in 12, the cytologic findings from shunt CSF were negative for malignant cells, but those from lumbar CSF were positive; in two, the reverse was true. Malignant cells were detected at a higher rate in lumbar CSF than in shunt CSF (P =.0018). When repeat analyses were excluded, examination of lumbar CSF remained significantly more sensitive in detecting malignant cells (P =.011). Analysis of the subset of patients with embryonal tumors showed similar results (P =.0008). Cytologic examination of lumbar CSF is clearly superior to cytologic examination of VP shunt CSF for detecting leptomeningeal metastases in pediatric patients with primary CNS tumors.


Application of small fragment restriction endonuclease analysis (SF-REA) to the epidemiological fingerprinting of Staphylococcus aureus.
Total cell DNA of 14 isolates of Staphylococcus aureus from patients of an intensive care unit (ICU) and 180 unrelated strains was examined by restriction endonuclease analysis (REA). EcoRI-generated DNA fragments were either subjected to conventional REA on agarose gels and stained with ethidium bromide or separated by polyacrylamide gel electrophoresis and visualised by silver staining (SF-REA). Both methods were compared for inter-strain discriminatory ability, reproducibility and handling. All DNA-cleavage patterns of unrelated strains clearly differed from each other when subjected to SF-REA. In contrast, all S. aureus isolates from the ICU gave identical restriction fragment patterns. These findings supported the suspicion of nosocomial infection in these patients. Conventional REA proved the identity of the ICU isolates, but it failed to differentiate between some of the unrelated strains. Therefore SF-REA of total cell DNA seemed to be superior. It has proved to be a very useful technique for studying the epidemiology of S. aureus in hospitals.


Optical properties of a vibrationally modulated solid state Mott insulator.
Optical pulses at THz and mid-infrared frequencies tuned to specific vibrational resonances modulate the lattice along chosen normal mode coordinates. In this way, solids can be switched between competing electronic phases and new states are created. Here, we use vibrational modulation to make electronic interactions (Hubbard-U) in Mott-insulator time dependent. Mid-infrared optical pulses excite localized molecular vibrations in ET-F2TCNQ, a prototypical one-dimensional Mott-insulator. A broadband ultrafast probe interrogates the resulting optical spectrum between THz and visible frequencies. A red-shifted charge-transfer resonance is observed, consistent with a time-averaged reduction of the electronic correlation strength U. Secondly, a sideband manifold inside of the Mott-gap appears, resulting from a periodically modulated U. The response is compared to computations based on a quantum-modulated dynamic Hubbard model. Heuristic fitting suggests asymmetric holon-doublon coupling to the molecules and that electron double-occupancies strongly squeeze the vibrational mode.


Increasing the size limit of benign thyroid lesions resectable by endoscopic thyroidectomy via a unilateral axillo-breast approach without gas insufflation.
Endoscopic thyroidectomy is rarely attempted in patients with large goitrous lesions. We examined the feasibility and safety of endoscopic thyroidectomy via a unilateral axillo-breast approach without gas insufflation for resection of large thyroid tumors (≥4 cm). The study included 111 patients: 82 in group 1 (tumor diameter <4 cm) and 29 in group 2 (≥ 4 cm). Ninety-one patients underwent hemithyroidectomy and 20 underwent total thyroidectomy. Local complications, surgical outcomes, and pathological outcomes were compared between groups. Postoperative permanent pathology revealed 24 follicular adenomas and 87 nodular hyperplasias. The mean tumor size in group 2 was 51.10 ± 7.66 mm compared to 25.24 ± 8.14 mm in group 1. The mean volume of the thyroid gland in group 2 was 15.60 ± 3.45 cm(3) compared to 11.27 ± 2.40 cm(3) in group 1 (p = 0.000). Mean operating time did not differ significantly between groups (p = 0.520). Postoperatively, minor hematomas were encountered in three patients (3.7%) in group 1. Three patients in group 1 (3.7%) and two in group 2 (6.9%) developed transient unilateral vocal cord palsy (p = 0.604). Temporary hypocalcemia was observed in six and one patients in groups 1 and 2, respectively (p = 1.000). No permanent recurrent laryngeal nerve palsy or hypoparathyroidism occurred in either group. Our data support the safety and feasibility of endoscopic thyroidectomy via a unilateral axillo-breast approach without gas insufflation, even for the treatment of benign thyroid lesions ≥4 cm.


[Mild dementia syndrome in middle and old age].
95 elderly and senile patients with mild dementia were followed up: 20 patients with Alzheimer's disease, 25 patients with senile dementia of Alzheimer's type (DAT), 25 patients with vascular dementia (VD), 25 patients with combined vascular and Alzheimer's type of dementia (DAT/VD). Follow-up of patients for 1 and 3 years demonstrated that the diagnosis of mild dementia according to CDR and ICD-10 criteria had a differential-diagnostic specificity and reliability. It was also noticed that the nosologic qualification of mild dimentia syndrome was difficult or even impossible in patients with DAT/VD in conditions of a single examination. Only follow-up studies (during 3 years as a rule) may give a chance to define the diagnostic belonging of mild dementia syndrome more precisely.


The expression and intranuclear distribution of nucleolin in HL-60 and K-562 cells after repeated, short-term exposition to rotating magnetic fields.
The aim of the study was to analyze the influence of rotating magnetic fields (RMF) on the expression and intranuclear distribution of nucleolin, protein involved in ribosome biosynthesis, in HL-60 (acute promyelocytic leukemia) and K-562 (chronic myelogenous leukemia) established human cell lines. Cells were exposed to RMF for two chosen states of the magnetic field induction: B=10 mT and B=20 mT in experimental set-up for 30 min with 24-h intervals for four days. Cytospin slides were prepared and expression of nucleolin was detected using monoclonal antibodies. Parameters of fluorescence related to nucleolin were measured in at least 2000 tumor cells in each slide by a laser scanning cytometer with an argon laser. Percentages of cells in different phases of cell cycle were also analyzed. The repeated exposition of cells to RMF caused significant increase in nucleolin expression in the whole nucleus and in the nucleolin aggregates (NUA). The redistribution of nucleolin measured by changes in number of NUA was also observed. The exposition of both cell lines studied to RMF did not alter the cell cycle. The nucleolin is responsive to RMF in HL-60 and K-562. The increase of its expression may indicate a reaction of cells to RMF and it may influence their other biological properties.


Using D-Amino Acids to Delineate the Mechanism of Protein Folding: Application to Trp-cage.
Using the miniprotein Trp-cage as a model, we show that D-amino acids can be used to facilitate the delineation of protein folding mechanism. Specifically, we study the folding-unfolding kinetics of three Trp-cage mutants where the native glycine residue near the C-terminus of the α-helix is replaced by a D-amino acid. A previous study showed that these mutations increase the Trp-cage stability, due to a terminal capping effect. Our results show that the stabilizing effect of D-asparagine and D-glutamine originates almost exclusively from a decrease in the unfolding rate, while the D-alanine mutation results in a similar decrease in the unfolding rate, but it also increases the folding rate. Together, these results support a folding mechanism wherein the α-helix formation in the transition state is nucleated at the N-terminus, whereas those long-range native interactions stabilizing this helix are developed at the downhill side of the folding free energy barrier.


Spleen SORT LNP Generated in situ CAR T Cells Extend Survival in a Mouse Model of Lymphoreplete B Cell Lymphoma.
Chimeric Antigen Receptor (CAR) T cell immunotherapy is revolutionizing treatment for patients suffering from B-cell lymphoma (BL). However, the current method of CAR T cell production is complicated and expensive, requiring collection of patient blood to enrich the T cell population, ex vivo engineering/activation, and quality assessment before the patient can receive the treatment. Herein we leverage Spleen Selective ORgan Targeted (SORT) Lipid Nanoparticles (LNPs) to produce CAR T cells in situ and bypass the extensive and laborious process currently used. Optimized Spleen SORT LNPs containing 10 % 18 : 1 PA transfected CD3+, CD8+, and CD4+ T cells in wild-type mice. Spleen SORT LNPs delivered Cre recombinase mRNA and CAR encoding mRNA to T cells in reporter mice and in a lymphoreplete B cell lymphoma model (respectively) after intravenous injection without the need for active targeting ligands. Moreover, in situ CAR T cells increased the overall survival of mice with a less aggressive form of B cell lymphoma. In addition, in situ transfected CAR T cells reduced tumor metastasis to the liver by increasing tumor infiltrating lymphocytes. Overall, these results offer a promising alternative method for CAR T cell production with pre-clinical potential to treat hematological malignancies.


