Production of isotopically labeled standards from a uniformly labeled precursor for quantitative volatile metabolomic studies.
Optimal accuracy and precision in small-molecule profiling by mass spectrometry generally requires isotopically labeled standards chemically representative of all compounds of interest. However, preparation of mixed standards from commercially available pure compounds is often prohibitively expensive and time-consuming, and many labeled compounds are not available in pure form. We used a single-prototype uniformly labeled [U-(13)C]compound to generate [U-(13)C]-labeled volatile standards for use in subsequent experimental profiling studies. [U-(13)C]-α-Linolenic acid (18:3n-3, ALA) was thermally oxidized to produce labeled lipid degradation volatiles which were subsequently characterized qualitatively and quantitatively. Twenty-five [U-(13)C]-labeled volatiles were identified by headspace solid-phase microextraction-gas chromatography/time-of-flight mass spectrometry (HS-SPME-GC/TOF-MS) by comparison of spectra with unlabeled volatiles. Labeled volatiles were quantified by a reverse isotope dilution procedure. Using the [U-(13)C]-labeled standards, limits of detection comparable to or better than those of previous HS-SPME reports were achieved, 0.010-1.04 ng/g. The performance of the [U-(13)C]-labeled volatile standards was evaluated using a commodity soybean oil (CSO) oxidized at 60 °C from 0 to 15 d. Relative responses of n-decane, an unlabeled internal standard otherwise absent from the mixture, and [U-(13)C]-labeled oxidation products changed by up to 8-fold as the CSO matrix was oxidized, demonstrating that reliance on a single standard in volatile profiling studies yields inaccurate results due to changing matrix effects. The [U-(13)C]-labeled standard mixture was used to quantify 25 volatiles in oxidized CSO and low-ALA soybean oil with an average relative standard deviation of 8.5%. Extension of this approach to other labeled substrates, e.g., [U-(13)C]-labeled sugars and amino acids, for profiling studies should be feasible and can dramatically improve quantitative results compared to use of a single standard.


Using Personal Mobile Phones to Assess Dietary Intake in Free-Living Adolescents: Comparison of Face-to-Face Versus Telephone Training.
Traditional paper-based methods to assess food intake can be cumbersome for adolescents; use of mobile phones to track and photograph what they eat may be a more convenient, reliable, and compelling way to collect data. Our aims were to determine (1) the feasibility of using personal mobile phones to send food records with digital images (FRDIs) among free-living adolescents and (2) whether the quality of food records differed between a high-level intervention group (ie, face-to-face training plus real-time support) and a low-level intervention group (ie, telephone training plus next-day follow-up). Adolescents (N=42, 11 males and 31 females) aged 12-18 years who had a mobile phone with camera enrolled in the study via consecutive sampling. The first group (n=21) received face-to-face training while the second group (n=21) was trained via telephone. Participants received a fiducial marker (FM) and completed a 1-day FRDI using their mobile phones. At every eating occasion, participants were to (1) take clear images of their meals/food with a correctly placed fiducial marker before eating, (2) send the image immediately to a designated email address, (3) right after completing a meal, send a text message listing the time and name of the meal, foods eaten, and amounts eaten, and (4) before sleep, send an "end" text message to indicate completion of food recording. Those who received face-to-face training received real-time support during reporting; those trained by telephone received next-day follow-up. Descriptive statistics and comparison tests were used to determine performance of the groups. All participants (N=42) who underwent training completed their 1-day FRDI. A significantly greater proportion of the low-level intervention group compared to the high-level intervention group placed their FM correctly in the image (95% vs 43%, P<.001), had complete information for each meal in their food record (95% vs 71%, P=.04), and had a higher overall score in meeting the criteria for food recording (4.3 vs 3.4 out of 5 points). Both groups had energy intake values that moderately correlated with their estimated energy requirements: low-intervention r=.55; high-intervention r=.51. Using personal mobile phones to report dietary intake via texting and digital images is feasible among free-living adolescents. Real-time support or high-level intervention does not guarantee better food recording quality among adolescents.


Reconceptualizing successful aging among black women and the relevance of the strong black woman archetype.
Although there are multiple pathways to successful aging, little is known of what it means to age successfully among black women. There is a growing body of literature suggesting that black women experience a number of social challenges (sexism and racism) that may present as barriers to aging successfully. Applying aspects of the Strong Black Women ideal, into theoretical concepts of successful aging, may be particularly relevant in understanding which factors impair or promote the ability of black women to age successfully. The Strong Black Women archetype is a culturally salient ideal prescribing that black women render a guise of self-reliance, selflessness, and psychological, emotional, and physical strength. Although this ideal has received considerable attention in the behavioral sciences, it has been largely absent within the gerontology field. Nevertheless, understanding the dynamics of this cultural ideal may enhance our knowledge while developing an appreciation of the black woman's ability to age successfully. Rather than summarize the social, physical, and mental health literature focusing on health outcomes of black women, this conceptual review examines the Strong Black Women archetype and its application to the lived experiences of black women and contributions to current theories of successful aging. Focusing on successful aging exclusively among black women enhances our understanding of this group by considering their identity as women of color while recognizing factors that dictate their ability to age successfully.


Hybrid modelling of biological systems: current progress and future prospects.
Integrated modelling of biological systems is becoming a necessity for constructing models containing the major biochemical processes of such systems in order to obtain a holistic understanding of their dynamics and to elucidate emergent behaviours. Hybrid modelling methods are crucial to achieve integrated modelling of biological systems. This paper reviews currently popular hybrid modelling methods, developed for systems biology, mainly revealing why they are proposed, how they are formed from single modelling formalisms and how to simulate them. By doing this, we identify future research requirements regarding hybrid approaches for further promoting integrated modelling of biological systems.


Accidental monensin sodium intoxication of feedlot cattle.
Of 1,994 yearling and 2-year-old cattle in a winter feeding program, 117 died within 42 days of being fed toxic amounts of monensin sodium in a liquid protein supplement. Death losses commenced on the third day after ingestion of a toxic amount in the feed. Clinical signs in cattle that died in less than 9 days included anorexia, pica, diarrhea, depression, mild hindlimb ataxia, and dyspnea. Gross necropsy findings in cattle dying in the acute phase of the illness included hydrothorax, ascites, and pulmonary edema, as well as petechial hemorrhages, edema, and yellow streaking in skeletal and cardiac muscle. Cattle dying after 9 days had gray streaks in heart and skeletal muscle, generalized ventral edema, enlarged, firm, bluish discolored liver, and enlarged heart. Microscopic changes in cattle dying in the acute phase (less than 9 days) consisted of pulmonary edema, congestion, and hemorrhage. Cardiac and skeletal muscle had localized areas of edema, hemorrhage, and coagulative necrosis. In cattle dying after 9 days of illness, the changes included lymphocytic infiltration, sarcolemmal nuclear proliferation, and fibrosis in skeletal and cardiac muscle. Lungs contained increased alveolar macrophages and a few neutrophils. Centrilobular necrosis and mild fibrosis were found in the liver. Changes varied somewhat according to the area of heart or skeletal muscle that was affected. Active muscles, eg, those in the heart ventricles and diaphragm, were altered most severely. Intoxication appeared to be a result of sedimentation of monensin in the molasses carrier to give remarkable concentrations of the substance at the bottom of the holding tank.


Relationship of impaired-driving enforcement intensity to drinking and driving on the roads.
It is principally the area of enforcement that offers the greatest opportunity for reducing alcohol-impaired driving in the near future. How much of a reduction in drinking and driving would be achieved by how much improvement in enforcement intensity? We developed logistic regression models to explore how enforcement intensity (6 different measures) related to the prevalence of weekend nighttime drivers in the 2007 National Roadside Survey who had been drinking (blood alcohol concentration [BAC] ≥ 0.00 g/dl), who had BACs ≥ 0.05 g/dl, and who were driving with an illegal BAC ≥ 0.08 g/dl. Drivers on the roads in our sample of 30 communities who were exposed to fewer than 228 traffic stops per 10,000 population aged 18 and older had 2.4 times the odds of being BAC positive, 3.6 times the odds of driving with a BAC ≥ 0.05, and 3.8 times the odds of driving with a BAC ≥ 0.08 compared to those drivers on the roads in communities with more than 1,275 traffic stops per 10,000 population. Drivers on the roads in communities with fewer than 3.7 driving under the influence (DUI) arrests per 10,000 population had 2.7 times the odds of BAC-positive drivers on the roads compared to communities with the highest intensity of DUI arrest activity (>38 DUI arrests per 10,000 population). The number of traffic stops and DUI arrests per capita were significantly associated with the odds of drinking and driving on the roads in these communities. This might reflect traffic enforcement visibility. The findings in this study may help law enforcement agencies around the country adjust their traffic enforcement intensity to reduce impaired driving in their community.


A comparison of quadratic versus segmented regression procedures for estimating nutrient requirements.
Continued improvements in dietary formulation will require increasingly detailed knowledge of nutrient requirements. The objective of this study was to evaluate bias and precision of estimates of nutrient requirements from quadratic versus segmented regression. One hundred 0-to-3-wk turkey growth experiments were simulated to provide data with known nutrient requirements. Nine diets contained levels of an arbitrary nutrient ranging from 80 to 120% of recommended. The true nutrient requirement was uniformly randomly distributed between 90 and 110% of recommended. The requirements were estimated as the intersection of the segmented regression lines from a two-slope model, and 0.90 and 0.95 of the maximum gain predicted from quadratic regression coefficients. The mean true requirement was 99.42%, and predictions were 102.14+/-0.61, 107.81+/-0.61, and 99.59+/-0.61% for 0.90 of quadratic maximum, 0.95 of quadratic maximum and segmented regression, respectively. The segmented regression resulted in the closest prediction to the true nutrient requirement in 73 of 100 replicates. The average squared deviation of the requirement from their estimates were 15.18 for 0.90 of quadratic maximum, 78.72 for 0.95 of quadratic maximum, and 2.41 for segmented regression. The quadratic regressions yielded overestimates, particularly when the experimental diets were not centered on the requirement, suggesting that a bias can be introduced by experimental design. Segmented regression procedures resulted in more precise estimates of nutrient requirements, were less likely to suffer from bias, and required less a priori knowledge of the true requirement than did quadratic regression procedures.


