Geographic Variations in Dietary Patterns and Their Associations with Overweight/Obesity and Hypertension in China: Findings from China Nutrition and Health Surveillance (2015-2017).
Regional dietetic cultures were indicated in China, but how dietary patterns geographically varied across China is unknown. Few studies systematically investigated the association of dietary patterns with overweight/obesity and hypertension and the potential mechanism with a national sample. This study included 34,040 adults aged 45 years and older from China Nutrition and Health Surveillance (2015−2017), who had complete outcome data, reliable intakes of calorie and cooking oils, unchanged diet habits, and without diagnosed cancer or cardiovascular disease. Outcomes were overweight/obesity and hypertension. By using the Gaussian finite mixture models, four dietary patterns were identified—common rice-based dietary pattern (CRB), prudent diversified dietary pattern (PD), northern wheat-based dietary pattern (NWB), and southern rice-based dietary pattern (SRB). Geographic variations in dietary patterns were depicted by age−sex standardized proportions of each pattern across 31 provinces in China. We assessed the association of these dietary patterns with outcomes and calculated the proportion mediated (PM) by overweight/obesity in the association of the dietary patterns with hypertension. Evident geographic disparities in dietary patterns across 31 provinces were observed. With CRB as reference group and covariates adjusted, the NWB had higher odds of being overweight/obese (odds ratio (OR) = 1.44, 95% confidence interval (CI): 1.36−1.52, p < 0.001) and hypertension (OR = 1.07, 95%CI: 1.01−1.14, p < 0.001, PM = 43.2%), while the SRB and the PD had lower odds of being overweight/obese (ORs = 0.84 and 0.92, 95%CIs: 0.79−0.89 and 0.85−0.99, p < 0.001 for both) and hypertension (ORs = 0.93 and 0.87, 95%CIs: 0.87−0.98 and 0.80−0.94, p = 0.038 for SRB and p < 0.001 for PD, PMs = 27.8% and 9.9%). The highest risk of overweight/obesity in the NWB presented in relatively higher carbohydrate intake (about 60% of energy) and relatively low fat intake (about 20% of energy). The different trends in the association of protein intake with overweight/obesity among dietary patterns were related to differences in animal food sources. In conclusion, the geographic distribution disparities of dietary patterns illustrate the existence of external environment factors and underscore the need for geographic-targeted dietary actions. Optimization of the overall dietary pattern is the key to the management of overweight/obesity and hypertension in China, with the emphasis on reducing low-quality carbohydrate intake, particularly for people with the typical northern diet, and selection of animal foods, particularly for people with the typical southern diet.


Evaluation of calcium dihydroxide- and silver-coated implants in the rat tibia.
Silver ions (Ag+) have strong antibacterial effects, and silver-coated materials are in widespread clinical use. However, the application of silver-coated medical devices is not without concerns: its use with direct bone contact is not established, and systemic toxic side effects of released Ag+ have been described. Therefore, alternative bactericidal coatings with a more localized way of acting - e.g., calcium dihydroxide, Ca(OH)2 (CH) - would be advantageous. A new rat model of the animal's tibial metaphysis was developed. In the left proximal tibiae of 36 male Wistar rats, titanium screws were implanted. The screws were coated with hydroxyapatite (HA; 12 animals: group I), low-dosed HA silver (HA-Ag; 12 animals: group II) and CH (12 animals: group III). After 6 weeks, all rats were sacrificed. The implants were evaluated for morphological changes on their surfaces, by light microscopy, scanning electron microscopy and energy-dispersive X-ray spectroscopy; for osteointegration, by measurement of resistance to removal; and for bacterial colonization, by quantitative culture analysis. Additionally, the tibial bone was investigated histologically for signs of osteomyelitis and sonicated to detect bacterial loads. (i) No microbiological or histological signs of infection could be determined on any of the screws or the surrounding bone. (ii) The bone-implant interface analysis revealed extensive bone formation and direct bone-implant contact on all HA, HA-Ag and HA-CH coated screws. (iii) HA and HA-Ag were partially, and CH was fully, degraded on the screw coating, allowing host bone to osteointegrate.


Chronic vitamin C deficiency promotes redox imbalance in the brain but does not alter sodium-dependent vitamin C transporter 2 expression.
Vitamin C (VitC) has several roles in the brain acting both as a specific and non-specific antioxidant. The brain upholds a very high VitC concentration and is able to preferentially retain VitC even during deficiency. The accumulation of brain VitC levels much higher than in blood is primarily achieved by the sodium dependent VitC transporter (SVCT2). This study investigated the effects of chronic pre-and postnatal VitC deficiency as well as the effects of postnatal VitC repletion, on brain SVCT2 expression and markers of oxidative stress in young guinea pigs. Biochemical analyses demonstrated significantly decreased total VitC and an increased percentage of dehydroascorbic acid, as well as increased lipid oxidation (malondialdehyde), in the brains of VitC deficient animals (p < 0.0001) compared to controls. VitC repleted animals were not significantly different from controls. No significant changes were detected in either gene or protein expression of SVCT2 between groups or brain regions. In conclusion, chronic pre-and postnatal VitC deficiency increased brain redox imbalance but did not increase SVCT2 expression. Our findings show potential implications for VitC deficiency induced negative effects of redox imbalance in the brain and provide novel insight to the regulation of VitC in the brain during deficiency.


[The technique and technicism in surgery].
Characterization is given to the present-day stage of the development of surgery using complex medical technique and considerable growth of the number of laboratory-instrumental investigations is characterized. The estimation is given of the negative tendency to dehumanize medicine because of the technicism of doctors' thinking.


Autism Spectrum Disorder and Transition-Aged Youth.
This article discusses common issues surrounding transition to adulthood in youth with autism spectrum disorder (ASD). We review recent evidence on co-occurring medical and mental health conditions and topics of education and employment, sexuality and relationships, independent living, and financial support. Transitioning individuals with ASD have increased risk for several medical and behavioral health comorbidities and should be routinely screened for co-occurring conditions. Evidence on interventions for mental health disorders is limited but emerging, particularly with respect to mindfulness training and cognitive behavioral therapy. Many autistic adults or their families express a desire for independent living, participation in education/employment, and intimacy and social relationships, but they often lack skills and/or resources to successfully achieve these outcomes. The time of transition to adulthood for adolescents with ASD is an opportunity for physicians to provide anticipatory guidance and necessary supports around issues of community participation. To allow time for planning, these discussions should occur well before the child reaches adulthood. Clinicians should also routinely screen for and address medical and/or behavioral health comorbidities.


Specific oxidative cleavage of carotenoids by VP14 of maize.
The plant growth regulator abscisic acid (ABA) is formed by the oxidative cleavage of an epoxy-carotenoid. The synthesis of other apocarotenoids, such as vitamin A in animals, may occur by a similar mechanism. In ABA biosynthesis, oxidative cleavage is the first committed reaction and is believed to be the key regulatory step. A new ABA-deficient mutant of maize has been identified and the corresponding gene, Vp14, has been cloned. The recombinant VP14 protein catalyzes the cleavage of 9-cis-epoxy-carotenoids to form C25 apo-aldehydes and xanthoxin, a precursor of ABA in higher plants.


[Temporal illusory conjunction in RSVP tasks: effects of target complexity].
We examined the complexity effects of stimuli and tasks on temporal illusory conjunction in the Rapid Serial Visual Presentation (RSVP) tasks. Subjects were asked to report the partially defined target. We found that error patterns greatly depended on the visual complexity of stimuli. In the case of visually complex stimuli such as Kanji characters consisting of many strokes, pre-target intrusion errors were dominant. In contrast, post-target intrusion errors mainly occurred for visually simple stimuli such as alphabetic letters. Moreover, when target letters were not defined by a specific feature, pre-target intrusion errors were dominant for alphabetic letters. These results were discussed in view of the limited capacity of visual attention.


Proteomic and phosphoproteomic landscape of salivary extracellular vesicles to assess OSCC therapeutical outcomes.
Circulating extracellular vesicles (EVs) have emerged as an appealing source for surrogates to evaluate the disease status. Herein, we present a novel proteomic strategy to identify proteins and phosphoproteins from salivary EVs to distinguish oral squamous cell carcinoma (OSCC) patients from healthy individuals and explore the feasibility to evaluate therapeutical outcomes. Bi-functionalized magnetic beads (BiMBs) with Ti (IV) ions and a lipid analog, 1,2-Distearoyl-3-sn-glycerophosphoethanolamine (DSPE) are developed to efficiently isolate EVs from small volume of saliva. In the discovery stage, label-free proteomics and phosphoproteomics quantification showed 315 upregulated proteins and 132 upregulated phosphoproteins in OSCC patients among more than 2500 EV proteins and 1000 EV phosphoproteins, respectively. We further applied targeted proteomics by coupling parallel reaction monitoring with parallel accumulation-serial fragmentation (prm-PASEF) to measure panels of proteins and phosphoproteins from salivary EVs collected before and after surgical resection. A panel of three total proteins and three phosphoproteins, most of which have previously been associated with OSCC and other cancer types, show sensitive response to the therapy in individual patients. Our study presents a novel strategy to the discovery of effective biomarkers for non-invasive assessment of OSCC surgical outcomes with small amount of saliva.


Can Halophilic and Psychrophilic Microorganisms Modify the Freezing/Melting Curve of Cold Salty Solutions? Implications for Mars Habitability.
We present the hypothesis that microorganisms can change the freezing/melting curve of cold salty solutions by protein expression, as it is known that proteins can affect the liquid-to-ice transition, an ability that could be of ecological advantage for organisms on Earth and on Mars. We tested our hypothesis by identifying a suitable candidate, the well-known psycrophile and halotolerant bacteria Rhodococcus sp. JG3, and analyzing its response in culture conditions that included specific hygroscopic salts relevant to Mars-that is, highly concentrated magnesium perchlorate solutions of 20 wt % and 50 wt % Mg(ClO4)2 at both end members of the eutectic concentration (44 wt %)-and subfreezing temperatures (263 K and 253 K). Using a combination of techniques of molecular microbiology and aqueous geochemistry, we evaluated the potential roles of proteins over- or underexpressed as important players in different mechanisms for the adaptability of life to cold environments. We recorded the changes observed by micro-differential scanning calorimetry. Unfortunately, Rhodococcus sp. JG3 did not show our hypothesized effect on the melting characteristics of cold Mg-perchlorate solutions. However, the question remains as to whether our novel hypothesis that halophilic/psychrophilic bacteria or archaea can alter the freezing/melting curve of salt solutions could be validated. The null result obtained after analyzing just one case lays the foundation to continue the search for proteins produced by microorganisms that thrive in very cold, high-saline solutions, which would involve testing different microorganisms with different salt components. The immediate implications for the habitability of Mars are discussed.


