Effects of transdermal nicotine on symptoms, moods, and cardiovascular activity in the everyday lives of smokers and nonsmokers with attention-deficit/hyperactivity disorder.
The aim of the study was to test the self-medication hypothesis by examining the effects of nicotine in the everyday lives of smokers and nonsmokers with attention-deficit/hyperactivity disorder (ADHD). Fifty-two adults with ADHD (25 abstinent smokers and 27 nonsmokers) participated in a double-blind placebo controlled study with one nicotine patch condition and one placebo patch condition in counterbalanced order. Each condition continued for two consecutive days in which patches were administered each morning. The effects of nicotine on ADHD symptoms, moods, and side effects were assessed with electronic diaries. Cardiovascular activity was recorded with ambulatory blood pressure monitors and physical activity was monitored with actigraphs. Nicotine reduced reports of ADHD symptoms by 8% and negative moods by 9%, independent of smoking status. In addition, nicotine increased cardiovascular activity during the first 3 to 6 hours after nicotine patch administration. The results support the self-medication hypothesis for nicotine in adults with ADHD and suggest that smoking cessation and prevention efforts for individuals with ADHD will need to address both the symptom reducing and mood enhancing effects of nicotine.


A Novel Superabsorbent Polymer from Crosslinked Carboxymethyl Tragacanth Gum with Glutaraldehyde: Synthesis, Characterization, and Swelling Properties.
Nowadays, current global environmental problems include measures to eliminate or reduce the negative impact of chemicals from petroleum sources and, therefore, the use of materials from natural resources is increasingly recommended. In this context, natural-based superabsorbent polymers derived from polypeptides and polysaccharides have undergone chemical and biochemical modifications to improve their ability to absorb and retain large amounts of liquids. In the present paper, a new process has been used to overcome the side effects of radical polymerization in the manufacture of conventional polyacrylate superabsorbents (SAPs). Tragacanth gum (TG) was selected to prepare a new superabsorbent material (CMTG-GA) based on carboxymethyl tragacanth (CMTG) crosslinked with glutaraldehyde (GA). The characterization of the polymer was carried out by FTIR, TGA, XRD, and SEM. The effect of the amount of crosslinking agent and the pH on the water absorption capacity was also examined. Subsequently, swelling studies were performed using free swelling capacity (FSC) and centrifuge retention capacity (CRC) techniques in distilled water, tap water, and saline solution. The results showed that the CRC of the new material is not less than 42.1 g/g, which was observed for a ratio of 20% by weight of GA to CMTG. Likewise, the maximum absorption results were 43.9 and 32.14 g/g, respectively, for FSC and CRC at pH 8.0. In addition, a comparison of the swelling capacities of the synthesized product with a commercial SAP extracted from a baby diaper, well known in the Moroccan market, showed that the performances were very similar.


Regulation of the germinal center reaction by Foxp3+ follicular regulatory T cells.
Follicular helper T (T(FH)) cells participate in humoral responses providing selection signals to germinal center B cells. Recently, expression of CXCR5, PD-1, and the transcription factor Bcl-6 has allowed the identification of T(FH) cells. We found that a proportion of follicular T cells, with phenotypic characteristics of T(FH) cells and expressing Foxp3, are recruited during the course of a germinal center (GC) reaction. These Foxp3(+) cells derive from natural regulatory T cells. To establish the in vivo physiologic importance of Foxp3(+) follicular T cells, we used CXCR5-deficient Foxp3(+) cells, which do not have access to the follicular region. Adoptive cell transfers of CXCR5-deficient Foxp3(+) cells have shown that Foxp3(+) follicular T cells are important regulators of the GC reaction following immunization with a thymus-dependent Ag. Our in vivo data show that Foxp3(+) follicular T cells can limit the magnitude of the GC reaction and also the amount of secreted Ag-specific IgM, IgG1, IgG2b, and IgA. Therefore, Foxp3(+) follicular regulatory T cells appear to combine characteristics of T(FH) and regulatory T cells for the control of humoral immune responses.


Paying for physician services in state Medicaid programs.
This article presents new information on both methods and rates of payment for physician services in State Medicaid programs. A variety of indices comparing State programs with each other and with Medicare are developed and discussed. The information is important for both State policymakers considering cost-containment strategies and for those concerned with Medicaid access to physician services.


Ritodrine serum levels: influence of dose and route of administration.
Serum levels of ritodrine were measured by radio-immunoassay both after single and during chronic administration. In 50 non-pregnant women, the maximum ritodrine levels found after a single dose of 10 mg p.o. were 7.4 +/- 4.7 (ng/ml, +/- SD, n = 10); after 20 mg p.o.: 23.8 +/- 5; after 10 mg i.m.: 30.7 +/- 8.2; after 9.3 mg i.v.: 34.7 +/- 5.5; and after 18 mg i.v.: 75.1 +/- 20.7. Ritodrine determinations during chronic intravenous infusion in 116 pregnant women, at one of the seven infusion rates, showed that the serum steady-state ritodrine levels were proportional to the infusion rates below 400 micrograms/min; above that rate the ritodrine levels flattened out. In 91 pregnant women the ritodrine serum levels were measured at one of a number of different time intervals during chronic oral administration of 5 mg (n = 52) or 10 mg (n = 39) every 4 h. During the chronic oral administration of 10 mg every 4 h, the mean ritodrine levels ranged between 14.3 ng/ml at the peak and 4.6 ng/ml just prior to the subsequent dose. For rapid and controlled tocolysis, intravenous infusion is the most appropriate method; intramuscular administration has no obvious advantage. In this respect, a daily dose of 60 mg, 6 X 10 mg, administered by oral route is probably too low; moreover, the bioavailability of the drug by this route was quite different in two volunteers. Although the absolute bioavailability of the drug was estimated in only a small group of volunteers, consistent results (around 40%) were obtained with the 20-mg oral formulation.