Role of neutrophil-derived matrix metalloproteinase-9 in tissue regeneration.
Ischemic tissue regeneration depends on neovascularization, the growth of new blood vessels. Bone marrow (BM)-derived cells, including neutrophils, have been shown to contribute to neovascularization during hind limb ischemia and inflammation. Neutrophils produce a broad array of angiogenic growth factors and proteases, which promote remodeling of arterioles into arteries through proteolytic mechanisms. Matrix metalloproteinases (MMPs) have been shown to play a role in the recruitment of neutrophils to sites of inflammation, which requires the extravascular migration of neutrophils through the extracellular matrix. Neutrophils control critical steps during angiogenesis and neutrophil-derived MMPs can promote neoangiogenesis, and collateral growth and perfusion recovery, in part by liberating vital angiogenic growth factors, including vascular endothelial growth factor-A (VEGF-A). This review focuses on the role of neutrophils as key players in the control of the angiogenic process during ischemic tissue regeneration. Aspects of neutrophil regulation, in particular regulation by its major growth factor granulocyte colony-stimulating factor (G-CSF), the role of the unique, readily available, neutrophil-derived MMP-9, and the functional consequences of this MMP-9 activation for angiogenesis, such as MMP-mediated release of biologically relevant cytokines from the matrix and cell surfaces, will be discussed.


[Characteristics of Modified Biochars and Their Immobilization Effect on Cu and Cd in Polluted Farmland Soil Around Smelter].
Heavy metals in farmland soil are one of the most hazardous pollutants in the environment, owing to their universality and irreversibility. Modified biochar has been widely used in the adsorption and immobilization of heavy metals in soil, and its applicability is mainly determined by the types of heavy metals, pollution levels, and soil environmental conditions. Soil pollution is gradually becoming more complex and diversified, and heavy metal pollutants mostly occur in the form of compound pollution. However, most studies have focused on single heavy metal pollutant or the addition of heavy metal to soil. This study used rice straw as a raw material to prepare biochar, and modified it with K3PO4, KMnO4, and NaOH. The physicochemical and structural characteristics of the modified biochars were detected using a BET accelerated surface area and porosimetry system, scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), and the biochars were then analyzed for the availability and forms of Cd and Cu in soils contaminated with heavy metals in the mining area. The results showed that the surface roughness of the modified biochar increased to different degrees with increases in specific surface area and pore volume, with the NaOH modified biochar showing the most significant increases from 4.96 m2·g-1 to 60.79 m2·g-1, and from 0.02 cm3·g-1 to 0.12 cm3·g-1, respectively. The pore diameter changed in the opposite direction. The absorption peaks of the functional groups of the modified biochar were all changed, with K3PO4 modified biochar exhibiting the greatest degree of change. The addition of biochar significantly improved the soil pH value (P<0.05), and the pH value of the soil treated with K3PO4 modified biochar exhibited the largest increase. With an application of 20.5% K3PO4 modified biochar, the availability of Cu and Cd in the soil was significantly reduced, by 75.44% and 67.70%, respectively. The immobilization efficiency of Cu was much higher than that of Cd. The best immobilization efficiency of Cu and Cd in soil was achieved with K3PO4 modified biochar. With an addition of 2% K3PO4 modified biochar, the immobilization efficiency of Cu and Cd was 61.06% and 4.12%, respectively. In summary, K3PO4 modified biochar had a better immobilization effect on both Cu and Cd in compound contaminated soil.


"Click" chemistry in polymeric scaffolds: Bioactive materials for tissue engineering.
Polymeric scaffolds have attracted great interests in recent years, due to their fascination with a large variety of examples with promising utilization. Recently, extensive efforts have been devoted to the exploitation of robust and functional polymer-based biomaterial scaffolds with high efficiency. The recent entry of so-called "click" reactions that include kinds of selective and orthogonal reactions under mild conditions have generated real stimulus not only in preparing elegant bioactive materials of choice but also in making the leap to industrial scale build-up of multifunctional products. In this review paper, we account several kinds of polymeric scaffolds prepared/modified via "click" reactions, with emphasis on their synthetic/functionalized strategies, tunable properties, and biomedical applications.


[The place of radiologic research procedures in the diagnosis of aortic dissection].
Aortic dissection is a rare but life-threatening disease that requires a prompt and exact diagnosis. That is why the radiologist now assumes a central role due to the introduction of new imaging modalities. Each of them can make a contribution while having its own limitations. The choice of the right examination procedure and its correct application determine a successful radiological diagnosis. On the basis of experience with more than 150 operated patients we explain our diagnostic strategy in aortic dissection.


Skin renewal activity of non-thermal plasma through the activation of β-catenin in keratinocytes.
For recent years, devices that generate non-thermal plasma (NTP) have been introduced into the field of dermatology. Since NTP has demonstrated strong anti-pathogenic activity with safety of use, NTP was first applied to sterilize the skin surface to aid in the healing of various kinds of skin diseases. However, the effect of NTP on skin regeneration has not yet been fully explored. In this study, the effect of NTP on the growth of keratinocytes was tested using the HaCaT human keratinocyte cell line and HRM2 hairless mice. Treatment with NTP allowed confluent keratinocytes to escape from G1 cell cycle arrest and increased the proportion of cells in S and G2 phases. In particular, NTP treatment immediately dispersed E-cadherin-mediated cell-to-cell interactions, resulting in the translocation of β-catenin to the nucleus and leading to the enhanced transcription of target genes including c-MYC and cyclin D1. Moreover, repeated treatment of the mice with NTP also stimulated epidermal expansion by activating β-catenin in the epidermal cells. The symptoms of cellular DNA damage were not detected after NTP treatment. Taken together, these results demonstrate that NTP may be employed as a new type of skin regenerating device.


BioMEMS for biosensors and closed-loop drug delivery.
The efficacy of pharmaceutical treatments can be greatly enhanced by physiological feedback from the patient using biosensors, though this is often invasive or infeasible. By adapting microelectromechanical systems (MEMS) technology to miniaturize such biosensors, previously inaccessible signals can be obtained, often from inside the patient. This is enabled by the device's extremely small footprint which minimizes both power consumption and implantation trauma, as well as the transport time for chemical analytes, in turn decreasing the sensor's response time. MEMS fabrication also allows mass production which can be easily scaled without sacrificing its high reproducibility and reliability, and allows seamless integration with control circuitry and telemetry which is already produced using the same materials and fabrication steps. By integrating these systems with drug delivery devices, many of which are also MEMS-based, closed loop drug delivery can be achieved. This paper surveys the types of signal transduction devices available for biosensing-primarily electrochemical, optical, and mechanical-looking at their implementation via MEMS technology. The impact of MEMS technology on the challenges of biosensor development, particularly safety, power consumption, degradation, fouling, and foreign body response, are also discussed.


Multicentric clinical trials for safety and efficacy evaluation of alpha;beta arteether in complicated P. falciparum malaria.
To evaluate efficacy of alpha;beta arteether in patients of P. falciparum malaria presenting with complications was undertaken in a multicentric clinical trial. Each patient who consented to undergo clinical trial with parenteral Arteether was treated with a fixed dose schedule of Arteether given intramuscularly in a dose of 150 mg once a day on three consecutive days. Every patient was followed upto 28 days with clinical, haematological and parasitological monitoring every day upto one week and thereafter at 14, 21 and 28 days. The response was assessed in terms of fever clearance time, parasite clearance time, cure rate and parasite reappearance rate. A total of 211 patients of P. falciparum malaria were included in the study from four centres (Bhilai, Guwahati, Jamshedpur and Rourkela). Results of this study showed that fever clearance time ranged between 24-168 hours, parasite clearance time ranged between 24-120 hours and overall mortality ranged between 4-8.5%. Out of 211, only 14 patients expired during the study, of these, 10 patients expired within first two days i.e. before completing the three day schedule of arteether therapy. Tolerability to arteether injection was good in all these patients and no untoward effects were experienced or reported during the study. Overall cure rate observed in these studies was 93%. This study shows a rapid parasite and fever clearance in patients of complicated P. falciparum malaria.


Minimally-invasive neonatal surgery: laparoscopic excision of choledochal cysts in neonates.
Improvements in surgical techniques and a better understanding of the unique anesthetic requirements in neonates undergoing laparoscopy have suggested that laparoscopic surgery may be effective in newborns. This study therefore evaluated the safety and feasibility of laparoscopic excision of the cyst (LEC) in neonates. This retrospective study included 43 neonates who underwent excision of choledochal cysts between November, 2001, and January, 2018, including 21 who underwent open excision and 22 who underwent LEC. Their perioperative and surgical outcomes were reviewed. The patients were followed up for a median 37 months (range, 3-141 months). Baseline characteristics did not differ significantly in the open and LEC groups. Mean intraoperative peak partial pressure of arterial CO2 (PaCO2) (45.5 mmHg vs. 48.0 mmHg) and total operation time (208.3 ± 71.0 minutes vs. 235.0 ± 47.2 minutes) were similar in both groups. Parents of the patients in the LEC group provided a more positive evaluation of scar scale and greater satisfaction with wound. No patient in either group experienced any critical complications. Three patients in the open excision group required readmission for cholangitis and 2 patients had ileus. No patient in the laparoscopic excision group experienced any postoperative complications during follow-up. Despite difficulties performing laparoscopic surgery in neonates, LEC was safe and feasible when intraperitoneal peak pressure was maintained under 10 mmHg and PaCO2 was closely monitored by a pediatric anesthesiologist. Compared with open excision, LEC provided improved cosmetic outcomes without severe complications. Prospective randomized studies with large numbers of patients are warranted.


Ozone inactivation of human alpha 1-proteinase inhibitor.
Ozone decreased the trypsin, chymotrypsin, and elastase inhibitory activities of human alpha 1-proteinase inhibitor (alpha 1-PI) both in plasma and in solutions of the pure inhibitor. The total loss of porcine elastase inhibitory activity required 18 mol of ozone/mol of pure alpha 1-PI and approximately 850 mol of ozone/mol of alpha 1-PI in plasma. A corresponding loss of the ability to inhibit human leukocyte elastase was observed. Inactivated alpha 1-PI contains four residues of methionine sulfoxide, in addition to oxidized tyrosine and tryptophan. Electrophoretic analysis demonstrated that the ozone-inactivated alpha 1-PI did not form normal complexes witrh serine proteinases. These findings suggest that the inhalation of ozone could inactivate alpha 1-PI on the airspace side of the lung to create a localized alpha 1-PI deficiency, which might contribute to the development of emphysema.