Musculoskeletal geometry accounts for apparent extrinsic representation of paw position in dorsal spinocerebellar tract.
Proprioception, the sense of limb position and motion, arises from individual muscle receptors. An important question is how and where in the neuroaxis our high level "extrinsic" sense of limb movement originates. In the 1990s, a series of papers detailed the properties of neurons in the dorsal spinocerebellar tract (DSCT) of the cat. Despite their direct projections from sensory receptors, it appeared that half of these neurons had consistent, high-level tuning to paw position rather than to joint angles (or muscle lengths). These results suggested that many DSCT neurons compute paw position from lower level sensory information. We examined the contribution of musculoskeletal geometry to this apparent extrinsic representation by simulating a three-joint hindlimb with mono- and biarticular muscles, each providing a muscle spindlelike signal, modulated by the muscle length. We simulated neurons driven by randomly weighted combinations of these signals and moved the paw to different positions under two joint-covariance conditions similar to the original experiments. Our results paralleled those experiments in a number of respects: 1) Many neurons were tuned to paw position relative to the hip under both conditions. 2) The distribution of tuning was strongly bimodal, with most neurons driven by whole-leg flexion or extension. 3) The change in tuning between conditions clustered around zero (median absolute change ~20°). These results indicate that, at least for these constraint conditions, extrinsic-like representation can be achieved simply through musculoskeletal geometry and convergent muscle length inputs. Consequently, they suggest a reinterpretation of the earlier results may be required.NEW & NOTEWORTHY A classic experiment concluding that many dorsal spinocerebellar tract neurons encode paw position rather than joint angles has been cited by many studies as evidence for high-level computation occurring within a single synapse of the sensors. However, our study provides evidence that such a computation is not required to explain the results. Using simulation, we replicated many of the original results with purely random connectivity, suggesting that a reinterpretation of the classic experiment is needed.


Right Diet: a television series to combat obesity among adolescents in Kuwait.
Adolescent obesity is a growing public health problem in Kuwait. Reducing obesity can lower the risk of several chronic diseases. Fourteen obese adolescent boys volunteered to participate in a 6-month multidimensional television series on weight loss. The adolescent boys were recruited through advertisements in schools. The program included counseling sessions, nutritional education, exercise, family support, peer group involvement, and incentives designed to motivate participants. The mean age of the boys was 15.6 ± 0.8 years. On average, subjects lost 10.6 ± 8.9 kg in weight and gained 3.3 ± 1.6 cm in height during the study period. The difference in mean body mass index at baseline and at 6 months following intervention was significant (P < 0.001) at 36.8 ± 4.6 and 32.0 ± 5.4, kg/m(2) respectively. Participants ranked counseling as the most important component of the program, followed by family support and type of program. This type of television series could be used as a model for future public health programs to prevent and control obesity among adolescents.


Anesthetic Management of a Child With Propionic Acidemia Complicated by Bacteremia and Severe Acute Respiratory Syndrome Coronavirus 2.
Propionic acidemia (PA) is a rare, multi-systemic inborn error of metabolism. PA results from an impaired activity of the mitochondrial enzyme, propionyl-CoA carboxylase (PCC). PCC holds an essential role in the catabolic pathways for odd-chain fatty acids, cholesterol side-chains and branched-chain amino acids. Errors in these pathways result in the accumulation of toxic metabolites that may advance into end-organ damage and dysfunction. Clinical manifestations of PA include relapsing courses of severe metabolic acidosis, concurrent viral or bacterial infection, episodic vomiting, gastroesophageal reflux disease (GERD), seizures, developmental delay, hypotonia, hyperammonemia, osteopenia, pancreatitis and cardiomyopathy. This case describes a 3-year-old boy with PA who presented with an acute metabolic crisis, precipitated by Staphylococcus epidermidis (S. epidermidis) bacteremia and severe acute respiratory syndrome due to coronavirus 2 (SARS-CoV-2) co-infection. He required anesthetic management for surgical removal of an infected central venous port. Anesthetic care for this patient presented the unique challenges of metabolic decompensation amidst infection with SARS-CoV-2. Options for anesthetic care for patients with PA have been elucidated in the literature. However, to our knowledge, this is the first case to describe anesthetic management in a PA patient with SARS-CoV-2.


Alveolar soft part sarcoma: unusual etiology of mediastinal mass in an adolescent.
Alveolar soft part sarcoma (ASPS) is a rare malignancy that usually arises in an extremity. Mediastinal involvement is uncommon, with only two reports of primary mediastinal disease and two reports of metastatic mediastinal disease in the literature, all referencing adult patients. To our knowledge, ours is the first report of ASPS presenting with a mediastinal mass in adolescence. Although ASPS is not generally included in the differential for adolescent mediastinal masses, it should be considered when clinical presentation and imaging appearance are characteristic.


A merge-based condensing strategy for multiple prototype classifiers.
A class-conditional hierarchical clustering framework has been used to generalize and improve previously proposed condensing schemes to obtain multiple prototype classifiers. The proposed method conveniently uses geometric properties and clusters to efficiently obtain reduced sets of prototypes that accurately represent the data while significantly keeping its discriminating power. The benefits of the proposed approach are empirically assessed with regard to other previously proposed algorithms which are similar in their foundations. Other well-known multiple prototype classifiers have also been taken into account in the comparison.


The Prognostic Impact of the Pathological Response to Neoadjuvant Dose-Dense Therapy for Ovarian Carcinoma.
The aim of this study was to assess the use of the pathological response to neoadjuvant chemotherapy (NAC) for predicting disease prognosis in patients with advanced ovarian cancer who received neoadjuvant dose-dense weekly paclitaxel and carboplatin (dd-TC) therapy. We retrospectively investigated patients with advanced epithelial ovarian, tubal, or peritoneal carcinoma treated at our hospital from July 2004 to October 2014. Patients received dd-TC therapy as NAC followed by interval debulking surgery (IDS). Specimens resected during IDS were divided into 4 groups based on pathological response: grade 1, most tumor cells appeared to be viable; grade 2a, most tumor cells had disappeared, whereas the remaining tumor cells were vacuolated or degenerated; grade 2b, small numbers of viable tumor cells were observed; and grade 3, small aggregations of macrophages were seen. Sixty-eight patients were enrolled. The median number of NAC cycles was 3 (range, 2-6), and 51 patients (75.0%) achieved complete resection at IDS. Regarding pathological response, 7 (10.3%) patients were classified as grade 1, 11 (16.2%) as grade 2a, 46 (67.7%) as grade 2b, and 4 (5.9%) as grade 3. In univariate and multivariate analyses, grades 2b and 3 pathological responses were significant favorable prognostic factors for progression-free survival (P = 0.028; hazard ratio, 0.48; 95% confidence interval, 0.26-0.92). Although the pathological complete response rate to NAC was low in this study, both complete and good pathological responses to NAC might be favorable prognostic factors for PFS in patients with advanced ovarian cancer who receive dd-TC.


[How I explore ... the risk of a patient developing type 2 diabetes].
Both the prevalence and the incidence of type 2 diabetes are increasing rapidly. Effective prevention measures, including lifestyle or drug prescription, have been recently reported. It is thus important to detect at risk individuals in order to provide appropriate diet and exercise recommendations or even pharmacological treatment. We summarize the most useful indices based on anamnesis, clinical examination and biological assays that can help to detect subjects at high risk of progression towards type 2 diabetes.


Monitoring the neural activity of the state of mental silence while practicing Sahaja yoga meditation.
To identify the neural correlates of the state of mental silence as experienced through Sahaja yoga meditation. Nineteen experienced meditators underwent functional magnetic resonance imaging during three short consecutive meditation periods, contrasted with a control relaxation condition. Relative to baseline, at the beginning of the meditation sessions there was a significant increase of activation in bilateral inferior frontal and temporal regions. Activation became progressively more reduced with deeper meditation stages and in the last meditation session it became localized to the right inferior frontal cortex/ right insula and right middle/superior temporal cortex. Furthermore, right inferior frontal activation was directly associated with the subjective depth of the mental silence experience. Meditators appear to pass through an initial intense neural self-control process necessary to silence their mind. After this they experience relatively reduced brain activation concomitant with the deepening of the state of mental silence over right inferior frontal cortex, probably reflecting an effortless process of attentional contemplation associated with this state.