Long-term results of patients with malignant carcinoid syndrome receiving octreotide LAR.
Octreotide LAR is an established treatment for malignant carcinoid syndrome. However, studies with large number of patients and long follow-up are lacking. To present long-terms results with octreotide LAR, assessing duration of clinical and objective response and treatment tolerance, in a large, homogeneous cohort of patients with malignant carcinoid syndrome. A total of 108 patients with metastatic midgut neuroendocrine tumours were included in this 8-year study. Clinical evaluation was based on a symptom score. Radiological assessment was based on RECIST (Response Evaluation Criteria In Solid Tumours) criteria. Of the 108 patients, 24% had a sustained symptomatic response. In the remaining patients, loss of symptomatic response with the initial dose was noted within 3-60 months. In 17% of them, symptoms were controlled by just an increase of octreotide LAR dose, whilst the other patients required additional treatment. Overall, in 45.3% of patients, symptoms were well controlled during the study period with only octreotide LAR, and no additional treatment was required. No significant adverse effects were noted. Octreotide LAR treatment provides a sustained symptomatic response in about half of the patients with malignant carcinoid syndrome and contributes to disease stabilization for a longer period than previously described.


Effects of psychosocial stress on endothelium-mediated dilation of atherosclerotic arteries in cynomolgus monkeys.
The objectives of this study were to determine if psychosocial stress impairs dilation through endothelium-derived relaxing factor (EDRF)-mediated mechanisms and if this effect is long lasting. Monkeys were fed an atherogenic diet for 36 mo while in one of three experimental conditions: (a) stable social groups ("unstressed," n = 6); (b) unstable social groups for the first half of the experiment and stable groups for the second half ("early stress," n = 8); and (c) stable groups for the first half of the experiment and unstable groups for the second half ("late stress," n = 6). Iliac arteries were studied in organ chambers containing Krebs' buffer and 10(-6) M indomethacin. Arteries from the late stress group had impaired dilation (shift of the dose-response curve down and to the right) to acetylcholine and the calcium ionophore A23187 (for both, P < 0.05), but not to nitroprusside (P > 0.05), compared with unstressed or early stress monkeys. NG-methyl-L-arginine reduced the dose-response curve to both acetylcholine and A23187 in the unstressed group and resulted in similar vascular responses among all three groups (P > 0.05). We conclude that current, but not previous, exposure to chronic stress impairs endothelium-mediated dilation of atherosclerotic iliac arteries of cynomolgus monkeys through an EDRF-mediated mechanism.


Violence and sexual risk taking reported by young people at Swedish youth clinics.
Early identification of sexual risk taking and exposure to violence is fundamental when seeking to strengthen young people's health. The purpose of this study was to study factors associated with sexual risk taking and ill health, as well as to study gender differences, and the associations amongst exposure to multiple forms of violence, sexual risk taking and ill health. This was a cross-sectional study based on data from 3,205 young people answering a questionnaire belonging to the Sexual health Identification Tool (SEXIT 2.0), during consultations at 12 youth clinics in Sweden. The analyses are based on descriptive statistics and nominal multiple regression analysis. Male, transgender and non-binary youths reported significantly more events of sexual risk taking and ill health compared to women. Those who reported sexual initiation before the age of 15 (OR 2.87, CI 1.81-4.56), three or more sexual partners in the past 12 months (OR 2.68, CI 1.70-4.22) and to have ever experienced an unintended pregnancy (OR 2.29, CI 1.32-3.97) were more than twice as likely to report exposure to physical, emotional and sexual violence. Transgender, non-binary youths and women were more exposed to multiple violence (OR 3.68, 13.50) compared to men. Transgender and non-binary youths are exposed to significantly more violence compared to women and men. Experiences of sexual risk taking and ill health demonstrated strong associations with exposure to multiple violence.


Attempting to explore chiropractors and their clinical choices: an examination of a failed study.
Recent studies have shown that psychological factors, attitudes and beliefs impact on the quality of chiropractic student clinical decisions. This association has not been studied among qualified chiropractors. Our objective was to investigate if personality, psychological factors and/or unorthodox beliefs among chiropractors are related to choices of management in specific clinical scenarios. In February 2018, a subsample of chiropractors (N = 700) from a practitioner-based research network in Australia known as ACORN (N = 1680), were invited to respond to an on-line anonymous questionnaire. Questions included items relating to management of specific clinical scenarios, intolerance of uncertainty (IU) and the 'Big-5' personality score, adoption of a prescriptive technique system, self-rating of chiropractic abilities, and the level of importance of subluxation and chiropractic philosophy in the delivery of care. Descriptive analysis was to be reported and associations examined between i) personality and psychology factors, unorthodox beliefs and ii) scores obtained for management of specific clinical scenarios, numbers of interdisciplinary referrals, and guideline-based X-ray use. The number of respondents was 141 (20%) and 33 of their responses were largely incomplete resulting in a final response rate of 108 (15.4%). In addition, some questions were left unanswered. These related mainly to IU and Big-5 personality measurements. Some sample characteristics (age, number of patients per week, hours worked per week) were similar to the larger ACORN project sample. However, the low response rate indicated that the final study sample was unlikely to be truly representative of the study population and the low number of participants made association testing unsuitable. The low response rate and small study sample in this study made any substantive analysis inappropriate. For these reasons, the study was not concluded. However, the potential reasons for the low response from this large database of volunteer research participants are of interest and need to be investigated. Clearly, it is necessary to engage this population better to explore sensitive issues such as personality inventories and different practice profiles in the interest of effective health care delivery and patient safety.


