[Cellular oncogenes and antioncogenes in thyroid tumors].
Analysis of literature indicates that genetic mechanisms of thyroid tumor development are connected with two main classes of genes: oncogenes whose activation may stimulate tumor growth and anti-oncogenes which acquire oncogenic properties due to the loss of their function through point mutation or deletion. Protooncogene Ras mutation plays a role in the early events in tumor development. Restructuration of Ret and Trk oncogenes, overexpression of Met and Ras point mutations are characteristic for papillary thyroid carcinoma.


Determination of haloacetic acids in water using layered double hydroxides as a sorbent in dispersive solid-phase extraction followed by liquid chromatography with tandem mass spectrometry.
In the present study, highly efficient and simple dispersive solid-phase extraction procedure for the determination of haloacetic acids in water samples has been established. Three different types of layered double hydroxides were synthesized and used as a sorbent in dispersive solid-phase extraction. Due to the interesting behavior of layered double hydroxides in an acidic medium (pH˂4), the analyte elution step was not needed; the layered double hydroxides are simply dissolved in acid immediately after extraction to release the analytes which are then directly introduced into a liquid chromatography with tandem mass spectrometry system for analysis. Several dispersive solid-phase extraction parameters were optimized to increase the extraction efficiency of haloacetic acids such as temperature, extraction time and pH. Under optimum conditions, good linearity was achieved over the concentration range of 0.05-100 μg/L with detection limits in the range of 0.006-0.05 μg/L. The relative standard deviations were 0.33-3.64% (n = 6). The proposed method was applied to different water samples collected from a drinking water plant to determine the concentrations of haloacetic acids.


Factors related to apical root resorption of maxillary incisors in orthodontic patients.
THE MAIN OBJECTIVE of the study was to determine the extent of external apical root resorption at the end of orthodontic treatment and to identify the possible pre-treatment and treatment factors that would allow to predict the possible incidence of root resorption before the start of treatment. Panoramic radiographs of 75 patients that had been treated with full fixed appliances were used to assess apical root resorption in maxillary incisors. The degree of root resorption was measured in millimetres and the scale of Shape was used. The results showed that the resorption in the maxillary incisors is on the average 1.5 mm, the severe resorption was seen in 2.6% of patients. The worst resorption was seen in teeth with abnormal root shape. There were no differences in the severity of root resorption when comparing males and females as well as children and adults. Increased overjet, overbite and extraction therapy were not associated with greater root resorption. Duration of treatment and length of treatment time with rectangular wires were associated with greater root resorption. Patients wearing composite brackets with a metal slot had more resorption than patients wearing metal brackets. Pre-treatment risk indicator for root resorption was abnormal root shape. Risk indicators for root resorption that were related to treatment procedures included length of treatment time with rectangular wires, duration of treatment and treatment with composite brackets with a metal slot.


A gossypiboma masquerading as a mesenteric cyst.
Gossypiboma refers to foreign bodies left inside the body during surgery, such as sponges and gauze. These foreign bodies represent a significant cause of morbidity and mortality. A 57-year-old female presented to us with right upper abdominal pain. Her past history was non-contributory except for an open cholecystectomy 20 years previously. A physical examination revealed tenderness to palpation on the right of the abdomen, while the remaining examination was normal. An abdominal computed tomography (CT) and magnetic resonance imaging (MRI) scan revealed a well-defined calcified mass of 5 cm that was compatible with a mesenteric cyst. During surgery, the mass was found to be adherent to the mesocolon and to have invaded the colon wall. A right hemicolectomy and ileotransverse anastomosis was performed. The pathological mass was considered to be a gossypiboma that had been left behind during the earlier cholecystectomy. The body's reaction to the foreign body was seen to extend beyond the lamina propria and muscularis propria. Gossypiboma is an undesired and life-threatening but preventable surgical complication. This condition may present with non-specific findings and a clinical scenario that mimics various disorders, even after many years. A diagnosis of gossypiboma should be kept in mind for patients with a history of previous operations and undergoing surgery due to the suspicion of a mesenteric cyst.


[Rickettsial diseases in Switzerland, update for the general practitioner].
Rickettsial diseases are arthropod-borne zoonosis. They are still misdiagnosed in Switzerland. Since development in molecular genetics, number of pathogenic species increased dramatically. In recent years, the incidence rise worldwide. Climatic conditions and development of tropical travels could explain it. In a near future, the Swiss general practitioner may face an increase of cases. Clinical presentation is unspecified. The eschar is the key diagnostic element but can be easily overlooked. Serology, the indirect immunofluorescence assay is the reference method. PCR can give the diagnosis in acute phase. However empirical treatment should be prescribed as soon as diagnosis is suspected. No vaccine is currently available and use of repellent is still the best way of prevention.


[Variability in the delivery of care in stroke units: analysis of the protocols].
In spite of the existing guidelines, the strategies and behaviours adopted in the care of the patients admitted to stroke units may vary widely across centres. The aim of this study was to quantify and quality the degree of real variability of the protocols enforced a sample of 13 of such units. There is no uniform behaviour for the monitoring of patients admitted with a stroke: vital signs are collected with different range intervals, i.e. blood pressure 15 for the first 6 hours, from every 15 minutes to 2-3 hours. The assessment of dysphagia can be performed with the swallow test or having the patient drink a spoonful 10 ml of water, or 50 ml without stopping. The variability of behaviours is not, per se, a negative characteristic but it becomes a potential and unacceptable risk when solid evidences of effective practice are available. In the absence of clear cut recommendations the protocols should be defined trying to find a balance between effectiveness of the behaviours recommended and workload for nurses.


Linear stapler closure of the pharynx during total laryngectomy: a 15-year experience (from closed technique to semi-closed technique).
Personal experience in performing linear stapler closure of the pharynx during 70 total laryngectomies is reported. Laryngeal staplers (55 and 60 cm) with an angled handle were used, permitting vertical closure with 19 or 20 metal staples in a double row. A closed technique was initially used, but, over the years, this has gradually been replaced by the semi-closed technique to avoid trapping the suprahyoid part of the epiglottis between the jaws of the stapler. The stapler is inserted below the larynx after having separated it from all muscular and neurovascular connections, and after performing a mini-pharyngotomy at the vallecula epiglottica in order to extract the epiglottis, evert it ventrally and suture it to the hyothyroepiglottic space. The jaws of the stapler are closed and the staples are fired while the flaps of the mini-pharyngotomy are raised above the jaws. The scalpel is inserted above the stapler to remove the larynx. When the stapler is opened, the vertical linear suture of the pharynx is evident and can be examined. This procedure takes only a few minutes to perform. It guarantees a long-term stable watertight closure, dramatically reduces contamination of the operating field by pharyngeal secretions, and permits rapid healing time, greatly lowering patient management costs. In the cases presented here, there was a 1.8% rate of pharyngocutaneous fistulae in patients who were not radiated, whereas the rate was 13.1% in pre-radiated patients. In agreement with the international literature, this procedure does not increase the rate of fistulae and, in fact, it seems to reduce it. Moreover, it is particularly indicated for pre-radiated patients. Nevertheless, the Authors recommend reserving this type of procedure to cases in which, based on meticulous pre-operative assessment by means of endoscopy and imaging, the endolaryngeal site of the tumour has been assessed and there is no need for peri-operative exploration of the pharynx or tongue base.


Adrenaline-induced hypertension in rats.
Rats were given a slow-release depot implantation containing adrenaline (0.33 mumole/kg). Adrenaline was released from the implant, giving a plasma level of 1.0 nmole/liter the day after implantation. Adrenaline-treated rats had elevated blood pressures compared to control rats from 1 day to 8 weeks after treatment. However, 8 weeks after treatment no adrenaline from the implant was found in the plasma, suggesting that at this time factors other than the adrenaline were responsible for maintaining the rise in blood pressure. In rats given metoprolol tartrate (5 mg/kg/day, p.o.), adrenaline treatment did not increase the blood pressure.


GWAS provides biological insights into mechanisms of the parasitic plant (Striga) resistance in sorghum.
Sorghum yields in sub-Saharan Africa (SSA) are greatly reduced by parasitic plants of the genus Striga (witchweed). Vast global sorghum genetic diversity collections, as well as the availability of modern sequencing technologies, can be potentially harnessed to effectively manage the parasite. We used laboratory assays - rhizotrons to screen a global sorghum diversity panel to identify new sources of resistance to Striga; determine mechanisms of resistance, and elucidate genetic loci underlying the resistance using genome-wide association studies (GWAS). New Striga resistant sorghum determined by the number, size and biomass of parasite attachments were identified. Resistance was by; i) mechanical barriers that blocked parasite entry, ii) elicitation of a hypersensitive reaction that interfered with parasite development, and iii) the inability of the parasite to develop vascular connections with hosts. Resistance genes underpinning the resistance corresponded with the resistance mechanisms and included pleiotropic drug resistance proteins that transport resistance molecules; xylanase inhibitors involved in cell wall fortification and hormonal regulators of resistance response, Ethylene Response Factors. Our findings are of fundamental importance to developing durable and broad-spectrum resistance against Striga and have far-reaching applications in many SSA countries where Striga threatens the livelihoods of millions of smallholder farmers that rely on sorghum as a food staple.


Secondary colorectal carcinoma after childhood cancer.
Colorectal carcinoma (CRC) has been described as a subsequent malignant neoplasm (SMN), although little is known about associated risk factors. We aimed to quantify the long-term risk of secondary CRC and identify treatment-related risk factors. In this nested case-control study, 19 cases of adenocarcinoma of the colon or rectum were identified from 13,048 oncology patients treated for childhood cancer at St Jude Children's Research Hospital. Group 1 controls (n = 148) were matched for age at primary malignancy and follow-up interval. Group 2 controls (n = 72) were matched on primary diagnosis in addition to group 1 criteria. Exact conditional logistic regression was performed to calculate odds ratios (ORs) for chemotherapy and radiation exposure. Forty-year cumulative incidence of secondary CRC was 1.4%. Standardized incidence ratio was 10.9 (95% CI, 6.6 to 17.0) compared with that in the general US population. Secondary CRC was more likely in an irradiated segment of the colon (group 1 OR, 7.7; P = .001; group 2 OR, 15.4; P = .002). Risk increased by 70% with each 10-Gy increase in radiation dose. Increasing radiation volume increased risk (group 1 OR, 1.5; P < .001; group 2 OR, 1.8; P < .001). Alkylating agent exposure was associated with an 8.8-fold increased risk of secondary CRC (P = .03). In matched analyses, radiation and alkylator exposure are associated with secondary CRC. This risk is proportional to dose and volume of radiation. Surveillance should be initiated at a young age among survivors receiving high-risk exposures.