Anatomy of the pubovisceral muscle origin: Macroscopic and microscopic findings within the injury zone.
The levator ani muscle (LA) injury associated with vaginal birth occurs in a characteristic site of injury on the inner surface of the pubic bone to the pubovisceral portion of the levator ani muscle's origin. This study investigated the gross and microscopic anatomy of the pubic origin of the LA in this region. Pubic origin of the levator ani muscle was examined in situ then harvested from nine female cadavers (35-98 years). A combination of targeted feature sampling and sequential sampling was used where each specimen was cut sequentially in approximately 5 mm thick slices apart in the area of known LA injury. Histological sections were stained with Masson's trichrome. The pubovisceral origin is transparent and thin as it attaches tangentially to the pubic periosteum, with its morphology changing from medial to lateral regions. Medially, fibers of the thick muscle belly coalesce toward multiple narrow points of bony attachment for individual fascicles. In the central portion there is an aponeurosis and the distance between muscle and periosteum is wider (∼3 mm) than in the medial region. Laterally, the LA fibers attach to the levator arch where the transition from pubovisceral muscle to the iliococcygeal muscle occurs. The morphology of the levator ani origin varies from the medial to lateral margin. The medial origin is a rather direct attachment of the muscle, while lateral origin is made through the levator arch.


Pushing concentration of stationary solar concentrators to the limit.
We give the theoretical limit of concentration allowed by nonimaging optics for stationary solar concentrators after reviewing sun- earth geometry in direction cosine space. We then discuss the design principles that we follow to approach the maximum concentration along with examples including a hollow CPC trough, a dielectric CPC trough, and a 3D dielectric stationary solar concentrator which concentrates sun light four times (4x), eight hours per day year around.


Paraganglioma of the organ of Zuckerkandl associated with a somatic HIF2α mutation: A case report.
Paragangliomas of the organ of Zuckerkandl (OZ-PGL) are rare tumors that, in >70% of cases, occur in association with succinate dehydrogenase complex iron sulfur subunit B (SDHB) or SDHD gene mutations. The aim of the current study was to determine whether a somatic genetic defect in the hypoxia-inducible factor 2α (HIF2α) gene was present in a case of sporadic OZ-PGL. A 32-year-old African female presented with uncontrolled hypertension during the first trimester of pregnancy. A diagnostic hysteroscopy was performed 3 months after delivery, precipitating a hypertensive crisis. Thereafter, the patient was diagnosed with noradrenaline-secreting OZ-PGL. A complete blood count identified mild normocytic anemia of an inflammatory origin. Surgical removal of the tumor resulted in normalization of plasma and urinary normetanephrine levels. Genetic testing for germline mutations (including large deletions) in the von Hippel-Lindau tumor suppressor, SDHB, SDHC and SDHD genes was normal. However, a heterozygous missense mutation (c.1589Cys>Tyr) was detected in exon 12 of HIF2α, which results in a substitution of alanine 530 with valine (Ala530Val) in the HIF2α protein. A germline mutation was excluded based on the negative results of blood DNA testing. A three-dimensional homology model of Ala530Val was constructed, which showed impaired HIF2α/VHL interaction and decreased HIF2α ubiquitination. 1H-high-resolution magic-angle-spinning nuclear magnetic resonance spectroscopy detected low succinate levels and high α and β glucose levels. To the best of our knowledge, the present case represents the first of its kind to associate a somatic HIF2α gain-of-function mutation with OZ-PGL. It is therefore recommended that patients without germline SDHx mutations should be tested for HIF2α mutations.


[Taxonomy and systematics of pathogenic microorganisms].
The modern state of the problem of the systematics of microorganisms is analyzed and the data on the taxonomy of bacteria belonging to the family Enterobacteriaceae are presented. The importance of studies on the taxonomy of microorganisms is emphasized. These studies play a vital role in the development of diagnostic preparations and techniques for the identification of infective agents, as well as in the realization of epidemiological surveillance. Much attention is given to the works of Soviet microbiologists, discussing such problems as the unification of the classification scheme of dysentery bacteria, the intraspecific taxonomy of Francisella tularensis, the systematic position of Allomonas and the antigenic scheme of Hafnia, included into Bergey's Determinative Bacteriology, edition IX (1984).


Towards high energy density lithium battery anodes: silicon and lithium.
Silicon and lithium metal are considered as promising alternatives to state-of-the-art graphite anodes for higher energy density lithium batteries because of their high theoretical capacity. However, significant challenges such as short cycle life and low coulombic efficiency have seriously hindered their practical applications. In the past decades, various strategies have been proposed to address the major problems of Si and Li anodes. In this review, we summarize the understanding on Si and Li anodes, highlight the recent progress in the development and introduce advanced characterization techniques. We also indicate the remaining challenges of Si and Li anodes requiring more efforts for future widespread applications. We expect that this review provides an overall picture of the recent progress and inspires more efforts in the fundamental understanding and practical applications of Si and Li anodes.


Brief psychodynamic interpersonal psychotherapy for patients with multisomatoform disorder: randomised controlled trial.
Multisomatoform disorder is characterised by severe and disabling bodily symptoms, and pain is one of the most common and impairing of these. Furthermore, these bodily symptoms cannot be explained by an underlying organic disorder. Patients with multisomatoform disorder are commonly found at all levels of healthcare and are typically difficult to treat for physicians as well as for mental health specialists. To test whether brief psychodynamic interpersonal therapy (PIT) effectively improves the physical quality of life in patients who have had multisomatoform disorder for at least 2 years. We recruited 211 patients (from six German academic outpatient centres) who met the criteria for multisomatoform disorder for a randomised, controlled, 12-week, parallelgroup trial from 1 July 2006 to 1 January 2009 (International Standard Randomised Controlled Trial Number ISRCTN23215121). We randomly assigned the patients to receive either 12 weekly sessions of PIT (n = 107) or three sessions of enhanced medical care (EMC, n = 104). The physical component summary of the Short Form Health Survey (SF-36) was the pre-specified primary outcome at a 9-month follow-up. Psychodynamic interpersonal therapy improved patients' physical quality of life at follow-up better than EMC (mean improvement in SF-36 score: PIT 5.3, EMC 2.2), with a small to medium between-group effect size (d = 0.42, 95% CI 0.15-0.69, P = 0.001). We also observed a significant improvement in somatisation but not in depression, health anxiety or healthcare utilisation. This trial documents the long-term efficacy of brief PIT for improving the physical quality of life in patients with multiple, difficult-to-treat, medically unexplained symptoms.


Ununited lower limb fractures.
Nonunion is a fairly common complication of fracture management, with an overall rate of about 3% for the skeleton as a whole and 9% for the tibia. High-energy injury fractures have a nonunion rate as high as 75%. Other factors that may lead to nonunion are inappropriate treatment, infection, and preexisting disease. The diagnosis of nonunion is based largely on clinical examination. Plain radiographs and tomograms, computed tomograms, and contrast imaging may be used to confirm nonhealing. Radionuclide imaging can help determine the presence of infection, an impaired blood supply, or impaired osteogenic activity at the fracture site. The treatment of ununited fractures is based on the principles of good fracture management: adequate immobilization, asepsis and soft tissue cover, osteoconduction (bone contact), osteoinduction (stimulation of bone growth), and metabolic well-being. New modalities for osteoinduction are promising adjuncts to standard treatment, the autogenous bone graft, but conclusive proof of efficacy in humans does not yet exist.


Artificial beta-barrels.
In biology, beta-barrels, cylindrically rolled-up forms of beta-sheets, are ubiquitous structural motifs within various binding proteins, pores, and enzymes. This biological multifunctionality suggested that synthetic artificial beta-barrels would provide access to many different functions beyond the limitations of peptide chemistry. Unlike the relative ease of formation of synthetic (de novo) alpha-helix bundles, the synthesis of artificial beta-barrels remains a challenge. To bypass the folding problems involved, we have employed "unfoldable" rigid-rod scaffolds as privileged staves (staves are the wood strips that form the sides of macroscopic barrels); the resulting barrel-stave supramolecules exhibit their expected multifunctionality. Several "rigid rod" beta-barrels that act as receptors, ion channels, pores, catalysts, and sensors have been prepared and studied. The most recent topic of interest concerns the use of artificial beta-barrels as multicomponent sensors ("artificial tongues") in complex analyte matrices. For multicomponent sensing, we have designed artificial beta-barrels to form pores that can open and close in response to chemical stimulation within lipid bilayers. With use of fluorogenic vesicles, changes in pore activity are readily detectable with either the naked eye or multiwell screening formats. The varying responsiveness to substrates and products makes synthetic pores versatile detectors of chemical reactions, of the activity of the enzymes that catalyze these reactions, and of their inhibitors. In sensing applications, the "perfect" selectivity of enzymes is exploited to generate analyte-specific signals. Reactive signal amplifiers are then covalently linked to the products of enzymatic signal generation to enhance their pore blockage potency. With the help of signal generators and amplifiers, we have employed artificial beta-barrel pores to sense sweet (sucrose, lactose), sour (acetate, lactate, citrate), and umami ("deliciousness", glutamate) components in various food samples. This breakthrough naturally led us to design and synthesize refined pores for advanced sensing applications. We have developed methods to build guest-binding sites not only at internal and external barrel surfaces but also near the core or near the periphery of the pore. Further refinements include the introduction of asymmetric staves for voltage gating and anchoring of the pore at the membrane-water interface.