Mortality Pattern in Surgical Wards in Northwestern Nigeria: A Single-Center Study.
Surgical pathologies contribute to a huge portion of the global burden of diseases. Surgical needs therefore remain high and is projected to increase even further in the near future with increasing life expectancy and comorbidities, given the projection that 16% of the world's population will be older than 65 years by 2050. The outcome of patients with surgical pathologies could be influenced by several factors. Key amongst them is the quality of care. Mortality as an outcome is one metric that could be used to assess the quality of surgical care in a health facility, hence this study with the objective of determining the pattern of inpatient mortality in our surgical wards and suggesting possible ways of addressing identified gaps in their care delivery, which may also improve the care in other centers. A retrospective cohort study of surgical inpatients' mortality in the surgical wards of Ahmadu Bello university teaching hospital from January 1st 2016 to December 31st 2019. Data was analyzed using the Statistical Package for the Social Sciences (SPSS) version 20.0, and presented as descriptive statistics. A total of 8862 admissions were made into the surgical wards, with 655 deaths, giving a crude mortality rate of 7.4%. Most of the deaths occurred in patients in the 46-60 years age group (217, 33.1%). Malignancy was the commonest surgical condition, 294 (48.7%, n=604). This was followed by trauma-related conditions, 96 (15.9%, n=604). Civil gunshot injury admissions showed an upward trend from 19 in 2017, with an exponential rise to 45 in 2019. Although malignancy- related deaths predominated amongst our surgical inpatients, the incidences of deaths from road traffic and burns injuries, as well as septic surgical conditions are also worrisomely high. There is a rise in civil gunshot- related injury admissions and deaths.


Biosynthesis of xyloglucan in suspension-cultured soybean cells. Occurrence and some properties of xyloglucan 4-beta-D-glucosyltransferase and 6-alpha-D-xylosyltransferase.
A particulate enzyme fraction that catalyzes the transfer of glucose from UDP-[14C]glucose and of xylose from UDP-[14C]xylose into a xyloglucan has been isolated from suspension-cultured soybean cells. The incorporation of radioactivity from [14C]xylose into the polysaccharide was dependent on the presence of UDP-glucose in the incubation mixture, and that from [14C]glucose was dependent on the concentration of UDP-xylose in the mixture. Mn2+ was required for the incorporation of xylose and the optimum concentration of Mn2+ was about 10 mM. This reaction showed a pH optimum at 6.5 to 7.0 in 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid buffer and was inhibited by phosphate buffer and Tris buffer. On hydrolysis with Trichoderma endoglucanase, the polysaccharide synthesized in vitro gave a pentasaccharide, a hepatasaccharide, and a small amount of non-asaccharide. Based on the results from fragmentation and methylation analyses, the following structures were proposed for the penta- and the heptasaccharides from the xyloglucan synthesized in vitro: (formula, see text).


Multiple sclerosis serum and cerebrospinal fluid immunoglobulin binding to Fc receptors of oligodendrocytes.
Suspensions of bovine oligodendrocytes were used to study the immunofluorescent staining properties of sera from multiple sclerosis (MS) patients and normal individuals. All sera (14 MS patients, 8 patients with other neurological diseases, and 11 normal individuals) showed positive oligodendrocyte staining by indirect immunofluorescence. Staining persisted after extensive absorption of sera with bovine liver to remove nonspecific binding. Similar findings were obtained for cerebrospinal fluid from all 5 MS patients as well as all 5 patients with other neurological diseases. In additional studies to determine if binding is mediated by the Fc fragment of IgG, results were: (1) ultracentrifuged normal and MS sera failed to react with oligodendrocytes, (2) positive staining with oligodendrocytes was observed after heat aggregation of IgG, (3) ox red blood cells, complexed with antibody, reacted with oligodendrocytes to produce strong rosette formation, and (4) the rosette formation could be blocked by prior treatment of oligodendrocytes with heat-aggregated IgG. The studies fail to support a previous claim for specific binding of immunoglobulins to oligodendrocytes in MS. However, they confirm and extend previous findings that the binding of IgG to oligodendrocytes may not necessarily be an antigen-antibody reaction. Therefore, adherence reactions with a putative antibody must exclude Fc-mediated binding.


Need for improved diabetes support among people with psychiatric disorders and diabetes treated in psychiatric outpatient clinics: results from a Danish cross-sectional study.
People with psychiatric disorders have increased risk of premature death partly due to diabetes. This study aims to explore the quality of diabetes care, diabetes management, diabetes support and well-being of people with psychiatric disorders and diabetes. A total of 107 participants aged ≥18 years with diabetes and psychiatric disorders treated at psychiatric outpatient clinics in Denmark were recruited from August 2018 to June 2019. This descriptive cross-sectional study includes data from medical records on quality of diabetes care (eg, level and annual examination of hemoglobin A1c (HbA1c)) and questionnaires on diabetes management (measured on items from the Summary of Diabetes Self-Care Activities Scale and diabetes distress based on Problem Areas in Diabetes Scale (PAID-5)), diabetes support (no, some or high support from eight potential support persons and experience of care actions measured on items from Patient Assessment of Chronic Illness Care) and well-being (WHO 5-Item Scale and self-rated general health). The mean age was 52 years, 56% were men, the mean body mass index was 31.9 kg/m2, the median HbA1c was 53 mmol/mol (7.0%) and the mean blood pressure was 131/83 mm Hg. The proportion with annual measurements of HbA1c was 93%, blood pressure 80%, cholesterol 93%, foot examination 77% and eye examination 75%. Fifty-one per cent had high diabetes distress (PAID-5 score ≥8). Diabetologists and general practitioners (39% and 37%) were the health professionals most frequently reported to provide high diabetes support. This study highlights a need for improved diabetes support in people with psychiatric disorders and diabetes. Although a high proportion received appropriate diabetes care, we found high levels of diabetes distress, moderate levels of optimal self-management behaviors, low well-being and low diabetes support from psychiatric health professionals, while one-third of the population found it relevant to receive diabetes support from psychiatric health professionals.