Hyperactive KRAS/MAPK signaling disrupts normal lymphatic vessel architecture and function.
Complex lymphatic anomalies (CLAs) are sporadically occurring diseases caused by the maldevelopment of lymphatic vessels. We and others recently reported that somatic activating mutations in KRAS can cause CLAs. However, the mechanisms by which activating KRAS mutations cause CLAs are poorly understood. Here, we show that KRASG12D expression in lymphatic endothelial cells (LECs) during embryonic development impairs the formation of lymphovenous valves and causes the enlargement of lymphatic vessels. We demonstrate that KRASG12D expression in primary human LECs induces cell spindling, proliferation, and migration. It also increases AKT and ERK1/2 phosphorylation and decreases the expression of genes that regulate the maturation of lymphatic vessels. We show that MEK1/2 inhibition with the FDA-approved drug trametinib suppresses KRASG12D-induced morphological changes, proliferation, and migration. Trametinib also decreases ERK1/2 phosphorylation and increases the expression of genes that regulate the maturation of lymphatic vessels. We also show that trametinib and Cre-mediated expression of a dominant-negative form of MEK1 (Map2k1 K97M) suppresses KRASG12D-induced lymphatic vessel hyperplasia in embryos. Last, we demonstrate that conditional knockout of wild-type Kras in LECs does not affect the formation or function of lymphatic vessels. Together, our data indicate that KRAS/MAPK signaling must be tightly regulated during embryonic development for the proper development of lymphatic vessels and further support the testing of MEK1/2 inhibitors for treating CLAs.


Invasive Erysipelothrix rhusiopathiae infection in northeast Thailand.
Three cases of invasive Erysipelothrix rhusipathiae infection, which is considered rare, presented to a hospital in Ubon Ratchathani, northeast Thailand during 2006. Patients presented with variable clinical manifestations including diffused cutaneous lesions, bacteremia and endocarditis. Erysipelothrix infection may be an emerging infection in immunocompromized individuals in Thailand.


Preferred versus Actual Place of Care and Factors Associated with Home Discharge among Korean Patients with Advanced Cancer: A Retrospective Cohort Study.
Respecting the preference for a place of care is essential for advance care planning in patients with advanced cancer. This retrospective study included adult patients with cancer referred to an inpatient palliative care consultation team at a tertiary acute care hospital in South Korea between April 2019 and December 2020. Patients' preference for place of care and demographic and clinical factors were recorded, and the actual discharge locations were categorized as home or non-home. Patients discharged home but with unintended hospital visits within 2 months were also investigated. Of the 891 patients referred to the palliative care consultation team, 210 (23.6%) preferred to be discharged home. Among them, 113 (53.8%) were discharged home. No significant differences were found between patients who preferred home discharge and those who did not. Home discharge was higher among female patients (p = 0.04) and lower in those with poor oral intake (p < 0.001) or dyspnea (p = 0.02). Of the 113 patients discharged home, 37 (32.8%) had unintended hospital visits within 2 months. Approximately one-quarter of hospitalized patients with advanced cancer preferred to be discharged home, but only half of them received the home discharge. To meet patients' preferences for end-of-life care, individual care planning considering relevant factors is necessary.


[Induced pluripotent stem cells: a new paradigm to study human tissues].
Induced pluripotent stem cells (iPSCs) are obtained by reprogramming differentiated cells through forced expression of four embryonic transcription factors. The discovery of this technology, able to transform a differentiated cell into a pluripotent cell, has profoundly shifted the paradigm of the concept of cell identity, since it is now possible to obtain in vitro any cell type from an initial sample of skin or blood cells from a healthy volunteer or patient. Applications of iPSCs are exceedingly large, and comprise the in vitro modeling of normal or pathological tissues, including for massive drug screening. They also open new therapeutic avenues in the field of regenerative medicine.


Large degenerated adrenal adenomas: radiologic-pathologic correlation.
To correlate the radiologic and pathologic findings and differential diagnosis of large, degenerated adrenal adenomas. The authors reviewed the radiologic and pathologic characteristics of 30 large adenomas with cystic regions or areas of heterogeneity that were either intrinsic or demonstrated at contrast material-enhanced computed tomography (CT) or magnetic resonance (MR) imaging. Images of 24 adrenocortical carcinomas were also reviewed to determine whether differentiating characteristics existed. Most of the adrenocortical adenomas were in asymptomatic women. Ten adenomas contained calcification. Pathologic examination revealed good correlation between heterogeneity and liquefied regions. Histologic examination confirmed regions of adenomatous tissue with areas of hemorrhage, amorphous degenerated material, calcification, and fibrosis. Some tumors contained myelolipomatous foci. Although some clinical and imaging findings differed between the groups, no features could be found that enabled the radiologic differentiation of adenomas from carcinomas. A subgroup of adrenal adenomas are larger, more heterogeneous, and more frequently calcified than those with the usual imaging findings. Central necrosis, hemorrhage, or both are responsible for many of the imaging features. Differentiation of these lesions from other large adrenal masses, including adrenal carcinoma, cannot be made by means of imaging alone; resection is required for the definitive diagnosis.


Prey food quality affects flagellate ingestion rates.
Flagellate feeding efficiency appears to depend on morphological characteristics of prey such as cell size and motility, as well as on other characteristics such as digestibility and cell surface characteristics. Bacteria of varying morphological characteristics (cell size) and mineral nutrient characteristics or food quality (as determined by the C:N:P ratio) were obtained by growing Pseudomonas fluorescens in chemostats at four dilution rates (0.03, 0.06, 0.10, and 0.13 h-1) and three temperatures (14 degrees C, 20 degrees C, and 28 degrees C). Cells of a given food quality were heat-killed and used to grow the flagellate Ochromonas danica. Ingestion and digestion rates were determined by using fluorescently labeled bacteria of the same food quality as the bacteria supporting growth. Ingestion rates were affected by both food quality and cell size. Cells of high food quality (low carbon:element ratio) were ingested at higher rates than cells of low food quality. Multiple regression analysis indicated that cell size also influenced ingestion rate but to a much lesser extent than did food quality. Digestion rates were not correlated with either food quality or cell size. Results suggest that flagellates may adjust feeding efficiency based on the quality of food items available.


Effective connectivity within the distributed cortical network for face perception.
Face perception elicits activation within a distributed cortical network in the human brain. The network includes visual ("core") regions, as well as limbic and prefrontal ("extended") regions, which process invariant facial features and changeable aspects of faces, respectively. We used functional Magnetic Resonance Imaging and Dynamic Causal Modeling to investigate effective connectivity and functional organization between and within the core and the extended systems. We predicted a ventral rather than dorsal connection between the core and the extended systems during face viewing and tested whether valence and fame would alter functional coupling within the network. We found that the core system is hierarchically organized in a predominantly feed-forward fashion, and that the fusiform gyrus (FG) exerts the dominant influence on the extended system. Moreover, emotional faces increased the coupling between the FG and the amygdala, whereas famous faces increased the coupling between the FG and the orbitofrontal cortex. Our results demonstrate content-specific dynamic alterations in the functional coupling between visual-limbic and visual-prefrontal face-responsive pathways.


A Forward Genetic Approach to Identify Plasmodesmal Trafficking Regulators Based on Trichome Rescue.
Plasmodesmata (PD) are channels in the walls of plant cells which enable cell-to-cell information transfer. This includes the selective transport of specific transcription factors that control cell fate during plant development. KNOTTED1 (KN1) homeobox (KNOX) family transcription factors that are essential for the maintenance and function of stem cells in shoot meristems use this trafficking pathway, but its mechanism is largely unknown. Here we describe a forward genetic approach to the identification of regulators of selective KN1 trafficking through PD, using a trichome rescue system that permits simple visual analysis in Arabidopsis leaves. A KN1 trafficking regulator identified in this approach had the capacity to regulate the transport not only of KN1 but also of another mobile regulatory protein, TRANSPARENT TESTA GLABRA1 (TTG1). Our system could be easily adapted to reveal the mechanism underlying the selective transport of additional mobile signals through PD.


Inhibition of NaCl appetite when DOCA-treated rats drink saline.
Marked increases in the consumption of concentrated NaCl solution were elicited in rats by daily injection of the synthetic mineralocorticoid, deoxycorticosterone acetate (DOCA). DOCA-treated rats drank different volumes of NaCl solution depending on its concentration (between 0.15 M and 0.50 M), with less consumed (in milliliters) the more concentrated the fluid was. In consequence, total Na(+) intake (in milliequivalents) was roughly similar in all groups. Gastric emptying of Na(+) also diminished as the concentration of the ingested NaCl solution increased, and the delivery of Na(+) to the small intestine was remarkably similar in all groups. Cumulative volume of ingested fluid in the stomach and small intestine was very closely related to intake (in milliliters) of the concentrated NaCl solutions. Systemic plasma Na(+) levels did not increase until after rats stopped consuming concentrated NaCl solution, although they were elevated at the onset of water ingestion. The situation appeared to be different when 0.15 M NaCl was consumed. This isotonic solution emptied and was absorbed relatively rapidly, and DOCA-treated rats drank larger amounts of it throughout a 1-h test period than when they drank concentrated NaCl solutions. Collectively, these findings suggest that saline consumption by DOCA-treated rats may be inhibited by two presystemic factors, one related to the volume of ingested fluid (i.e., distension of the stomach and small intestine) and one related to its concentration (i.e., elevated osmolality of fluid in the small intestine and/or in adjacent visceral tissue).


Vaginal atresia and cryptomenorrhea.
Six cases of congenital vaginal atresia are described. Three of these patients had cryptomenorrhea while the other 3 had severe coital difficulties. Despite the fact that normal coitus was impossible in these 3 women, 2 of them achieved successful pregnancies and had to be delivered by emergency cesarean section followed by resection of the occluding membranes. The third patient (with dyspareunia) resorted to paraurethral coitus for more than 2 years before seeking advice. The management of vaginal atresia proved difficult because of the recurrence of stenosis at the site of the excised membrane. This was particularly marked in the young adolescent females not exposed to regular coitus. An operative method that could minimize this complication is discussed.