Intracapsular Enucleation of Brachial Plexus Schwannoma With Intraoperative Neuromonitoring: A Case Series Study and a Review of Literature.
Brachial plexus schwannoma (BPS) is a rare clinical entity that poses a significant challenge for head and neck surgeons due to its neuroanatomical complexity and potential severe complications, such as major motor or sensory neurological deficits or pain of the corresponding upper extremity. This article summarizes our experience in its diagnosis and intracapsular enucleation with intraoperative neuromonitoring (INM). A retrospective review of BPS cases treated at our tertiary medical institution was conducted between April 2020 and May 2023. The clinical and demographic data were retrieved from case notes. Totally, 3 cases were included. All 3 patients were male, aged 43 to 54 years (median age = 52). The presenting symptom was a palpable supraclavicular mass in all these cases (2 on the left side and 1 on the right side). Neuromonitoring was performed with a 4-channel nerve integrity monitor, with the electrodes placed in the upper arm and forearm muscles, as demonstrated in the literature. After exposing the mass and identifying its origin from the brachial plexus, a unipolar stimulating probe was used to stimulate the tumor surface or the nerves with a 1.0-mA current, and a longitudinal incision into the tumor capsule was made along a carefully mapped line with no INM response. Then the mass was carefully exposed and meticulously dissected from its capsule to achieve an intact enucleation. Immediate postoperative neurological deficit was documented in Case 1 as a mild grasping weakness. The recovery of the other 2 patients was uneventful. The follow-up duration was 7 to 38 months (median = 8 months). The minor motor deficit of Case 1 recovered completely 1 month after surgery. No recurrence of BPS was observed. Intracapsular enucleation with INM could result in complete removal of BPS and minimal postoperative neurological deficit, whose recovery was quick and satisfactory.


A hydroxyproline-containing glycopeptide released from the walls of sycamore tissue-culture cells by hydrazinolysis.
Degradation of the sycamore cell wall by hydrazinolysis yielded soluble glycopeptides. The peptide portion of the predominant glycopeptide was shown to be cyclic (4-trans-hydroxy-l-prolyl)-4-trans-hydroxy- l-proline. From this structure and the composition of the major glycopeptide it was deduced that only short oligosaccharides are attached to the hydroxyprolyl residues of the wall glycoprotein. Detailed evidence for the structure of the peptide is given in a supplementary paper that has been deposited as Supplementary Publication SUP 50020, at the National Lending Library for Science and Technology, Boston Spa, Yorks. LS23 7BQ, U.K., from whom copies can be obtained on the terms indicated in Biochem. J. (1973) 131, 5.


Laparoscopic cholecystectomy in patients with portal cavernoma without portal vein decompression.
Laparoscopic cholecystectomy (LC) in patients with extrahepatic portal vein obstruction causing portal cavernoma (PC) is considered high risk because of portosystemic collateral veins in the hepatocystic triangle. The literature is limited to isolated case reports. We describe our experience of LC in patients with PC. Data of patients with PC who underwent LC for symptomatic gallstones or related complications was reviewed. Patients with simultaneous cholecystectomy with splenorenal shunt and open cholecystectomy were excluded. Pre-operative evaluation consisted of complete blood count, international normalisation ratio and liver function tests, ultrasound of the abdomen with Doppler, contrast-enhanced computerised tomography, magnetic resonance cholangiopancreatography and esophagogastroscopy as indicated. A standard four-port LC was performed. The technical principles followed were to avoid injury to the collateral veins, liberal use of energy sources and division of dominant collateral veins between clips. Seven adult patients including three females underwent LC. Three patients had thrombosis of previous surgical shunt with persistent PC. The remaining four patients did not have any indication for shunt surgery. Successful LC was performed in six patients. The median duration of surgery was 170 (130-250 min). Blood transfusion was not required. All the patients had uneventful post-operative recovery. The histopathology of gall bladder consists of acute cholecystitis in three patients and chronic cholecystitis in four. LC is feasible in patients with PC at a centre with experience in both laparoscopic and portal hypertension surgeries. Excellent outcome with low rate of conversion to open surgery can be achieved.


Water formation at low temperatures by surface O2 hydrogenation II: The reaction network.
Water is abundantly present in the Universe. It is the main component of interstellar ice mantles and a key ingredient for life. Water in space is mainly formed through surface reactions. Three formation routes have been proposed in the past: hydrogenation of surface O, O(2), and O(3). In a previous paper [Ioppolo et al., Astrophys. J., 2008, 686, 1474] we discussed an unexpected non-standard zeroth-order H(2)O(2) production behaviour in O(2) hydrogenation experiments, which suggests that the proposed reaction network is not complete, and that the reaction channels are probably more interconnected than previously thought. In this paper we aim to derive the full reaction scheme for O(2) surface hydrogenation and to constrain the rates of the individual reactions. This is achieved through simultaneous H-atom and O(2) deposition under ultra-high vacuum conditions for astronomically relevant temperatures. Different H/O(2) ratios are used to trace different stages in the hydrogenation network. The chemical changes in the forming ice are followed by means of reflection absorption infrared spectroscopy (RAIRS). New reaction paths are revealed as compared to previous experiments. Several reaction steps prove to be much more efficient (H + O(2)) or less efficient (H + OH and H(2) + OH) than originally thought. These are the main conclusions of this work and the extended network concluded here will have profound implications for models that describe the formation of water in space.


Sex Differences in Autonomic Cardiac Control and Oxygen Saturation Response to Short-Term Normobaric Hypoxia and Following Recovery: Effect of Aerobic Fitness.
Introduction: The main aims of this study were to investigate autonomic nervous system (ANS) and arterial oxygen saturation (SpO2) responses to simulated altitude in males and females, and to determine the association between maximal oxygen uptake (VO2max) and these responses. Materials and Methods: Heart rate variability (HRV) and SpO2 were monitored in a resting supine position during Preliminary (6 min normoxia), Hypoxia (10 min, fraction of inspired oxygen (FiO2) of 9.6%, simulated altitude ~6,200 m) and Recovery (6 min normoxia) phases in 28 males (age 23.7 ± 1.7 years, normoxic VO2max 59.0 ± 7.8 ml.kg-1.min-1, body mass index (BMI) 24.2 ± 2.1 kg.m-2) and 30 females (age 23.8 ± 1.8 years, VO2max 45.1 ± 8.7 ml.kg-1.min-1, BMI 21.8 ± 3.0 kg.m-2). Spectral analysis of HRV quantified the ANS activity by means of low frequency (LF, 0.05-0.15 Hz) and high frequency (HF, 0.15-0.50 Hz) power, transformed by natural logarithm (Ln). Time domain analysis incorporated the square root of the mean of the squares of the successive differences (rMSSD). Results: There were no significant differences in SpO2 level during hypoxia between the males (71.9 ± 7.5%) and females (70.8 ± 7.1%). Vagally-related HRV variables (Ln HF and Ln rMSSD) exhibited no significant differences between sexes across each phase. However, while the sexes demonstrated similar Ln LF/HF values during the Preliminary phase, the males (0.5 ± 1.3) had a relatively higher (p = 0.001) sympathetic activity compared to females (-0.6 ± 1.4) during the Hypoxia phase. Oxygen desaturation during resting hypoxia was significantly correlated with VO2max in males (r = -0.45, p = 0.017) but not in females (r = 0.01, p = 0.952) and difference between regression lines were significant (p = 0.024). Conclusions: Despite similar oxygen desaturation levels, males exhibited a relatively higher sympathetic responses to hypoxia exposure compared with females. In addition, the SpO2 response to resting hypoxia exposure was related to maximal aerobic capacity in males but not females.


A Community-Level Sodium Reduction Intervention, Boston, 2013-2015.
To evaluate a community-level sodium-reduction intervention in Boston, Massachusetts. Reducing sodium in the food offerings of community settings may help reduce hypertension disparities. We examined changes in the proportion of prepackaged foods with greater than 200 milligrams of sodium in 7 hospitals, 8 YMCAs, 4 community health centers, and 2 organizations serving homeless populations. Research assistants documented prepackaged items in cafeterias, kiosks, and vending machines before and after the intervention (2013-2015). We assessed intervention change via linear mixed models accounting for repeated observations. There were 161 access points at baseline (4347 facings) and 171 (4996 facings) at follow-up. The percentage of prepackaged products with greater than 200 milligrams of sodium decreased from 29.0% at baseline to 21.5% at follow-up (P = .003). Changes were driven by improvements in hospital cafeterias and kiosks (P = .003). The percentage of products with greater than 200 milligrams of sodium in YMCA vending decreased 58% (from 27.2% to 11.5%; P = .017); other organizations had nonsignificant declines. We found modest reductions in the percentage of higher-sodium prepackaged products across community institutions. Community-level interventions may increase availability of lower-sodium products in the food supply.


[Analysis of fatty acids from strains of Mycobacterium habana and Mycobacterium simiae].
A comparative analysis of mycobacterial fatty acid fractions of Mycobacteriun habana and Mycobacterium sineae strains was made. This study used the gas-liquid chromatography coupled with mass spectrometry. Chromatographic profiles obtained from this technique were exposed and compared. This technique proves to be valuable as an alternative element in mycobacterial characterization and makes it possible to analyze the possible differences that may exist among mycobacterial species and to identify the present fatty acid fractions. The outcome proved that the studied strains had quantifiable quantities of over 20 C atom chain fatty acids. There are small differences among the strains in terms of these organic components. It was confirmed that each of then describes a characteristic chromatographic pattern although the composition of present fatty acids is very similar in both studied species.


Comparative study of 14C-labeled purified protein derivative from various mycobacteria. II. Skin cross-reactivity in sensitized guinea pigs.
A study on skin cross-reactivity between stabilized (14)C-labeled mycobacterial antigens, namely tuberculin purified protein derivative (PPD; from Mycobacterium tuberculosis), PPD-A (M. avium), PPD-Y (M. kansasii), PPD-G (M. scrofulaceum), PPD-B (M. intracellulare), and PPD-F (M. fortuitum), has been carried out in groups of guinea pigs sensitized with one of the following heat-killed mycobacteria: M. tuberculosis, M. avium, M. kansasii, M. scrofulaceum, M. intracellulare, or M. fortuitum. For each type of sensitization, the average response for the corresponding PPD antigen was higher than the average response for any of the other antigens. However, the responses to the heterologous PPD antigens were not necessarily significantly different among themselves, and the significant differences of the heterologous PPD antigens were distributed differently according to the type of sensitization. Therefore, (14)C-PPD antigens skin cross-reacted in guinea pigs essentially in the same manner as reported by others for nonradioactive PPD antigens.