Cell mediated responses in a porcine enterovirus infection in piglets.
Sixteen pathogen-free piglets were infected orally with procine enterovirus strain T80 and the cell mediated response to the virus was measured at intervals after infection. Five uninfected piglets were used as controls. Indirect macrophage migration inhibition tests were performed with lymphocytes from blood, ileal lamina propria and mesenteric lymph node. Blood lymphocyte culture supernatants showed no consistent T80 specific on macrophage migration, suggesting the absence of a systemic cell-mediated response. Ileal lamina propria lymphocyte culture supernatants showed irregular migration stimulation. The mesenteric lymph node lymphocyte culture supernatants produced migration inhibition at seven days postinfection, followed by stimulation of migration from ten to 22 days postinfection. Subsequently, migration was again inhibited from 24 to 31 days postinfection. Mesenteric lymph node lymphocyte culture supernatants contained only trace amounts of interferon activity at 28 and 31 days postinfection. It was concluded that the cell mediated responses in this infection were weak and localized and not associated with significant antiviral activity.


β-Glucocerebrosidase gene mutations in two cohorts of Greek patients with sporadic Parkinson's disease.
An increasing number of clinical, neuropathological and experimental evidence linking Gaucher disease and a spectrum of synucleinopathies, including Parkinson's disease (PD) has emerged over the last decade. In particular, several studies, despite individual differences, have shown that mutations in the β-glucocerebrosidase gene (GBA) are a risk factor for PD. Recently a study from Northern Greece has shown a significant overrepresentation of such mutations only in patients with early onset PD. In the present study 8 different GBA mutations covering 87% of the mutations identified in Gaucher disease patients diagnosed in Greece were investigated in two ethnic Greek cohorts of patients with sporadic Parkinson's disease. Cohort A included patients residing and originating from Thessaly, Central Greece (n=100) and cohort B included patients residing and/or originating from the greater area of Athens (n=105). Age-gender-ethnicity matched healthy individuals from the same areas were included as controls (n=206). In patients of cohort A 11 carriers of GBA mutations were identified (5/11:N370S, 2/11:L444P, 2/11: D409H;H255Q, 1/11:H255Q, 1/11D409H) as opposed to 3 in the controls (n=105) (1/3:N370S, 1/3:H255Q, 1/3:Y108C) (p=0.021, OR 4.2, 95% CI=1.14-15.54). In patients of cohort B 10 carriers of GBA mutations were identified (4/10:L444P, 4/10:D409H;H255Q, 1/10:N370S, 1/10:IVS10-1G→A) as opposed to 4 in controls (n=101) (3/4:N370S, 1/4:L444P). However the difference was not statistically significant (p=0.113, OR 2.5, 95% CI=0.77-8.42). In both cohorts, patients with PD harboring a GBA mutation had an earlier onset of symptoms than non-carriers (p=0.034, p=0.004). The overall difference in the number of carriers identified in PD patients and controls was statistically significant (p=0.006; OR 3.24; 95% CI=1.35-7.81). The association was reinforced in the early onset PD patients (EOPD; n=28, p=0.000, OR 11.37; 95% CI=3.73-34.6). In conclusion GBA mutations were identified with increased frequency in both geographical cohorts of patients with sporadic PD studied compared to control individuals, with the difference being statistically significant only in cohort A. An impressive association with EOPD was found and one third of the EOPD patients examined harbored a GBA mutation. Qualitative differences regarding the type of mutations and/or their relative frequencies were observed between cohorts A and B of PD patients. Genetic and/or environmental factors may account for the observed differences.


Analysis of the clinical effect of the concept of "shoulder preservation" in the treatment of proximal humeral fractures: a retrospective cohort study of 66 patients.
The three- and four-part fractures of the proximal humerus are often combined with rotator cuff injury, and shoulder joint replacement is often selected clinically. The concept of "shoulder preservation" can greatly restore the function of the shoulder joint through internal fixation of the proximal humerus fracture and rotator cuff suture. This study investigated the clinical effect of the concept of "shoulder preservation" in the treatment of three- and four-part fractures of the proximal humerus. We conducted a retrospective analysis of 66 patients with proximal humeral fractures (PHFs) who were treated at the Affiliated Hospital of Qinghai University between 2016 and 2019. The patients were divided into 3 groups according to the Neer fracture classification system, and the fracture healing time of the 3 groups was compared. A visual analog scale (VAS) was used to evaluate the pain, and the Neer score was used to evaluate shoulder joint function. The operations were successfully completed and the 3 groups of patients were compared in pairs. All incisions healed by first intention after operation, and no early complications occurred. The average follow-up time was 18 months. All fractures had healed. The VAS score of the 3 groups of patients was 1.5±0.5 at 1 month after operation and 1.0±0.5 at the final follow-up, which was significantly improved compared with preoperative scores, although the difference was not statistically significant (P>0.05). The Neer scores of the first group of patients at 1, 3, and 9 months postsurgery were higher than those of the second and third groups, and the difference was statistically significant (P<0.05). There was no significant difference among the 3 groups in Neer score 12 months after the operation (P>0.05). Proximal humeral internal locking osteosynthesis system (PHILOS) fixation + rotator cuff suture is a reliable treatment method involving a simple operation, firm fixation, and good postoperative recovery. It can restore shoulder joint function to the greatest extent, but it also has some shortcomings, including slow recovery time.


Perspectives in renal disease progression: the endothelium as a treatment target in chronic kidney disease.
The endothelial cell layer is the "guardian" of molecular traffic between the blood and surrounding tissue, and endothelial integrity plays a pivotal role in many aspects of vascular function: e.g., control of vasomotor tone and permeability. Cardiovascular risk factors such as hypertension may cause endothelial dysfunction and even disintegration, finally resulting in small vessel disappearance (vascular rarefaction) and tissue hypoxia. In patients with chronic kidney diseases (CKD), ongoing endothelial damage in the capillary system of the renal medulla and accompanying vascular rarefaction are thought to be central processes toward progressive kidney damage. In this respect, reduced nitric oxide synthesis by endothelial cells due to accumulation of endogenous inhibitors of the nitric oxide synthase such as asymmetric dimethylarginine (ADMA) has been accused of accelerating progression. Thus, reducing ADMA blood levels could be potentially beneficial in clinical trials aimed at reducing the loss of kidney function in CKD patients. Another molecule coming into the focus of cardiovascular medicine is erythropoietin (EPO). Recent experimental studies have shown that EPO - beside its effect on hematopoietic cells - protects endothelial cell function and integrity and has vasculoprotective properties. EPO could therefore prevent renal tissue injury and CKD progression due to vascular rarefaction and hypoxia.


Inhibition of rotavirus replication by a non-neutralizing, rotavirus VP6-specific IgA mAb.
Rotaviruses are the leading cause of severe diarrheal disease in young children. Intestinal mucosal IgA responses play a critical role in protective immunity against rotavirus reinfection. Rotaviruses consist of three concentric capsid layers surrounding a genome of 11 segments of double-stranded RNA. The outer layer proteins, VP4 and VP7, which are responsible for viral attachment and entry, are targets for protective neutralizing antibodies. However, IgA mAb's directed against the intermediate capsid protein VP6, which do not neutralize the virus, have also been shown to protect mice from rotavirus infection and clear chronic infection in SCID mice. We investigated whether the anti-VP6 IgA (7D9) mAb could inhibit rotavirus replication inside epithelial cells and found that 7D9 acted at an early stage of infection to neutralize rotavirus following antibody lipofection. Using electron cryomicroscopy, we determined the three-dimensional structure of the virus-antibody complex. The attachment of 7D9 IgA to VP6 introduces a conformational change in the VP6 trimer, rendering the particle transcriptionally incompetent and preventing the elongation of initiated transcripts. Based on these observations, we suggest that anti-VP6 IgA antibodies confers protection in vivo by inhibiting viral transcription at the start of the intracellular phase of the viral replication cycle.


Overweight and obesity prevalence among public servants in Nadowli district, Ghana, and associated risk factors: a cross-sectional study.
Globally, overweight and obesity are becoming a mounting concern, impacting negatively on the health of populations especially in low-income settings. However, there is paucity of epidemiological information available in Ghana to support intervention activities. We conducted a study among public servants to estimate overweight/obesity, hypertension and diabetes prevalence and associated risk factors. A descriptive cross sectional survey involving 271 purposively sampled public servants aged 20 to 59 years was conducted. We used a structured questionnaire to collect data on eating patterns, risk factors for overweight and obesity, as well as data on socio-demographics and physical activity. Anthropometric measurements were carried out and body mass index (BMI) calculated. Information on blood pressure and diabetes was also gathered. We used descriptive statistical and logistic regression analyses to, respectively, estimate overweight/obesity prevalence, and examine associations between behavioral factors and overweight/obesity and hypertension/diabetes. The overall hypertension/diabetes, overweight and obesity prevalence were 20, 29.9 and 4.8% respectively. The study found that marital status (p < 0.001), leisure time with physical activity and level of physical activity during work (p < 0.035) as well as morbidities such as diabetes and hypertension (p < 0.012) were significantly associated with BMI. Findings showed no significant relationship between mealtime, eating habits, education, age and body mass index. Even though prevalence of overweight/obesity was higher among respondents who travelled to work by car compared to respondents who used motor bikes or walked, the association between weight status and means of transport was not statistically significant. Both smoking (p = 0.730) and alcohol consumption (p = 0.109) were not linked to weight status. Population-based interventions are needed to promote nutritious food selection and consumption, physical activity and healthy life styles. We also recommend that age and gender-specific interventions should be designed and implemented by relevant authorities to promote and support healthy living and healthy-lifestyles at home and in workplaces.


The role of chondrocyte-to-osteoblast trans-differentiation in fetal bone dysplasia of mice caused by prenatal exposure to dexamethasone.
Maternal exposure to dexamethasone can cause developmental toxicity of long bones in offspring. However, the effect of dexamethasone on the trans-differentiation of growth plate chondrocytes into osteoblasts and its role in bone dysplasia of fetuses caused by prenatal dexamethasone exposure (PDE) remains unclear. In this study, pregnant mice were treated with different doses, stages, and courses of dexamethasone according to clinical practice to reveal the phenomenon. Further, growth plate chondrocytes were treated with dexamethasone in vitro to clarify the phenomenon and mechanism. The results showed that PDE caused dysplasia of fetal long bones in female and male mice, accompanied by the delayed formation of the primary ossification center and the widening hypertrophic zone of growth plate cartilage. Meanwhile, PDE increased the number of hypertrophic chondrocytes at growth plate cartilage and decreased the number of osteoblasts at the primary ossification center. Moreover, PDE significantly decreased the expression of osteogenic transcription factor Runx2 but increased the expression of hypertrophic chondrocytes marker Col10. These above phenomena were more significant in the high dose, early stage, and double courses of dexamethasone exposure groups, and the male fetal mice showed more obvious than the female fetal mice. In vitro, dexamethasone significantly inhibited the trans-differentiation of growth plate chondrocytes into osteoblasts, accompanied by a decrease in Runx2 expression and an increase in Col10 expression. In conclusion, this study revealed the phenomenon and mechanism of fetal bone dysplasia caused by PDE from the new perspective of trans-differentiation disorder of growth plate chondrocytes to osteoblasts.