Axillary lymph node dissection: is it required in T1a breast cancer?
Several authors have questioned the need for axillary lymph node dissection in T1a breast cancer (primary tumors 5 mm or less in diameter), although current practice typically includes routine axillary lymph node dissection. We retrospectively reviewed the records of 2,242 breast cancers in our tumor registries from 1987 to 1994. The incidence of axillary lymph node metastases was determined according to primary breast cancer size. The objective was to determine the need for axillary lymph node dissection in T1a breast cancers, and our data included 74 T1a cancers. Axillary lymph node dissection was performed in 66 of these patients. Axillary lymph node metastases were found in 3 of 66 cases (4.5 percent). We also reviewed several other institutional series of T1a breast cancers and found no statistical difference in the reported axillary lymph node metastases and our data (p < .10). The combined single-institution data included 256 T1a breast cancers and had a 3.9 percent incidence of axillary lymph node metastases. The Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute published data statistically different from ours. From 1977 to 1982, 339 T1a lesions had a 21 percent incidence of axillary lymph node metastases (p < .005), and from 1983 to 1987, 1,491 T1a lesions had an 11 percent metastatic rate (p < .001). We believe that the SEER data is flawed, because SEER results do not require histologic confirmation of axillary lymph node status. We believe the single-institution rate of 3.9 percent axillary lymph node metastases in T1a breast tumors results from state-of-the-art breast cancer screening and detection of earlier and smaller lesions. Our data support abandoning routine axillary lymph node dissection in T1a breast cancer.


Synthesis of side-chain oxysterols and their enantiomers through cross-metathesis reactions of Δ22 steroids.
A synthetic route that utilizes a cross-metathesis reaction with Δ22 steroids has been developed to prepare sterols with varying C-27 side-chains. Natural sterols containing hydroxyl groups at the 25 and (25R)-26 positions were prepared. Enantiomers of cholesterol and (3β,25R)-26-hydroxycholesterol (27-hydroxycholesterol) trideuterated at C-19 were prepared for future biological studies.


si-PDGFRβ-Loaded Exosomes Suppress the Progression of Glioma by Inhibiting the Oxidative Associated PI3K/Akt/EZH2 Signaling Pathway.
This study investigated the possibility of exosomes loaded with si-PDGFRβ ability to suppress the progression of glioma. Common gliomas develop from neuroglial progenitor cells. Many variables affect the survival rate and occurrence of gliomas. Understanding oxidative stress processes and creating new, efficient treatments are crucial because oxidative stress is linked to the development of brain tumors. For this purpose, selected clinical samples were subjected to various tests like quantitative real-time PCR, Cignal Finder RTK signaling 7-pathway reporter array analysis, CCK-8 analysis, flow cytometry, and immunoblotting. Here, we demonstrated that PDGFRβ expression was increased in glioma patients. Following that, cell-derived exosomes were extracted and collected and traced in vivo, and selected tissue samples were subjected to immunohistochemical analysis. The results indicated that the knockdown of PDGFRβ (si-PDGFRβ) inhibited the proliferation of glioma cells. Besides this, si-PDGFRβ-loaded exosomes induced a similar antitumor effect in glioma cells. The anticancer effect of si-PDGFRβ-loaded exosomes was mediated by the inactivation of the PI3K/Akt/EZH2 pathway. Finally, we verified that this exosome delivery system, si-PDGFRβ-loaded exosomes, had robust targeting and no associated toxicity. In conclusion, the study confirmed that si-PDGFRβ-loaded exosomes inhibit glioma progression via inactivating the PI3K/Akt/EZH2 signaling pathway.


Temperature and organic matter dependence of the distribution of organochlorine compounds in mountain soils from the subtropical Atlantic (Teide, Tenerife Island).
Surface soil samples from Teide mountain (Canary Islands) have been analyzed for polychlorobiphenyls (PCBs), DDTs, hexachlorocyclohexanes (HCHs), hexachlorobenzene (HCB), and pentachlorobenzene. The samples were situated between 10 and 3400 m above sea level being distributed below, at, and above the permanent inversion layer system characteristic of the subtropical Atlantic. All OC concentrations were, in general, low when compared with the data from urban, agricultural, or woodland soils reported elsewhere. Typical ranges were 0.04-9.2, 0.01-40, 0.001-1, or 0.01-3.2 ng x g(-1) dry weight for total PCBs, DDTs, HCHs, or HCB, respectively. These compounds exhibited a high dependence from the soil total organic carbon (TOC), showing high coefficients in the log(OC) versus log(TOC) correlations. The slopes of the curve fitted straight lines were, in turn, highly correlated to the log-transformed octanol-air coefficients of the compounds. This overall OC distribution points to steady-state conditions for the concentrations of these compounds in these mountain soils, in equilibrium with TOC. The equilibrium conditions are reached, despite the restrictions to convective air movement associated to the permanent atmospheric inversion layer at these latitudes. In addition, the log-transformed TOC-normalized concentrations of most PCBs, HCB, and pentachlorobenzene exhibit a good correlation with the reciprocal of average annual atmospheric temperatures also showing a temperature dependence for their distribution in the high mountain system. The calculated pseudo-enthalpies for this dependence, 120-160 kJ x mol(-1), exhibit higher values than those of octanol-air phase change calculated from laboratory experiments in previous studies, 66-93 kJ x mol(-1). The difference suggests a higher affinity of OC to soils than that corresponding to simple adsorption mechanisms.


Bioinspired All-Polyester Diblock Copolymers Made from Poly(pentadecalactone) and Poly(2-(2-hydroxyethoxy)benzoate): Synthesis and Polymer Film Properties.
The bioinspired diblock copolymers poly(pentadecalactone)-block-poly(2-(2-hydroxyethoxy)-benzoate) (PPDL-block-P2HEB) were synthesized from pentadecalactone and dihydro-5H-1,4-benzodioxepin-5-one (2,3-DHB). No transesterification between the blocks was observed. In a sequential approach, PPDL obtained by ring-opening polymerization (ROP) was used to initiate 2,3-DHB. Here, the molar mass Mn of the P2HEB block was limited. In a modular approach, end-functionalized PPDL and P2HEB were obtained separately by ROP with functional initiators, and connected by 1,3-dipolar Huisgen reaction ("click-chemistry"). Block copolymer compositions from 85:15 mass percent to 28:72 mass percent (PPDL:P2HEB) were synthesized, with Mn of from about 30,000-50,000 g mol-1. The structure of the block copolymer was confirmed by proton NMR, FTIR spectroscopy, and gel permeation chromatography. Morphological studies by atomic force microscopy (AFM) further confirmed the block copolymer structure, while quantitative nanomechanical AFM measurements revealed that the DMT moduli of the block copolymers ranged between 17.2 ± 1.8 MPa and 62.3 ± 5.7 MPa, i.e. between the values of the parent P2HEB and PPDL homopolymers (7.6 ± 1.4 MPa and 801 ± 42 MPa, respectively). Differential scanning calorimetry showed that the thermal properties of the homopolymers were retained by each of the copolymer blocks (melting temperature 90 °C, glass transition temperature 36 °C).


Hypo-fractionated IMRT for patients with newly diagnosed glioblastoma multiforme: a 6 year single institutional experience.
Glioblastoma (GBM) is the most common malignant primary brain tumour in adults. Surgery and radiotherapy constitute the cornerstones for the therapeutic management of GBM. The standard treatment today is maximal surgical resection followed by concomitant chemo-radiation therapy followed by adjuvant TMZ according to Stupp protocol. Despite the progress in neurosurgery, radiotherapy and oncology, the prognosis still results poor. In order to reduce the long time of standard treatment, maintaining or improving the clinical results, in our institute we have investigated the effects of hypo-fractionated radiation therapy for patients with GBM. Sixty-seven patients affected by GBM who had previously undergone surgical resection (total, subtotal or biopsy) were enrolled between October 2005 and December 2011 in a single institutional study of hypo-fractionated intensity modulated radiation therapy (IMRT) followed or not by adjuvant chemotherapy with TMZ (6-12 cycles). The most important eligibility criteria were: biopsy-proven GBM, KPS ≥ 60, age ≥ 18 years, no previous brain irradiation, informed consensus. Hypo-fractionated IMRT was delivered to a total dose of 25 Gy in 5 fractions prescribed to 70% isodose. Response to treatment, OS, PFS, toxicity and patterns of recurrence were evaluated, and sex, age, type of surgery, Karnofsky performance status, Recursive Partitioning Analysis (RPA) classification, time between surgery and initiation of radiotherapy were evaluated as potential prognostic factors for survival. All patients have completed the treatment protocol. Median age was 64.5 years (range 41-82 years) with 31 females (46%) and 36 males (54%). Median KPS at time of treatment was 80. The surgery was gross total in 38 patients and subtotal in 14 patients; 15 patients underwent only biopsy. No grade 3-4 acute or late neurotoxicity was observed. With median follow-up of 14.9 months, the median OS and PFS were 13.4 and 7.9 months, respectively. The hypo-fractionated radiation therapy can be used for patients with GBM, resulting in favourable overall survival, low rates of toxicity and satisfying QoL. Future investigations are needed to determine the optimal fractionation for GBM.


Dom Pedro I of Brazil and IV of Portugal: epilepsy and peculiar behavior.
We present medical issues related to Dom Pedro de Alcântara Bragança e Bourbon (1798-1834), first Emperor of Brazil. This is made by means of narrative revision on historical facts starting from primary and secondary sources. Dom Pedro presented familiar incidence of epilepsy. His seizures were relatively benign and scattered, supposedly started at the age of 13: idiophatic epilepsy with generalized tonic-clonic seizures only or juvenile myoclonic epilepsy. He also had behavioral disorder characterized by hypersexuality, agitation and impulsiveness. It could have facilitated his opportunistic behavior necessary for daring to transgress the conservatism of the Portuguese crown, to create the constitutional monarchism in Brazil and in Portugal.