Activation of erythroid-specific promoters during anthracycline-induced differentiation of K562 cells.
Anthracycline antitumor drugs such as aclacinomycin (ACM) and doxorubicin (DOX) used in subtoxic concentrations induce erythroid differentiation of the erythroleukemic cell line K562. To elucidate the possible role of erythroid genes of the erythropoietin receptor (EpoR) and the transcription factor GATA-1 in this effect, the regulatory regions of the above genes and human epsilon- and gamma-globin and porphobilinogen deaminase (PBGD) genes were fused to the firefly luciferase gene. The resulting reporter constructs were tested in a transfection assay of the erythroleukemic cell line K562 stimulated to differentiate by treatment with the anthracycline drugs ACM and DOX or hemin (HEM). The results showed activation of the tested promoters after cell treatment with ACM, but not with DOX or HEM. In contrast to the mouse EpoR gene promoter, the activity of the human EpoR gene promoter (-659/-60) in the reporter construct was not modified by addition of the first intron sequence. In ACM-treated K562 cells, EpoR gene promoter activity completely correlated with EpoR and GATA-1 mRNA levels and the degree of erythroid maturation. In addition, ACM strongly activated the erythroid gene promoters that contain GATA binding sites. Nevertheless, less activation was also observed for the GATA-1 gene promoter (-312/-31) lacking any known GATA binding sites. Insertion of the GATA-1 gene enhancer with two canonic GATA binding sites, stimulated the ACM activation effect for EpoR and GATA-1 promoter-containing constructs. Mutation of the enhancer GATA binding sites abolished this effect. All the regulatory regions tested (except gamma-globin promoter) were completely inactive in nonerythroid COS7 cells. These data indicate that (1) two structurally different anthracycline analogues, DOX and ACM, differ in their differentiation mechanisms, and (2) ACM switches on the erythroid program of K562 cells, at least in part because of interaction with a factor(s) that recognizes the GATA binding sites in the promoter region of erythroid genes leading to their activation.


Trends in incidence rates of ulcerative colitis and Crohn's disease.
Between 1960 and 1979, three studies were conducted in the Baltimore Standard Metropolitan Statistical Area to ascertain the incidence rates of first hospitalizations for ulcerative colitis and Crohn's disease. The age-adjusted rates per 100,000 population for the 1977-1979 survey for ulcerative colitis in white and nonwhite males and females were 2.92, 1.79, 1.29, and 2.90, respectively; the Crohn's disease rates were 3.39, 3.54, 1.29, and 4.08, respectively. In Baltimore the age-adjusted rate for Crohn's disease has increased to exceed the ulcerative colitis rate for whites of both sexes and nonwhite females. The ulcerative colitis and Crohn's disease rates for nonwhite males are similar. The rate for white males exceeds that for nonwhite males for both ulcerative colitis and Crohn's disease, but the converse is true for females. Females have higher rates than males for Crohn's disease in both color groups and for ulcerative colitis among nonwhites. White ulcerative colitis rates are higher for males than for females. From the first to the second surveys, the white male and female rates for ulcerative colitis converge with increasing male and decreasing female rates, but then both decline from the second to the third surveys. For Crohn's disease, the age-adjusted rates increased for whites of both sexes and nonwhite females from the first to second surveys. The Crohn's disease rates appeared to stabilize for whites of both sexes between the second and present surveys, but they increased for nonwhites of both sexes. Trends in age-adjusted rates for other areas are also discussed.


Ultra-large nonlinear parameter in graphene-silicon waveguide structures.
Mono-layer graphene integrated with optical waveguides is studied for the purpose of maximizing E-field interaction with the graphene layer, for the generation of ultra-large nonlinear parameters. It is shown that the common approach used to minimize the waveguide effective modal area does not accurately predict the configuration with the maximum nonlinear parameter. Both photonic and plasmonic waveguide configurations and graphene integration techniques realizable with today's fabrication tools are studied. Importantly, nonlinear parameters exceeding 10(4) W(-1)/m, two orders of magnitude larger than that in silicon on insulator waveguides without graphene, are obtained for the quasi-TE mode in silicon waveguides incorporating mono-layer graphene in the evanescent part of the optical field. Dielectric loaded surface plasmon polariton waveguides incorporating mono-layer graphene are observed to generate nonlinear parameters as large as 10(5) W(-1)/m, three orders of magnitude larger than that in silicon on insulator waveguides without graphene. The ultra-large nonlinear parameters make such waveguides promising platforms for nonlinear integrated optics at ultra-low powers, and for previously unobserved nonlinear optical effects to be studied in a waveguide platform.


A portable tensiometer for assessing surgeon's knot tying technique.
The purpose of this study was to determine the influence of surgeon's tying technique on knot security using O and 2-O monofilament and multifilament nylon sutures. By use of an Instron Tensile Tester and a portable tensiometer, knot security was achieved with these sutures using four-throw square knots (1 = 1 = 1 = 1). After didactic and psychomotor skill training, medical students were taught to construct the four-throw square knot using either a two-hand tie or an instrument tie. By use of the portable tensiometer, their knot tying techniques were judged to be superior to those used by a cohort of obstetricians and gynecologists. The surgeon's faulty technique can easily be corrected by didactic information and psychomotor skill training.


Advanced diabetic nephropathy with nephrotic range proteinuria: a pilot study of the long-term efficacy of subcutaneous ACTH gel on proteinuria, progression of CKD, and urinary levels of VEGF and MCP-1.
Adrenocorticotropic hormone (ACTH) is able to reduce proteinuria in nondiabetic glomerulopathies through activation of melanocortin receptors (MCR) expressed in the podocyte. To determine the efficacy of ACTH, we conducted a randomized, open-label pilot trial of ACTH gel in patients with advanced diabetic nephropathy. Twenty-three (23) patients with diabetic nephropathy were randomized to daily subcutaneous (SQ) injections of 16 or 32 units of ACTH gel for six months. Outcome. The primary endpoint was the percentage of patients achieving a complete remission (<300 mg/24 hours) within 6 months. Exploratory endpoints included the percentage of partial (50% reduction) remissions, changes in Cr, and urinary cytokine markers. After 6 months of ACTH gel therapy, 8 of 14 (57%) patients achieved a complete (n = 1) or partial (n = 7) remission. In the low-dose ACTH gel group (16 units), urinary protein fell from 6709 + 953 to 2224 + 489 mg/24 hrs (P < 0.001). In contrast, 2 of 6 patients in the 32-unit group achieved partial remission, but aggregate proteinuria (5324 + 751 to 5154 + 853 mg/24 hours) did not change. Urinary VEGF increased from 388 to 1346 pg/mg urinary creatinine (P < 0.02) in the low-dose group but remained unchanged in the high-dose group. ACTH gel stabilizes renal function and reduces urinary protein for up to 6 months after treatment. The ClinTrials.gov identifier is NCT01028287.