[Immunophenotypic and Clinical Characteristics of SET-CAN Fusion Gene Positive Acute Leukemia Patients].
To analyze the flow immunophenotype and clinical characteristics of leukemia patients with positive SET-CAN fusion gene. A total of 7 newly diagnosed acute leukemia patients with SET-CAN fusion gene admitted to Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology from February 2016 to February 2020 were collected. Multiplex reverse transcriptase-polymerase chain reaction (RT-PCR) was used to detect the expression of SET-CAN fusion gene. The immunophenotype was detected by four-color flow cytometry. The case information of 17 literatures published at home and abroad was extracted for statistical analysis. Among the 7 patients, 2 cases were diagnosed as mixed phenotype acute leukemia (MPAL), 2 cases as acute myeloid leukemia (AML), and 3 cases as T-acute lymphoblastic leukemia (ALL)/lymphoblastic lymphoma (LBL). Leukemia cells in bone marrow specimens of all cases expressed or partially expressed CD34, CD33 and CD7. CD5 and cytoplasmic CD3 were expressed in 5 patients except 2 patients diagnosed with AML. Bone marrow and lymph node specimens were both detected in 2 patients, and the immunophenotypes of the two specimens were not completely consistent, with differences in lineage or maturity related markers. Two patients with MPAL showed differentiated response to treatment. One AML patient gave up treatment, and another AML patient with FLT3-ITD gene mutation had a poor prognosis. All three T-ALL/LBL patients maintained a long duration of remission after induced remission, and one case underwent allogeneic hematopoietic stem cell transplantation. There are common characteristics of immunophenotype in patients with positive SET-CAN fusion gene. Differential expression of immunophenotype in samples from different parts is observed in some cases. The prognosis of these diseases varies.


Quantitative Eye Gaze and Movement Differences in Visuomotor Adaptations to Varying Task Demands Among Upper-Extremity Prosthesis Users.
New treatments for upper-limb amputation aim to improve movement quality and reduce visual attention to the prosthesis. However, evaluation is limited by a lack of understanding of the essential features of human-prosthesis behavior and by an absence of consistent task protocols. To evaluate whether task selection is a factor in visuomotor adaptations by prosthesis users to accomplish 2 tasks easily performed by individuals with normal arm function. This cross-sectional study was conducted in a single research center at the University of Alberta, Edmonton, Alberta, Canada. Upper-extremity prosthesis users were recruited from January 1, 2016, through December 31, 2016, and individuals with normal arm function were recruited from October 1, 2015, through November 30, 2015. Eight prosthesis users and 16 participants with normal arm function were asked to perform 2 goal-directed tasks with synchronized motion capture and eye tracking. Data analysis was performed from December 3, 2018, to April 15, 2019. Movement time, eye fixation, and range of motion of the upper body during 2 object transfer tasks (cup and box) were the main outcomes. A convenience sample comprised 8 male prosthesis users with acquired amputation (mean [range] age, 45 [30-64] years), along with 16 participants with normal arm function (8 [50%] of whom were men; mean [range] age, 26 [18-43] years; mean [range] height, 172.3 [158.0-186.0] cm; all right handed). Prosthesis users spent a disproportionately prolonged mean (SD) time in grasp and release phases when handling the cups (grasp: 2.0 [2.3] seconds vs 0.9 [0.8] seconds; P < .001; release: 1.1 [0.6] seconds vs 0.7 [0.4] seconds; P < .001). Prosthesis users also had increased mean (SD) visual fixations on the hand for the cup compared with the box task during reach (10.2% [12.1%] vs 2.2% [2.8%]) and transport (37.1% [9.7%] vs 22.3% [7.6%]). Fixations on the hand for both tasks were significantly greater for prosthesis users compared with normative values. Prosthesis users had significantly more trunk flexion and extension for the box task compared with the cup task (mean [SD] trunk range of motion, 32.1 [10.7] degrees vs 21.2 [3.7] degrees; P = .01), with all trunk motions greater than normative values. The box task required greater shoulder movements compared with the cup task for prosthesis users (mean [SD] flexion and extension; 51.3 [12.6] degrees vs 41.0 [9.4] degrees, P = .01; abduction and adduction: 40.5 [7.2] degrees vs 32.3 [5.1] degrees, P = .02; rotation: 50.6 [15.7] degrees vs 35.5 [10.0] degrees, P = .02). However, other than shoulder abduction and adduction for the box task, these values were less than those seen for participants with normal arm function. This study suggests that prosthesis users have an inherently different way of adapting to varying task demands, therefore suggesting that task selection is crucial in evaluating visuomotor performance. The cup task required greater compensatory visual fixations and prolonged grasp and release movements, and the box task required specific kinematic compensatory strategies as well as increased visual fixation. This is the first study to date to examine visuomotor differences in prosthesis users across varying task demands, and the findings appear to highlight the advantages of quantitative assessment in understanding human-prosthesis interaction.


ICAM-1 is required for resistance to herpes simplex virus type 1 but not interferon-alpha1 transgene efficacy.
The purpose of this study was to determine the role of ICAM-1 in ocular herpes simplex virus type 1 (HSV-1) infection. Wild-type and ICAM-1 knockout mice were assessed for resistance to ocular HSV-1 infection in the presence of naked DNA plasmid vector or plasmid DNA encoding interferon-alpha1 topically applied to the cornea of the mice. Wild-type mice showed greater resistance to HSV-1 infection compared to ICAM-1 knockout mice as measured by cumulative survival. The absence of ICAM-1 did not affect the efficacy of the interferon-alpha1 transgene against ocular HSV-1. Both ICAM-1 and wild-type mice treated with the transgene showed a reduction in viral load and antigen expression in the trigeminal ganglion compared to the plasmid vector-treated counterparts. In contrast, the presence of the transgene reduced the number of infiltrating cells into the cornea in comparison to plasmid vector DNA controls in the wild-type mice but not in the ICAM-1 knockout mice. Collectively, these results suggest that the IFN-alpha1 transgene can restore resistance against HSV-1 infection in ICAM-1-deficient mice.


HIV infection with concomitant cerebral toxoplasmosis and disseminated histoplasmosis in a 45-year-old man.
Although disseminated histoplasmosis is a common opportunistic infection in HIV patients in endemic areas, it is not widely known in Japan. We report a rare case of a man from Ghana infected with HIV who was hospitalized in Japan and who suffered from coinfection with cerebral toxoplasmosis and disseminated histoplasmosis. The diagnosis of cerebral toxoplasmosis was confirmed by a brain biopsy, and the therapy for the disease resulted in almost complete resolution of the brain lesion. However, fever of unknown origin continued for 2 weeks, and disseminated histoplasmosis was diagnosed by examination of a blood smear and by the detection of the histoplasma genome in the peripheral blood by means of polymerase chain reaction. The isolate was confirmed to be Histoplasma capsulatum var. duboisii. Therapy with amphotericin B was initiated, and no histoplasma genome in the peripheral blood was detected 3 days later. Unfortunately, the patient died after 10 days from acute respiratory syndrome. This case highlights that histoplasmosis should be included in the differential diagnosis of opportunistic infections in AIDS patients when patients have a history of travel to or arrival from endemic areas.


CRISPR editing of the GLI1 first intron abrogates GLI1 expression and differentially alters lineage commitment.
GLI1 is one of three GLI family transcription factors that mediate Sonic Hedgehog signaling, which plays a role in development and cell differentiation. GLI1 forms a positive feedback loop with GLI2 and likely with itself. To determine the impact of GLI1 and its intronic regulatory locus on this transcriptional loop and human stem cell differentiation, we deleted the region containing six GLI binding sites in the human GLI1 intron using CRISPR/Cas9 editing to produce H1 human embryonic stem cell (hESC) GLI1-edited clones. Editing out this intronic region, without removing the entire GLI1 gene, allowed us to study the effects of this highly complex region, which binds transcription factors in a variety of cells. The roles of GLI1 in human ESC differentiation were investigated by comparing RNA sequencing, quantitative-real time PCR (q-rtPCR), and functional assays. Editing this region resulted in GLI1 transcriptional knockdown, delayed neural commitment, and inhibition of endodermal and mesodermal differentiation during spontaneous and directed differentiation experiments. We found a delay in the onset of early osteogenic markers, a reduction in the hematopoietic potential to form granulocyte units, and a decrease in cancer-related gene expression. Furthermore, inhibition of GLI1 via antagonist GANT-61 had similar in vitro effects. These results indicate that the GLI1 intronic region is critical for the feedback loop and that GLI1 has lineage-specific effects on hESC differentiation. Our work is the first study to document the extent of GLI1 abrogation on early stages of human development and to show that GLI1 transcription can be altered in a therapeutically useful way.


Alternative diagnosis to heparin-induced thrombocytopenia in two critically ill patients despite a positive PF4/heparin-antibody test.
Thrombocytopenia can cause diagnostic challenges in patients who have received heparin. Heparin-induced thrombocytopenia (HIT) is often considered in the differential diagnosis, and a positive screening can be mistaken as confirmation of the disorder. We present two patients who both received low-molecular-weight heparin for several days. In the first patient, clinical judgment rejected the suspicion of HIT despite a positive screening assay, and treatment for the alternative diagnosis of post-transfusion purpura was correctly initiated. In the second patient, the inaccurate diagnosis HIT was pursued due to a positive screening assay, while the alternative diagnosis of drug-dependent thrombocytopenia caused by piperacillin/tazobactam was rejected. This resulted in re-exposure to piperacillin/tazobactam which caused a second episode of severe thrombocytopenia. A positive screening assay for platelet factor 4/heparin-antibody should be verified by a functional assay, especially in patients with low pretest probability for HIT.


Decisions about parental care in response to perceived paternity.
Evolutionary ecologists are attempting to explain how parents make behavioural decisions about how much care to provide to their young. Theory predicts that when genetic relatedness to young is decreased by cuckoldry, for example, parents should reduce their care in favour of alternative broods that provide greater reproductive success. Experimental manipulation of perceived paternity has been used to test the theory, but such studies have generated mixed results. Some manipulations can fail to alter a parent's perceived paternity, whereas others may directly affect parental behaviour when, for instance, the manipulation involves capturing the parent. No study has demonstrated parental care adjustment in a manner uncomplicated by experimental design or life history correlates. Here I test the theory using the fact that nest-tending parental male bluegill sunfish (Lepomis macrochirus) can assess their paternity using both the visual presence of parasitic cuckolder males during spawning, and olfactory cues released by newly hatched eggs. By manipulating both types of cues I show that parental males dynamically adjust their parental care, favouring broods that are apparently most closely related. These results confirm the importance of genetic relatedness in parental care decision-making.