[Diagnostic usefulness of optical coherence tomography (OCT), scanning laser tomography (HRT-II) and laser polarimetry (GDx) in open-angle glaucoma].
To evaluate the diagnostic ability of three digital imaging technologies (HRT-II, OCT and GDx VCC) in detecting glaucomatous damage. A total of 427 eyes from 427 subjects were included in this cross-sectional study. Each subject was classified as healthy, ocular hypertensive or glaucomatous, according to intraocular pressure levels, standard automated perimetry and optic disc morphology. All of them underwent examination by means of HRT, OCT and GDx VCC. Receiver operating characteristic (ROC) curves were plotted and sensitivities at fixed specificities (85% and 95%) were calculated for each parameter assessed. The parameters with the higher diagnostic ability were: FSM discriminant function from HRT-II (AUC=0.899), retinal nerve fiber layer average thickness from OCT (AUC=0.929) and NFI from GDx VCC (AUC=0.879), with no statistically significant differences between them. The HRT-II, OCT and GDx VCC provide measurements of the retinal nerve fiber layer and the optic nerve head with high discriminating ability in open-angle glaucoma.


A Rare Case of Unilateral Auditory Neuropathy Induced by Proton Therapy.
Hearing loss (HL) is one of the most common complications of the treatment in head and neck oncology. Most cases of HL are due to the ototoxicity of platinum-based chemotherapy (PBC) - resulting usually in a symmetric bilateral sensorineural hearing loss (SNHL) - or radiotherapy. Radiation-induced SNHL is progressive, permanent, and dose-dependent. Total dose and follow-up time are important factors affecting incidence rates. However, the hearing consequences of proton radiation therapy (PRT), a radiation-type therapy especially used in pediatric malignancies of the central nervous system (CNS), remains unclear and poorly documented. We report here a case of a four-year-old patient with unilateral auditory neuropathy spectrum disorder (ANSD) related to PRT. This case highlights the need for appropriate auditory monitoring in patients undergoing PRT for CNS or head and neck malignancies.


An NAD(P)H:quinone oxidoreductase 1 (NQO1) enzyme responsive nanocarrier based on mesoporous silica nanoparticles for tumor targeted drug delivery in vitro and in vivo.
The synthesis and characterization of an quinone oxidoreductase 1 (NQO1) enzyme responsive nanocarrier based on mesoporous silica nanoparticles (MSNPs) for on-command delivery applications has been described in this paper. Gatekeeping of MSNPs is achieved by the integration of mechanically interlocked rotaxane nanovalves on the surface of MSNPs. The rotaxane nanovalve system is composed of a linear stalk anchoring on the surface of MSNPs, an α-cyclodextrin ring that encircles it and locks the payload "cargo" molecules in the mesopores, and a benzoquinone stopper incorporated at the end of the stalk. The gate opening and controlled release of the cargo are triggered by cleavage of the benzoquinone stopper using an endogenous NQO1 enzyme. In addition to having efficient drug loading and controlled release mechanisms, this smart biocompatible carrier system showed obvious uptake and consequent release of the drug in tumor cells, could selectively induce the tumor cell death and enhance the capability of inhibition of tumor growth in vivo. The controlled drug delivery system demonstrated its use as a potential theranostic material.


Vessel Remodeling after Intima-to-Intima Contact Anastomosis.
Intima-to-intima microanastomotic vascular remodeling was explored, utilizing a polylactide-caprolactone absorbable vein coupler model (PAVCM), which was designed to simulate a non-absorbable counterpart system with the sole exception of being absorbable. Six New Zealand white rabbits were used. After transection of the jugular vein, 2 PAVCMs were placed, 1 at each transected end. The stumps were slipped through the PAVCMs, and the venous wall was everted 90° to achieve intima-to-intima contact. Reanastomosis of the transected jugular vein was performed bilaterally in 3 rabbits. In the other 3 rabbits, the jugular vein (20 mm) harvested from one side was interpositionally grafted to the jugular vein on the opposite side to ease the anastomotic tension. Patency testing, ultrasonography, and histologic assessments were conducted postoperatively at weeks 2, 4, 12, 16, 22, and 26. All anastomotic sites were patent, without stenosis, occlusion, or dilatation. In the histologic sections, immature endothelial regeneration was observed at week 2, which was completed by week 4. Regeneration of the tunica media was noted at week 12. Between week 22 and week 26, the tunica media fully regenerated and the coupler dissipated entirely. Despite the absence of a coupler to act as an anastomotic buttress, the structure and function of all the vessels appeared normal, even histologically. These outcomes are true milestones in the development of an absorbable vein coupler.


[Epidemiological study of sleep disorder in the elderly].
As a common health problem in modern society, sleep disorder have a high incidence in the elderly population, which seriously affect the quality of life and physical and mental health of the elderly, and can even aggravate to cause diseases. This review summarizes main research findings in the field of sleep disorder during the past 20 years, describes the sleeping characteristics of elderly, the epidemiological distribution of sleep disorder and possible influencing factors, and finally suggests appropriate measures for the prevention of sleep disorder.


Differences in elbow extensor muscle characteristics between resistance-trained men and women.
Muscular strength is suggested to be dependent upon muscle characteristics. Yet, sex-specific relationships of muscle characteristics to strength in the resistance-trained require investigation. Therefore, the purpose was to evaluate sex differences in muscle characteristics and isometric strength in the elbow extensors, as well as their respective associations. Resistance-trained men (n = 15, mean ± SD 22 ± 4 years, 87.5 ± 12.8 kg, 16.9 ± 2.9% body fat) and women (n = 15, mean ± SD 25 ± 5 years, 59.3 ± 7.3 kg, 22.4 ± 4.2% body fat) were tested. B-mode ultrasound images assessed muscle thickness, pennation angle, and echo intensity. Muscle volume and fascicle length were estimated from previously validated equations. Maximal voluntary isometric contraction measured elbow extensors isometric strength. Independent samples t-tests and Fisher's r-to-z test examined differences between sexes. Sex differences existed in all muscle characteristics (p < 0.05). Men's absolute strength (27.86 ± 3.55 kg) was significantly greater than women (16.15 ± 3.15 kg), but no differences were noted when controlling for muscle volume (men 0.069 ± 0.017, women 0.077 ± 0.022 kg/cm3). Sex differences did not exist in the relationships of muscle characteristics to strength with muscle size having the largest correlations. However, the relationship between echo intensity and body fat was different in men (r = - 0.311) and women (r = 0.541, p = 0.0143). Sex differences in isometric elbow extensor strength are eliminated when expressed relative to muscle volume. Relationships of echo intensity and body fat were different between men and women and may be indicative of greater adipose infiltration in women.


Automated Analysis and Quantification of Human Mobility Using a Depth Sensor.
Analysis and quantification of human motion to support clinicians in the decision-making process is the desired outcome for many clinical-based approaches. However, generating statistical models that are free from human interpretation and yet representative is a difficult task. In this paper, we propose a framework that automatically recognizes and evaluates human mobility impairments using the Microsoft Kinect One depth sensor. The framework is composed of two parts. First, it recognizes motions, such as sit-to-stand or walking 4 m, using abstract feature representation techniques and machine learning. Second, evaluation of the motion sequence in the temporal domain by comparing the test participant with a statistical mobility model, generated from tracking movements of healthy people. To complement the framework, we propose an automatic method to enable a fairer, unbiased approach to label motion capture data. Finally, we demonstrate the ability of the framework to recognize and provide clinically relevant feedback to highlight mobility concerns, hence providing a route toward stratified rehabilitation pathways and clinician-led interventions.


Association between tumour volume and recurrence of squamous cell carcinoma of the head and neck.
To evaluate the prognostic significance of computerized tomography derived tumour volume for squamous cell cancers of the head and neck, treated primarily by surgery. The retrospective review study comprised 72 patients with head and neck malignancies who were treated primarily by surgery at Aga Khan University Hospital, Karachi, with/without adjuvant. It was done from May 2007 to November 2008. Each patient was followed up for a minimum of one year to check for recurrence. For statistical analysis SPSS 17 was used. Frequencies, cross-tabulations with chi square tests to find associations, binary logistic regression analysis, Cox regression analysis and receiver operating characteristic curve tests were run on the data. Overall, the median tumour volume for patients with recurrent disease was 52cm3 compared to 22cm3 for those who did not have a recurrence. It was found that large tumour volume was associated with a significantly higher chance of recurrence (p = 0.009). Laryngeal cancers with volumes greater than 46cm3 and oral cancers with volumes greater than 23.1cm3 were associated with poor prognosis. The primary tumour volume can represent an important prognostic factor for treatment outcome. Patients with larger primary tumour volumes should be treated more aggressively.


Biologic response of immediately versus delayed loaded implants supporting ill-fitting prostheses: an animal study.
Computer-assisted preoperative implant planning and transfer toward the patient allow the production of a prosthesis prior to surgery. This implies that the prosthesis can be installed immediately following implant insertion. An inherent disadvantage of this is a cumulated error, which can lead to prosthesis misfit owing to topographic deviations of the planned versus the installed implants. The aim of this study was to determine whether prosthesis misfit is compromising the osseointegration of immediately versus delayed loaded implants and whether freshly installed implants adapt to the prosthesis. In each of five New Zealand White rabbits, two experimental conditions were compared. One tibia harbored the so-called test implant, which originally showed a vertical misfit of about 500 microm with the prosthesis to which it was tightened immediately after implant installation. The control implant was installed in the other tibia and was allowed to heal during 9 weeks before the prosthesis with the vertical misfit of about 500 microm was connected to it. The prostheses were left in place for 12 weeks, after which the animals were sacrificed. All implants healed uneventfully. There were no statistically significant differences between the biologic responses of test and control implants. With a three-dimensional laser scanner, significantly more displacement of the test implants toward the prostheses was observed compared with the control implants. This led to a significant decrease in prosthesis misfit for the test implants compared with the control implants. This study indicates that prosthesis misfit does not per se lead to biologic failure of immediately loaded or of already osseointegrated implants. In addition, immediately loaded implants seem to topographically adapt to the prosthesis, thereby minimizing the existing misfit.


An ex vivo gene therapy approach to treat muscular dystrophy using inducible pluripotent stem cells.
Duchenne muscular dystrophy is a progressive and incurable neuromuscular disease caused by genetic and biochemical defects of the dystrophin-glycoprotein complex. Here we show the regenerative potential of myogenic progenitors derived from corrected dystrophic induced pluripotent stem cells generated from fibroblasts of mice lacking both dystrophin and utrophin. We correct the phenotype of dystrophic induced pluripotent stem cells using a Sleeping Beauty transposon system carrying the micro-utrophin gene, differentiate these cells into skeletal muscle progenitors and transplant them back into dystrophic mice. Engrafted muscles displayed large numbers of micro-utrophin-positive myofibers, with biochemically restored dystrophin-glycoprotein complex and improved contractile strength. The transplanted cells seed the satellite cell compartment, responded properly to injury and exhibit neuromuscular synapses. We also detect muscle engraftment after systemic delivery of these corrected progenitors. These results represent an important advance towards the future treatment of muscular dystrophies using genetically corrected autologous induced pluripotent stem cells.