Odor structure-activity relationships of carboxylic acids correspond between squirrel monkeys and humans.
With use of a conditioning paradigm, the ability of four squirrel monkeys to distinguish n-valeric acid from n-forms and isoforms of other carboxylic acids (acetic acid to octanoic acid) was investigated. All four animals were clearly able to discriminate between all odor pairs tested and showed a significant negative correlation between discrimination performance and structural similarity of odorants in terms of differences in carbon chain length of the carboxylic acids. Branching of the carbon chain was also found to affect odorant quality because all animals performed better in discriminating n-valeric acid from isoforms of other carboxylic acids compared with the corresponding n-forms of these substances. With use of a triple forced-choice procedure, 10 human subjects were tested on the same tasks in parallel and showed a very similar pattern of discrimination performance compared with the squirrel monkeys. Thus the results of this study provide evidence of well-developed olfactory discrimination ability in squirrel monkeys for carboxylic acids and support the assumption that human and nonhuman primates may share common principles of odor quality perception.


NUP98/NSD1 and FLT3/ITD coexpression is more prevalent in younger AML patients and leads to induction failure: a COG and SWOG report.
NUP98/NSD1 has recently been reported in association with poor outcome in acute myeloid leukemia (AML). Previous studies also observed a high overlap between NUP98/NSD1 and FLT3/ITD, raising the question as to whether the reported poor outcome is due to NUP98/NSD1 or caused by the co-occurrence of these 2 genetic lesions. We aimed to determine the prognostic significance of NUP98/NSD1 in the context of FLT3/ITD AML. A total of 1421 patients enrolled in 5 consecutive Children's Oncology Group/Children's Cancer Group and SWOG trials were evaluated. NUP98/NSD1 was found in 15% of FLT3/ITD and 7% of cytogenetically normal (CN)-AML. Those with dual FLT3/ITD and NUP98/NSD1 (82% of NUP98/NSD1 patients) had a complete remission rate of 27% vs 69% in FLT3/ITD without NUP98/NSD1 (P < .001). The corresponding 3-year overall survival was 31% vs 48% (P = .011), respectively. In CN-AML, patients with concomitant NUP98/NSD1 and FLT3/ITD had a worse outcome than those harboring NUP98/NSD1 only. In multivariate analysis, the dual NUP98/NSD1 and FLT3/ITD remained an independent predictor of poor outcome, and NUP98/NSD1 without FLT3/ITD lost its prognostic significance. Our study demonstrates that it is the interaction between NUP98/NSD1 and FLT3/ITD that determines the poor outcome of patients with NUP98/NSD1 disease.


Construction of lncRNA-Mediated Competing Endogenous RNA Networks Correlated With T2 Asthma.
Background: Precise classification has been reported as a central challenge in the clinical research on diagnosis and prediction of treatment efficacy in asthma. In this study, the aim was to investigate the underlying competing endogenous RNA network mechanism of asthma, especially T2 asthma, as well as to find more diagnostic biomarkers and effective therapeutic targets. Methods: Multiple sets of T2 asthma airway biopsy transcription profiles were collected, which involved long non-coding RNA (lncRNA), mRNA, and microRNA (miRNA). DIANA-LncBase, targetscan, mirwalk, and miRDB databases were employed to predict interactions between lncRNAs, miRNAs and target mRNAs. To identify mRNAs correlated with T2 asthma, differential expression and network analyses were conducted through weighted gene co-expression network analysis (WGCNA). Subsequently, the expressions of potential biomarkers were examined through qRT-PCR analysis in the T2 asthma coreinteracting cellular factor (IL-13/IL-33) induced experimental model. Lastly, the ceRNA network was confirmed by plasmid transfection and RNAi experiments in a 16HBE cell line. Results: 30 lncRNAs, 22 miRNAs and 202 mRNAs were differentially expressed in airway biopsies from T2 asthma patients. As indicated by the ROC analysis, the lncRNA, PCAT19, had high diagnostic accuracy (AUC >0.9) in distinguishing T2 asthma patients from non-T2 asthma patients and healthy controls. Furthermore, a competing ceRNA network was established, consisting of 13 lncRNAs, 12 miRNAs, as well as eight mRNAs. The reliability of this network was verified by testing several representative interactions in the network. Conclusion: To the best of our knowledge, this study has been the first to establish an lncRNA-mediated ceRNA regulatory network for studying T2 asthma. The findings of this study may elucidate the pathogenesis and help find potential therapeutic targets for T2 asthma. In T2 asthma, PCAT19-dominated ceRNA regulation networks may play a critical role, and PCAT19 may serve as a potential immune-related biomarker for asthma and other respiratory diseases correlated with eosinophilic inflammation.


A Theoretical Analysis of Electrogastrography (EGG) Signatures Associated With Gastric Dysrhythmias.
Routine screening and accurate diagnosis of chronic gastrointestinal motility disorders represent a significant problem in current clinical practice. The electrogastrography (EGG) provides a noninvasive option for assessing gastric slow waves, as a means of diagnosing gastric dysrhythmias, but its uptake in motility practice has been limited partly due to an incomplete sensitivity and specificity. This paper presents the development of a human whole-organ gastric model to enable virtual (in silico) testing of gastric electrophysiological dispersion in order to improve the diagnostic accuracy of EGG. The model was developed to simulate normal gastric slow wave conduction as well as three types of dysrhythmias identified in recent high-resolution gastric mapping studies: conduction block, re-entry, and ectopic pacemaking. The stomach simulations were then applied in a torso model to identify predicted EGG signatures of normal and dysrhythmic slow wave profiles. The resulting EGG data were compared using percentage differences and correlation coefficients. Virtual EGG channels that demonstrated a percentage difference over 100% and a correlation coefficient less than ±0.2 (threshold relaxed to ±0.5 for the ectopic pacemaker case) were further investigated for their specific distinguishing features. In particular, anatomical locations from the epigastric region and specific channel configurations were identified that could be used to clinically diagnose the three classes of human gastric dysrhythmia. These locations and channels predicted by simulations present a promising methodology for improving the clinical reliability and applications of EGG.


Growing more positive with age: The relationship between reproduction and survival in aging flies.
Populations of laboratory animals that are selected for increased lifespan often show negative correlated responses in early fecundity. However, late fecundity and/or total lifetime fecundity can be higher in the populations selected for increased lifespan. This has been interpreted by some as being at odds with the disposable soma theory, which predicts decreased lifespan to increase total reproductive output. Alternatively, the Y-model explores the effects of variation in resource allocation and acquisition on life histories. In this model, a negative relationship between lifespan and reproduction can be viewed as variation in allocation, whereas a positive relationship is the result of variation in acquisition. However, a frequently neglected complication of the Y-model is that older individuals often show a decline in resource acquisition. Therefore, differential allocation to maintenance and survival might affect this decline in late-life acquisition which will affect resource availability across the whole lifespan. In this paper we show that a model which incorporates the ideas of the Y-model, the disposable soma theory, and an age-related decrease in resource acquisition, i.e. feeding senescence, can explain how the relationship between fecundity and lifespan changes with age. Furthermore, by modeling environments with contrasting extrinsic mortality rates, we explored how the outcome of the model depended on the relative importance of early and late-life reproduction. In high mortality environments a relatively higher early fecundity, lower late fecundity, and lower lifespans were more optimal, whereas the opposite was true for low mortality environments. We applied predictions from the model to a cohort of individually-housed female Drosophila melanogaster flies for which we measured age specific fecundity and lifespan. Early fecundity was negatively associated with lifespan, while late fecundity related positively with lifespan in the same cohort. This verified that the mechanism of feeding senescence could explain patterns for age specific relationships between lifespan and fecundity.


Coexistence of pulmonary sclerosing hemangioma and primary adenocarcinoma in the same nodule of lung.
Pulmonary sclerosing hemangiomas (PSH) of the lung are uncommon tumors and may present cytological atypia with unusual manifestations. The development of PSH combined with other different tumors in lung is extremely rare. We report a case of coexistence of PSH and primary adenocarcinoma in a young female occurring in the same pulmonary nodular mass of right lower lobe. The solitary mass of lung was well-circumscribed on chest computed tomography (CT) and gross examination. Histologically, the mass contained two separated portions and displayed typically histological features of PSH and acinar adenocarcinoma, respectively. In PSH portion, the tumor was composed of sheets of round cells with scattered surface cuboidal cells forming small tubules. Both round and surface cells were diffusely positive for epithelial membrane antigen (EMA) and thyroid transcription factor-1 (TTF-1), but lack immunoreactivity for pancytokeratin in round cells. In adenocarcinoma portion, the tumor cells formed irregular-shaped glands with cytologically malignant cells infiltrating in fibroblastic stroma, and no TTF-1-positive round cells could be observed in this portion. Under the microscopy, there was no gradual transition of these two portions observed in mass. A diagnosis of PSH combined with primary adenocarcinoma of lung was made. There was no evidence of tumor recurrence during the period of postoperative 6-month follow-up. To our knowledge, this is the first case of coexistence of PSH and adenocarcinoma in the same nodule of lung. In addition, the biological behavior and histological differential diagnosis of this tumor were also discussed.