The Canadian cooperative trial of cyclophosphamide and plasma exchange in progressive multiple sclerosis. The Canadian Cooperative Multiple Sclerosis Study Group.
To find out whether non-specific immunosuppression is beneficial in multiple sclerosis (MS) a randomised, placebo-controlled, single-masked trial was carried out in nine university centres. 168 patients with clinically or laboratory-supported definite MS in progressive phase (deterioration by at least 1.0 on the expanded disability status scale [EDSS] in the previous year) were randomised to receive intravenous cyclophosphamide and oral prednisone (n = 55); daily oral cyclophosphamide, alternate day prednisone (22 weeks), and weekly plasma exchange (20 weeks) (n = 57); or placebo medications and sham plasma exchange (n = 56). All patients were followed for at least 12 months (mean 30.4 months) by a monitoring neurologist, who was aware of treatment allocation, and an evaluating neurologist, who was not. The primary analysis was a comparison of rates of treatment failure (worsening of evaluating neurologist's assessment of EDSS by 1.0 or more on two consecutive 6-monthly assessments). There were no significant differences among the groups in this primary analysis (19 [35%] treatment failures with cyclophosphamide; 18 [32%] with plasma exchange; 16 [29%] with placebo). Nor were there any differences in the proportions improved, stabilised, or worsened at each 6 month assessment or in the mean change in the EDSS at the final assessment (0.81 cyclophosphamide; 0.69 plasma exchange; 0.69 placebo). A slight trend favouring the plasma exchange group at 12-24 months of follow-up was not sustained at the final assessment. This study fails to confirm previous reports that immunosuppressive treatments result in stabilisation or improvement in progressive MS.


[Chromosomal aberrations induced by thio-TEPA in cells of malignant ovarian tumors in humans].
Chromosome abberations in cells of 4 ovarian cancer patients have been studied prior to and during the treatment with ThioTEPA. ThioTEPA was injected intraperitoneally once a week in a dose of 40 mg. The amount of abberant cells prior to the therapy averaged 7.8%. 14 days following the treatment the amount of cells with chromosome abberations reached its peak (88.6%). By the 21st day of ThioTEPA treatment, when a total dose of the drug was 120 mg, the number of cells with abberations rapidly decreased, and by the 28-35th day of treatment there was a fall up to the initial values. ThioTEPA induced in tumor cells chiefly abberations of chromatoid type that evidenced the injury of cells in a phase G2 of the cellular cycle. A decrease in the number of chromosome abberations in tumor cells during the treatment with chemotherapeutic drugs is a morphological indication of the appearance of drug resistance.


[Effect of N- and M-cholinergic-potentiating and cholinergic-blocking agents on the epileptogenesis of a penicillin focus in the dorsal hippocampus].
Chronic experiments on rabbits with penicillin epilepsy have shown that intravenous injections of the ACHE inhibitor galanthamine (1 mg/kg), and N-cholinergic-blockers, ganglerone (3 mg/kg) and eterofen (8 mg/kg), decreased or suppressed completely epileptogenesis manifestations. Combination of galanthamine with one of the N-cholinergic-blockers markedly increased their anticonvulsive actions. On the contrary, combination of galanthamine with the M-cholinergic-blocker metamizil (0.5 mg/kg) enhanced epileptogenesis activity. It is postulated that both M- and N-cholinergic mechanisms take part in the genesis of penicillin epilepsy. The use of N-cholinergic-blockers and their combinations with M-cholinomimetics as anticonvulsants seems expedient.


[Total arch replacement for ruptured Stanford type B aortic dissection with thrombosed pseudolumen presenting hemodynamic deterioration].
We report 2 cases of ruptured type B aortic dissection with thrombosed pseudolumen presenting hemodynamic deterioration which is a life-threatening condition. In such cases, surgical treatment often resulted in high mortality rates. We underwent total arch replacement via median sternotomy. In both cases, postoperative courses were uneventful. This approach ensured us wider operative field to establish cardiopulmonary bypass quickly, and to perform distal anastomosis without much difficulty.


[Rickettsia infections in Portugal].
After a brief introduction about rickettsioses, we analyse Mediterranean Spotted Fever (MSF) in Portugal, and review Portuguese medical literature. We focussed on the seasonal summer pattern of the disease. MSF is very frequent in Portugal, nearly 1,000 cases are reported every year and young age groups are the most afflicted. Although usually regarded as a benign condition, MSF has emerged as a potentially lethal disease in recent years. The clinical presentation is protean, but usually suggestive enough to allow a clinical diagnosis. The complications are well documented, elderly and people with chronic debilitating diseases being the most affected. Q fever is also endemic in Portugal, although with more modest numbers (about 50 cases a year). Serological studies, however, suggest a higher incidence, probably because the disease is unfamiliar to many clinicians and, as such, it is difficult to diagnose and, consequently, then an important number of subclinical or self-limited cases. In Portugal, fever with hepatic involvement is the most common clinical presentation. Other less frequent clinical forms are atypical pneumonia and CNS involvement. Chronic Q fever is a rare condition.


Comparison of the pathogenicity of two US porcine reproductive and respiratory syndrome virus isolates with that of the Lelystad virus.
The Lelystad virus or one of two US isolates (VR2385, VR2431) of porcine reproductive and respiratory syndrome virus were given intranasally to 25 4-week-old cesarian-derived colostrum-deprived pigs. Pigs from these groups were necropsied at 1, 2, 3, 5, 7, 10, 15, 21, or 28 days postinoculation. The Lelystad virus and VR2431 induced mild transient pyrexia, dyspnea, and tachypnea. VR2385 induced labored and rapid abdominal respiration, pyrexia, lethargy, anorexia, and patchy dermal cyanosis. All three isolates induced multifocal tan-mottled consolidation involving 6.8% (n = 9; SEM = 3.4) of the lung for Lelystad, 9.7% (n = 9, SEM = 2.7) of the lung for VR2431, and 54.2% (n = 9, SEM = 4.4) of the lung for VR2385 at 10 days postinoculation. Characteristic microscopic lung lesions consisted of type 2 pneumocyte hypertrophy and hyperplasia, necrotic debris and increased mixed inflammatory cells in alveolar spaces, and alveolar septal infiltration with mononuclear cells. Lymphadenopathy with follicular hypertrophy, hyperplasia, and necrosis was consistently seen. Similar follicular lesions were also seen in Peyer's patches and tonsils. Lymphohistiocytic myocarditis and encephalitis were reproduced with all three isolates. Clinical respiratory disease and gross and microscopic lung lesion scores were considerably and significantly more severe in the VR2385-inoculated pigs. All three viruses were readily isolated from sera, lungs, and tonsils throughout the 28 days of the study. The lymphoid and respiratory systems have the most remarkable lesions and appear to be the major site of replication of these viruses. This work demonstrated a marked difference in pathogenicity of porcine reproductive and respiratory syndrome isolates.


Protein phosphatases: properties and role in cellular regulation.
Protein phosphorylation is a principal regulatory mechanism in the control of almost all cellular processes. The nature of the protein phosphatases that participate in these reactions has been a subject of controversy. Four enzymes, termed protein phosphatases 1, 2A, 2B, and 2C, account for virtually all of the phosphatase activity toward phosphoproteins involved in controlling glycogen metabolism, glycolysis, gluconeogenesis, fatty acid synthesis, cholesterol synthesis, and protein synthesis. The properties, physiological roles, and mechanisms for regulating the four protein phosphatases are reviewed.


Subunit composition of brain voltage-gated potassium channels determined by hongotoxin-1, a novel peptide derived from Centruroides limbatus venom.
Five novel peptidyl inhibitors of Shaker-type (Kv1) K+ channels have been purified to homogeneity from venom of the scorpion Centruroides limbatus. The complete primary amino acid sequence of the major component, hongotoxin-1 (HgTX1), has been determined and confirmed after expression of the peptide in Escherichia coli. HgTX1 inhibits 125I-margatoxin binding to rat brain membranes as well as depolarization-induced 86Rb+ flux through homotetrameric Kv1.1, Kv1. 2, and Kv1.3 channels stably transfected in HEK-293 cells, but it displays much lower affinity for Kv1.6 channels. A HgTX1 double mutant (HgTX1-A19Y/Y37F) was constructed to allow high specific activity iodination of the peptide. HgTX1-A19Y/Y37F and monoiodinated HgTX1-A19Y/Y37F are equally potent in inhibiting 125I-margatoxin binding to rat brain membranes as HgTX1 (IC50 values approximately 0.3 pM). 125I-HgTX1-A19Y/Y37F binds with subpicomolar affinities to membranes derived from HEK-293 cells expressing homotetrameric Kv1.1, Kv1.2, and Kv1.3 channels and to rat brain membranes (Kd values 0.1-0.25 pM, respectively) but with lower affinity to Kv1.6 channels (Kd 9.6 pM), and it does not interact with either Kv1.4 or Kv1.5 channels. Several subpopulations of native Kv1 subunit oligomers that contribute to the rat brain HgTX1 receptor have been deduced by immunoprecipitation experiments using antibodies specific for Kv1 subunits. HgTX1 represents a novel and useful tool with which to investigate subclasses of voltage-gated K+ channels and Kv1 subunit assembly in different tissues.


Towards the core structure of Strychnos alkaloids using samarium diiodide-induced reactions of indole derivatives.
This report describes the development of a first and second generation approach towards the synthesis of the ABCEG pentacyclic core structure of Strychnos alkaloids. First, we discuss a sequential approach applying a series of functional group transformations to prepare suitable precursors for cyclization reactions. These include attempts of samarium diiodide-induced cyclizations or a Barbier-type reaction of a transient lithium organyl, which successfully led to a tetracyclic key building block earlier used for the synthesis of strychnine. Secondly, we account our first steps towards the development of an atom-economical samarium diiodide-induced cascade reaction using "dimeric" indolyl ketones as cyclization precursors. In this context, we discuss plausible mechanisms for the samarium diiodide-induced cascade reaction as well as transformations of the obtained tetracyclic dihydroindoline derivatives.


Use of native plants for the remediation of abandoned mine sites in Mediterranean semiarid environments.
Abandoned tailing dumps from mining industry represent important sources of metal contamination in the surrounding environments. This study evaluates the potential of two Mediterranean native plants, Pistacia lentiscus and Phragmites australis, for phytoremediation of two Sardinian contaminated mine sites. A 6 months study has been conducted at greenhouse-controlled conditions with the aim of investigating the plant capability to tolerate high metal concentrations and to extract or immobilize them within the roots. The possibility to mitigate stress on the plants and improve treatment efficiency by adding compost as amendment was also evaluated. Both species were able to restrict accumulation of Cd, Pb and Zn to the root tissues exhibiting a metal concentration ratio of plant roots to soil bioavailable fraction higher than two (four in the case of Zn). However, the two species showed different adaptation responses, being the survival of P. australis after 6 months in contaminated soil lower (25 %-58 %) than that observed for P. lentiscus (77 %-100 %). Compost addition resulted in a lower metal uptake in tissues of both plants and a higher survival of P. australis, whilst almost no effect was observed as regard the growth of both species. The two tested species appear to be promising candidates for phytostabilization, P. lentiscus exhibiting a greater adaptability to heavy metal contaminated matrices than P. australis.