Attention's grasp: early and late hand proximity effects on visual evoked potentials.
Behavioral studies suggest that visual attention is biased toward stimuli in the region of space near the palm of the hand, but it is unclear whether this effect is universal or selective for goal/task-related stimuli. We examined event-related potentials (ERPs) using a visual detection task in which the hand was placed near or kept far from target and non-target stimuli that were matched for frequency and visual features to avoid confounding factors. Focusing on attention-sensitive ERP components, we found that P3 (350-450 ms) amplitudes were increased for Hand Near conditions for targets only, demonstrating a selective effect consistent with the P3's cross-modal and task-relevance influences. An N1 variant implicated in visuo-tactile integration (central Nd1; 120-190 ms) showed similar target-specific effects. P1 (80-110 ms) effects for target stimuli were also apparent, but may have applied to non-targets as well, which would be consistent with the P1's association with early, pre-categorical increases in sensory gain. Collectively, these findings suggest that by the time stimuli are categorized as relevant/irrelevant for action, the proprioceptive effects of the hand on visual attention are selective for goal/task-related stimuli. At the same time, hand proximity appears to bias attention early, starting with a facilitation of processing for perhaps any visual stimuli near the hand, and continuing with enhancements that are selective to those stimuli categorized as task-relevant.


Hereditary amyloidosis in early childhood associated with a novel insertion-deletion (indel) in the fibrinogen Aalpha chain gene.
Systemic amyloidosis occurring in early childhood is extremely rare, and is usually of AA type complicating chronic inflammatory diseases. We report the molecular basis of amyloidosis in a Korean girl who presented at 7 years of age with asymptomatic proteinuria and developed amyloid hepatomegaly and end-stage renal failure within 2 years. Renal biopsy showed enlarged glomeruli virtually replaced by amyloid, but without interstitial or vascular involvement. The histologic appearance was identical to that seen in patients with hereditary fibrinogen Aalpha chain Glu526Val amyloidosis, and the amyloid deposits stained specifically with antibodies to fibrinogen. Mutations were sought in the genes of the amyloidogenic proteins, transthyretin, apolipoprotein AI, lysozyme and fibrinogen Aalpha chain genes by polymerase chain reaction (PCR) and sequencing. A unique frameshift insertion-deletion (indel) mutation was identified in one allele of her fibrinogen Aalpha chain gene, which encodes a partly novel peptide and a premature stop signal, similar to the two previously reported amyloidogenic point deletions at codons 522 and 524 in this molecule. The mutation was absent in samples verified to be from her parents, indicating that it had occurred de novo. This is the first description of hereditary fibrinogen Aalpha chain amyloidosis in an Asian individual, and the distinctive renal histology offered a strong clue to the diagnosis. The disease is potentially curable by combined hepatorenal transplantation.


Espalier: Efficient Tree Reconciliation and Ancestral Recombination Graphs Reconstruction Using Maximum Agreement Forests.
In the presence of recombination individuals may inherit different regions of their genome from different ancestors, resulting in a mosaic of phylogenetic histories across their genome. Ancestral recombination graphs (ARGs) can capture how phylogenetic relationships vary across the genome due to recombination, but reconstructing ARGs from genomic sequence data is notoriously difficult. Here, we present a method for reconciling discordant phylogenetic trees and reconstructing ARGs using maximum agreement forests (MAFs). Given two discordant trees, a MAF identifies the smallest possible set of topologically concordant subtrees present in both trees. We show how discordant trees can be reconciled through their MAF in a way that retains discordances strongly supported by sequence data while eliminating conflicts likely attributable to phylogenetic noise. We further show how MAFs and our reconciliation approach can be combined to select a path of local trees across the genome that maximizes the likelihood of the genomic sequence data, minimizes discordance between neighboring local trees, and identifies the recombination events necessary to explain remaining discordances to obtain a fully connected ARG. While heuristic, our ARG reconstruction approach is often as accurate as more exact methods while being much more computationally efficient. Moreover, important demographic parameters such as recombination rates can be accurately estimated from reconstructed ARGs. Finally, we apply our approach to plant infecting RNA viruses in the genus Potyvirus to demonstrate how true recombination events can be disentangled from phylogenetic noise using our ARG reconstruction methods.


The Influence of Overweight and Obesity on Treatment Response in Juvenile Idiopathic Arthritis.
Background: There is evidence that obesity could be a risk factor for the severity and response to treatment in adult patients with rheumatoid arthritis (RA) due both to the mechanical effect of overweight and to the potential pro-inflammatory effects of cytokines produced by adipose tissue. Objectives: To evaluate the role of overweight and obesity in a cohort of young patients with juvenile idiopathic arthritis (JIA) in terms of incidence, disease activity, outcome, and response to treatments. Methods: This single-center retrospective cohort study evaluated 110 children affected by JIA under treatment with conventional disease-modifying antirheumatic drugs (DMARDs) and biologic agents. Body mass index (BMI) categories of 5-84th (normal weight), 85-94th (overweight), and ≥95th (obese) percentile were used. Patients with systemic JIA, uveitis, chronic comorbidities, or under other potentially confounding systemic treatments were excluded. Uni- and multivariate analyses were performed. Results: One hundred and ten JIA patients (polyarticular n = 50, oligoarticular n = 38, psoriatic n = 12, enthesitis-related arthritis n = 8, undifferentiated n = 2) were enrolled in the study, 75% girls and 25% boys. The mean age at treatment onset was 6.09 years. Baseline BMI was ≥5th and ≤84th percentile in 80 patients, 85-94th in 27, and ≥95th in 3. We did not observe a significant association between BMI and erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), or number of active joints at baseline, while involvement of the joints of lower limbs was significantly greater ( p = 0.025) in overweight/obese patients. However, a trend toward lower remission rates and higher number of relapses, both after DMARDs and biologics, in patients with higher BMI was observed. Conclusion: This study focuses on the relationship between overweight/obesity and JIA. A significant correlation between obesity and a greater involvement of the joints of the lower limbs at baseline was demonstrated. Furthermore, our data suggest that obesity could negatively influence the course of the disease as well as treatment response.


The Internet as a health information source: findings from the 2007 Health Information National Trends Survey and implications for health communication.
A wealth of health information is available online, but we do not fully understand the implications for health communication. This study examined whether health information seekers who turn to the Internet first differ from those who turn elsewhere. Data from the 2,338 respondents to the mail portion of the National Cancer Institute's Health Information National Trends Survey (HINTS) 2007 who reported looking for health information for themselves were analyzed. Logistic regression was used to examine whether health information seekers turning to the Internet first differed in terms of demographics, information preferences and seeking confidence, and communication with providers from those using other sources. In the final model, Internet users were younger, more educated, higher income, preferred numbers rather than words to describe chance, and think it is very important to get personal medical information electronically. There were no differences in terms of gender, health status, confidence seeking health information, or communication with providers. Health information seekers who turn to the Internet first are different, both in terms of demographics and information preferences. As the use of communication technologies increases, health communicators need to be attentive to the potential for communication inequalities.


Enhancement of the local inflammatory response to bacterial infection by muramyl dipeptide.
The effect of the synthetic immuno-adjuvant compound, muramyl dipeptide (MDP), upon the local inflammatory response to experimental bacterial infection was assessed by histological examination. Within 24 h of the insertion of a bacteria-laden suture into the medial thigh musculature of mice treated with either MDP or placebo, an enhanced degree of polymorphonuclear leucocyte infiltration in the muscle around the suture was observed in the MDP-treated animals. The inflammatory response around a sterile suture was less intense in both treatment groups and specific correlation between the degree of local inflammation and the extent of bacteraemia developing in either group of animals was not noted. The extent of bacteraemia developing in either group of animals was not noted. The previously observed protection conferred by MDP against the local impact of bacterial challenge appears to be mediated in part by enhancement of the acute local inflammatory response.


Linking Childhood Maltreatment with Girls' Internalizing Symptoms: Early Puberty as a Tipping Point.
Early pubertal timing in girls is one of the most frequently replicated antecedents of adolescent emotional distress. Yet understanding the impact of pubertal timing in psychosocial development has presented something of a conundrum for developmentalists, as earlier physical maturation may often be preceded by a range of early adversities and life stressors. The present paper disentangles these associations by investigating childhood maltreatment, adolescent internalizing symptoms, and perceived pubertal timing in girls who were residing in foster care at study entry (N = 100, M = 11.54 years old at Time 1). Girls were assessed at two time points two years apart. There were no significant direct effects of maltreatment on internalizing symptoms; rather, childhood sexual abuse predicted earlier perceived pubertal development at study onset which, in turn, was associated with higher levels of internalizing symptomatology. These higher levels of internalizing symptoms persisted over the two years of the study. This distinctive role for early pubertal timing - even within a sample subject to stressors and risks which far exceed the developmental norm - confirms the unique salience of pubertal timing in emotional adjustment, and suggests that the heightened sexual circumstances of puberty may be especially disturbing for girls whose lives have already been traumatically disrupted by inappropriate and unwanted sexual experiences.


Criterions for selection of patients for, and results of, a new technique for construction of the modified Blalock-Taussig shunt.
We describe alternative surgical techniques for construction of systemic-to-pulmonary arterial shunts, and propose criterions for their application in selected patients. We constructed a variety of modified systemic-to-pulmonary arterial shunts, using polytetrafluoroethylene grafts, in 92 selected patients with cyanotic congenital heart disease and anomalies of the aortic arch and systemic veins. Their age ranged from 7 days to 3.6 years, with a mean of 7.08 months. We performed 88 operations through a thoracotomy. Of this cohort, 60 patients underwent a second-stage operation, with 15 receiving a superior cavopulmonary connection, 16 a total cavopulmonary connection, and 29 proceeding to biventricular repair after a mean interval of 15.6 months. We have 21 patients awaiting their second or final stage of palliation. There were five early (5.4%) and six late deaths (6.8%), two of which were related to construction of the shunts. At a mean follow-up of 45.29 months, the increase in diameter of pulmonary trunk and its right and left branches was uniform and significant (p value less than 0.001). Pulmonary arterial distortion requiring correction at the time of second-stage operation was observed in 5 patients (6.1%). Adequate overall palliation was achieved in 98% of the cohort at 8 months, 91% at 12 months, and 58% at 18 months. Patients with a right- or left-sided aortic arch and right-sided descending thoracic aorta, those with anomalies of systemic venous drainage masking the origin of great arterial branches, and those with disproportionately small subclavian arteries, constitute the ideal candidates for our suggested modification of the construction of a modified Blalock-Taussig shunt. The palliation provided by these shunts was satisfactory, with predictable growth of pulmonary arteries, insignificant distortion in the great majority, and easy take-down.