Impairment of virulence of in vitro subcultures of Mycobacterium lepraemurium.
Mycobacterium lepraemurium was cultivated in vitro on Ogawa egg-yolk medium. The pathogenicity of the third and eighth subcultures for C3H and C57BL mice was compared with that of in vivo grown murine bacilli by evaluating the mean survival time of infected mice. The results strongly suggest that a significant drop of virulence occurs during the in vitro cultivation of M. lepraemurium.


Brain metastases.
An estimated 20% of all patients with cancer will develop brain metastases, with the majority of brain metastases occurring in those with lung, breast and colorectal cancers, melanoma or renal cell carcinoma. Brain metastases are thought to occur via seeding of circulating tumour cells into the brain microvasculature; within this unique microenvironment, tumour growth is promoted and the penetration of systemic medical therapies is limited. Development of brain metastases remains a substantial contributor to overall cancer mortality in patients with advanced-stage cancer because prognosis remains poor despite multimodal treatments and advances in systemic therapies, which include a combination of surgery, radiotherapy, chemotherapy, immunotherapy and targeted therapies. Thus, interest abounds in understanding the mechanisms that drive brain metastases so that they can be targeted with preventive therapeutic strategies and in understanding the molecular characteristics of brain metastases relative to the primary tumour so that they can inform targeted therapy selection. Increased molecular understanding of the disease will also drive continued development of novel immunotherapies and targeted therapies that have higher bioavailability beyond the blood-tumour barrier and drive advances in radiotherapies and minimally invasive surgical techniques. As these discoveries and innovations move from the realm of basic science to preclinical and clinical applications, future outcomes for patients with brain metastases are almost certain to improve.


Castrated men exhibit bone loss: effect of calcitonin treatment on biochemical indices of bone remodeling.
To test the hypothesis that the reduction in gonadal function can lead to bone mass loss, a group of 12 men who had undergone bilateral orchidectomy at the age of 28.2 +/- 6.8 yr was evaluated. A progressive loss of the lumbar bone density was observed as a function of time after orchidectomy. Both the biochemical indices of bone resorption (urinary hydroxyproline/creatinine ratio and plasma tartrate-resistant acid phosphatase) and bone formation (serum osteocalcin and bone isoenzyme of alkaline phosphatase) were significantly increased in the patients compared with healthy controls. A positive correlation was found between urinary hydroxyproline excretion and percent change in spinal bone mineral density per yr. Because of this increase in the biochemically indicated bone resorption, nine of the patients were studied again after 1-3 yr and were thereafter treated with intranasal calcitonin. Urinary hydroxyproline excretion normalized after 3 months of treatment, and a significant decrease, but not to normal levels, was also observed in the mean values for the other biochemical indices of bone remodeling. Thus, testosterone deficiency, like estrogen deficiency, is associated with accelerated bone loss. The increase in osteoresorption was partially corrected by calcitonin treatment.


Correlation analyses of phytochemical composition, chemical, and cellular measures of antioxidant activity of broccoli (Brassica oleracea L. Var. italica).
Chemical measures of antioxidant activity within the plant, such as the oxygen radical absorbance capacity (ORAC) assay, have been reported for many plant-based foods. However, the extent to which chemical measures relate to cellular measures of oxidative stress is unclear. The natural variation in the phytochemical content of 22 broccoli genotypes was used to determine correlations among chemical composition (carotenoids, tocopherols and polyphenolics), chemical antioxidant activity (ORAC), and measures of cellular antioxidation [prevention of DNA oxidative damage and of oxidation of the biomarker dichlorofluorescein (DCFH) in HepG2 cells] using hydrophilic and lipophilic extracts of broccoli. For lipophilic extracts, ORAC (ORAC-L) correlated with inhibition of cellular oxidation of DCFH (DCFH-L, r = 0.596, p = 0.006). Also, DNA damage in the presence of the lipophilic extract was negatively correlated with both chemical and cellular measures of antioxidant activity as measured by ORAC-L (r = -0.705, p = 0.015) and DCFH-L (r = -0.671, p = 0.048), respectively. However, no correlations were observed for hydrophilic (-H) extracts, except between polyphenol content and ORAC (ORAC-H; r = 0.778, p < 0.001). Inhibition of cellular oxidation by hydrophilic extracts (DCFH-H) and ORAC-H were approximately 8- and 4-fold greater than DCFH-L and ORAC-L, respectively. Whether ORAC-H has more biological relevance than ORAC-L because of its magnitude or whether ORAC-L bears more biological relevance because it relates to cellular estimates of antioxidant activity remains to be determined. Chemical estimates of antioxidant capacity within the plant may not accurately reflect the complex nature of the full antioxidant activity of broccoli extracts within cells.


Self-Testing with Dishonest Parties and Device-Independent Entanglement Certification in Quantum Communication Networks.
We consider the task of device-independent quantum state certification in a network where some of the nodes may collude and act dishonestly. We introduce the paradigm of self-testing with dishonest parties and provide a certification protocol for the Greenberger-Horne-Zeilinger state in this framework, together with robust statements about the fidelity of the shared state. We extend our results to the cluster scenario, where many subgroups of parties may collude. Our findings provide a new operational motivation for the strong definition of genuine multipartite nonlocality originally introduced by Svetlichny.


Psychological evaluations, referrals, and follow-up of adolescents after their exposure to Hurricane Hugo.
There is little understanding of adolescent appraisal of stress and crisis intervention for adolescents who are exposed to major stress such as that of a natural disaster. A description of the psychological evaluations, referrals, and follow-up assessments made by nurse practitioners (NPs) and a nurse psychotherapist (NPT) of adolescents (N = 507) in two South Carolina high schools who experienced Hurricane Hugo. The NPs' evaluations concluded that 63 adolescents (12%) exhibited symptoms of psychological distress. The NPs referred 36 of these adolescents to high school counselors for minor distress or school-related problems and 27 for more intensive clinical evaluation by an NPT. Of the 27 adolescents who were referred to the NPT, 10 had symptoms associated with adolescent adjustment reaction, 8 showed symptoms of depression, 5 revealed symptoms of posttraumatic stress disorder, and 4 complained of serious family problems. Based on these data and the mental processes described by these adolescents, the authors propose a model and suggest adolescent appraisal of stress and crisis is a critical issue to consider when intervening with adolescents who are exposed to major stressors, including those associated with a disaster.


Fatigue Damage Evaluation Using Nonlinear Lamb Waves with Quasi Phase-Velocity Matching at Low Frequency.
Due to the dispersive and multimode natures, only nonlinear Lamb waves with exact phase-velocity matching were generally used in previous studies to evaluate the evenly distributed microstructural evolution in the incipient stage of material degradation, because of the cumulative generation of second harmonics, which was also found within a significant propagation distance for mode pair S0-s0 with quasi phase-velocity matching at low frequency. To explore the feasibility of fatigue damage evaluation by using this mode pair and fully utilize its unique merits, the cumulative second harmonic analysis was performed on aluminum alloy specimens with various material damage produced by the continuous low cycle fatigue tests. Similar to mode pair S1-s2 with exact phase-velocity matching, a mountain shape curve between the normalized acoustic nonlinearity parameter and the fatigue life was also achieved with the peak point at about 0.65 fatigue life for mode pair S0-s0, even though a relatively higher sensitivity to fatigue damage was observed for mode pair S1-s2. The excited frequency selection was further analyzed in a certain frequency range, where the quasi phase-velocity matching condition was satisfied for mode pair S0-s0 owing to the less dispersive property. Results show that the fatigue damage can be effectively detected using the mode pair S0-s0, and a relatively lower excited frequency was preferred due to its higher sensitivity to microstructural evolution.


Determination of elastic moduli of rock samples using resonant ultrasound spectroscopy.
Resonant ultrasound spectroscopy (RUS) is a method whereby the elastic tensor of a sample is extracted from a set of measured resonance frequencies. RUS has been used successfully to determine the elastic properties of single crystals and homogeneous samples. In this paper, we study the application of RUS to macroscopic samples of mesoscopically inhomogeneous materials, specifically rock. Particular attention is paid to five issues: the scale of mesoscopic inhomogeneity, imprecision in the figure of the sample, the effects of low Q, optimizing the data sets to extract the elastic tensor reliably, and sensitivity to anisotropy. Using modeling and empirical testing, we find that many of the difficulties associated with using RUS on mesoscopically inhomogeneous materials can be mitigated through the judicious choice of sample size and sample aspect ratio.


Effects of Aerobic and Resistance Exercise Training on Carotid Intima-Media Thickness in Abdominal Obese Women.
Aims: The purpose of this study was to investigate the effects of a 12-week aerobic and resistance training program on waist circumference (WC) and carotid intima-media thickness (CIMT) in abdominal obese middle-aged women. Methods: Subjects were 40 middle-aged women with abdominal obesity (WC >85 cm) but no specific diseases. Subjects were divided into a combined exercise group (aerobic and resistance exercise) and a control group that did not participate in any lifestyle modification. Carotid variables were measured using B-mode ultrasound. A treadmill exercise test was conducted to directly assess the peak oxygen uptake (VO2peak). Differences in the carotid variables and relative changes between baseline and after 12 weeks were evaluated. Results: After 12 weeks, body weight (70.6 ± 7.8 to 65.6 ± 6.3 kg, P < 0.05), WC (88.8 ± 3.6 to 85.6 ± 3.1 cm, P < 0.01), total cholesterol (215.5 ± 38.4 to 188.2 ± 25.8 mmHg, P < 0.05), low-density lipoprotein cholesterol (150.5 ± 30.6 to 131.6 ± 22.3 mmHg, P < 0.05), triglycerides (164.5 ± 82.3 to 119.9 ± 60.6 mmHg, P < 0.01), VO2peak (24.2 ± 6.2 to 28.7 ± 4.4 mL/kg/min, P < 0.01), and CIMT (0.61 ± 0.13 to 0.58 ± 0.12 mm, P < 0.05) were significantly improved in the combined exercise group but not in the control group; changes in CIMT were associated with changes in WC decrease (r = 0.41, P < 0.01) and VO2peak (r = -0.53, P < 0.01). Conclusions: Combined exercise training in abdominal obese women decreased CIMT; these changes were also associated with reduced WC and improved VO2peak.