Multicanonical Molecular Dynamics Simulations of the N-terminal Domain of Protein L9.
We describe multicanonical molecular dynamic simulations of the N-terminal domain of the protein L9. Analyzing free energy landscapes and thermal ordering, we propose a possible folding mechanism for the protein. By comparing our results with that of molecular dynamics runs of the protein at constant temperature, we find that multicanonical molecular dynamics leads to orders of magnitude higher sampling of folding transitions.


A rare nonincisional lateral abdominal wall hernia.
A 68-year-old woman presented a rare lateral abdominal wall hernia. Three month before admission to Chungbuk National University Hospital, she found a large protruding mass measuring 8 cm in diameter in the midaxillary line just below the costal margin upon heavy coughing. She had no history of abdominal trauma, infection, or operation previously. The mass was easily reduced manually or by position change to left lateral decubitus. CT scan showed a defect of the right transversus abdominis muscle and internal oblique muscle at the right flank with omental herniation. Its location is different from that of spigelian hernia or lumbar hernia. The peritoneal lining of the hernia sac was smooth and there was no evidence of inflammation or adhesion. The hernia was successfully repaired laparoscopically using Parietex composite mesh with an intraperitoneal onlay mesh technique. The patient was discharged uneventfully and did not show any evidence of recurrence at follow-up visits.


Characterization of Chloroplast Clp proteins in Arabidopsis: Localization, tissue specificity and stress responses.
The ATP-dependent Clp protease is one of the newly identified proteolytic systems in plant organelles that incorporate the activity of molecular chaperones to target specific polypeptide substrates and avoid inadvertent degradation of others. We describe new nuclear-encoded ClpC (ClpC1) and ClpP (ClpP3-5) isomers in Arabidopsis thaliana that raise the total number of identified Clp proteins to 19. The extra Clp proteins are localized within the stroma of chloroplasts along with the ClpD, -P1 and -P6 proteins. Potential differential regulation among these Clp proteins was analysed at both the mRNA and protein level. A comparison between different tissues showed increasing amounts of all plastid Clp proteins from roots to stems to leaves suggested the greatest abundance of proteins was in chloroplasts. The increases in protein were mirrored at the mRNA level for most ClpP isomers (ClpP1, -3, -4 and -6) but not for the three Hsp100 proteins (ClpC1, -C2 and -D) and ClpP5, which exhibited little change in transcript levels, suggesting post-transcriptional/translational regulation. Potential stress induction was also tested for all chloroplast Clp proteins by a series of brief and prolonged stress conditions. Short-term moderate and severe stresses (desiccation, high salt, cold, heat, oxidation, wounding and high light) all failed to elicit significant or rapid increases in any chloroplast Clp protein. However, increases in mRNA and protein content for ClpD and several ClpP isomers did occur during long-term high light and cold acclimation of Arabidopsis plants. These results reveal the great complexity of Clp proteins within the stroma of plant chloroplasts, and that these proteins, rather than being rapidly induced stress proteins, are primarily constitutive proteins that may also be involved in plant acclimation to different physiological conditions.


Neandertal talus bones from El Sidrón site (Asturias, Spain): A 3D geometric morphometrics analysis.
The El Sidrón tali sample is assessed in an evolutionary framework. We aim to explore the relationship between Neandertal talus morphology and body size/shape. We test the hypothesis 1: talar Neandertal traits are influenced by body size, and the hypothesis 2: shape variables independent of body size correspond to inherited primitive features. We quantify 35 landmarks through 3D geometric morphometrics techniques to describe H. neanderthalensis-H. sapiens shape variation, by Mean Shape Comparisons, Principal Component, Phenetic Clusters, Minimum spanning tree analyses and partial least square and regression of talus shape on body variables. Shape variation correlated to body size is compared to Neandertals-Modern Humans (MH) evolutionary shape variation. The Neandertal sample is compared to early hominins. Neandertal talus presents trochlear hypertrophy, a larger equality of trochlear rims, a shorter neck, a more expanded head, curvature and an anterior location of the medial malleolar facet, an expanded and projected lateral malleolar facet and laterally expanded posterior calcaneal facet compared to MH. The Neandertal talocrural joint morphology is influenced by body size. The other Neandertal talus traits do not co-vary with it or not follow the same co-variation pattern as MH. Besides, the trochlear hypertrophy, the trochlear rims equality and the short neck could be inherited primitive features; the medial malleolar facet morphology could be an inherited primitive feature or a secondarily primitive trait; and the calcaneal posterior facet would be an autapomorphic feature of the Neandertal lineage.


A high-throughput scintillation proximity-based assay for human DNA ligase IV.
Ionizing radiation (IR) and certain chemotherapeutic drugs are designed to generate cytotoxic DNA double-strand breaks (DSBs) in cancer cells. Inhibition of the major DSB repair pathway, nonhomologous end joining (NHEJ), will enhance the cytotoxicity of these agents. Screening for inhibitors of the DNA ligase IV (Lig4), which mediates the final ligation step in NHEJ, offers a novel target-based drug discovery opportunity. For this purpose, we have developed an enzymatic assay to identify chemicals that block the transfer of [α-(33)P]-AMP from the complex Lig4-[α-(33)P]-AMP onto the 5' end of a double-stranded DNA substrate and adapted it to a scintillation proximity assay (SPA). A screen was performed against a collection of 5,280 compounds. Assay statistics show an average Z' value of 0.73, indicative of a robust assay in this SPA format. Using a threshold of >20% inhibition, 10 compounds were initially scored as positive hits. A follow-up screen confirmed four compounds with IC(50) values ranging from 1 to 30 μM. Rabeprazole and U73122 were found to specifically block the adenylate transfer step and DNA rejoining; in whole live cell assays, these compounds were found to inhibit the repair of DSBs generated by IR. The ability to screen and identify Lig4 inhibitors suggests that they may have utility as chemo- and radio-sensitizers in combination therapy and provides a rationale for using this screening strategy to identify additional inhibitors.


Questionnaire Measures and Physiological Correlates of Presence: A Systematic Review.
The published literature has produced several definitions for the sense of presence in a simulated environment, as well as various methods for measuring it. The variety of conceptualizations makes it difficult for researchers to interpret, compare, and evaluate the presence ratings obtained from individual studies. Presence has been measured by employing questionnaires, physiological indices, behavioral feedbacks, and interviews. A systematic literature review was conducted to provide insight into the definitions and measurements of presence in studies from 2002 to 2019, with a focus on questionnaires and physiological measures. The review showed that scholars had introduced various definitions of presence that often originate from different theoretical standpoints and that this has produced a multitude of different questionnaires that aim to measure presence. At the same time, physiological studies that investigate the physiological correlates of the sense of presence have often shown ambiguous results or have not been replicated. Most of the scholars have preferred the use of questionnaires, with Witmer and Singer's Presence Questionnaire being the most prevalent. Among the physiological measures, electroencephalography was the most frequently used. The conclusions of the present review aim to stimulate future structured efforts to standardize the use of the construct of presence, as well as inspire the replication of the findings reported in the published literature.


One-carbon metabolism-related micronutrients intake and risk for hepatocellular carcinoma: A prospective cohort study.
Deficient intake of micronutrients involved in one-carbon metabolism (eg, choline, methionine, vitamin B12 and folic acid) leads to hepatocellular carcinoma (HCC) development in rodents, but is under-investigated in humans. We investigated the association between one-carbon metabolism-related micronutrient intake and HCC risk in a prospective cohort of 494 860 participants with 16 years of follow-up in the NIH-AARP study. Dietary intakes and supplement use were ascertained at baseline using a food-frequency questionnaire. Total intake (diet plus supplements) of the following one-carbon metabolism-related micronutrients were calculated: folate, methionine and vitamins B2 (riboflavin), B3 (niacin), B6 and B12 . These micronutrients were examined both individually and simultaneously, with adjustment for covariates. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Over the 16-year follow-up period, 647 incident HCC cases were diagnosed. When examined individually, higher total vitamin B3 intake was associated with a lower HCC risk (HRQ5 vs Q1 = 0.60; 95% CI = 0.42-0.85; Ptrend = .008), and the association remained significant when all six micronutrients were examined simultaneously (HRQ5 vs Q1 = 0.32; 95% CI = 0.18-0.55; Ptrend < .0001). Among participants with >3 years of follow-up, higher total vitamin B3 intake was again associated with lower risk (HRQ5 vs Q1 = 0.37; 95% CI = 0.20-0.68; Ptrend = .001), whereas higher total vitamin B6 intake was associated with higher risk (HRQ5 vs Q1 = 2.04; 95% CI = 1.02-4.07; Ptrend = .04). Restricted cubic spline analyses showed a dose-response inverse association between total vitamin B3 intake and HCC risk, and dose-response positive association between total vitamin B6 intake and HCC risk. The study suggests that higher vitamin B3 intake is associated with lower HCC risk, whereas higher vitamin B6 intake is associated with increased risk.