Dynamic elastic constants of anisotropic materials by resonant ultrasound spectroscopy.
Resonant ultrasound spectroscopy (RUS) has been applied to the anisotropic elastic stiffness determination of SiC/Al composites and highly textured Zr-2.5 Nb alloys. To determine the elastic stiffness of anisotropic materials, the resonant frequencies of a rectangular parallelepiped specimen were measured and compared with the calculated frequencies based on the input data of the estimated stiffness, dimensions, and density. The initial estimates of the elastic stiffness of SiC/Al composites were calculated using the Mori-Tananka (MT) theory and the concept of effective aspect ratio of reinforcements. For highly textured Zr-2.5 Nb alloy, the initial estimates were obtained from its orientation distribution function, determined by X-ray diffraction, and the reported elastic stiffness of a single crystal zirconium. Through a comparison of calculated frequencies with those measured by RUS, elastic stiffness values have been determined very accurately by iteration and convergence processes.


Association of dietary inflammatory potential, dietary oxidative balance score and biological aging.
The interaction between diet, inflammation, and oxidative stress significantly influences aging, but the available evidence has been limited. We evaluated potential associations of dietary inflammatory index (DII), dietary oxidative balance score (DOBS), and measures of biological aging. This cross-sectional study was performed among 8839 individuals from NHANES 2003-2014. DII and DOBS were determined by aggregating data from 26 to 17 a priori selected dietary components. Biological aging metrics included homeostatic dysregulation (HD), Klemera-Doubal method (KDM), phenotypic age (PA), and allostatic load (AL). Binomial logistic regression models and multivariate linear regression models were conducted. The associations of dietary inflammation and oxidative stress potential and biological aging metrics were significant among American adults nationwide. Consuming foods with higher DII was significantly associated with accelerated HD 1.26 (1.10, 1.44), KDM 1.24 (1.06, 1.45), and PA 1.54 (1.33, 1.78). Compared with the lowest DOBS, the hazard ratios of accelerated HD, KDM, PA, and AL were 0.74 (0.64, 0.86), 0.80 (0.70, 0.92), 0.61 (0.52, 0.72) and 0.78 (0.63, 0.97), respectively. The adverse effects of pro-inflammatory and pro-oxidative diets on accelerated HD, KDM, and PA were 1.39 (1.18, 1.62), 1.28 (1.08, 1.51), and 1.76 (1.47, 2.10). Serum AST/ALT ratio and globulin were implicated in and mediate the aging effects. Higher DII and/or lower DOBS are associated with higher markers of biological aging. Our research elucidates that diets may mitigate biological aging resulting from inflammation and/or oxidative stress.


Effect of Strain Variations on Lassa Virus Z Protein-Mediated Human RIG-I Inhibition.
Mammarenaviruses include several known human pathogens, such as the prototypic lymphocytic choriomeningitis virus (LCMV) that can cause neurological diseases and Lassa virus (LASV) that causes endemic hemorrhagic fever infection. LASV-infected patients show diverse clinical manifestations ranging from asymptomatic infection to hemorrhage, multi-organ failures and death, the mechanisms of which have not been well characterized. We have previously shown that the matrix protein Z of pathogenic arenaviruses, including LASV and LCMV, can strongly inhibit the ability of the innate immune protein RIG-I to suppress type I interferon (IFN-I) expression, which serves as a mechanism of viral immune evasion and virulence. Here, we show that Z proteins of diverse LASV isolates derived from rodents and humans have a high degree of sequence variations at their N- and C-terminal regions and produce variable degrees of inhibition of human RIG-I (hRIG-I) function in an established IFN-β promoter-driven luciferase (LUC) reporter assay. Additionally, we show that Z proteins of four known LCMV strains can also inhibit hRIG-I at variable degrees of efficiency. Collectively, our results confirm that Z proteins of pathogenic LASV and LCMV can inhibit hRIG-I and suggest that strain variations of the Z proteins can influence their efficiency to suppress host innate immunity that might contribute to viral virulence and disease heterogeneity.


[Telemedicine--organizational consequences more than just talk?].
In the telemedicine community, the possibility of organisational consequences of the technology have been mentioned frequently. But little has been published on the subject. We may speak of five categories of application of the new technology: clinical use, medical service functions, extramural applications, skills enhancement; and management and administration. Organisational consequences may be of four types: changes in distribution of tasks between levels of care and between organisations at the same levels, new division of work and change in skills; groups of individuals who are not co-located may co-operate in problem-solving, and the technology may become a tool of co-ordination for organisations. Empirical studies of the impact on organisation are few, but a Norwegian study confirmed that telemedicine already has such impact on the health service.


Economics and dementia: Challenges and responses.
Economics and dementia are interconnected in many ways. There is, for example, accumulating evidence of the ways in which dementia impacts on the economic status of individuals and families, on health and social care system budgets, and on national economies. An individual's economic status can affect their risk of dementia and their ability to respond to it. Governments and other strategic decision-makers are aware of the (growing, indeed urgent) need to take action - whether that is prevention, treatment or care - but also very aware of the limited resources available to them and to the general population. Research evidence can potentially inform the difficult decisions that government and others need to take. We briefly summarise some economic evaluation studies in the dementia area as a basis for identifying the main challenges of moving from evidence to better policy and practice. We then discuss some possible responses (from a range of stakeholders) to these challenges, and how the STRiDE study has sought to contribute to this fast-moving field.


POLAROGRAPHIC INVESTIGATION OF CONJUGATED FAT-SOLUBLE VITAMINS.
The half-wave potentials of all-trans beta-carotene, all-trans retinol, 13-cis retinol, all-trans retinyl acetate, all-trans retinal, and vitamins D(2) and D(3) were related to the number of double bonds in conjugation. A minimum of three double bonds in conjugation was required before reduction took place at the dropping-mercury electrode. As the number of conjugated bonds increased in the fat-soluble vitamins, the initial reduction took place at a lower half-wave potential. All of the waves were linearly proportional to the concentration of the vitamins in the concentration range studied.


The biological sciences in India: aiming high for the future.
India is gearing up to become an international player in the life sciences, powered by its recent economic growth and a desire to add biotechnology to its portfolio. In this article, we present the history, current state, and projected future growth of biological research in India. To fulfill its aspirations, India's greatest challenge will be in educating, recruiting, and supporting its next generation of scientists. Such challenges are faced by the US/Europe, but are particularly acute in developing countries that are racing to achieve scientific excellence, perhaps faster than their present educational and faculty support systems will allow.


Adsorption of lysozyme, beta-casein and their layer-by-layer formation on hydrophilic surfaces: Effect of ionic strength.
The adsorbed amount and layer structure of lysozyme, beta-casein and mixed layers of the two proteins were studied on hydrophilic silica and quartz surfaces using the following techniques: ellipsometry, quartz crystal microbalance with dissipation monitoring (QCM-D) and total internal reflection fluorescence (TIRF). Particular emphasis was put on the effect of solution ionic strength on the layer formation. Both lysozyme and beta-casein showed a higher affinity for the silica surface when adsorbed from a solution of low ionic strength even though beta-casein and silica are negatively charged at the pH used. No beta-casein remained adsorbed after rinsing with a 150mM buffer solution. The adsorbed amount of lysozyme on silica exceeded a monolayer coverage irrespective of the solution conditions and displayed a rigid structure. beta-Casein forms more than a single layer on pre-adsorbed lysozyme; an inner flat layer and an outer layer with an extended structure, which largely desorbs on rinsing. The build-up through sequential adsorption of lysozyme and beta-casein is favoured at intermediate and high ionic strength. The total adsorbed amount increased slightly with each deposition cycle and the mixed lysozyme/beta-casein layers contain higher amounts of protein compared to those of pure lysozyme or beta-casein. Sequential adsorption gives rise to a proteinaceous layer consisting of both lysozyme and beta-casein. The protein layers are probably highly interpenetrated with no clear separation between them.


Computational technique for improvement of the position-weight matrices for the DNA/protein binding sites.
Position-weight matrices (PWMs) are broadly used to locate transcription factor binding sites in DNA sequences. The majority of existing PWMs provide a low level of both sensitivity and specificity. We present a new computational algorithm, a modification of the Staden-Bucher approach, that improves the PWM. We applied the proposed technique on the PWM of the GC-box, binding site for Sp1. The comparison of old and new PWMs shows that the latter increase both sensitivity and specificity. The statistical parameters of GC-box distribution in promoter regions and in the human genome, as well as in each chromosome, are presented. The majority of commonly used PWMs are the 4-row mononucleotide matrices, although 16-row dinucleotide matrices are known to be more informative. The algorithm efficiently determines the 16-row matrices and preliminary results show that such matrices provide better results than 4-row matrices.


Myxoma virus is oncolytic for human pancreatic adenocarcinoma cells.
Viral oncolytic therapy, which seeks to exploit the use of live viruses to treat cancer, has shown promise in the treatment of cancers resistant to conventional anticancer therapies. Among the most difficult to treat cancers is advanced pancreatic adenocarcinoma. Our study investigates the ability of a novel oncolytic agent, myxoma virus, to infect, productively replicate in, and kill human pancreatic cancer cells in vitro. The myxoma virus vMyxgfp was tested against a panel of human pancreatic adenocarcinoma cell lines. Infectivity, viral proliferation, and tumor cell kill were assessed. Infection of tumor cells was assessed by expression of the marker gene enhanced green fluorescent protein (e-GFP). vMyxgfp had the ability to infect all pancreatic cancer cell lines tested. Killing of tumor cells varied among the 6 cell lines tested, ranging from >90% cell kill at 7 days for the most sensitive Panc-1 cells, to 39% in the most resistant cell line Capan-2. Sensitivity correlated to replication of virus, and was found to maximally exhibit a four-log increase in foci-forming units for the most sensitive Panc-1 cells within 72 h. Our study demonstrates for the first time the ability of the myxoma virus to productively infect, replicate in, and lyse human pancreatic adenocarcinoma cells in vitro. These data encourage further investigation of this virus, which is pathogenic only in rabbits, for treatment of this nearly uniformly fatal cancer.


Décrypthon grid - grid resources dedicated to neuromuscular disorders.
Thanks to the availability of computational grids and their middleware, a seamless access to computation and storage resources is provided to application developers and scientists. The Décrypthon project is one example of such a high performance platform. In this paper, we present the architecture of the platform, the middleware developed to facilitate access to several servers deployed in France, and the data center for integrating large biological datasets over multiple sites, supported by a new query language and integration of various tools. The SM2PH project represents an example of a biological application that exploits the capacities of the Décrypthon grid. The goal of SM2PH is a better understanding of mutations involved in human monogenic diseases, their impact on the 3D structure of the protein and the subsequent consequences for the pathological phenotypes.