Population pharmacokinetics and exposure-response of trastuzumab emtansine in advanced breast cancer previously treated with ≥2 HER2-targeted regimens.
We conducted population pharmacokinetic (PopPK) and exposure-response analyses for trastuzumab emtansine (T-DM1), to assess the need for T-DM1 dose optimization in patients with low exposure by using TH3RESA [A Study of Trastuzumab Emtansine in Comparison With Treatment of Physician's Choice in Patients With human epidermal growth factor receptor 2 (HER2)-positive Breast Cancer Who Have Received at Least Two Prior Regimens of HER2-directed Therapy] study data (NCT01419197). The randomized phase III TH3RESA study investigated T-DM1 vs. treatment of physician's choice (TPC) in patients with heavily pretreated HER2-positive advanced breast cancer. We compared a historical T-DM1 PopPK model with T-DM1 pharmacokinetics in TH3RESA and performed exposure-response analyses using model-predicted cycle 1 maximum concentration (Cmax ), cycle 1 minimum concentration (Cmin ) and area under the concentration-time curve at steady state (AUCss ). Kaplan-Meier analyses [overall survival (OS), progression-free survival (PFS)] and logistic regression [overall response rate (ORR), safety] were stratified by T-DM1 exposure metrics. Survival hazard ratios (HRs) in the lowest exposure quartile (Q1) of cycle 1 Cmin were compared with matched TPC-treated patients. T-DM1 concentrations in TH3RESA were described well by the historical PopPK model. Patients with higher cycle 1 Cmin and AUCss exhibited numerically longer median OS and PFS and higher ORR than patients with lower exposure. Exposure-response relationships were less evident for cycle 1 Cmax . No relationship between exposure and safety was identified. HRs for the comparison of T-DM1-treated patients in the Q1 subgroup with matched TPC-treated patients were 0.96 [95% confidence interval (CI) 0.63, 1.47] for OS and 0.92 (95% CI 0.64, 1.32) for PFS. Exposure-response relationships for efficacy were inconsistent across exposure metrics. HRs for survival in patients in the lowest T-DM1 exposure quartile vs. matched TPC-treated patients suggest that, compared with TCP, the approved T-DM1 dose is unlikely to be detrimental to patients with low exposure.


Receipt of adjuvant endometrial cancer treatment according to race: an NRG Oncology/Gynecologic Oncology Group 210 Study.
Black women with endometrial cancer are more likely to die of their disease compared with white women with endometrial cancer. These survival disparities persist even when disproportionately worse tumor characteristics among black women are accounted. Receipt of less complete adjuvant treatment among black patients with endometrial cancer could contribute to this disparity. We assessed the hypothesis that black women with endometrial cancer are less likely than their white counterparts to receive adjuvant treatment within subgroups defined by tumor characteristics in the NRG Oncology/Gynecology Oncology Group 210 Study. Our analysis included 615 black and 4283 white women with endometrial cancer who underwent hysterectomy. Women completed a questionnaire that assessed race and endometrial cancer risk factors. Tumor characteristics were available from pathology reports and central review. We categorized women as low-, intermediate-, or high-risk based on the European Society for Medical Oncology definition. Adjuvant treatment was documented during postoperative visits and was categorized as no adjuvant treatment (54.3%), radiotherapy only (16.5%), chemotherapy only (15.2%), and radiotherapy plus chemotherapy (14.0%). We used polytomous logistic regression to estimate odds ratios and 95% confidence intervals for multivariable-adjusted associations between race and adjuvant treatment in the overall study population and stratified by tumor subtype, stage, or European Society for Medical Oncology risk category. Overall, black women were more likely to have received chemotherapy only (odds ratio, 1.40; 95% confidence interval, 1.04-1.86) or radiotherapy plus chemotherapy (odds ratio, 2.01; 95% confidence interval, 1.54-2.62) compared with white women in multivariable-adjusted models. No racial difference in the receipt of radiotherapy only was observed. In tumor subtype-stratified models, black women had higher odds of receiving radiotherapy plus chemotherapy than white women when diagnosed with low-grade endometrioid (odds ratio, 2.04; 95% confidence interval, 1.06-3.93) or serous tumors (odds ratio, 1.81; 95% confidence interval, 1.07-3.08). Race was not associated with adjuvant treatment among women who had been diagnosed with other tumor subtypes. In stage-stratified models, we observed no racial differences in the receipt of adjuvant treatment. In models that were stratified by European Society for Medical Oncology risk group, black women with high-risk cancer were more likely to receive radiotherapy plus chemotherapy compared with white women (odds ratio, 1.41; 95% confidence interval, 1.03-1.94). Contrary to our hypothesis, we observed higher odds of specific adjuvant treatment regimens among black women as compared with white women within specific subgroups of endometrial cancer characteristics.


β-Blockers for the prevention of acute exacerbations of chronic obstructive pulmonary disease (βLOCK COPD): a randomised controlled study protocol.
A substantial majority of chronic obstructive pulmonary disease (COPD)-related morbidity, mortality and healthcare costs are due to acute exacerbations, but existing medications have only a modest effect on reducing their frequency, even when used in combination. Observational studies suggest β-blockers may reduce the risk of COPD exacerbations; thus, we will conduct a randomised, placebo-controlled trial to definitively assess the impact of metoprolol succinate on the rate of COPD exacerbations. This is a multicentre, placebo-controlled, double-blind, prospective randomised trial that will enrol 1028 patients with at least moderately severe COPD over a 3-year period. Participants with at least moderate COPD will be randomised in a 1:1 fashion to receive metoprolol or placebo; the cohort will be enriched for patients at high risk for exacerbations. Patients will be screened and then randomised over a 2-week period and will then undergo a dose titration period for the following 6 weeks. Thereafter, patients will be followed for 42 additional weeks on their target dose of metoprolol or placebo followed by a 4-week washout period. The primary end point is time to first occurrence of an acute exacerbation during the treatment period. Secondary end points include rates and severity of COPD exacerbations; rate of major cardiovascular events; all-cause mortality; lung function (forced expiratory volume in 1 s (FEV1)); dyspnoea; quality of life; exercise capacity; markers of cardiac stretch (pro-NT brain natriuretic peptide) and systemic inflammation (high-sensitivity C reactive protein and fibrinogen). Analyses will be performed on an intent-to-treat basis. The study protocol has been approved by the Department of Defense Human Protection Research Office and will be approved by the institutional review board of all participating centres. Study findings will be disseminated through presentations at national and international conferences and publications in peer-reviewed journals. NCT02587351; Pre-results.


A frameshift mutation destabilizes androgen receptor messenger RNA in the Tfm mouse.
A composite mouse androgen receptor DNA sequence was obtained by amplifying genomic DNA or cDNA using the polymerase chain reaction. The open reading frame was 2,697 basepairs, encoding a polypeptide of 899 amino acids (98,204 mol wt). Amino acid sequence comparisons indicated that the mouse androgen receptor (AR) is 97% homologous with rat AR and 83% with human AR. The amino acid sequences of the three receptors are identical within the DNA- and steroid-binding domains. Northern blot analysis revealed the predominant mouse AR mRNA to be 10 kilobases (kb). A 1.7-kb mRNA species was detected in mouse kidney using a cDNA probe containing only 5' untranslated AR sequence. Lack of hybridization with AR-coding sequence probes suggested that the 1.7-kb mRNA was not a truncated form of AR mRNA. Sequencing of genomic DNA isolated from testicular feminized (Tfm) mice revealed a single base deletion in the N-terminal domain, resulting in a frameshift mutation. Cycloheximide treatment caused a dramatic increase in AR mRNA in kidneys of Tfm mice, but not wild-type mice, suggesting that the Tfm mutation results in an unstable AR mRNA.


[Effects of ω-3 polyunsaturated fatty acids on lymphocyte apoptosis rate in rats with sepsis].
To investigate the effects of ω-3 polyunsaturated fatty acids (ω-3 PUFAs) on the apoptosis of thymic and splenic lymphocytes in rats with sepsis. A total of 80 female Sprague-Dawley rats aged 7-8 weeks were randomly divided into model group, conventional lipid emulsion group (0.1 g/kg daily), low-dose ω-3 PUFAs group (0.1 g/kg daily), middle-dose ω-3 PUFAs group (0.2 g/kg daily), and high-dose ω-3 PUFAs group (0.3 g/kg daily). Cecal ligation and puncture were used to establish a rat model of sepsis. The treatment groups were then given tail vein injection of lipid emulsion or glucose diluents of ω-3 PUFAs at different doses, and the model group was given glucose injection via the tail vein at the same dose. According to the time of sacrifice, each group was further divided into 24-hour and 72-hour subgroups, with 8 rats in each subgroup. Hematoxylin and eosin staining was used to observe the pathological changes in the thymus and spleen. TUNEL was used to measure the apoptosis rates of thymic and splenic lymphocytes. In the three ω-3 PUFAs groups, the rats had a complete thymic lobular structure and clear structures of the cortex and medulla. In the model and the conventional lipid emulsion groups, the boundaries of the cortex and medulla were unclear and the number of lymphocytes was significantly reduced. In the ω-3 PUFAs groups, the structure of the red and white pulp of the spleen was maintained with the presence of splenic follicles, while in the model and the conventional lipid emulsion groups, the structure of the red and white pulp of the spleen was disordered and splenic follicles were significantly reduced or disappeared. Compared with the model and the conventional lipid emulsion groups, the ω-3 PUFAs groups showed significant reductions in the apoptosis rates of thymic and splenic lymphocytes at 24 and 72 hours (P<0.01). Compared with the low-dose ω-3 PUFAs group, the high-dose ω-3 PUFAs group had significantly reduced apoptosis rates of splenic lymphocytes at 24 and 72 hours (P<0.05). ω-3 PUFAs can reduce the apoptosis of thymic and splenic lymphocytes in rats with sepsis in a dose-dependent manner.


Cyanide in blood by gas chromatography with NP detector and acetonitrile as internal standard. Application on air accident fire victims.
An improved gas chromatographic method for HCN in blood with acetonitrile as an internal standard has been developed. The necessity to test for cyanide on samples from air accident fire victims is discussed in view of the fact that carbon monoxide measurements usually do not correlate with cyanide findings. Nine cases (out of 67), with blood CO saturation of less than 20% and cyanide concentration over 2 mg/L, are described.