Impact of an emergency department electronic sepsis surveillance system on patient mortality and length of stay.
The purpose of this study was to determine whether an electronic health record-based sepsis alert system could improve quality of care and clinical outcomes for patients with sepsis. We performed a patient-level interrupted time series study of emergency department patients with severe sepsis or septic shock between January 2013 and April 2015. The intervention, introduced in February 2014, was a system of interruptive sepsis alerts triggered by abnormal vital signs or laboratory results. Primary outcomes were length of stay (LOS) and in-hospital mortality; other outcomes included time to first lactate and blood cultures prior to antibiotics. We also assessed sensitivity, positive predictive value (PPV), and clinician response to the alerts. Mean LOS for patients with sepsis decreased from 10.1 to 8.6 days (P < .001) following alert introduction. In adjusted time series analysis, the intervention was associated with a decreased LOS of 16% (95% CI, 5%-25%; P = .007, with significance of α = 0.006) and no change thereafter (0%; 95% CI, -2%, 2%). The sepsis alert system had no effect on mortality or other clinical or process measures. The intervention had a sensitivity of 80.4% and a PPV of 14.6%. Alerting based on simple laboratory and vital sign criteria was insufficient to improve sepsis outcomes. Alert fatigue due to the low PPV is likely the primary contributor to these results. A more sophisticated algorithm for sepsis identification is needed to improve outcomes.


Progression through key stages of haemopoiesis is dependent on distinct threshold levels of c-Myb.
The c-Myb transcription factor is expressed in immature haemopoietic cells and at key stages during differentiation. Loss of the c-myb gene results in embryonic lethality because mature blood cells fail to develop, although commitment to definitive haemopoiesis occurs. We have generated a knockdown allele of c-myb, expressing low levels of the protein, which has enabled us to investigate further the involvement of c-Myb in haemopoiesis. Low levels of c-Myb are sufficient to allow progenitor expansion but, importantly, we show that progression of progenitors towards terminal differentiation is significantly altered. Suboptimal levels of c-Myb favour differentiation of macrophage and megakaryocytes, while higher levels seem to be particularly important in the control of erythropoiesis and lymphopoiesis. We provide evidence that the transition from the CFU-E to erythroblasts is critically dependent on c-Myb levels. During thymopoiesis, c-Myb appears to regulate immature cell numbers and differentiation prior to expression of CD4 and CD8. Overall, our results point to a complex involvement of c-Myb in the regulation of proliferation and commitment within the haemopoietic hierarchy.


[Etiology of lower acute respiratory infections in hospitalized infants. 3. Investigation of Chlamydia trachomatis].
Five infants with Chlamydia trachomatis associated pneumonia are analyzed. They were diagnosed out of 80 infants admitted to the hospital with pneumonia whose etiology was studied for virus, bacteria and Chlamydia trachomatis. Serum IgM antibodies to Chlamydia tr. were measured by indirect immunofluorescence (IIF), which is considered to be specific in high titers (1 greater than or equal to 32). The five cases represented 10.4% of infants studied younger than six months. One child was born by cesarean section suggesting the possibility of other non oculogenital still undefined mechanism of transmission. Clinical symptoms and laboratory findings were characteristics of those described in Chlamydia tr. pneumonia. Chlamydia trachomatis must be considered an etiologic agent in infantile pneumonia specially in the first six months of life. The high specificity and sensitivity of the IFF makes this serologic test the best non-invasive method for diagnosis of Chlamydia tr. pneumonia currently available.


Enhanced removal of antibiotics using Eichhornia crassipes root biomass in an aerobic hollow-fiber membrane bioreactor.
The impact of water hyacinth (Eichhornia crassipes) root biomass (WHRB) on pharmaceutical wastewater treatment with an aerobic hollow-fiber membrane bioreactor (HF-MBR) was investigated. The performance of the bioreactor was assessed in terms of COD (Chemical Oxygen Demand) and antibiotic removal and membrane biofouling rate. For deeper insight, microbial communities in sludge and biofilm layers were analyzed through Illumina sequencing. The addition of WHRB into the HF-MBR increased the COD (by 6%), as well as antibiotics and transformation products removal efficiency. Removal efficiencies of 97%, 98% and 84% were obtained for removal of erythromycin, sulfamethoxazole, and tetracycline. Furthermore, WHRB modified the biodegradation network, increased the relative abundances of Chloroflexi, Proteobacteria and Nitrospirae and decreased Firmicutes, compared with the control with antibiotics. The addition of WHRB also enriched Actinobacteria and Bacteroidetes while decreasing the phylla Chloroflexi and Saccharibacteria in the biofilm.


Capturing circulating tumor cells of hepatocellular carcinoma.
Early metastases of hepatocellular carcinoma (HCC) may be detected by the isolation of circulating tumor cells (CTCs) in the bloodstream. During the course of therapeutic attempts, monitoring CTC changes in patients with HCC is helpful for the efficacy assessment. Nevertheless, the markers used for the detection, such as α-feto protein, asialoglycoprotein receptor or epithelial cell adhesion molecule, CD133 or CD90, are not specific for HCC CTCs. In spite of these limitations, a timely determination of the existence of CTCs will be beneficial for the monitoring of distant metastases, the evaluation of therapeutic attempts, and the prediction of prognosis.


[Hypothermia in patients with a high spinal cord lesion].
Two women aged 54 and 69 years with high spinal cord injuries and tetraparesis developed hypothermia (30.4 and 29.4 degrees C, respectively); normalization was accomplished by external heating using insulation blankets. Even moderately lowered environmental temperatures may lead to hypothermia in these patients with abnormal temperature sensation, incapacity to compensate and autonomous dysfunction. The symptoms are aspecific and the differential diagnosis is extensive. Recommendations for prevention of hypothermia include daily measurement of the core temperature, adjustment of the environmental temperature and humidity of the air, adequate closing and avoidance of vasodilator drugs.


Suicidal germination for parasitic weed control.
Parasitic weeds of the genera Striga and Orobanche spp. cause severe yield losses in agriculture, especially in developing countries and the Mediterranean. Seeds of these weeds germinate by a chemical signal exuded by the roots of host plants. The radicle thus produced attaches to the root of the host plant, which can then supply nutrients to the parasite. There is an urgent need to control these weeds to ensure better agricultural production. The naturally occurring chemical signals are strigolactones (SLs), e.g. strigol and orobanchol. One option to control these weeds involves the use of SLs as suicidal germination agents, where germination takes place in the absence of a host. Owing to the lack of nutrients, the germinated seeds will die. The structure of natural SLs is too complex to allow multigram synthesis. Therefore, SL analogues are developed for this purpose. Examples are GR24 and Nijmegen-1. In this paper, the SL analogues Nijmegen-1 and Nijmegen-1 Me were applied in the field as suicidal germination agents. Both SL analogues were formulated using an appropriate EC-approved emulsifier (polyoxyethylene sorbitol hexaoleate) and applied to tobacco (Nicotiana tabacum L.) fields infested by Orobanche ramosa L. (hemp broomrape), following a strict protocol. Four out of 12 trials showed a reduction in broomrape of ≥95%, two trials were negative, two showed a moderate result, one was unclear and in three cases there was no Orobanche problem in the year of the trials. The trial plots were ca 2000 m2 ; half of that area was treated with stimulant emulsion, the other half was not treated. The optimal amount of stimulant was 6.25 g ha-1 . A preconditioning prior to the treatment was a prerequisite for a successful trial. In conclusion, the suicidal germination approach to reducing O. ramosa in tobacco fields using formulated SL analogues was successful. Two other options for weed control are discussed: deactivation of stimulants prior to action and biocontrol by Fusarium oxysporum. © 2016 Society of Chemical Industry.