Tissue engineering and regenerative medicine: past, present, and future.
Tissue and organ repair still represents a clinical challenge. Tissue engineering and regenerative medicine (TERM) is an emerging field focused on the development of alternative therapies for tissue/organ repair. This highly multidisciplinary field, in which bioengineering and medicine merge, is based on integrative approaches using scaffolds, cell populations from different sources, growth factors, nanomedicine, gene therapy, and other techniques to overcome the limitations that currently exist in the clinics. Indeed, its overall objective is to induce the formation of new functional tissues, rather than just implanting spare parts. This chapter aims at introducing the reader to the concepts and techniques of TERM. It begins by explaining how TERM have evolved and merged into TERM, followed by a short overview of some of its key aspects such as the combinations of scaffolds with cells and nanomedicine, scaffold processing, and new paradigms of the use of stem cells for tissue repair/regeneration, which ultimately could represent the future of new therapeutic approaches specifically aimed at clinical applications.


[Effect of xiaochaihu decoction and different herbal formulations of its components on cytokines of carrageenan induced pleuritis in rats].
To explore the anti-inflammatory effect and possible mechanism of Xiaochaihu Decoction (XCHD) and the different herbal formulations of its components. Rat model of pleuritis was established by thoracic injecting 0.2 ml of 1% carrageenan. Rats in the treated groups were medicated with XCHD (11 g/kg) and the different herbal formulations of its components respectively as follows: thorowax root-scutellaria root (A, 3.5 g/kg), fresh ginger-pinellia tuber (B, 3 g/kg), ginseng-licorice root-jujube (C, 4.5 g/kg), A + B (6.5 g/kg), A + C (8 g/kg) and B + C (7.5 g/kg), and those in the normal group and the model group were given equal volume of instilled water, by way of gastrogavage for successive 5 days. Modeling was performed 2 hrs after the last medication. The amount of pleurorrhea, and leucocyte (WBC), marrow peroxidase (MPO), tumor necrosis factor alpha (TNF-alpha) and interleukin-1beta (IL-1beta) in pleurorrhea, and serum level of interleukin-8 (IL-8) were measured 12 hrs after modeling. As compared with the model group, all the parameters measured were lower in all the treated group (P < 0.05) , and IL-1beta content in pleurorrhea in the XCHD group and Group A, B and C were significantly lower (P < 0.01). XCHD and the different herbal formulations have obvious anti-inflammatory effect, showing certain preventive and therapeutic effect on pleuritis. Among the different formulations, the XCHD, A, B and C had better effects. The effects might be related to inhibiting the increase of cytokines as TNF-alpha, IL-1beta, and IL-8 to suppress the activation, infiltration and wandering of leucocytes.


Direct interaction between the intracellular domains of bullous pemphigoid antigen 2 (BP180) and beta 4 integrin, hemidesmosomal components of basal keratinocytes.
Bullous pemphigoid antigen 2 (BPAG2/BP180, also known as type XVII collagen) and alpha 6 beta 4 integrin are both transmembrane proteins and hemidesmosomal components of basal keratinocytes. In this study, using yeast two-hybrid system, we demonstrate direct protein-protein interaction between the intracellular domains of BP180 and the beta 4 integrin subunit. Detailed analysis revealed that a bait construct spanning amino acids 13-89 of BP180 contained sufficient information for the protein protein interaction, but further deletion of 13 amino-terminal amino acids, which eliminates a predicted beta-sheet, abolished the interaction. The intracellular domain of the beta 4 integrin subunit contains two pairs of fibronectin type III (FNIII) repeats separated by a connecting segment. Series of expression constructs, sequentially deleting each domain, revealed that the connecting segment, the second pair of FNIII repeats and the tail region of the beta 4 integrin subunit were necessary for the interaction with BP180 in yeast two-hybrid system.


[Assessment of consumer satisfaction with public health and medical services in the city of Iaşi].
The study was designed to assess patient satisfaction regarding the quality of medical care delivered in 2010, the financial accessibility of the used services, the time span accessibility to the services used, doctor-patient relationship, and quality of health services. This study was carried out on a series of 150 randomly selected patients, age-range l8 to 70 years. These patients were asked to fill out a 44-item questionnaire including demographic data (age, education, environment--rural or urban area, difficult financial situation) and questions on the quality of the delivered medical care and the performance of the qualified medical staff. The global assessment of the quality of health services shows that it is mainly satisfactory (42.00%) and good (31.33%). The primary health services (family medicine) are mostly regarded as very good (38.00%), good (28.67%) and satisfactory (24.67%). As to the specialized outpatient services, most investigated subjects found them satisfactory (32.67%), good (27.33%), and poor and very poor (8.00%). A percentage of 35.33 of the respondents think that the services provided in hospitals are satisfactory, 18.00% good and 9.33% very good. Drug administration was considered satisfactory by 37.33%, while 22.00% and 12.6% believe it to be good and very good, respectively. The regular application of questionnaires to measure patient satisfaction and the setting up of a system for measuring the quality of medical care will improve quality of the health services.


Association between hypertension, obesity and dietary intake in post-menopausal women from rural Zambian communities.
Amongst the cardiovascular risk (CVR) factors, hypertension (HT) and obesity appear to be prominent in post-menopausal women. The underlying mechanisms of HT development in menopause are not fully understood. To determine the association between HT, obesity and dietary intakes in post-menopausal women from rural Zambia. This study was conducted in Twatasha Compound of Kitwe and Ndeke Community of Ndola. Blood pressure (BP), weight, height and dietary intakes (24-h recall) were measured in 153 women (> 50 years) from households. The South African Hypertension Society (SAHS), the World Health Organization (WHO) and estimated average requirements (EARs) guidelines were followed for HT, obesity and dietary intake definitions, respectively. Statistical Package for the Social Sciences (SPSS) version 26 was used for descriptive and inferential statistical analyses. Prevalence of HT was 70%, whilst 37.25% and 28.10% of the participants were overweight and obese, respectively. The median interquartile range (IQR) dietary intakes showed inadequate intakes for most nutrients, except for carbohydrates (170 g [133; 225]). The total fat intake represented 14% of total energy intake. All median fatty acid intakes and sodium intakes (409 mg [169; 662]) were below the recommended levels. Only body mass index (BMI) correlated with HT (r = 0.268; p = 0.001). Despite low dietary intakes, an alarming prevalence of HT and obesity was found in our population. Hormonal changes, a high energy-dense diet and poor treatment adherence, may be possible underlying factors. We recommend measures to better manage HT as a CVR factor. This article supplements evidence on the prevalence of obesity-related hypertension in post-menopausal women and the link to dietary intake.


Characterisation of Bacillus subtilis transcriptional regulators involved in metabolic processes.
Transcriptional repressors and activators are principal control elements in bacterial gene expression. They are involved in the regulation of metabolic pathways, cell division, response to environmental signals, sporulation, replication, to name only a few. Whereas the discovery of these regulators was often fortuitous, a number of molecular, biochemical and biophysical methods have been established that allow to investigate these proteins in great detail and to help understand their functions in the living cell. In this review we focus on a selected set of well characterized transcriptional regulators from Bacillus subtilis and their analysis by methods like EMSA, DNase I footprinting, chemical interference footprinting, in vitro transcription, SELEX, CD measurements, FRET and determination of three-dimensional structure.


The diagnosis and management of hirsutism.
Approximately 10% of women of childbearing age are hirsute, which is defined as the presence of coarse terminal hairs in androgen-dependent areas on the face and body. It not only is a source of psychological discomfort but also may be a sign of an underlying medical condition. This article reviews the pathophysiology, diagnosis, evaluation, and treatment of hirsutism.


Encapsulation of Vitamin A palmitate for animal supplementation: Formulation, manufacturing and stability implications.
Two manufacturing methods and numerous formulative approaches have been evaluated to obtain a stable oral pharmaceutical form of Vitamin A palmitate (VAP), a substance very sensitive to light, temperature, humidity and metal ions. The best results were obtained by formulating VAP, stabilized with butylated hydroxytoluene (BHT), in double layer microcapsules constituted by a core of chitosan, Tween 20, CaCl(2) and EDTA surrounded by a first chitosan-alginate membrane and an outer membrane of calcium-alginate. This formulation design enabled the production of beads with high drug loading (42% w/w) and high encapsulation efficiency (94%). The stability of VAP-loaded microcapsules was assessed according to EMEA guidelines. This formulation design showed the best performance in terms of VAP recovery (t(50%) > 360 days) after 1 year of storage at room conditions. This is a very important result considering the poor shelf-life (45 days) of pure VAP stabilized with BHT stored at the same conditions.


Glycyrrhiza in old and new perspectives.
A chronological, documented summary of the reputed uses of glycyrrhiza since 2100 B.C. to the present with correlations made to modern pharmacological research. Many early claims for a broad spectrum of uses for this drug appear to be borne out by conclusions from modern research.


Broadband 2.12 GHz Ti:sapphire laser compressed to 5.9 femtoseconds using MIIPS.
We report a self-starting prismless femtosecond Ti:sapphire ring laser whose repetition rate has been gradually increased from 1 to 2.12 GHz. A broadband spectrum extending from 650 to 1040 nm, in which 17% of the intracavity power is generated in a single-pass through the crystal, is preserved in spite of the reduction in peak power. An average power of 0.95 W was obtained for 7.5 W of pump power, with very stable operation verified over 22 hours. Pulses from this laser have been fully characterized in spectral phase, and then compressed to 5.9 femtoseconds using multiphoton intrapulse interference phase scan (MIIPS).


Multi-channel time-resolved system for functional near infrared spectroscopy.
We have designed a compact dual wavelength multi-channel time-resolved system for functional near infrared spectroscopy. The system enables 16 sources and up to 64 collection points, with a minimum acquisition time of 5 ms per channel. Performances of the system have been tested on tissue phantoms in terms of linearity, noise, stability and reproducibility. Preliminary measurements on volunteers have been performed to validate the instrument capability to acquire in vivo maps of the hemodynamic parameters in the muscle during arterial occlusion and in the adult head during a finger tapping experiment.