Surgical treatment of painful neuroma in medial antebrachial cutaneous nerve.
The branches of the medial antebrachial cutaneous nerve (MACN) are located at the medial site of the elbow. The MACN, especially the posterior branches, may be injured or transected during cubital tunnel surgery or other medial approaches to the elbow. Damage to the nerve can cause a neuroma, which leads to disabling pain and restriction of elbow movement. The initial treatment of the neuroma is nonsurgical, and includes local massage, desensitization, physiotherapy, and systemic medication. If after 6 months of these nonsurgical treatments there is no improvement, surgery is indicated. The authors report their experience with 12 patients treated surgically for painful neuroma by high resection of the proximal end or its implantation into the triceps muscle. After surgery there was a high success rate of pain relief and functional improvement in both elbow movement and handgrip strength.


Method for the time-resolved measurement of the size and position of a moving particle using an image sensor.
A new method for the continuous measurement of both the size and position of a moving particle using a two-dimensional metal-oxide-semiconductor-type image sensor is described. With this method the particle position is determined precisely by the number of the scanning line and the pixel number within one frame image in place of the frame number used in ordinary video camera methods. This simple and novel sizing method, associated with the image storage property of the image sensor over one field interval, was first described and applied by König et al. [J. Aerosol. Sci. 17, 157 (1986)]. The numerical analysis and the experiment to verify the sizing method are performed. Details of the system and its application for a freely falling small glass sphere are presented.


Intrapericardial lipoma compressing the right atrium.
We report a case of intrapericardial lipoma compressing the right atrium. Cardiac lipomas are very rare benign tumors that may cause life-threatening complications by rapid growth. A 67-year-old woman presented with dyspnea and palpitations on effort due to compression of the right atrium. The tumor was surgically resected. There was no local recurrence after surgery.


Verification of the assumptions underlying the forecast of Poland's population to the year 2020.
"The forecast of Poland's population to the year 2020 was developed in two stages. The paper briefly discusses the basic assumptions of the demographic forecast...." Aspects considered include fertility, mortality, and migration. The impact of economic conditions and changes in the labor market are considered.


[Disease burden caused by suicide in the Chinese population, in 1990 and 2013].
Objective: To provide basic suicide prevention strategy through analyzing the disease burden of suicide in the Chinese population, in 1990 and 2013. Methods: Indicators including mortality rate, years of life lost due to premature mortality (YLL), years lived with disability (YLD), and disability-adjusted of life years (DALY) on suicide, were from the results of Global Burden of Disease 2013 and used to describe the burden of disease caused by suicide in Chinese population. Data described the disease burden of suicide in China by comparing the corresponding parameters in 1990 and 2013. Results: In 2013, the standard mortality on suicide was 9.08 per 100 000, and 73.39 per 100 000 in the 80 and above year-old, with the highest rates on DALY and YLL seen in the 75-79-year-old. Each parameter related to suicide burden in males appeared higher than that in females. Compare to data in the 1990s, these parameters declined in 2013, especially seen in females. The rate of YLLs/YLDs on suicide was 90.03 in 2013, 89.83 in males and 89.00 in females. Conclusion: The disease burden of suicide decreased sharply between 1990 and 2013 but was still a serious issue in the elderly that called for more attention.


Necrotizing ulcerative gingivitis: a discussion of four dissimilar presentations.
Necrotizing ulcerative gingivitis (NUG) is a periodontal disease characterized by pain, bleeding, and necrosis of interdental papillae. This series details treatment of four cases, followed by a discussion of the disease. Four patients presented to four practitioners for treatment of severe gingival pain, each eventually being diagnosed with NUG. All patients in this series were successfully treated using accepted protocols, and though each was different with regard to presenting signs and symptoms, all responded similarly to treatment. Similar to the patients described in this series, NUG cases in general can present with varying degrees of involvement from barely-noticeable to starkly severe. The most severe cases of NUG are often more destructive in appearance than those most commonly seen in textbooks, while in the mildest cases the appearance can almost be mistaken for health.


Analysis of an mRNA exhibiting anomalous translational specificity.
Gene 6 mRNA of Bacillus subtilis phage phi 29 is inefficiently translated under standard in vitro conditions by Escherichia coli, while it is efficiently translated by the in vitro system derived from B. subtilis. This is a rare example of the inability of E. coli to translate mRNA translated by B. subtilis. The ionic condition in the translation systems was the key component in the differential recognition of the gene 6 message by E. coli and B. subtilis ribosomes. Its translation by E. coli ribosomes was preferentially inhibited by moderate levels of KCl, while its translation by B. subtilis ribosomes was unaffected by these concentrations of salt. This preferential inhibition with E. coli ribosomes was observed in vitro as well as in vivo. While not influencing the general phenomenon of preferential inhibition, anion-specific effects were observed in overall protein synthesis. Glutamate and acetate promoted efficient synthesis over a broad range of concentrations, whereas chloride was inhibitory at all concentrations tested.


Regulatory Th2-type T cell lines against insulin and GAD peptides derived from orally- and nasally-treated NOD mice suppress diabetes.
Non-obese diabetic (NOD) mice spontaneously develop diabetes. Ourselves and others have previously shown that oral and nasal administration of insulin or glutamic acid decarboxylase (GAD) suppresses development of diabetes in the NOD mouse and that this suppression appears secondary to the generation of regulatory T cells that act by secreting anti-inflammatory cytokines such as IL-4 and TGF-beta. In the present study, we analysed cytokine patterns associated with mucosal administration of insulin B-chain, B-chain peptide 10-24 and GAD peptide 524-543 and derived lines and clones from mucosally-treated animals. Mice were fed five times (400-600 microg/feed) or nasally-treated three times (60 microg/application), and 2 days after the last treatment were immunized in the footpad with the mucosally administered antigen in CFA. Primary immune responses in the popliteal lymph node were measured 10 days after immunization and lines and clones were then established from the primary cultures. There was significantly less IFN-gamma production in mucosally-treated mice associated with increased production of IL-10 and TGF-beta. The nature of the antigen appeared to determine cytokine production as the B-chain given either orally or nasally primed for TGF-beta responses, whereas mucosally administered B-chain peptide 10-24 primed for IL-10. T cell clones, established from draining lymph nodes of fed or nasally-treated animals, secreted IL-4, IL-10 and TGF-beta whereas those from non-fed mice secreted IL-2 and IFN-gamma. Transfer of Th1 lines with splenocytes from diabetic NOD mice into NOD or NOD/SCID animals accelerated diabetes, whereas transfer of Th2 lines suppressed the development of diabetes. Our results further support a role for Th2-type cells in the regulation of diabetes in NOD mice.