DUSP11 - An RNA phosphatase that regulates host and viral non-coding RNAs in mammalian cells.
Dual-specificity phosphatase 11 (DUSP11) is a conserved protein tyrosine phosphatase (PTP) in metazoans. The cellular substrates and physiologic activities of DUSP11 remain largely unknown. In nematodes, DUSP11 is required for normal development and RNA interference against endogenous RNAs (endo-RNAi) via molecular mechanisms that are not well understood. However, mammals lack analogous endo-RNAi pathways and consequently, a role for DUSP11 in mammalian RNA silencing was unanticipated. Recent work from our laboratory demonstrated that DUSP11 activity alters the silencing potential of noncanonical viral miRNAs in mammalian cells. Our studies further uncovered direct cellular substrates of DUSP11 and suggest that DUSP11 is part of regulatory pathway that controls the abundance of select triphosphorylated noncoding RNAs. Here, we highlight recent findings and present new data that advance understanding of mammalian DUSP11 during gene silencing and discuss the emerging biological activities of DUSP11 in mammalian cells.


Documentation of e-cigarette use and associations with smoking from 2012 to 2015 in an integrated healthcare delivery system.
It is unclear whether use of electronic nicotine delivery systems (ENDS) precedes cigarette smoking initiation, relapse, and/or quitting. Healthcare systems with electronic health records (EHRs) provide unique data to examine ENDS use and changes in smoking. We examined the incidence of ENDS use (2012-2015) based on clinician documentation and tested whether EHR documented ENDS use is associated with twelve-month changes in patient smoking status using a matched retrospective cohort design. The sample was Kaiser Permanente Northern California (KPNC) patients aged ≥12 with documented ENDS use (N = 7926); 57% were current smokers, 35% former smokers, and 8% never-smokers. ENDS documentation incidence peaked in 2014 for current and former smokers and in 2015 for never-smokers. We matched patients with documented ENDS use to KPNC patients without documented ENDS use (N = 7926) on age, sex, race/ethnicity, and smoking status. Documented ENDS use predicted the likelihood of smoking in the following year. Among current smokers, ENDS use was associated with greater odds of quitting smoking (OR = 1.17, 95%CI = 1.05-1.31). Among former smokers, ENDS use was associated with greater odds of smoking relapse (OR = 1.53, 95%CI = 1.22-1.92). Among never-smokers, ENDS use was associated with greater odds of initiating smoking (OR = 7.41, 95%CI = 3.14-17.5). The overall number of current smokers at 12 months was slightly higher among patients with (N = 3931) versus without (N = 3850) documented ENDS use. Results support both potential harm reduction of ENDS use (quitting combustibles among current smokers) and potential for harm (relapse to combustibles among former smokers, initiation for never-smokers).


Transient neurological symptoms in the older population: report of a prospective cohort study--the Medical Research Council Cognitive Function and Ageing Study (CFAS).
Transient ischaemic attack (TIA) is a recognised risk factor for stroke in the older population requiring timely assessment and treatment by a specialist. The need for such TIA services is driven by the epidemiology of transient neurological symptoms, which may not be caused by TIA. We report prevalence and incidence of transient neurological symptoms in a large UK cohort study of older people. Longitudinal cohort study The Medical Research Council Cognitive Function and Aging Study (CFAS) is a population representative study based on six centres across England and Wales. Random samples of people in their 65th year were obtained from Family Health Service Authority lists. The participation rate was 80% (n=13 004). Interview at baseline included questions about stroke and three transient neurological symptoms, repeated in a subsample after 2 years. Patients were flagged for mortality. Prevalence and 2-year incidence of transient neurological symptoms. In 11 903 participants without a history of stroke, 271 (2.3%) reported transient problems with speech, 872 (7.6%) with sight and 596 (5.1%) weakness in a limb with 1456 (12.7%) reporting at least one symptom. Of those reinterviewed (n=6748), 675 (9.8%) reported at least one symptom over 2 years. Lifetime prevalence and incidence of transient neurological symptoms in people aged 65 years and over is high and is substantially greater than the incidence of TIA in hospital-based and population-based studies. These high rates of transient neurological symptoms in the community in the older population should be considered when planning TIA services.


Donor mucosal immunocytes perpetuate refractory GVHD after intestinal transplantation without engrafting in recipient bone marrow: Case report and review of the literature.
GVHD as a complication of SOT presents both a diagnostic and therapeutic challenge. Typically affecting the skin, gastrointestinal tract, and liver, GVHD occurs when donor lymphocytes engrafted in recipient tissues are activated by host antigen-presenting cells resulting in cytokine release and donor cell-mediated cytotoxicity to host tissue. Here, we describe a 5-year-old girl who developed fatal, refractory GVHD after isolated intestinal transplantation when recipient immune cells failed to repopulate the allograft in the setting of CMV viremia. Persistence of the donor immune cells in the allograft mucosa, rather than engraftment in the recipient bone marrow, likely perpetuated this refractory GVHD. Early diagnosis and intervention are critical to reduce morbidity and mortality. Thus, periodic monitoring of peripheral blood and allograft mucosal chimerism with sensitive detection methods may allow early detection and potentially curative enterectomy in similar cases of refractory GVHD.


Quantum Machine Learning over Infinite Dimensions.
Machine learning is a fascinating and exciting field within computer science. Recently, this excitement has been transferred to the quantum information realm. Currently, all proposals for the quantum version of machine learning utilize the finite-dimensional substrate of discrete variables. Here we generalize quantum machine learning to the more complex, but still remarkably practical, infinite-dimensional systems. We present the critical subroutines of quantum machine learning algorithms for an all-photonic continuous-variable quantum computer that can lead to exponential speedups in situations where classical algorithms scale polynomially. Finally, we also map out an experimental implementation which can be used as a blueprint for future photonic demonstrations.


Resolution enhancement via guided filtering for spatial-frequency multiplexing single-shot high-speed imaging.
The frequency recognition algorithm for multiple exposures (FRAME) is a progressive single-shot high-speed videography technique that employs the spatial-frequency multiplexing concept to provide high temporal and spatial resolution. However, the inherent crosstalk from the zero-frequency component to the carrier-frequency component leads to resolution degradation and artifacts. To improve recovered frames' quality, we propose a FRAME reconstruction method using guided filters for a removal of the zero-frequency component, which can minimize the artifacts while enhance spatial resolution. A total variation (TV) denoising operation is involved to remove artifacts further to achieve optimized performances. Simulations and experiments were conducted to demonstrate the robust and efficient post-processing capability of the proposed method. With a two-frame experimental system, the results of a USAF 1951 resolution target reveal a 1.8-fold improvement in spatial resolution from 16 lp/mm to 28.5 lp/mm. For complex dynamic scenarios, the wide field of high-speed fuel spray was shot and the proposed method can resolve two droplets with a 30 μm distance which outperforms the traditional method.


Measurement Invariance of a Classroom Engagement Measure among Academically At-Risk Students.
The current study investigated the measurement invariance of a classroom engagement measure across time points, genders, and ethnicities using a sample of 523 academically at-risk students across grades 7 through 9; this measure was based on Skinner et al.'s (1990) original engagement measure. The engagement measure was comprised of 16 items, yielding three factors: Behavioral Engagement, Behavioral Disaffection, and Emotional Engagement. Configural, metric, and scalar invariance held across the three time points, as did invariance of factor covariances and means, indicating that scores have a similar meaning across all 3 years. The engagement measure also featured adequate configural, metric, and scalar invariance, and invariance of factor covariances and means across genders and ethnicities. These findings suggest the measure is appropriate for investigating substantive hypotheses regarding classroom engagement across different grade levels, genders, and ethnicities. In summary, the current results indicate this measure of classroom engagement is suitable for testing hypotheses regarding group differences in engagement across grade levels, genders, and ethnicities. Researchers may also use this measure to examine relationships between the engagement factors and other important academic outcomes. Limitations of the current study, such as certain caveats regarding convergent validity and internal consistency, are also discussed.


[Analysis on risk factors for norovirus outbreaks in Guangdong province, 2008-2015].
Objective: To analyze transmission factors of norovirus outbreaks in Guangdong province during 2008-2015 and provide evidence for the prevention and control of norovirus infection. Methods: Epidemiological analysis was performed on the data of norovirus outbreaks reported in Guangdong from January 1, 2008 to December 31, 2015, which were obtained from the Public Health Emergency Management Information System of Guangdong province. The samples collected from the norovirus outbreaks were detected for norovirus by RT-PCR and the gene sequencing of the positive PCR products were performed. Results: A total of 96 norovirus outbreaks were reported in Guangdong during 2008-2015. Sixteen outbreaks were reported during 2008-2012 and 80 outbreaks were reported during 2013-2015 (83.3%). Eighty-two outbreaks (85.4%) occurred in schools. The infection routes included foodborne transmission in 39 outbreaks (40.6%), person to person transmission in 23 outbreaks (24.0%) and waterborne transmission in 8 outbreaks (7.3%). The gene sequencing results showed that variant GⅡ.4/Sydney2012 was the predominant pathogen for 6 of the 20 outbreaks (30.0%) during 2012-2013. Variant GⅡ.17 was the predominant pathogens for 33 of the 53 outbreaks (62.3%) during 2014-2015. Conclusion: The norovirus outbreaks in Guangdong during 2008-2015 were caused by foodborne and person to person transmissions of two emerging variant: GⅡ.4/Sydney2012 and GⅡ.17.