Body mass index and waist circumference cutoffs to define obesity in indigenous New Zealanders.
The suggestion that body mass index (BMI) cutoffs to define obesity should differ in persons of Polynesian descent compared with Europeans is based principally on the observation that persons of Polynesian descent have a relatively higher proportion of lean body mass for a given BMI. The objectives were to determine whether the relation between BMI, waist circumference, and metabolic comorbidity differs in the 2 major ethnic groups in New Zealand and to ascertain whether ethnicity-specific BMI and waist circumference cutoffs for obesity are justified for Māori (indigenous New Zealanders). Subjects included a convenience sample of 1539 men and women aged 17-82 y (47% Māori, 53% white) with measures of BMI, waist circumference, blood pressure, fasting insulin, glucose, and lipids. The sensitivity and specificity of BMI (in kg/m(2); 30 and 32), waist circumference (80 and 88 cm in women, 94 and 102 cm in men), and waist-to-height ratio (WHtR; > or =0.6) in relation to insulin sensitivity, insulin resistance, and the metabolic syndrome were determined. Receiver operating characteristic curves and areas under the curve (AUCs) were also calculated. No ethnic or sex differences between AUCs were observed for BMI, waist circumference, or WHtR, which showed that these anthropometric measures perform similarly in Māori and European men and women and correctly discriminate between those with and without insulin resistance or the metabolic syndrome 79-87% of the time. Any increase in specificity from a higher BMI cutoff of 32 in Māori was offset by appreciable reductions in sensitivity. These findings argue against having different BMI or waist circumference cutoffs for people of Polynesian descent.


Direct measurement of thermophoretic forces.
We study the thermophoretic motion of a micron sized single colloidal particle in front of a flat wall by evanescent light scattering. To quantify thermophoretic effects we analyse the nonequilibrium steady state (NESS) of the particle in a constant temperature gradient perpendicular to the confining walls. We propose to determine thermophoretic forces from a "generalized potential" associated with the probability distribution of the particle position in the NESS. Experimentally we demonstrate, how this spatial probability distribution is measured and how thermophoretic forces can be extracted with 10 fN resolution. By varying temperature gradient and ambient temperature, the temperature dependence of Soret coefficient ST(T) is determined for r = 2.5 μm polystyrene and r = 1.35 μm melamine particles. The functional form of ST(T) is in good agreement with findings for smaller colloids. In addition, we measure and discuss hydrodynamic effects in the confined geometry. The theoretical and experimental technique proposed here extends thermophoresis measurements to so far inaccessible particle sizes and particle solvent combinations.


Genetic alteration of phospholipase C beta3 expression modulates behavioral and cellular responses to mu opioids.
Morphine and other micro opioids regulate a number of intracellular signaling pathways, including the one mediated by phospholipase C (PLC). By studying PLC beta3-deficient mice, we have established a strong link between PLC and mu opioid-mediated responses at both the behavioral and cellular levels. Mice lacking PLC beta3, when compared with the wild type, exhibited up to a 10-fold decrease in the ED(50) value for morphine in producing antinociception. The reduced ED(50) value was unlikely a result of changes in opioid receptor number or affinity because no differences were found in whole-brain B(max) and K(d) values for mu, kappa, and delta opioid receptors between wild-type and PLC beta3-null mice. We also found that opioid regulation of voltage-sensitive Ca(2+) channels in primary sensory neurons (dorsal root ganglion) was different between the two genotypes. Consistent with the behavioral findings, the specific mu agonist [D-Ala(2),(Me)Phe(4),Gly(ol)(5)]enkephalin (DAMGO) induced a greater whole-cell current reduction in a greater proportion of neurons isolated from the PLC beta3-null mice than from the wild type. In addition, reconstitution of recombinant PLC protein back into PLC beta3-deficient dorsal root ganglion neurons reduced DAMGO responses to those of wild-type neurons. In neurons of both genotypes, activation of protein kinase C with phorbol esters markedly reduced DAMGO-mediated Ca(2+) current reduction. These data demonstrate that PLC beta3 constitutes a significant pathway involved in negative modulation of mu opioid responses, perhaps via protein kinase C, and suggests the possibility that differences in opioid sensitivity among individuals could be, in part, because of genetic factors.


Specific inhibition of spermidine synthesis in Mycobacteria spp. by the dextro isomer of ethambutol.
Only the dextro isomer of ethambutol inhibited mycobacterial spermidine synthase and spermidine biosynthesis. Inhibition of mycobacterial spermidine synthase appeared to be specific. Spermidine synthase from Mycobacterium fortuitum, which was resistant to ethambutol in vitro, required a higher concentration of ethambutol for its inhibition than the enzyme of susceptible Mycobacterium bovis.


Increased survival of cirrhotic patients with a hepatocellular carcinoma detected during surveillance.
Significant improvements in management of hepatocellular carcinoma (HCC) have occurred in the last years, but their impact on surveillance outcome is unknown. To clarify this, we compared survival of HCC patients identified along 3 consecutive quinquennia of surveillance. A cohort of 417 HCC-free outpatients with compensated cirrhosis was prospectively followed for 148 months (range, 1-213 months) with periodic ultrasound examinations. HCC developed in 112 patients, at a 3.4% rate per year, and was the prime cause of death (n = 54). Forty-six (41%) patients had a single tumor, with a mean size of 3.7 cm, 3.0 cm, and 2.2 cm in the 3 quinquennia (first vs. second: ns; first vs. third: P = 0.017; second vs. third: P = 0.02), and 38 (44%) underwent radical therapy. Mortality rates in HCC patients fell from 45% in the first quinquennium to 37% in the second and 10% in the third (first vs. second: ns; first vs. third: P = 0.0009; second vs. third: P = 0.018) in parallel with a reduction in yearly mortality of treated patients (34%, 28%, and 5%, respectively; first vs. second: ns; second vs. third: P = 0.036; first vs. third: P = 0.0024). After stratification for quinquennium, tumor staging, according to Cancer of the Liver Italian Program (CLIP), was the only independent predictor of survival (P = 0.015). Cirrhotic patients developing a HCC during the last 5 years of surveillance survived longer than previously, as a consequence of improved management of the tumor and complications of cirrhosis.


Nuclear medicine imaging of bone infections.
Osteomyelitis is a broad group of infectious diseases that involve the bone and/or bone marrow. It can arise haematogenously, via extension from a contiguous infection, or by direct inoculation during surgery or trauma. The diagnosis is not always obvious and imaging tests are frequently performed as part of the diagnostic work-up. Commonly performed radionuclide tests include technetium-99m ((99m)Tc)-diphosphonate bone scintigraphy (bone), and gallium-67 ((67)Ga) and in vitro labelled leukocyte (white blood cell; WBC) imaging. Although they are useful, each of these tests has limitations. Bone scintigraphy is sensitive but not specific, especially when underlying osseous abnormalities are present. (67)Ga accumulates in tumour, trauma, and in aseptic inflammation; furthermore, there is typically an interval of 1-3 days between radiopharmaceutical injection of and imaging. Currently, this agent is used primarily for spinal infections. Except for the spine, WBC imaging is the nuclear medicine test of choice for diagnosing complicating osteomyelitis. The in vitro leukocyte labelling process requires skilled personnel, is laborious, and is not always available. Complementary marrow imaging is usually required to maximise accuracy. Not surprisingly, alternative radiopharmaceuticals are continuously being investigated. Radiolabelled anti-granulocyte antibodies and antibody fragments, investigated as in vivo leukocyte labelling agents, have their own limitations and are not widely available. (111)In-biotin is useful for diagnosing spinal infections. Radiolabelled synthetic fragments of ubiquicidin, a naturally occurring human antimicrobial peptide that targets bacteria, have shown promise as infection specific radiopharmaceuticals. 2-[(18)F]-fluoro-2-deoxy-d-glucose (FDG) positron-emission tomography (PET) with or without computed tomography (CT) is very useful in musculoskeletal infection. Sensitivities of more than 95% and specificities ranging from 75-99% have been reported in acute and subacute bone and soft-tissue infection. FDG is the radionuclide test of choice for spinal infection. It is sensitive, has a high negative predictive value, and can differentiate degenerative from infectious vertebral body end-plate abnormalities. Data on the accuracy of FDG for diagnosing diabetic pedal osteomyelitis and prosthetic joint infection are inconclusive and its role for these indications remains to be determined. Other PET radiopharmaceuticals that are under investigation as infection imaging agents include gallium-68 citrate ((68)Ga) and iodine-124 fialuridine ((124)I -FIAU).


The role of the immune response in age-related macular degeneration.
Age-related macular degeneration (AMD) is the leading cause of blindness in developed countries; with the aging population, the negative health impacts and costs of the disease will increase dramatically over the next decade. Although the exact cause of AMD is unknown, genetic studies have implicated the complement system as well as other immune responses in disease pathogenesis and severity. Furthermore, histologic studies have shown the presence of macrophages, lymphocytes, and mast cells, as well as fibroblasts, in both atrophic lesions and with retinal neovascularization. This review summarizes discussions from the fifth annual conference of the Arnold and Mabel Beckman Initiative for Macular Research by the Inflammation and Immune Response Task Force. These deliberations focused on the role of inflammatory immune responses, including complement, inflammasomes, adaptive immune responses, and para-inflammation, unanswered questions and studies to address these questions, and potential immune-related therapeutic targets for AMD.


Negative Trauma Appraisals and PTSD Symptoms in Sri Lankan Adolescents.
The cognitive model posits that negative appraisals play an important role in posttraumatic stress disorder, in children as well as in adults. This study examined correlates of negative appraisals in relation to trauma exposure and their relationship to posttraumatic stress symptoms (PTSS) in 414 Sri Lankan adolescents, aged 12 to 16, living in areas impacted in varying degrees by the 2004 tsunami. In 2008, participants completed measures of negative appraisals, lifetime traumatic events, posttraumatic stress symptoms, internalizing symptoms, ongoing adversity, and social support. The majority (70 %) of the participants reported multiple traumatic events; 25 % met DSM-IV criteria for full or partial PTSD. Adolescents who had experienced more severe events, abusive events, greater cumulative trauma, or greater current adversity reported more negative appraisals. In regression analyses controlling for known risk factors such as female gender, cumulative trauma, ongoing adversity, and low social support, negative appraisals were the best predictor of PTSS, explaining 22 % of the variance. This relationship appeared specific to PTSS, as negative appraisals did not predict internalizing symptoms. Findings confirm the link between negative cognitions concerning traumatic events and persistent PTSS in adolescents, but longitudinal studies are needed to determine whether appraisals contribute to symptom maintenance over time.