Pars plana vitrectomy assisted by intravitreal injection of conbercept enhances the therapeutic effect and quality of life in patients with severe proliferative diabetic retinopathy.
To explore the application value of intravitreal injection of Conbercept (IVC)-assisted pars plana vitrectomy (PPV) in patients with severe proliferative diabetic retinopathy (PDR). Forty-eight patients with severe PDR who underwent surgical treatment in Chongqing Aier Eye Hospital between October 2019 and June 2021 were retrospectively enrolled, and their clinical data were analyzed. Of them, 22 patients receiving PPV alone were assigned to the PPV group, and the remaining 26 patients treated with IVC-assisted PPV were included in the PPV+IVC group. The intra-operative indicators, postoperative complication rate, visual acuity (VA) improvement, and postoperative quality of life (QoL) were compared between the two groups. The levels of vascular endothelial growth factor (VEGF), placental growth factor (PIGF), and basic fibroblast growth factor (bFGF) in aqueous humor (AH) as well as serum contents of interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) were determined by Enzyme Linked Immunosorbent Assay (ELISA). Compared to the PPV group, the operation time of the PPV+IVC group was significantly shorter, and the incidence of severe intraoperative blood loss (IBL), bipolar electrocoagulation hemostasis, iatrogenic retinal breaks (IRBs), postoperative silicone oil tamponade (SOT), and overall complications were significantly reduced. After surgery, the central macular thickness (CMT) was lower and the best corrected visual acuity (BCVA) assessed by the standard visual acuity chart and VA were significantly more improved in the PPV+IVC group versus the PPV group. After the use of Conbercept, the AH levels of VEGF, PIGF, and bFGF in the PPV+IVC group decreased and were significantly lower than those in the PPV group. The PPV+IVC group also showed lower serum levels of TNF-α, IL-6, and IL-1β than the PPV group. IVC-assisted PPV can effectively reduce the difficulty of surgical treatment for PDR, better improve the postoperative VA of patients, and reduce inflammation with fewer complications.


Covalent disulfide binding of human IL-1 beta to alpha 2-macroglobulin: inhibition by D-penicillamine.
Secreted human IL-1 beta is known to have two free SH groups due to unpaired cysteines (positions 8 and 71). Alpha 2-Macroglobulin (alpha 2-M) has internal thioester bonds between cysteine and glutamate residues. Free SH groups may be generated at these alpha 2M residues through the action of proteinases, amines such as methylamine, or at a slow rate, by H2O ("aging" of alpha 2M). Thus, the possibility that IL-1 beta forms a disulfide bond with alpha 2M was investigated. 125I-labeled human rIL-1 beta (15 kDa) was incubated with fresh normal human serum or with purified alpha 2M, treated or not with methylamine. The mixtures were submitted to nondenaturing and denaturing polyacrylamide gel electrophoresis (PAGE) followed by autoradiography. IL-1 beta bound to commercially purified "aged" alpha 2M and to alpha 2M in methylamine-treated serum but not to native serum alpha 2M. It did not bind detectably to any other serum proteins. The addition of D-penicillamine (D-pen) during the reaction of [125I]rIL-1 beta with serum or purified alpha 2M blocked the covalent binding of rIL-1 beta to alpha 2M. [125I]rIL-1 beta was removed from alpha 2M by 2-mercaptoethanol in SDS. Thus, disulfide bonds were formed between the free SH groups on [125I]rIL-1 beta and those resulting from the cleavage of the internal thioester bonds of alpha 2M. "Cold" rIL-1 beta and a Cys71----Ser71 rIL-1 beta mutant effectively competed with [125I]rIL.1 beta for binding sites on alpha 2M. When complexes of rIL-1 beta or the mutant rIL-1 beta and alpha 2M were subjected to nonreducing SDS-PAGE and subsequent Western blot analysis, the rIL-1 beta molecules were found to be present in the alpha 2M bands in a dose-dependent manner. rIL-1 beta attached to alpha 2M in the presence or absence of D-pen showed similar biological activity in the mouse thymocyte-assay. Thus, rIL-1 beta attached noncovalently to alpha 2M is biologically active. The lack of inhibition of rIL-1 beta activity by binding to methylamine-treated alpha 2M in the absence of D-pen suggests, but does not prove, that the covalently bound rIL-1 beta is also active. We concluded that human rIL-1 beta binds to alpha 2M through the Cys at position 8 and that D-pen inhibits this binding. We speculate that this inhibitory effect may contribute to the therapeutic benefits of D-pen in patients with rheumatoid arthritis.


Evaluation of five guidelines for option development in multiple-choice item-writing.
This paper evaluates certain guidelines for writing multiple-choice test items. The analysis of the responses of 5013 subjects to 630 items from 21 university classroom achievement tests suggests that an option should not differ in terms of heterogeneous content because such error has a slight but harmful effect on item discrimination. This also occurs with the "None of the above" option when it is the correct one. In contrast, results do not show the supposedly negative effects of a different-length option, the use of specific determiners, or the use of the "All of the above" option, which not only decreases difficulty but also improves discrimination when it is the correct option.


Intrapetrous internal carotid artery aneurysm diagnosed on the basis of middle ear effusion: A case report.
The present study reports a rare case of a giant intrapetrous internal carotid aneurysm that compressed the internal jugular vein causing recurrent middle ear effusion in a 13-year-old female. Images obtained by computed tomography revealed middle ear effusion occupying the right side of the attic. Digital subtraction angiography (DSA) resulted in a diagnosis of a giant aneurysm of the right intrapetrous carotid artery, with a diameter of 25 mm and a neighboring area of compression of the internal jugular vein. The patient was treated successfully using coil embolization. The present study therefore indicates that DSA should be considered in the differential diagnosis of patients with middle ear effusion. Early treatment with coil embolization or other surgical treatments can be a life-saving therapeutic approach.