Skin optical properties in the obese and their relation to body mass index: a review.
Obesity is a worldwide epidemic contributing directly to several cardiovascular risk factors including hypertension and type 2 diabetes. Wearable devices are becoming better at quantifying biomarkers relevant for the management of health and fitness. Unfortunately, both anecdotal evidence and recent studies indicate that some wearables have higher levels of error when utilized by populations with darker skin tones and high body mass index (BMI). There is an urgent need for a better evaluation of the limits of wearable health technologies when used by obese individuals. (1) To review the current know-how on changes due to obesity in the skin epidermis, dermis, and subcutis that could affect the skin optical properties; (2) for the green wavelength range, to evaluate the difference in absorption and scattering coefficients from the abdominal skin between individuals with and without elevated BMI. The changes include alterations in layer thickness and cell size, as well as significant differences in chromophores and scatterer content, e.g., water, hemoglobin, collagen, and lipids. We have summarized literature pertaining to changes in skin and its components in obesity and report the results of our search using articles published between years 1971 and 2020. A linear model was used to demonstrate the absorption and reduced scattering coefficient of the abdominal skin of individuals with and without elevated BMI in the green wavelength range (530 to 550 nm) that is typically found in most wearables. The general trends indicate a decrease in absorption for both dermis and subcutis and an increase in reduced scattering for both epidermis and dermis. At 544-nm wavelength, a typical wavelength used for photoplethysmography (PPG), the absorption coefficient's relative percentage difference between high and low BMI skin, was 49% in the subcutis, 19% in the dermis, and negligible in the epidermis, whereas the reduced scattering coefficient relative difference was 21%, 29%, and 165% respectively. These findings suggest that there could be significant errors in the output of optical devices used for monitoring health and fitness if changes due to obesity are not accounted for in their design.


Modulation of NMDA receptors in the cerebellum. 1. Properties of the NMDA receptor that modulate its function.
NMDA receptors modulate important cerebral processes such as synaptic plasticity, long-term potentiation, learning and memory, etc. NMDA receptors in cerebellum have specific characteristics that make their function and modulation different from those of NMDA receptors in other brain areas. In this and the accompanying review we summarize the information available on the modulation of NMDA receptors in cerebellum. We review the properties of the NMDA receptor that modulate its function: subunit composition, post-translational modifications and synaptic localization. NMDA receptors are heteromeric ligand-gated ion channels assembled from two families of subunits, NR1 and NR2. There are at least eight splicing variant isoforms of the NR1 subunit and four types of NR2 subunits: NR2A, NR2B, NR2C and NR2D. NMDA receptors with different subunit composition or different splice variants of NR1 subunit have different properties. The expression of the different subunits and splicing variants varies during development. Two special characteristics of NMDA receptors in cerebellum that do not occur in other brain areas are the enrichment in the NR2C subunit and in the splice variant NR1b. As a consequence of these and other factors the pharmacology of NMDA receptors is also different in cerebellum than in other brain areas. The function and localization of NMDA receptors is also modulated by postranslational modifications including phosphorylation, glycosylation and nytrosylation. NMDA receptors are phosphorylated in serines of both NR1 and NR2 subunits and in tyrosines of NR2 subunits. Another factor modulating NMDA receptors function is the synaptic localization. The trafficking and clustering of NMDA receptors is modulated by phosphorylation and by interaction with other proteins. The signaling pathways and physiological modulators regulating NMDA receptor function as well as the role of these receptors in motor learning and coordination are reviewed in an accompanying article.


The role of ultraviolet-B in corneal healing following excimer laser in situ keratomileusis.
Corneal photoablation with the 193 nm argon fluoride excimer laser during photorefractive keratectomy (PRK) in high diopter range is frequently associated with subepithelial haze and consequent refractive regression due to avascular corneal wound healing. The wound healing response can be augmented by Ultraviolet-B (UV-B) exposure originating from sun or solarium. Clinically Laser in situ Keratomileusis (LASIK) even in high diopter range is associated with less subepithelial haze and regression than PRK. In an animal model, the morphologic changes of the rabbit cornea were evaluated following LASIK and secondary UV-B exposure. Light microscpic changes were found to be insignificant. Transmission electron microscopy (TEM) normal epithelium, epithelial adhesion structures and normal anterior stroma showed in the LASIK treated UV-B irradiated rabbit eyes. Around the peripheral LASIK cut, migrating keratocytes with pseudopodia were observed. Under the flap (160 microm depth) the overall stromal collagen structure was normal, some activated keratocytes and mild extracellular matrix formation within and around keratocytes were noted. Within activated keratocytes TEM showed prominent rough endoplasmic reticulum, Golgi apparatus, mitochondria and extracellular vacuoles, which showed resolution with time. These changes were much milder than in PRK treated-UV-B irradiated eyes. Secondary UV-B caused no long-term disturbance in corneal transparency in LASIK and UV-B treated rabbit eyes.


Conversion of bio-derived crude glycerol into renewable high-octane gasoline-stock.
Here, we report an efficient catalytic process that operates on a bi-metallic ZSM-5 supported catalyst (0.1Ga-1Zn/ZSM-5) for 100% carbon conversion of glycerol to produce 71.4C% liquid fuel-stock possessing a high concentration of alkyl-aromatics and octane potential (>97 RON) for fuel applications, achieved and reported for the first time to the best of our knowledge. In addition, the H2-rich (36 mol%) gas stream produced as a byproduct is attractive for green fuel applications. The process adds up to an ∼80% increase in the value addition of bio-glycerol, which improves the overall fuel yield of the biodiesel production process towards improved atom efficiency and process economy.


[Distribution of chloroquine and desethylchloroquine in blood, plasma and erythrocytes of healthy subjects and malaria patients. Assay using HPLC].
Chloroquine (Cq) and desethyl-chloroquine ( CqM ) levels were measured by HPLC in the blood, plasma, and erythrocytes of 9 healthy subjects under standard prophylactic treatment (100 mg/day for 10 days) and 8 malarial patients given a therapeutic regimen (10 or 25 mg/kg). Chloroquine levels in various fractions of the healthy subjects were as follows: whole blood: 1 265 +/- 598 nmol/l; plasma: 145 +/- 63 nmol/l of whole blood; erythrocytes: 827 +/- 460 nmol/l of whole blood. The CqM /Cq ratio in malarial patients varied from 0.4 to 0.8. These results show that Cq levels and Cq metabolization varied significantly from one individual to the next. Above all, they demonstrate the presence of Cq in other types of blood cells. This underlines the practical importance of the conditions of chloroquine assay in blood.


Regulation of OX40 gene expression in graft-versus-host disease.
OX40 (CD134), a member of the tumor necrosis factor receptor superfamily, is expressed on activated T cells, including CD4(+)CD25(+) T regulatory (Treg) cells. To investigate the kinetics of OX40-OX40L in graft-versus-host disease (GVHD), OX40 mRNA transcript levels were temporally examined in peripheral blood mononuclear cells (PBMCs) from patients undergoing either allogeneic (allo) bone marrow transplantation (alloBMT) or autologous (auto) BMT with the induction of autoGVHD by cyclosporine (CsA) treatment posttransplant. Real-time quantitative PCR analysis revealed that OX40 mRNA expression decreased significantly in PBMCs from patients with either alloGVHD or autoGVHD compared with healthy individuals. No differences were detected between patients developing alloGVHD and those who did not develop this posttransplant complication. On the other hand, a decrease in OX40 mRNA levels correlated directly with the development of autoGVHD. Moreover, the upregulation of OX40 gene expression coincided with the resolution of autoGVHD. Interestingly, expression of OX40 by CD4(+) T lymphocytes after stimulation with autoantigen (Ag) was significantly (>700-fold) increased with a concomitant increase in expression of the Foxp3 regulatory gene. Expression of OX40 was increased (maximum 11-fold) after allo-Ag via mixed-lymphocyte reaction response. CsA suppressed the upregulation of OX40 expression after allo-Ag in a dose-dependent manner. Taken together, these results suggest that the decrease in OX40 expression posttransplant includes the defective reconstitution of Treg cells, and the active inhibition of gene transcription by CsA.


Advancements in the study of inward rectifying potassium channels on vascular cells.
Inward rectifier potassium channels (Kir channels) exist in a variety of cells and are involved in maintaining resting membrane potential and signal transduction in most cells, as well as connecting metabolism and membrane excitability of body cells. It is closely related to normal physiological functions of body and the occurrence and development of some diseases. Although the functional expression of Kir channels and their role in disease have been studied, they have not been fully elucidated. In this paper, the functional expression of Kir channels in vascular endothelial cells and smooth muscle cells and their changes in disease states were reviewed, especially the recent research progress of Kir channels in stem cells was introduced, in order to have a deeper understanding of Kir channels in vascular tissues and provide new ideas and directions for the treatment of related ion channel diseases.


On the coverage of the pMSSM by simplified model results.
We investigate to which extent the SUSY search results published by ATLAS and CMS in the context of simplified models actually cover the more realistic scenarios of a full model. Concretely, we work within the phenomenological MSSM (pMSSM) with 19 free parameters and compare the constraints obtained from SModelS v1.1.1 with those from the ATLAS pMSSM study in arXiv:1508.06608. We find that about 40-45% of the points excluded by ATLAS escape the currently available simplified model constraints. For these points we identify the most relevant topologies which are not tested by the current simplified model results. In particular, we find that topologies with asymmetric branches, including 3-jet signatures from gluino-squark associated production, could be important for improving the current constraining power of simplified models results. Furthermore, for a better coverage of light stops and sbottoms, constraints for decays via heavier neutralinos and charginos, which subsequently decay visibly to the lightest neutralino are also needed.


Regulators of angiogenesis in renal ischemia/reperfusion injury in normotensive and hypertensive rats: effect of tacrolimus.
The aim of this study was to evaluate the role of proangiogenic growth factors in an experimental model of ischemia/reperfusion injury (I/R) in both normotensive and hypertensive rats. Renal ischemic injury was induced in transgenic rats rendered hypertensive due to renin overproduction [TGR (mREN-2)-27] and in normotensive Hannover Sprague-Dawley rats (HanSD). Animals were treated for 12 weeks with either tacrolimus (TAC, 0.1 mg/kg per day, intramuscularly [IM]) or placebo. After 12 weeks, kidneys were harvested for morphologic, immunohistochemical, and RT-PCR analysis. Both normotensive and hypertensive untreated rats developed significantly greater proteinuria and glomerulosclerosis compared with TAC-treated rats. Immunohistologically, TGR showed higher basic fibroblast growth factor (bFGF) protein expression compared with normotensive HanSD. TAC-treated rats had higher bFGF protein expression than untreated rats. Vascular endothelial growth factor (VEGF) protein expression in glomeruli was more increased in TGR after I/R than in sham-operated animals. TAC-treated TGR hosts developed higher VEGF mRNA expression compared with both untreated and sham groups; however, there were no differences between treated and untreated normotensive HanSD animals. bFGF is involved in the fibrogenesis induced by hypertension and I/R injury. The nature of the increase in proangiogeneic growth factor expression among tacrolimus-treated animals remains to be elucidated.