Gaming hospital-level pneumonia 30-day mortality and readmission measures by legitimate changes to diagnostic coding.
Risk-standardized 30-day mortality and hospital readmission rates for pneumonia are increasingly being tied to hospital reimbursement to incentivize the delivery of high-quality care. Such measures may be susceptible to gaming by recoding patients with pneumonia to a primary diagnosis of sepsis or respiratory failure. We sought to determine the degree to which hospitals can game mortality or readmission measures and change their rankings by recoding patients with pneumonia. Simulated experimental study of 2,906 U.S. acute care hospitals with at least 25 admissions for pneumonia using 2009 Medicare data. Elderly (age ≥ 65 yr) Medicare fee-for-service beneficiaries hospitalized with pneumonia. Patients eligible for recoding to sepsis or respiratory failure were those with a principal International Classification of Diseases, 9th Edition, Clinical Modification, discharge code for pneumonia and secondary codes for respiratory failure or acute organ dysfunction. None. We measured the number of hospitals that improved their pneumonia mortality or readmission rates after recoding eligible patients. When a sample of 100 hospitals with pneumonia mortality rates above the 50th percentile recoded all eligible patients to sepsis or respiratory failure, 90 hospitals (95% CI, 84-95) improved their mortality rate (mean improvement, 1.09%; 95% CI, 0.94-1.28%) and 41 hospitals dropped below the 50th percentile (95% CI, 33-52). When a sample of 100 hospitals with pneumonia readmission rates above the 50th percentile recoded all eligible patients, 66 hospitals (95% CI, 54-75) improved their readmission rate (mean improvement, 0.34%; 95% CI, 0.19-0.45%) and 15 hospitals (95% CI, 9-22) dropped below the 50th percentile. Hospitals can improve apparent pneumonia mortality and readmission rates by recoding pneumonia patients. Centers for Medicare and Medicaid Services should consider changes to their methods used to calculate hospital-level pneumonia outcome measures to make them less susceptible to gaming.


Cyclooxygenase-2 inhibitors in colorectal cancer prevention: counterpoint.
Aspirin is the best chemoprevention agent for colorectal cancer risk reduction despite the fact that the evidence for a decrease in mortality is weak. The cyclooxygenase-2 selective agents (COXIBS) have an efficacy similar to that of aspirin for most gastrointestinal (GI) lesions but not esophagus. Specifically, there are beneficial short term effects of COXIBs on the risk of colorectal adenoma as shown in the Approve, PreSAP, and APC studies. However, there is still an increased risk of upper GI complications with COXIBs when compared with placebo, and this risk may increase further in some people when aspirin is also consumed. Whereas aspirin reduces the risk of cardiovascular events, COXIBs and most traditional nonsteroidal anti-inflammatory drugs (but not all) are both associated with an increased risk of thrombotic cardiovascular events compared with placebo. In conclusion, COXIBs have a niche role for patients with familial adenomatous polyposis. The value of aspirin remains with respect for efficacy, mainly in the esophagus, and the side effect profile, especially in the elderly if given with acid suppression therapy. COXIBs should be used in younger populations, but if they are considered in the elderly because of increased GI risks, and the cardiovascular risk is also increased, then combination treatment with aspirin and a proton-pump inhibitor should also be considered instead, such as in the ASPECT trial.


Classification of Alzheimer's Disease Using Whole Brain Hierarchical Network.
Regions of interest (ROIs) based classification has been widely investigated for analysis of brain magnetic resonance imaging (MRI) images to assist the diagnosis of Alzheimer's disease (AD) including its early warning and developing stages, e.g., mild cognitive impairment (MCI) including MCI converted to AD (MCIc) and MCI not converted to AD (MCInc). Since an ROI representation of brain structures is obtained either by pre-definition or by adaptive parcellation, the corresponding ROI in different brains can be measured. However, due to noise and small sample size of MRI images, representations generated from single or multiple ROIs may not be sufficient to reveal the underlying anatomical differences between the groups of disease-affected patients and health controls (HC). In this paper, we employ a whole brain hierarchical network (WBHN) to represent each subject. The whole brain of each subject is divided into 90, 54, 14, and 1 regions based on Automated Anatomical Labeling (AAL) atlas. The connectivity between each pair of regions is computed in terms of Pearson's correlation coefficient and used as classification feature. Then, to reduce the dimensionality of features, we select the features with higher scores. Finally, we use multiple kernel boosting (MKBoost) algorithm to perform the classification. Our proposed method is evaluated on MRI images of 710 subjects (200 AD, 120 MCIc, 160 MCInc, and 230 HC) from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. The experimental results show that our proposed method achieves an accuracy of 94.65 percent and an area under the receiver operating characteristic (ROC) curve (AUC) of 0.954 for AD/HC classification, an accuracy of 89.63 percent and an AUC of 0.907 for AD/MCI classification, an accuracy of 85.79 percent and an AUC of 0.826 for MCI/HC classification, and an accuracy of 72.08 percent and an AUC of 0.716 for MCIc/MCInc classification, respectively. Our results demonstrate that our proposed method is efficient and promising for clinical applications for the diagnosis of AD via MRI images.


Update of a study of crude oil production workers 1946-94.
To update information on workers in the petroleum industry engaged in the production of crude oil to determine whether the patterns of mortality have changed with 14 additional years of follow up. All workers were employed at company production and pipeline locations sometime during 1946-94. The cohort now consists of 24 124 employees with an average of 22 years of follow up. The overall mortality, and most cause specific mortalities were lower than or similar to those for the general United States population. For white men (81% of the cohort), there were 4361 observed deaths and 5945 expected, resulting in a significantly lower standardised mortality ratio (SMR) of 73. There were significant deficits for all the leading causes of death in the United States including all cancers, cancer of the lung, stroke, heart disease, respiratory disease, and accidents. Slightly increased mortality was found for cancer of the prostate, cancer of the brain and central nervous system, and cancer of other lymphatic tissue. For benign and unspecified neoplasms, the SMR was 152 (95% confidence interval (95% CI) 95 to 230). There was a significant increase for acute myelogenous leukaemia that was restricted to people who were first employed before 1940 and who were employed in production and pipeline jobs for >30 years. Overall mortality patterns for non-white men and women were similar to those for white men. Mortality patterns for white men were also examined by duration of employment, time first employed, and by job group. The results of the updated study showed a favourable mortality experience for crude oil production workers compared with the United States population.


Hereditary common cancers: molecular and clinical genetics.
This review focuses on the functional role and structural features of the genes involved in common hereditary cancers. Most of these tumors are sporadic and the genetic alterations responsible for their genesis take place over several cell generations; nevertheless, 5 to 10% of the human tumors are hereditary, with a rapid development. Cancer susceptibility genes have been classified as "gatekeepers" (e.g. RB1, ki-ras) and "caretakers" (e.g. hMLH1 and hMSH2, BRCA1). The first step in identifying individuals at high risk of developing a specific inherited form of cancer, and who should therefore undergo genetic tests, is the detailed construction of family history (an accurate cancer family history that includes at least three generation pedigrees, an appropriate cancer risk assessment and an effective genetic counseling). At present, the most useful methods of risk assessment are those performed on the following genes: BRCA1 and BRCA2 especially for hereditary breast and ovarian cancer, hMLH1 and hMSH2 for hereditary non polyposis colorectal cancer, APC for familial adenomatous polyposis, ret for medullary thyroid carcinoma, p53 for the Li-Fraumeni syndrome, p16 for melanoma and RB1 for retinoblastoma. In conclusion, the development of new diagnostic tests will permit a more accurate assessment of risk in individuals who have not so far shown any sign or symptom of the disease.


Bilayer versus Polymeric Artificial Water Channel Membranes: Structural Determinants for Enhanced Filtration Performances.
Artificial water channels (AWCs) and their natural aquaporin counterparts selectively transport water. They represent a tremendous source of inspiration to devise biomimetic membranes for several applications, including desalination. They contain variable water-channel constructs with adaptative architectures and morphologies. Herein, we critically discuss the structural details that can impact the performances of biomimetic I quartets, obtained via adaptive self-assembly of alkylureido-ethylimidazoles HC4-HC18 in bilayer or polyamide (PA) membranes. We first explore the performances in bilayer membranes, identifying that hydrophobicity is an essential key parameter to increase water permeability. We compare various I quartets with different hydrophobic tails (from HC4 to HC18), and we reveal that a huge increase in single-channel water permeability, from 104 to 107 water molecules/s/channel, is obtained by increasing the size of the alkyl tail. Quantitative assessment of AWC-PA membranes shows that water permeability increases roughly from 2.09 to 3.85 L m-2 h-1 bar-1, for HC4 and HC6 reverse osmosis membranes, respectively, while maintaining excellent NaCl rejection (99.25-99.51%). Meanwhile, comparable HC8 loading induces a drop of performance reminiscent of a defective membrane formation. We show that the production of nanoscale sponge-like water channels can be obtained with insoluble, low soluble, and low dispersed AWCs, explaining the observed subpar performance. We conclude that optimal solubility enabling breakthrough performance must be considered to not only maximize the inclusion and the stability in the bilayer membranes but also achieve an effective homogeneous distribution of percolated particles that minimizes the defects in hybrid polyamide membranes.


Integrated analysis of a phase 2 study of cemiplimab in advanced cutaneous squamous cell carcinoma: extended follow-up of outcomes and quality of life analysis.
To provide pooled longer term data from three groups of a phase 2 study of cemiplimab in patients with advanced cutaneous squamous cell carcinoma (CSCC), and to determine duration of response (DOR) and impact on quality of life (QoL). Patients received cemiplimab 3 mg/kg every 2 weeks (group 1, metastatic CSCC [mCSCC], n=59; group 2, locally advanced CSCC, n=78) or cemiplimab 350 mg every 3 weeks (group 3, mCSCC, n=56). Primary endpoint was objective response rate (ORR) per independent central review (ICR). QoL was repeatedly measured at day 1 of each treatment cycle (groups 1 and 2: 8 weeks; group 3: 9 weeks). Median duration of follow-up was 15.7 months. Overall, ORR per ICR was 46.1% (95% CI: 38.9% to 53.4%). Complete response (CR) rates were 20.3%, 12.8%, and 16.1% for groups 1, 2, and 3, respectively. Median time to CR was 11.2 months. Among patients with partial response or CR, the estimated proportion of patients with ongoing response at 12 months from the first objective response was 87.8% (95% CI: 78.5% to 93.3%), with median DOR not reached. Kaplan-Meier estimated probability of overall survival (OS) was 73.3% (95% CI: 66.1% to 79.2%) at 24 months, with median OS not reached. Global Health Status (GHS)/QoL improvements were observed as early as cycle 2 and were significantly improved and durable until last assessment. Kaplan-Meier estimate of median time to first clinically meaningful improvement for pain was 2.1 (95% CI: 2.0 to 3.7) months and was significantly improved in responders versus non-responders (p<0.0001). This is the largest (n=193) clinical dataset for a programmed cell death-1 inhibitor against advanced CSCC, confirming the sustained substantial clinical activity of cemiplimab in these patients, including new findings of improved CR rates over time, increasing DOR, and durable pain control and GHS/QoL improvement. ClinicalTrials.gov Registry (NCT02760498), https://clinicaltrialsgov/ct2/show/NCT02760498.