Fixed-dose combination orally disintegrating tablets to treat cardiovascular disease: formulation, in vitro characterization and physiologically based pharmacokinetic modeling to assess bioavailability.
Cardiovascular disease (CVD) is the leading cause of death among men and women worldwide. In CVD, hypertension and dyslipidemia commonly coexist and are managed through coadministration of amlodipine and atorvastatin, respectively. The case for fixed-dose combination (FDC) oral dosage forms and orally disintegrating tablet (ODT) technology to enhance outcomes and compliance is strong. This work follows the development and characterization of single and FDC ODTs containing amlodipine and atorvastatin, followed by bioequivalence comparison between these single and FDC formulations, using in vitro dissolution and Caco-2 apparent permeability (Papp) and in silico physiologically based pharmacokinetic modeling approaches. ODTs containing amlodipine (5 mg) and atorvastatin (10 mg) either alone or in combination rapidly disintegrated (<30 s) while displaying a radial crushing strength in excess of 100 N and friability ≤1%. In vitro dissolution test was performed in fasted and fed-state simulated intestinal fluid (FeSSIF) and analyzed using high-performance liquid chromatography. Dissolution profiles for single and FDC ODTs were compared using US FDA recommended difference (f1) and similarity (f2) factor testing for bioequivalence. In all cases, there was no difference in active pharmaceutical ingredient dissolution between single or FDC ODTs, with the exception of amlodipine in FeSSIF. Pharmacokinetic clinical trial simulations were conducted using Simcyp (Version 14), incorporating Papp and dissolution data. Simulated clinical trials in healthy volunteers showed no difference in bioavailability based on pharmacokinetic parameters between single and combination doses with either active pharmaceutical ingredient. An increase in Cmax and AUC for atorvastatin in fed subjects was attributed to extended transit along the gut lumen and reduced atorvastatin metabolism due to lower CYP3A4 expression at more distal small intestine absorption sites. The results demonstrated bioequivalence of an FDC ODT for amlodipine and atorvastatin, while highlighting several limitations of f1 and f2 bioequivalence testing and strengths of mechanistic pharmacokinetic modeling for oral drug absorption.


Age and the gender gap in distress.
Women report more psychological distress than men and recent evidence suggests that this gap increases with age. It has been argued that the widening differential in distress reflects the progressive and cumulative nature of women's disadvantaged work and family roles. Drawing on the cumulative disadvantage hypothesis and social stress theory, we test: (1) whether exposure to chronic stress accounts for an increasingly larger proportion of the gender effect on distress with age; and (2) whether women are increasingly more vulnerable to the effects of chronic stress on distress with age. Data are from the 1994 wave of the Canadian National Population Health Survey, a national probability sample of women and men aged 20 and older (N = 13,798). Exposure to long-term stress helps us understand gender differences in distress for those in their pre-retirement years. However, contrary to the cumulative disadvantage hypothesis, the model became increasingly less likely to explain such differences with age. Gendered vulnerability to long-term stress was not evident in the sample. The implications of these findings are discussed with particular reference to our ongoing efforts to understand health in the context of social structure and subjectivity.


Molecular mechanisms of damage by excess nitrogen oxides: nitration of tyrosine by gas-phase cigarette smoke.
Nitric oxide (nitrogen monoxide, .NO) plays important physiological roles, but an excess can be toxic. .NO is present in cigarette smoke (CS) at up to 500 ppm, and probably represents one of the greatest exogenous sources of .NO to which humans are exposed. We show here that gas-phase CS is capable of converting tyrosine to 3-nitrotyrosine (3-NO2-Tyr) and dityrosine, to an extent dependent on time of exposure and pH. Glutathione, ascorbic acid and uric acid decreased the CS-induced formation of 3-NO2-Tyr and dityrosine. We suggest that nitrogen oxides in CS can modify proteins in the respiratory tract and may contribute to CS toxicity.


[Pulsatile vaginal expansion: Case report of an internal iliac aneurysm detected after an injury].
After a pelvic trauma, in a 78 years old women, systematic radiograms showed a polycyclic mass in the left side of the pelvis. This finding was confirmed by B-mode ultrasound echography. The vaginal touch found a pulsatile and expanding mass. At surgery, the diagnosis of a fissuring aneurysm of the internal iliac artery was confirmed, and a curative treatment was undertaken. Reviewing the literature, the authors emphasize the diagnostic usefulness of rectal and vaginal touch, and the importance of an early diagnosis using noninvasive imaging techniques. Surgery is the only treatment for isolated internal iliac aneurysms.


Patterns of alcohol use and attitudes toward drinking among Chinese and Korean American college students.
This study examined the alcohol consumption patterns and cultural attitudes toward drinking among Chinese and Korean American college students in California. Data were collected from a total of 294 participants comprising 127 Chinese and 167 Korean college students. Some of the major findings revealed that distinct ethnic and gender differences existed in the use of alcohol and attitudes toward drinking. Korean students in the study generally drank more frequently and consumed greater amounts of alcohol than their Chinese counterparts. Female participants were likely to drink less frequently and in smaller quantities than their male counterparts regardless of ethnicity. Korean students were more likely to view drinking as a socially acceptable practice and a means of facilitating social interactions than their Chinese counterparts. Culturally appropriate campus-wide strategies were presented for prevention and intervention of alcohol abuse on college campuses.


Trends in sexually transmitted infections (other than HIV) in older people: analysis of data from an enhanced surveillance system.
This study examines the distribution of selected sexually transmitted infections (STIs) in older people (aged >/=45 years) attending genitourinary medicine (GUM) clinics in the West Midlands, UK. Analysis of data from the regional enhanced STI surveillance system for the period 1996-2003. Selected STIs were chlamydia, genital herpes, genital warts, gonorrhoea and syphilis. Altogether, 4445 STI episodes were reported among older people during the study period. Between 1996 and 2003 older people accounted for 3.7% and 4.3%, respectively, of all GUM clinic attendances. The rate of STIs in older people more than doubled in 2003 compared with 1996 (p<0.0001). Rates for all five selected diagnoses were significantly higher in 2003 compared to 1996. A significantly increasing trend over time was seen overall (p<0.0001) and for each of the selected diagnoses. Overall, males and those aged 55-59 years of age were significantly more likely to be affected. This study provides evidence of significant increases in attendance at GUM clinics by older people. Although it is recognised that young people should remain the focus of sexual health programmes, the results indicate that sexual risk-taking behaviour is not confined to young people but also occurs among older people. There is therefore a need to develop and implement evidence-based multifaceted sexual health programmes that while aiming to reduce STI transmission among all age groups should include interventions aimed specifically at older people and address societal and healthcare attitudes, myths and assumptions about sexual activity among older people.


Clinical presentation and outcomes of patients with type 1 monoclonal cryoglobulinemia.
We describe a series of 102 patients diagnosed from January 1, 1990 to December 31, 2015 with Type 1 monoclonal cryoglobulinemia (MoC). Symptoms were seen in 89 (87%) patients, including: cutaneous symptoms in 64 (63%) patients, with purpura (n = 43, 42%) and ulcers/gangrene (n = 35, 34%) being most common; neurological findings in 33 (32%) patients, most frequently sensory neuropathy (n = 24, 24%); vasomotor symptoms, mainly Raynaud's phenomenon in 25 (25%); arthralgias in 24 (24%); and renal manifestations, primarily glomerulonephritis in 14 (14%) patients. An underlying lymphoproliferative disorder was identified in 94 (92%) subjects; MGUS-39, myeloma-20, lymphoplasmacytic lymphoma-21 and others-14. Treatment was initiated in 73 (72%) patients, primarily for cryoglobulinemia-related symptoms in 57. Treatment regimens consisted of: steroids ± alkylating agents in 29 (40%), novel myeloma therapies in 16 (22%), rituximab with alkylating agents in 12 (16%) and rituximab ± steroids in 11 (15%) patients; 22 patients received plasmapheresis. Six patients underwent autologous stem cell transplant. Cryocrit at treatment initiation, change in cryocrit and time to nadir cryocrit were predictive of symptom improvement. Treatment directed toward the underlying clonal disorder resulted in improvement (n = 47) or stabilization (n = 16) of symptoms in the majority of patients and disappearance of cryoglobulin in over one-half.


Tin-free radical alkylation of ketones via N-silyloxy enamines.
The radical alkylation of ketones is achieved by their conversion into corresponding N-silyloxy enamines, followed by a radical reaction with alkyl halides bearing electron-withdrawing groups.


A teaching strategy for identifying values: a clinical experience with the homeless.
Beginning baccalaureate students recorded their thoughts, feelings, and observations after participating in a clinical experience with the homeless. A content analysis protocol was used to uncover the meaning of the encounter. The findings suggest that assigning students to a homeless clinic is one way to help students identify professional values, such as altruism, equality, and human dignity.


Identification of a mutation associated with fatal Foal Immunodeficiency Syndrome in the Fell and Dales pony.
The Fell and Dales are rare native UK pony breeds at risk due to falling numbers, in-breeding, and inherited disease. Specifically, the lethal Mendelian recessive disease Foal Immunodeficiency Syndrome (FIS), which manifests as B-lymphocyte immunodeficiency and progressive anemia, is a substantial threat. A significant percentage (∼10%) of the Fell ponies born each year dies from FIS, compromising the long-term survival of this breed. Moreover, the likely spread of FIS into other breeds is of major concern. Indeed, FIS was identified in the Dales pony, a related breed, during the course of this work. Using a stepwise approach comprising linkage and homozygosity mapping followed by haplotype analysis, we mapped the mutation using 14 FIS-affected, 17 obligate carriers, and 10 adults of unknown carrier status to a ∼1 Mb region (29.8 - 30.8 Mb) on chromosome (ECA) 26. A subsequent genome-wide association study identified two SNPs on ECA26 that showed genome-wide significance after Bonferroni correction for multiple testing: BIEC2-692674 at 29.804 Mb and BIEC2-693138 at 32.19 Mb. The associated region spanned 2.6 Mb from ∼29.6 Mb to 32.2 Mb on ECA26. Re-sequencing of this region identified a mutation in the sodium/myo-inositol cotransporter gene (SLC5A3); this causes a P446L substitution in the protein. This gene plays a crucial role in the regulatory response to osmotic stress that is essential in many tissues including lymphoid tissues and during early embryonic development. We propose that the amino acid substitution we identify here alters the function of SLC5A3, leading to erythropoiesis failure and compromise of the immune system. FIS is of significant biological interest as it is unique and is caused by a gene not previously associated with a mammalian disease. Having identified the associated gene, we are now able to eradicate FIS from equine populations by informed selective breeding.