[Digital mammography: performance evaluation parameters and available systems in France].
The purpose of this article is to review the features of digital mammography systems available in France. This article includes three parts: definition of the different components of a digital mammography system, description of different performance evaluation parameters, and review of systems currently available in France. Data from the literature as well as questionnaires from different manufacturers were used. The following vendors agreed to participate: Agfa, Fujifilm, GE Healthcare, Hologic-Lorad, IMS, Kodak, Konica Minolta, Philips, Planmed, Sectra, Siemens. For each vendor, the type of detector, type of available mammographic units and workstation, optional features (CAD), archival and printing possibilities (when vendors specifically offer dedicated solutions).


Listeria monocytogenes as a vector for tumor-associated antigens for cancer immunotherapy.
As a facultative intracellular bacterium, Listeria monocytogenes has adapted to live within the cytosol of the host cell. It is actively taken up by antigen-presenting cells through phagocytosis, and as Listeria survive within these cells, it is an ideal vector for the delivery of antigens to be processed and presented through both the class I and II antigen-processing pathways. Once phagocytosed, Listeria produces virulence factors within the phagolysosome of the host cell, which allows it to break out of this organelle and live in the host cytosol. It is possible that these virulence factors can enhance the immunogenicity of tumor-associated antigens, which are poorly immunogenic. Recent progress in the development of this bacterium as a vaccine vector for tumor-associated antigens is discussed in the context of bacterial vectors in general. In several mouse models, Listeria-based vaccines have been demonstrated to be an effective method of influencing tumor growth and eliciting potent antitumor immune responses. Safety issues and the transition of Listeria into human clinical trials will also be discussed in this review.


Developing machine learning models to predict primary graft dysfunction after lung transplantation.
Primary graft dysfunction (PGD) is the leading cause of morbidity and mortality in the first 30 days after lung transplantation. Risk factors for the development of PGD include donor and recipient characteristics, but how multiple variables interact to impact the development of PGD and how clinicians should consider these in making decisions about donor acceptance remain unclear. This was a single-center retrospective cohort study to develop and evaluate machine learning pipelines to predict the development of PGD grade 3 within the first 72 hours of transplantation using donor and recipient variables that are known at the time of donor offer acceptance. Among 576 bilateral lung recipients, 173 (30%) developed PGD grade 3. The cohort underwent a 75% to 25% train-test split, and lasso regression was used to identify 11 variables for model development. A K-nearest neighbor's model showing the best calibration and performance with relatively small confidence intervals was selected as the final predictive model with an area under the receiver operating characteristics curve of 0.65. Machine learning models can predict the risk for development of PGD grade 3 based on data available at the time of donor offer acceptance. This may improve donor-recipient matching and donor utilization in the future.


Are socially disadvantaged neighbourhoods deprived of health-related community resources?
Recent work in a number of countries has identified growing geographical inequalities in health between deprived and non-deprived neighbourhoods. The health gaps observed cannot be entirely explained by differences in the characteristics of individuals living in those neighbourhoods, which has led to a concerted international public health research effort to determine what contextual features of neighbourhoods matter. This article reports on access to potentially health-promoting community resources across all neighbourhoods in New Zealand. Prevailing international opinion is that access to community resources is worse in deprived neighbourhoods. Geographical Information Systems were used to calculate geographical access to 16 types of community resources (including recreational amenities, and shopping, educational and health facilities) in 38,350 small census areas across the country. The distribution of these access measures by neighbourhood socioeconomic deprivation was determined. For 15 out of 16 measures of community resources, access was clearly better in more deprived neighbourhoods. For example, the travel time to large supermarkets was approximately 80% greater in the least deprived quintile of neighbourhoods compared with the most deprived quintile. These results challenge the widely held, but largely untested, view that areas of high social disadvantage have poorer access to community resources. Poor locational access to community resources among deprived neighbourhoods in New Zealand does not appear to be an explanation of poorer health in these neighbourhoods. If anything, a pro-equity distribution of community resources may be preventing even wider disparities in neighbourhood inequalities in health.


Cerebral and coronary gas embolism from the inhalation of pressurized helium.
Inhalation of helium, which produces a change in the voice, is frequently used among young rock singers to improve their performance. A case report. Adult medical intensive care unit in a university hospital. A 23-yr-old singer, who accidentally inhaled helium from a high pressurized tank without pressure reduction, presented with transient loss of consciousness and chest pain. Electrocardiogram, chest radiograph, biochemical and toxicological analyses, echocardiography, coronary angiography were performed. At admission, the patient slowly regained consciousness. An electrocardiogram showed significant ST elevations in leads I, aVL, and V4-V6. The chest radiograph was consistent with pulmonary congestion and pneumomediastinum. The echocardiogram showed normal sized heart chambers with hypokinesis of the left ventricular lateral wall. Ethanol and urine cannabinoids were present in low concentrations, but no presence of opiates, methadone, cocaine, or amphetamines was documented. Troponin T was positive. Elevation of ST segments gradually disappeared within 30 mins, the drowsiness within 10 hrs, and the thoracic pain within 24 hrs. Coronary angiography showed normal coronary arteries. The patient was discharged on day 3 without any symptoms and with normal electrocardiogram and chest radiograph. Accidental inhalation of helium under high pressure can cause symptomatic cerebral and coronary artery gas embolism.


Motion of the patella during walking: a video digital-fluoroscopic study in healthy volunteers.
The alignment of the quadriceps muscle and patella suggests that the patella should deviate laterally out of the patellar groove as the quadriceps muscle contracts during walking. The surgical treatment of patellar subluxation has been based on this presumption. The purpose of this study was to determine the movements of the patella in relation to the other bones of the knee joint during normal walking. This is the first study we know of that uses radiographs to show these movements. Eight healthy adult volunteers with no previous complaints referable to the knee walked on a slowly moving treadmill while their patellae were imaged fluoroscopically in the anteroposterior plane with a Toshiba C-arm. Images were retrieved, transferred to radiographic film, and randomized to prevent the observers from knowing the order of images. The position of the patella was measured and plotted in relation to fixed points of the knee. In each of the subjects at every gait cycle, the patella was observed to move vertically first, followed by a sudden shift to the medial side before returning to its original position. Contrary to conventional understanding, our results show that the patella deviates medially rather than laterally during walking. This occurs because of differential contraction of the components of the quadriceps muscle during walking. The management of painful and subluxated patellae must be reevaluated in light of this finding.


Fitting Nonlinear Ordinary Differential Equation Models with Random Effects and Unknown Initial Conditions Using the Stochastic Approximation Expectation-Maximization (SAEM) Algorithm.
The past decade has evidenced the increased prevalence of irregularly spaced longitudinal data in social sciences. Clearly lacking, however, are modeling tools that allow researchers to fit dynamic models to irregularly spaced data, particularly data that show nonlinearity and heterogeneity in dynamical structures. We consider the issue of fitting multivariate nonlinear differential equation models with random effects and unknown initial conditions to irregularly spaced data. A stochastic approximation expectation-maximization algorithm is proposed and its performance is evaluated using a benchmark nonlinear dynamical systems model, namely, the Van der Pol oscillator equations. The empirical utility of the proposed technique is illustrated using a set of 24-h ambulatory cardiovascular data from 168 men and women. Pertinent methodological challenges and unresolved issues are discussed.


Opioid analgesics-related pharmacokinetic drug interactions: from the perspectives of evidence based on randomized controlled trials and clinical risk management.
Multimorbidity results in complex polypharmacy which may bear a risk of drug interactions. A better understanding of opioid analgesics combination therapy used for pain management could help warrant medication safety, efficacy, and economic relevance. Until now there has been no review summarizing the opioid analgesics-related pharmacokinetic drug interactions from the perspective of evidence based on randomized controlled trials (RCTs). A literature search was performed using PubMed, MEDLINE, and the Cochrane Library, using a PRISMA flowchart. Fifty-two RCTs were included for data interpretation. Forty-two RCTs (80.8%) were conducted in healthy volunteers, whereas 10 RCTs (19.2%) enrolled true patients. None of the opioid-drug/herb pairs was listed as contraindications of opioids involved in this review. Circumstances in which opioid is comedicated as a precipitant drug include morphine-P2Y12 inhibitors, morphine-gabapentin, and methadone-zidovudine. Circumstances in which opioid is comedicated as an object drug include rifampin-opioids (morphine, tramadol, oxycodone, methadone), quinidine-opioids (morphine, fentanyl, oxycodone, codeine, dihydrocodeine, methadone), antimycotics-opioids (buprenorphine, fentanyl, morphine, oxycodone, methadone, tilidine, tramadol), protease inhibitors-opioids (ritonavir, ritonavir/lopinavir-oxycodone, ritonavir-fentanyl, ritonavir-tilidine), grapefruit juice-opioids (oxycodone, fentanyl, methadone), antidepressants-opioids (paroxetine-tramadol, paroxetine-hydrocodone, paroxetine-oxycodone, escitalopram-tramadol), metoclopramide-morphine, amantadine-morphine, sumatriptan-butorphanol nasal sprays, ticlopidine-tramadol, St John's wort-oxycodone, macrolides/ketolides-oxycodone, and levomepromazine-codeine. RCTs investigating the same combination, almost unanimously, drew consistent conclusions, except two RCTs on amantadine-intravenous morphine combination where a different amantadine dose was used and two RCTs on morphine-ticagrelor combination where healthy volunteers and true patients were enrolled, respectively. RCTs investigating in true patients may reflect a realistic clinical scenario and overcome the limitation of RCTs performed in healthy volunteers under standardized conditions. Further research opportunities are also presented in this review. Effective and safe combination therapy of opioids can be achieved by promoting the awareness of potential changes in therapeutic efficacy and toxicities, prescribing alternatives or changing administration strategy, tailoring dose, reviewing the appropriateness of orders, and paying attention to medication monitoring.