Cancer mortality in a higher-income black population in New York State. Comparison with rates in the United States as a whole.
In the 1980 Census the median family income among blacks in Suffolk County, New York (i.e., $19,604) was much higher than that for American blacks as a whole (i.e., $12,618) and 94.1% of that for American whites (i.e., $20,840), but the proportion below the poverty level was still higher for Suffolk County blacks than for American whites. Observed numbers of deaths from 1979 to 1985 for total cancers and most cancer sites in Suffolk County black men and women were not lower than expected on the basis of age-specific and gender-specific death rates for blacks in the US. Although numbers of deaths from cervical cancer and prostate cancer were slightly lower than expected in Suffolk County blacks versus American blacks, these numbers were still significantly greater than expected on the basis of death rates among American whites. Age-specific death rates for age groups 25 to 44 years to 55 to 64 years tended to be lower in Suffolk County for lung cancers in black men but not for breast cancer in black women. Specific cancer sites, which differ in the direction of the association between incidence and socioeconomic status, age, and gender must be considered in comparisons of cancer mortality by race and socioeconomic level. Implications of the comparisons were discussed with regard to the goal of reducing racial differences in cancer death rates.


Rac activation by the T-cell receptor inhibits T cell migration.
T cell migration is essential for immune responses and inflammation. Activation of the T-cell receptor (TCR) triggers a migration stop signal to facilitate interaction with antigen-presenting cells and cell retention at inflammatory sites, but the mechanisms responsible for this effect are not known. Migrating T cells are polarized with a lamellipodium at the front and uropod at the rear. Here we show that transient TCR activation induces prolonged inhibition of T-cell migration. TCR pre-activation leads to cells with multiple lamellipodia and lacking a uropod even after removal of the TCR signal. A similar phenotype is induced by expression of constitutively active Rac1, and TCR signaling activates Rac1. TCR signaling acts via Rac to reduce phosphorylation of ezrin/radixin/moesin proteins, which are required for uropod formation, and to increase stathmin phosphorylation, which regulates microtubule stability. T cell polarity and migration is partially restored by inhibiting Rac or by expressing constitutively active moesin. We propose that transient TCR signaling induces sustained inhibition of T cell migration via Rac1, increased stathmin phosphorylation and reduced ERM phosphorylation which act together to inhibit T-cell migratory polarity.


Association of renin and aldosterone with glucose metabolism in a Western European population: the KORA F4/FF4 study.
Primary aldosteronism is associated with impaired glucose tolerance. Whether plasma aldosterone and/or renin concentrations are associated with type 2 diabetes and continuous measures of glucose metabolism in the general population is still under debate. The analyses included 2931 participants of the KORA F4 study at baseline and 2010 participants of the KORA FF4 study after a median follow-up of 6.5 years. The associations of active plasma renin and aldosterone concentrations with type 2 diabetes and continuous measures of glucose metabolism were assessed using logistic and linear regression models. Results were adjusted for sex, age, body mass index (BMI), estimated glomerular filtration rate, potassium, use of ACE inhibitors, angiotensin receptor blockers, beta blockers, diuretics and calcium channel blockers. Cross-sectionally, renin was associated with type 2 diabetes (OR per SD: 1.25, 95% CI 1.10 to 1.43, p<0.001), fasting glucose, 2-hour glucose, insulin, proinsulin, HOMA-B (homeostasis model assessment of beta cell function) and HOMA-IR (homeostasis model assessment of insulin resistance) (all p values <0.001). Aldosterone was not associated with type 2 diabetes (OR: 1.04, 95% CI 0.91 to 1.19; p=0.547) but with insulin, proinsulin and HOMA-IR (all p values <0.001). The aldosterone-renin ratio was inversely associated with type 2 diabetes and several measures of glucose metabolism. Longitudinally, neither renin (OR: 1.12, 95% CI 0.92 to 1.36) nor aldosterone (OR: 0.91, 95% CI 0.74 to 1.11) were associated with incident type 2 diabetes. Renin was inversely associated with changes of insulin concentrations. In the KORA F4/FF4 study, renin and aldosterone were not associated with incident type 2 diabetes and largely unrelated to changes of measures of glucose metabolism. Cross-sectionally, aldosterone was associated with surrogate parameters of insulin resistance. However, these associations were not independent of renin.


Evaluation of Horn Bud Wound Healing Following Cautery Disbudding of Dairy Calves With and Without the Use of Oxytetracycline Aerosol Spray.
Oxytetracycline is commonly applied as a topical agent to burn lesions post cautery disbudding of calves. Judicial use of antibiotics dictates that they should only be used where necessary to reduce the development of resistance in target bacteria. The objective of this study, therefore, was to evaluate the efficacy of topical oxytetracycline spray on wound healing post cautery disbudding of dairy calves over a 6-week period. Dairy calves were disbudded by veterinarians, technicians, or veterinary surgeons, using a standard cautery disbudding protocol. Oxytetracycline spray was randomly applied to the right or left horn bud of each animal (OXY), while the other horn bud received no antibiotic spray (NA). The outcomes measured were wound diameter (WD) and lesion score (LS), either normal healing (NH) or abnormal healing (AH). These assessments were conducted every 14 days following disbudding, until 42 days. A total of 360 animals completed the study. There was a difference in wound diameter and lesion score on day 14 post disbudding between the two groups. Cautery lesions sprayed with oxytetracycline (OXY) were 0.5 ± 0.15 mm smaller than NA lesions (P = 0.001), and there were fewer abnormal healing lesions for OXY compared to the NA (2.5 vs. 11%, respectively; P ≤ 0.001). There were no differences at day 28 and day 42 post disbudding, and on day 42, 34% of wounds had healed in both groups. In summary, the authors were unable to demonstrate a difference in healing between the groups using the described methods.