The modulation of pacing-induced changes in intracellular sodium levels by extracellular Ca2+ in isolated perfused rat hearts.
This study demonstrates the inverse relationship between extracellular free calcium ([Ca(o)]f) and intracellular sodium ([Na(i)]) in isolated perfused rat hearts and thus supports the role of [Na(i)] in the "calcium paradox". It also shows that the extent of the increase in [Na(i)] (delta[Na(i)]), and the extent of the decrease in left ventricular developed pressure (deltaLVDP) in isolated perfused rat hearts, induced by pacing, is modulated by [Ca(o)]f. At low (0.24 mM) as well as normal (1.15 mM) [Ca(o)]f, [Na(i)] increased with pacing, progressively and significantly (P<0.01 and P<0.05, respectively), reaching a maximum of 12.56 +/- 0.46 and 9.22 +/- 0.16 mM at 500 beats/min, respectively. At high [Ca(o)]f (2.2 mM), however, no pacing-induced increase in [Na(i)] was observed. Simultaneously, within the pacing range of 250-500 beats/min, the interval-force relationship was negative for all [Ca(o)]f. With decreasing [Ca(o)]f, a gradually increasing delta[Na(i)] was induced. We hypothesise that a [Ca(o)]f-dependent Na-Ca exchanger activity modulates Na+ uptake, and thus baseline [Na(i)]. During incremental pacing, the increase in pacing rate induces a [Ca(o)]f-dependent delta[Na(i)], which may interact further with the sarcolemmal Na-Ca exchanger activity. As a result, both baseline [Na(i)] and the pacing-induced, [Ca(o)]f-dependent delta[Na(i)] modulate the net Ca2+ uptake, and thus SR Ca, in a manner that results in a modulated left ventricular force development.


A Single Amino Acid Change in Nramp6 from Sedum Alfredii Hance Affects Cadmium Accumulation.
SaNramp6 in Sedum alfredii encodes a membrane-localized metal transporter. We isolated the SaNramp6h allele from the hyperaccumulating ecotype (HE) of S. alfredii. When this allele was expressed in transgenic yeast and Arabidopsis thaliana, it enhanced their cadmium (Cd) sensitivity by increased Cd transport and accumulation. We isolated another allele, SaNramp6n, from a nonhyperaccumulating ecotype (NHE) of S. alfredii. Amino acid sequence comparisons revealed three amino acid differences between SaNramp6h and SaNramp6n. We investigated the Cd transport activity of the Nramp6 allele, and determined which residues are essential for the transport activity. We conducted structure-function analyses of SaNramp6 based on site-directed mutagenesis and functional assays of the mutants in yeast and Arabidopsis. The three residues that differed between SaNramp6h and SaNramp6n were mutated. Only the L157P mutation of SaNramp6h impaired Cd transport. The other mutations, S218N and T504A, did not affect the transport activity of SaNramp6h, indicating that these residues are not essential for metal selectivity. Transgenic plants overexpressing SaNramp6hL157P showed altered metal accumulation in shoots and roots. Our results suggest that the conserved site L157 is essential for the high metal transport activity of SaNramp6h. This information may be useful for limiting or increasing Cd transport by other plant natural resistance associated macrophage protein (NRAMP) proteins.


A discrete population of squamocolumnar junction cells implicated in the pathogenesis of cervical cancer.
Infection by carcinogenic human papillomaviruses (HPV) results in precancers [cervical intraepithelial neoplasia (CIN)] and cancers near the ectoendocervical squamocolumnar (SC) junction of the cervix. However, the specific cells targeted by HPV have not been identified and the cellular origin of cervical cancer remains elusive. In this study, we uncovered a discrete population of SC junctional cells with unique morphology and gene-expression profile. We also demonstrated that the selected junctional biomarkers were expressed by a high percentage of high-grade CIN and cervical cancers associated with carcinogenic HPVs but rarely in ectocervical/transformation zone CINs or those associated with noncarcinogenic HPVs. That the original SC junction immunophenotype was not regenerated at new SC junctions following excision, not induced by expression of viral oncoproteins in foreskin keratinocytes, and not seen in HPV-related precursors of the vagina, vulva, and penis further support the notion that junctional cells are the source of cervical cancer. Taken together, our findings suggest that carcinogenic HPV-related CINs and cervical cancers are linked to a small, discrete cell population that localizes to the SC junction of the cervix, expresses a unique gene expression signature, and is not regenerated after excision. The findings in this study uncover a potential target for cervical cancer prevention, provide insight into the risk assessment of cervical lesions, and establish a model for elucidating the pathway to cervical cancer following carcinogenic HPV infection.


Evaluation of renal function following treatment with extracorporeal shock wave lithotripsy (ESWL): the use of whole-kidney, parenchymal and pelvic transit times.
The aim of this prospective study was to assess the efficacy of using whole-kidney, mean parenchymal and pelvic transit times to evaluate renal function following treatment with extracorporeal shock wave lithotripsy (ESWL). Fifteen patients were evaluated 24-48 h before and after ESWL therapy using 99Tcm-DTPA renal scintigraphy. Using deconvolution analysis, whole-kidney, mean parenchymal and pelvic transit times were calculated and the pre-ESWL values were compared with the post-ESWL values. In both kidneys, there were no significant changes in the glomerular filtration rate or relative renal uptake when compared with the pre-ESWL values. The mean whole-kidney transit time of the tracer did not change significantly during the post-ESWL period. In the treated kidney, the mean post-ESWL parenchymal transit time was significantly increased (P < 0.05), while the mean pelvic transit time was significantly decreased (P < 0.05). In the untreated kidney, there were no significant changes in any of these parameters. We conclude that the dual use of parenchymal and pelvic transit times is more sensitive than the mean whole-kidney transit time and other measures, such as glomerular filtration rate and relative renal uptake, for the assessment of outcome of therapy and other related post-ESWL changes.


Increased systolic blood pressure associated with hypertriglyceridemia in female Sprague-Dawley rats.
The effect of hyperlipidemia on the cardiovascular system is uncertain in females. The aim of the present study was to determine whether administration of a lipogenic diet alters cardiovascular parameters in female rats. Fifty female Sprague-Dawley rats were assigned into 2 groups of rats receiving a standard or a high-fat, high-sucrose diet (HFHS) for 6 weeks (n = 25 per group). Body mass, blood lipids concentrations, triglycerides clearance, blood pressures (BPs), systolic and diastolic functions, as well as vascular reactivity were assessed at the end of the diet intervention. At termination, body mass was similar between the 2 groups. Fasting blood triglycerides concentration (BTG) was greater in the HFHS group. Triglycerides clearance was impaired in the HFHS group. High-density lipoprotein (HDL) cholesterol concentration was lower in the HFHS group. The early-to-late diastolic filling velocity ratio (E/A) was lower in the HFHS group and negatively associated with BTG. The sensitivity (EC50) of mesenteric arteries to phenylephrine was greater in HFHS and was negatively associated with BTG, but not HDL. Systolic BP was higher in the HFHS group and was positively associated with BTG and HDL. The association between systolic BP and BTG was independent of other lipids measured. In conclusion, hypertriglyceridemia may have increased resistance arteries responsiveness to alpha-agonist and systolic BP in female rats.


Developing evidence-based guidelines for referral for short stature.
To establish evidence-based guidelines for growth monitoring on a population basis. Several auxological referral criteria were formulated and applied to longitudinal growth data from four different patient groups, as well as three samples from the general population. Almost 30% of pathology can be detected by height standard deviation score (HSDS) below -3 or at least two observations of HSDS below -2.5 at a low false-positive rate (<1%) in 0-3-year-old infants. For 3-10-year olds, a rule concerning distance to target height of >2 SD in combination with HSDS <-2.0 has the best predictive value. In combination with a rule on severe short stature (<-2.5 SDS) and a minor contribution from a rule on "height deflection", 85.7% of children with Turner syndrome and 76.5% of children who are short because of various disorders are detected at a false-positive rate of 1.5-2%. The proposed guidelines for growth monitoring show high sensitivity at an acceptably low false-positive rate in 3-10-year-old children. Distance to target height is the most important criterion. Below the age of 3 years, the sensitivity is considerably lower. The resulting algorithm appears to be suitable for industrialised countries, but requires further testing in other populations.


The effectiveness of olibanum orally disintegrating tablet in the treatment of oral aphthous ulcers: A randomized, double-blind, placebo-controlled clinical trial.
Boswellia serrata oleo-gum-resin (frankincense; olibanum) has anti-inflammatory, analgesic, and antimicrobial effects. This study aimed to evaluate the clinical effectiveness of frankincense extract in the treatment of oral aphthous ulcers. In a randomized, double-blind, placebo-controlled clinical trial, patients with aphthous ulcers were randomly assigned to either experimental (Frankincense extract) or placebo groups to use orally disintegrating tablets (ODT) of frankincense and placebo, respectively, four times a day for 3 days. The size of aphthous ulcers and the pain severity by visual analogue scale were recorded at days 0, 2, and 4 and compared between the groups. Twenty-five patients in each group completed the study. Olibanum extract ODT significantly reduced the ulcer size on the second (P < 0.001) and fourth (P < 0.001) days as well as the pain score on the second (P = 0.002) and fourth (P < 0.001) days of the intervention compared to placebo. Furthermore, at the end of the intervention, the number of patients with complete ulcer healing and pain relief in the experimental group was significantly more than the placebo group (5 vs. 0, P = 0.02; and 11 vs. 0, P < 0.001, respectively). Taking olibanum extract ODTs reduces the ulcer size and pain severity and accelerates the healing process in the oral aphthous lesions.


MAEBL is essential for malarial sporozoite infection of the mosquito salivary gland.
Malarial sporozoites mature in the oocysts formed in the mosquito midgut wall and then selectively invade the salivary glands, where they wait to be transmitted to the vertebrate host via mosquito bite. Invasion into the salivary gland has been thought to be mediated by specific ligand-receptor interactions, but the molecules involved in these interactions remain unknown. MAEBL is a single transmembrane-like protein that is structurally related to merozoite adhesive proteins. We found MAEBL of the rodent malaria parasite, Plasmodium berghei, to be specifically produced by the sporozoites in the oocyst and localized in their micronemes, which are secretory organelles involved in malarial parasite invasion into the host cell. A targeted disruption experiment of the P. berghei MAEBL gene revealed that it was essential for sporozoite infection of the salivary gland and was involved in the attachment to the salivary gland surface. In contrast, the disruption of the MAEBL gene did not affect sporozoite motility in vitro nor infectivity to the vertebrate host. These results suggest that P. berghei MAEBL is a sporozoite attachment protein that participates in specific binding to and infection of the mosquito salivary gland.