K313dup is a recurrent CEBPA mutation in de novo acute myeloid leukemia (AML).
The CEBPA gene codes for a transcription factor that has a pivotal role in controlling proliferation and differentiation of myeloid progenitors. Acquired CEBPA mutations have been found in acute myeloid leukemias (AML) with a good prognosis, and most of these patients have a normal karyotype. In this paper, we report four cases that displayed the same K313dup in the CEBPA gene. All four had an AML-M1 with CD7 positivity and T-cell receptor gamma chain (TCR-gamma) rearrangement. This mutation could represent nearly 10% of all CEBPA mutations described to date. K313dup disappeared in samples from patients in complete remission. In transfected cells, the K313dup mutant had reduced protein stability with respect to the wild-type protein. K313dup seems to be selected in leukemic cells, and its frequency in other AML series could be determined using the screening method reported in this paper.


The cooperative function of arginine residues in the Prototype Foamy Virus Gag C-terminus mediates viral and cellular RNA encapsidation.
One unique feature of the foamy virus (FV) capsid protein Gag is the absence of Cys-His motifs, which in orthoretroviruses are irreplaceable for multitude functions including viral RNA genome recognition and packaging. Instead, FV Gag contains glycine-arginine-rich (GR) sequences at its C-terminus. In case of prototype FV (PFV) these are historically grouped in three boxes, which have been shown to play essential functions in genome reverse transcription, virion infectivity and particle morphogenesis. Additional functions for RNA packaging and Pol encapsidation were suggested, but have not been conclusively addressed. Here we show that released wild type PFV particles, like orthoretroviruses, contain various cellular RNAs in addition to viral genome. Unlike orthoretroviruses, the content of selected cellular RNAs in capsids of PFV vector particles was not altered by viral genome encapsidation. Deletion of individual GR boxes had only minor negative effects (2 to 4-fold) on viral and cellular RNA encapsidation over a wide range of cellular Gag to viral genome ratios examined. Only the concurrent deletion of all three PFV Gag GR boxes, or the substitution of multiple arginine residues residing in the C-terminal GR box region by alanine, abolished both viral and cellular RNA encapsidation (>50 to >3,000-fold reduced), independent of the viral production system used. Consequently, those mutants also lacked detectable amounts of encapsidated Pol and were non-infectious. In contrast, particle release was reduced to a much lower extent (3 to 20-fold). Taken together, our data provides the first identification of a full-length PFV Gag mutant devoid in genome packaging and the first report of cellular RNA encapsidation into PFV particles. Our results suggest that the cooperative action of C-terminal clustered positively charged residues, present in all FV Gag proteins, is the main viral protein determinant for viral and cellular RNA encapsidation. The viral genome independent efficiency of cellular RNA encapsidation suggests differential packaging mechanisms for both types of RNAs. Finally, this study indicates that analogous to orthoretroviruses, Gag - nucleic acid interactions are required for FV capsid assembly and efficient particle release.


Shosaiko-to and other Kampo (Japanese herbal) medicines: a review of their immunomodulatory activities.
The use of alternative medicine, including consumption of herbal products and dietary supplements, has been increasing substantially both in the United States and in Western Europe. One area that is garnering increased attention is the use of Oriental Medicine including Kampo, or Japanese herbal medicine. Herein, we review representative examples of research available on the most common use of Kampo medicinals, namely to improve the immune response. We also provide an extensive background on the history of Kampo. There are more than 210 different Kampo formulae used in Japan and most uses of Kampo are to modulate the immune response, i.e. to improve immunity. We have extracted data on seven common Kampo medicinals, and the data are reviewed with respect to in vitro and in vivo activities for both humans and experimental animals; the ingredients as well as the problems with classification of these materials are presented. Research suggests that Kampo herbals are biologically active and may have therapeutic potential. While it is believed that Kampo medicines have few side effects, there is a paucity of data on their toxicity as well as a relative lack of knowledge of the bioactive constituents and potential drug interactions of these agents.


Intestinal perineuriomas: clinicopathologic definition of a new anatomic subset in a series of 10 cases.
Benign peripheral nerve sheath tumors are uncommon in the gastrointestinal tract, and perineuriomas have not previously been reported to occur at this anatomic location. In this study, we analyzed the clinicopathologic and immunohistochemical features of 10 perineuriomas arising in the intestine. Eight patients were female and 2 male (median age, 51 years; range, 35-72 years). Eight of the lesions were intramucosal perineuriomas presenting as small sessile polyps detected during colonoscopy; 6 of these 8 patients were asymptomatic and undergoing colorectal cancer screening. The remaining 2 cases were submucosal masses, one each located in the colon and jejunum. Of the mucosal polyps, six were located in the rectosigmoid or sigmoid colon and one each was detected in the descending colon and transverse colon. The polyps ranged from 0.2 to 0.6 cm (median, 0.4 cm) in greatest dimension. The colonic and jejunal masses measured 3 cm and 4.5 cm, respectively. Histologically, the intramucosal perineuriomas were composed of uniform bland spindle cells having ovoid to elongated nuclei and pale indistinct cytoplasm, with no cytologic atypia, pleomorphism, or mitotic activity. The lesions had a fine collagenous stroma, demonstrated irregular borders with the adjacent lamina propria, and entrapped colonic crypts. Five cases exhibited hyperplastic changes in the adjacent or entrapped epithelium. The colonic submucosal tumor was microscopically well circumscribed, whereas the jejunal perineurioma showed focal infiltration through the muscularis propria into the subserosa. The stroma was collagenous in the colonic tumor and predominantly myxoid in the jejunal tumor. The spindle cells in the submucosal perineuriomas demonstrated tapered nuclei and elongated bipolar cytoplasmic processes. All tumors except one were positive for epithelial membrane antigen (EMA); 4 of 10 expressed claudin-1 and 2 of 10 expressed CD34. All tumors were negative for S-100 protein, glial fibrillary acidic protein, neurofilament protein, smooth muscle actin, desmin, caldesmon, KIT, and pan-keratin. Electron microscopy was performed on the tumor lacking EMA expression, revealing typical features of perineurioma, namely, spindle cells with long bipolar cytoplasmic processes and prominent pinocytotic vesicles, surrounded by discontinuous basal lamina. Clinical follow-up was available for 4 patients (median, 34 months; range, 8-53 months). No tumor recurred. In summary, perineuriomas may arise in the intestine, most often as intramucosal lesions detected as colorectal polyps with distinctive histologic features including entrapment of colonic crypts. Distinguishing perineuriomas from other spindle cell neoplasms of the gastrointestinal tract can be facilitated by immunostaining for EMA and claudin-1.


A noninvasive technique for the study of cardiac hemodynamics utilizing C15-O2 inhalation.
A new technique for the study of cardiac hemodynamics is described which utilizes single-breath inhalation of C15O2 (T 1/2 = 124 sec.) and the recording of activity vs. time curves with scintillation counters placed externally over the left ventricle and right lung. The results from 10 normal volunteers and 28 patients with acquired or congenital heart disease have been compared to the findings at cardiac catheterization. The technique is safe, rapid, and nontraumatic, and yielded no false positives or negatives in this series.


Insights into Hydration Dynamics and Cooperative Interactions in Glycerol-Water Mixtures by Terahertz Dielectric Spectroscopy.
We report relaxation dynamics of glycerol-water mixtures as probed by megahertz-to-terahertz dielectric spectroscopy in a frequency range from 50 MHz to 0.5 THz at room temperature. The dielectric relaxation spectra reveal several polarization processes at the molecular level with different time constants and dielectric strengths, providing an understanding of the hydrogen-bonding network in glycerol-water mixtures. We have determined the structure of hydration shells around glycerol molecules and the dynamics of bound water as a function of glycerol concentration in solutions using the Debye relaxation model. The experimental results show the existence of a critical glycerol concentration of ∼7.5 mol %, which is related to the number of water molecules in the hydration layer around a glycerol molecule. At higher glycerol concentrations, water molecules dispersed in a glycerol network become abundant and eventually dominate, and four distinct relaxation processes emerge in the mixtures. The relaxation dynamics and hydration structure in glycerol-water mixtures are further probed with molecular dynamics simulations, which confirm the physical picture revealed by the dielectric spectroscopy.


Study designs for evaluating different efficacy and effectiveness aspects of vaccines.
Vaccine efficacy and effectiveness (VE) are generally measured as 1 minus some measure of relative risk (RR) in the vaccinated group compared with the unvaccinated group (VE = 1 - RR). In designing a study to evaluate vaccination, the type of effect and the question of interest determine the appropriate choice of comparison population and parameter. Possible questions of interest include that of the biologic effect of vaccination on susceptibility, on infectiousness, or on progression to disease in individuals. The indirect effects, total effects, and overall public health benefits of widespread vaccination of individuals within the context of a vaccination program might also be of primary concern. The change in behavior induced by belief in the protective effects of vaccination might influence the estimates of these effects or might itself be of interest. In this paper, the authors present a framework of study designs that relates the scientific question of interest to the choice of comparison groups, the unit of observation, the level of information available for analysis, and the parameter of effect.


Twelfth thoracic vertebra erector spinae plane block for postoperative analgesia and early recovery after lumbar spine surgery in elderly patients: a single-blind randomized controlled trial.
Severe pain after lumbar spine surgery can delay recovery in elderly patients. We explored the efficacy of T12 erector spinal plane block (ESPB) in elderly patients who underwent lumbar spine surgery. A total of 230 patients undergoing lumbar spine surgery were divided and randomly allocated to ultrasound-guided ESPB (n = 115) and control (n = 115) groups. The ESPB group received 20 mL of 0.4% ropivacaine bilaterally at the T12 level after intubation, whereas the control group did not receive a block. The primary outcome was the numeric rating scale (NRS) score at 12 h after surgery. Secondary outcomes included the NRS score and tramadol use within 72 h postoperatively, intraoperative remifentanil use, incidence of postoperative delirium (POD), complications of ESPB, ambulation time, and length of hospitalization after surgery. The12-hour NRS (median (IQR)) score was remarkably lower in the ESPB group than in the control group (2 (1-3) vs. 3 (2-4), p = 0.004), as well as NRS score within 48 h (P < 0.01). The ESPB group had less intraoperative remifentanil use (P < 0.001), and less tramadol use within 72 h postoperatively (P < 0.001). Seven patients (6.7%) developed POD in the ESPB group and ten patients (9.3%) in the control group, without any statistically significant difference (P > 0.05). The ambulation time and length of hospitalization after surgery were shorter in the ESPB group than in the control group (P < 0.05). No ESPB-related complications were observed. Bilateral T12 ESPB lowered the NRS score within 48 h after lumbar spine surgery, decreased perioperative opioid use and resulted in faster recovery in elderly patients but did not significantly reduce the incidence of POD. The study was retrospectively registered at www.chictr.org.cn (ChiCTR2100042037) on January 12, 2021.


Putting guidelines into practice: improving documentation of pediatric asthma management using a decision-making tool.
To assess improvement in documentation of asthma indicators using the Asthma Toolbox, an asthma decision-making tool developed in accord with National Asthma Education and Prevention Program guidelines. Retrospective medical record review using cross-sectional, independent, random samples. Reviews were conducted for 1-year periods before and after implementation and after revision reflecting 2007 guideline modifications. Two inner-city, federally qualified health center programs providing pediatric primary care to housed and homeless populations. A total of 1246 patients aged 6 months to 18 years with at least 1 asthma visit to a community health center using paper records (n = 600) or a mobile medical program serving family homeless shelters using an electronic health record (EHR; n = 646). Implementation of the Asthma Toolbox incorporated into paper encounter forms and embedded in the EHR to guide providers (ie, physicians and nurse practitioners) through pediatric asthma assessment and management. Documentation of a subset of asthma severity/control measures, emergency department visits, hospitalizations, and percentage of persistent asthmatic patients prescribed controller medications. Documentation of each asthma indicator increased significantly after implementation (χ(2) tests; P < .001 all comparisons) for both programs. Documentation of severity/control increased from 25.5% to 77.5% in paper records and from 11.7% to 85.1% in the EHR (P < .001). Increases were sustained after Asthma Toolbox revision for all indicators. The percentage of patients with persistent/uncontrolled asthma prescribed controller medications reached 96% to 97% in both programs. Use of the Asthma Toolbox, an asthma decision-making tool, significantly increased documentation of pediatric asthma management among providers working in high-disparity, urban primary care settings.


Acute and chronic leptin treatment mediate contrasting effects on signaling, glucose uptake, and GLUT4 translocation in L6-GLUT4myc myotubes.
We have previously shown that in L6-GLUT4myc rat skeletal muscle cells, acute treatment with leptin reduced insulin-stimulated glucose uptake without altering insulin-stimulated GLUT4 translocation. In contrast, we show here that the ability of leptin to increase phosphorylation of its receptor and to reduce insulin-stimulated glucose uptake was lost in cells that were continuously exposed to leptin for 24 h. This desensitization correlated with an increase in expression of suppressor of cytokine signaling-3 (SOCS-3). Time course analysis demonstrated that the transition from acute to chronic effects of leptin occurs after 2 h. The desensitization of leptin action at 24 h was not reversed by 30 min washout period prior to re-exposing cells to leptin. However, despite insulin-stimulated glucose uptake being unaffected upon 24 h preincubation with leptin, a small but significant decrease (37%) in insulin-stimulated GLUT4 translocation and phosphorylation of Akt on T308 was detected. Insulin-stimulated phosphorylation of Akt on S473 or of p38 MAPK were unaffected. These results suggest that the chronic leptin treatment leads to desensitization of leptin signaling yet can simultaneously decrease the ability of insulin to phosphorylate Akt on T308 and translocate GLUT4. However, this does not manifest as a reduction in total glucose uptake into L6 myotubes.


Identification of Depressive Signs in Patients and Their Family Members During iPad-based Audiovisual Sessions.
Home parenteral nutrition requires a daily life-sustaining intravenous infusion over 12 hours. The daily intravenous infusion home care procedures are stringent, time-consuming tasks for patients and family caregivers who often experience depression. The purposes of this study were (1) to assess home parenteral nutrition patients and caregivers for depression and (2) to assess whether depressive signs can be seen during audiovisual discussion sessions using an Apple iPad Mini. In a clinical trial (N = 126), a subsample of 21 participants (16.7%) had depressive symptoms. Of those with depression, 13 participants were home parenteral nutrition patients and eight were family caregivers; ages ranged from 20 to 79 years (with 48.9 [standard deviation, 17.37] years); 76.2% were female. Individual assessments by the mental health nurse found factors related to depressive symptoms across all 21 participants. A different nurse observed participants for signs of depression when viewing the videotapes of the discussion sessions on audiovisual technology. Conclusions are that depression questionnaires, individual assessment, and observation using audiovisual technology can identify depressive symptoms. Considering the growing provision of healthcare at a distance, via technology, recommendations are to observe and assess for known signs and symptoms of depression during all audiovisual interactions.


Upon thyrotropin binding the thyrotropin receptor is internalized and localized to endosome.
To study the fate of TSH receptor (TSHR) on TSH binding, we constructed a chimeric cDNA that encodes a yellow fluorescent protein (YFP) fused to the carboxyl terminus of human TSHR. The protein expression in transfected cells was confirmed using flow cytometry. The functionality of the chimeric protein was determined by its ability to transduce signal leading to activation of cAMP in a TSH dose-dependent manner. The levels of cAMP produced by these cells were comparable with the levels seen in cells transfected with unfused TSHR without the YFP. Using deconvolution microscopy, we observed that the receptor is largely expressed on the cell surface, but on addition of TSH, some of the receptors were rapidly internalized. This conclusion was supported by several independent observations involving different cells expressing either native or recombinant TSHR. On TSH treatment, we observed internalization of human TSHR-YFP and human TSHR, expressed on 293 and CHO cells, respectively. This was further substantiated when we observed colocalization of rhodamine-labeled TSH with TSHR-YFP within the cell and by the uptake of radiolabeled TSH. Furthermore, shortly after ligand binding, there was a profound change in the morphology of the cells and some of the receptors accumulated in the perinuclear region of the cell. The TSHR-YFP was colocalized with RhoB-cyan fluorescent protein, indicating that it accumulated within the endosomes. These results indicate that the receptor internalization might in part be responsible for TSHR desensitization on TSH binding.


Induction of apoptosis by luteolin involving akt inactivation in human 786-o renal cell carcinoma cells.
There is a growing interest in the health-promoting effects of natural substances obtained from plants. Although luteolin has been identified as a potential therapeutic and preventive agent for cancer because of its potent cancer cell-killing activity, the molecular mechanisms have not been well elucidated. This study provides evidence of an alternative target for luteolin and sheds light on the mechanism of its physiological benefits. Treatment of 786-O renal cell carcinoma (RCC) cells (as well as A498 and ACHN) with luteolin caused cell apoptosis and death. This cytotoxicity was caused by the downregulation of Akt and resultant upregulation of apoptosis signal-regulating kinase-1 (Ask1), p38, and c-Jun N-terminal kinase (JNK) activities, probably via protein phosphatase 2A (PP2A) activation. In addition to being a concurrent substrate of caspases and event of cell death, heat shock protein-90 (HSP90) cleavage might also play a role in driving further cellular alterations and cell death, at least in part, involving an Akt-related mechanism. Due to the high expression of HSP90 and Akt-related molecules in RCC and other cancer cells, our findings suggest that PP2A activation might work in concert with HSP90 cleavage to inactivate Akt and lead to a vicious caspase-dependent apoptotic cycle in luteolin-treated 786-O cells.