Re-assessing the role of peri-operative nutritional therapy in patients with pancreatic cancer undergoing surgery: a narrative review.
Pancreatic cancer is the most common medical condition that requires pancreatic resection. Over the last three decades, significant improvements have been made in the conditions and procedures related to pancreatic surgery, resulting in mortality rates lower than 5%. However, it is important to note that the morbidity in pancreatic surgery remains r latively high, with a percentage range of 30-60%. Pre-operative malnutrition is considered to be an independent risk factor for post-operative complications in pancreatic surgery, such as impaired wound healing, higher infection rates, prolonged hospital stay, hospital readmission, poor prognosis, and increased morbidity and mortality. Regarding the post-operative period, it is crucial to provide the best possible management of gastrointestinal dysfunction and to handle the consequences of alterations in food digestion and nutrient absorption for those undergoing pancreatic surgery. The European Society for Clinical Nutrition and Metabolism (ESPEN) suggests that early oral feeding should be the preferred way to initiate nourishing surgical patients as it is associated with lower rates of complications. However, there is ongoing debate about the optimal post-operative feeding approach. Several studies have shown that enteral nutrition is associated with a shorter time to recovery, superior clinical outcomes and biomarkers. On the other hand, recent data suggest that nutritional goals are better achieved with parenteral feeding, either exclusively or as a supplement. The current review highlights recommendations from existing evidence, including nutritional screening and assessment and pre/post-operative nutrition support fundamentals to improve patient outcomes. Key areas for improvement and opportunities to enhance guideline implementation are also highlighted.


The little death: Rigoni-Stern and the problem of sex and cancer in 20th-century biomedical research.
Approaches to the organization and conduct of cancer research changed dramatically throughout the 20th century. Despite marked differences between the epidemiological approaches of the first half of the century and molecular techniques that gained dominance in the 1980s, prominent 20th-century researchers investigating the link between sexual activity and anogenital cancers continuously invoked the same 1842 treatise by Italian surgeon Domenico Rigoni-Stern, who is said to originate the problem of establishing a causal link between sex and cancer. In this article, I investigate 20th-century references to Rigoni-Stern as a case of a broader phenomenon: scientists situating their work through narratives of venerated ancestors, or originators. By explaining shifting versions of originator narratives in light of their authors' cultural context and research practices, we can reimagine as meaningful cultural symbols the references that previous scholars have treated as specious rhetorical maneuvers. In this case, references to Rigoni-Stern provide an interpretive anchor for American scientists to construct continuity between their work and a diverse historical legacy of cancer research.


Identification of Two Meloidogyne hapla Genes and an Investigation of Their Roles in the Plant-Nematode Interaction.
Root-knot nematodes are soil-borne pathogens that invade and establish feeding sites in plant roots. They have an extremely broad host range, including most vascular plants. During infection of a susceptible host, root-knot nematodes secrete molecules called effectors that help them establish an intimate interaction with the plant and, at the same time, allow them to evade or suppress plant immune responses. Despite the fact that Meloidogyne hapla is a significant pest on several food crops, no effectors have been characterized from this root-knot nematode species thus far. Using the published genome and proteome from M. hapla, we have identified and characterized two genes, MhTTL2 and Mh265. MhTTL2 encodes a predicted secreted protein containing a transthyretin-like protein domain. The expression of MhTTL2 was up-regulated during parasitic life stages of the nematode, and in situ hybridization showed that MhTTL2 was expressed in the amphids, suggesting it has a role in the nematode nervous system during parasitism. We also studied the gene Mh265. The Mh265 transcript was localized to the subventral esophageal glands. An upregulation in Mh265 expression coincided with the pre- and early-parasitic life stages of the nematode. When Mh265 was constitutively expressed in plants, it enhanced their susceptibility to nematodes. These transgenic plants were also compromised in flg22-induced callose deposition, suggesting the Mh265 is modulating plant basal immune responses.


An enteroendocrine-microbial axis in the large intestine controls host metabolism.
Nutrient handling is an essential function of the gastrointestinal tract. Most nutrient absorption occurs in the small intestine and is coordinated by hormone-producing intestinal epithelial cells known as enteroendocrine cells (EECs)1. In contrast, the colon mostly reclaims water and electrolytes, and handles the influx of microbially-derived metabolites, including short chain fatty acids (SCFA)2-4. Hormonal responses of small intestinal EECs have been extensively studied but much less in known about the role of colonic EECs in metabolic regulation. To address this core question, we investigated a mouse model deficient in colonic EECs. We found that colonic EEC deficiency leads to hyperphagia and obesity. Surprisingly, colonic EEC deficiency results in altered microbiota composition and metabolism, which we found through antibiotic treatment and transfer to germ free recipients, to be both necessary and sufficient for the development of obesity. Moreover, studying stool and blood metabolomes, we found that differential glutamate production by intestinal microbiota corresponds to increase appetite due to EEC loss. Finally, we show that colonic glutamate administration can directly increase food intake and activate appetite centers in the central nervous system. These observations shed light on an unanticipated host-microbiota axis in the colon, part of a larger gut-brain axis, that regulates host metabolism and body weight.


Formulation of ciprofloxacin-loaded oral self-emulsifying drug delivery system to improve the pharmacokinetics and antibacterial activity.
This study aims to increase the aqueous solubility of ciprofloxacin (CPN) to improve oral bioavailability. This was carried out by formulating a stable formulation of the Self-Emulsifying Drug Delivery System (SEDDS) using various ratios of lipid/oil, surfactant, and co-surfactant. A pseudo-ternary phase diagram was designed to find an area of emulsification. Eight formulations (F1-CPN-F8-CPN) containing oleic acid oil, silicone oil, olive oil, castor oil, sunflower oil, myglol oil, polysorbate-80, polysorbate-20, PEO-200, PEO-400, PEO-600, and PG were formulated. The resultant SEDDS were subjected to thermodynamic study, size, and surface charge studies to improve preparation. Improved composition of SEDDS F5-CPN containing 40% oil, 60% polysorbate-80, and propylene glycol (Smix ratio 6: 1) were thermodynamically stable emulsions having droplet size 202.6 nm, charge surface -13.9 mV, and 0.226 polydispersity index (PDI). Fourier transform infra-red (FT-IR) studies revealed that the optimized formulation and drug showed no interactions. Scanning electron microscope tests showed the droplets have an even surface and spherical shape. It was observed that within 5 h, the concentration of released CPN from optimized formulations F5-CPN was 93%. F5-CPN also showed a higher antibacterial action against S. aurous than free CPN. It shows that F5-CPN is a better formulation with a good release and high antibacterial activity.


High risk sexual behaviours among heroin sniffers who have no history of injection drug use: implications for HIV risk reduction.
The purpose of this paper is to assess sexual behaviours which place heroin sniffers (HSs) at high risk for HIV infection. A stratified network-based sample was used to recruit HSs who had no history of injection drug use was recruited from the streets of South Florida, USA. HSs displayed a high HIV seroprevalence rate of 12.1%; women (18.1%) were more likely than men (8.7%) to test positive for HIV. Both men and women HSs engaged in considerable high risk sex behaviour, including high risk sex-exchange behaviour. The use of crack cocaine was associated with increased sex exchange behaviour among women. The need for intervention programs targeted toward HSs is discussed.


Nonlinear Transport due to Magnetic-Field-Induced Flat Bands in the Nodal-Line Semimetal ZrTe_{5}.
The Dirac material ZrTe_{5} at very low carrier density was recently found to be a nodal-line semimetal, where ultraflat bands are expected to emerge in magnetic fields parallel to the nodal-line plane. Here, we report that in very low carrier-density samples of ZrTe_{5}, when the current and the magnetic field are both along the crystallographic a axis, the current-voltage characteristics presents a pronounced nonlinearity which tends to saturate in the ultra quantum limit. The magnetic-field dependence of the nonlinear coefficient is well explained by the Boltzmann theory for flat-band transport, and we argue that this nonlinear transport is likely due to the combined effect of flat bands and charge puddles; the latter appear due to very low carrier densities.


Engineering of Nitrogen Coordinated Single Cobalt Atom Moieties for Oxygen Electroreduction.
The nitrogen coordinated single cobalt atoms embedded in carbon matrix, i.e., Co/N/C material, is cost-efficient and free from iron-ion induced Fenton reagent, which has been thus considered as a promising candidate to replace the well-accepted Pt-based and Fe/N/C materials for oxygen reduction reaction (ORR). Recently, the pyrolysis of metal-organic framework (MOF) precursors has been investigated to achieve well-defined Co/N/C catalysts with high ORR activity. However, the relationships among the composition/structure of MOF precursor, the derived catalysts, and ORR performance have been rarely touched in specialty, while the regulations to achieve single-atom Co/N/C catalysts derived from MOF are confusing. Herein, we engineer several Co-doped MOF (zeolitic imidazolate frameworks, to be specific) precursors with different compositions and structures by tuning synthesis protocols (e.g., ratios, cobalt sources, and reaction time) and investigate the derived catalysts and their ORR properties. The regulations to single-atom Co/N/C are revealed in this work. The superior ORR activity and durability of the optimized Co/N/C catalysts are revealed and attributed to the well-defined Co-Nx moieties and their stable nanostructures.


Bcl2 expression and its correlation with neuroendocrine differentiation in colon carcinomas.
In this study we investigated the association between BCL2 expression and neuroendocrine differentiation in tubular adenomas and colon carcinomas. We also evaluated the prognostic significance of BCL2 expression and neuroendocrine differentiation in the carcinoma group. Forty-eight colon carcinomas and twelve tubular adenomas were stained immunohistochemically with BCL2 and chromogranin A (CgA). Staining patterns were scored semiquantitatively and correlated with tumor type, tumor grade, Dukes stage, and survival time. BCL2 expression was detected in 7 of 12 (58.3%) adenomas and 37 of 48 (77.0%) carcinomas. In normal mucosa we observed positive staining only in the basal portions of the crypts. However, diffuse positivity was observed in the adenomas and carcinomas. Carcinomas had significantly higher BCL2 scores than the normal group, but we did not observe any significant differences either between the adenoma and carcinoma group or between the adenoma and normal group. BCL2 scores were higher in stage B than in stage C tumors, and in adenocarcinomas than in mucinous carcinomas. CgA positivity was observed in 24 of 48 (50%) carcinomas. It was not detected in adenomas. We did not find a significant correlation between CgA expression and any of the clinicopathological parameters. On consecutive sections BCL2 and CgA positivity closely paralleled each other and a significant positive correlation was observed between CgA and BCL2 expression. These findings suggest a close association between BCL2 expression and neuroendocrine differentiation and indicate that BCL2 may be involved in neuroendocrine differentiation in addition to its role in protecting cells from apoptosis.