[mRNA expression alteration of two-pore potassium channels in the brain of beta-amyloid peptide25-35-induced memory impaired rats].
To study mRNA expression alteration of two-pore potassium channels in the brain of beta-amyloid peptide25-35 (beta-AP25-35)-induced memory impaired rats. Memory impairments induced in rats by single icv injection of beta-AP25-35 (2 mmol.L-1) 5 microL were assessed in the Morris water maze test. The mRNA expression levels of three two-pore potassium channels TREK-1, TREK-2 and TRAAK were detected in rat cerebral cortex and hippocampus by reverse transcription-polymerase chain reaction (RT-PCR). In the Morris water maze test, the escape latencies of the beta-AP25-35-treated rats were longer than those of the control group in 1st, 2nd and 4th training day, suggesting that the memory of beta-AP25-35-treated rats was obviously impaired. Compared with the control group, the mRNA levels of TREK-1, TREK-2 and TRAAK in the hippocampus of the beta-AP25-35-treated rats were increased by 40.0%, 27.9% and 18.9%, respectively; while no significant change of TREK-1, TREK-2 and TRAAK mRNA levels was observed in the cortex. The mRNA expression levels of two-pore potassium channels were increased significantly in the brain of beta-AP25-35-induced memory impaired rats.


Catalytic Asymmetric Roskamp Reaction of Silyl Diazoalkane: Synthesis of Enantioenriched α-Silyl Ketone.
A catalytic enantioselective Roskamp reaction of silyl diazoalkane to synthesize a highly optically active α-silyl ketone from aldehydes is described. In the presence of a chiral oxazaborolidinium ion catalyst, the reaction provides α-chiral silyl ketones with good yields (up to 97%) and high enantioselectivities (up to >99% ee). In addition, a one-pot procedure using an asymmetric Roskamp/reduction strategy gives highly optically active syn-β-hydroxysilane in good yields (up to 94%) with high enantioselectivities (up to 99% ee) and syn stereoselectivities (>20:1).


Synthesis and biological evaluation of a new series of phenylhydroquinone derivatives as inhibitors of EGF-R-associated PTK activity.
In order to design new potent inhibitors of the epidermal growth factor receptor (EGF-R) associated protein tyrosine kinase (PTK) activity as antitumor agents, several families of phenylhydroquinone derivatives were synthesized. Some of these compounds were shown to block PTK activity in vitro, but also efficiently to inhibit EGF-stimulated DNA synthesis in ER 22 cells (CCL 39 hamster fibroblasts transfected with EGF-R) with IC50 values in the range 1-10 microM. In some cases, a correlation between the two sets of data was observed, allowing structure-activity relationships to be established. However, inhibitors which had in vitro specificity with regard to other kinases were not specific in the cellular test. Similar effects on DNA synthesis were observed after stimulation by various activating agents, suggesting that our compounds may also act against other cellular targets involved in the EGF-dependent pathways leading to cell proliferation.


Glucagon-Like Peptide 1 Receptor Agonists - Potential Game Changers in the Treatment of Glaucoma?
Glaucoma is a common ocular neurodegenerative disease characterized by the progressive loss of retinal ganglion cells and their axons. It is the most common cause of irreversible blindness. With an increasing number of glaucoma patients and disease progression despite treatment, it is paramount to develop new and effective therapeutics. Emerging new candidates are the receptor agonists of the incretin hormone glucagon-like-peptide-1 (GLP-1), originally used for the treatment of diabetes. GLP-1 receptor (GLP-1R) agonists have shown neuroprotective effects in preclinical and clinical studies on neurodegenerative diseases in both the brain (e.g., Alzheimer's disease, Parkinson's disease, stroke and diabetic neuropathy) and the eye (e.g., diabetic retinopathy and AMD). However, there are currently very few studies investigating the protective effects of GLP-1R agonists in the treatment of specifically glaucoma. Based on a literature search on PubMed, the Cochrane Library, and ClinicalTrials.gov, this review aims to summarize current clinical literature on GLP-1 receptor agonists in the treatment of neurodegenerative diseases to elucidate their potential in future anti-glaucomatous treatment strategies.


DNA damage enhanced by the attenuation of SLD5 delays cell cycle restoration in normal cells but not in cancer cells.
SLD5 is a member of the GINS complex composed of PSF1, PSF2, PSF3 and SLD5, playing a critical role in the formation of the DNA replication fork with CDC45 in yeast. Previously, we had isolated a PSF1 orthologue from a murine hematopoietic stem cell DNA library and were then able to identify orthologues of all the other GINS members by the yeast two hybrid approach using PSF1 as the bait. These GINS orthologues may also function in DNA replication in mammalian cells because they form tetrameric complexes as observed in yeast, and gene deletion mutants of both PSF1 and SLD5 result in a lack of epiblast proliferation and early embryonic lethality. However, we found that PSF1 is also involved in chromosomal segregation in M phase, consistent with recent suggestions that homologues of genes associated with DNA replication in lower organisms also regulate cellular events other than DNA replication in mammalian cells. Here we analyzed the function of SLD5 other than DNA replication and found that it is active in DNA damage and repair. Attenuation of SLD5 expression results in marked DNA damage in both normal cells and cancer cells, suggesting that it protects against DNA damage. Attenuation of SLD5 delays the DNA repair response and cell cycle restoration in normal cells but not in cancer cells. These findings suggest that SLD5 might represent a therapeutic target molecule acting at the level of tumor stromal cells rather than the cancerous cells themselves, because development of the tumor microenvironment could be delayed or disrupted by the suppression of its expression in the normal cell types within the tumor.


Intravenous leiomyomatosis.
Intravenous leiomyomatosis of the uterus with extension to the right common iliac vein in a 34-year-old woman is reported. The successful treatment consisted of abdominal hysterectomy, bilateral salpingo-oophorectomy, venotomy and extraction of 3 cm long mobile tumour from the right common iliac vein. The presence of cytoplasmic oestrogen and progesterone receptors in the tumours indicates that intravenous leiomyoma is hormone-dependent.


Recombinant human parathyroid hormone (1-84) is effective in CASR-associated hypoparathyroidism.
Gain-of-function mutations in the CASR gene cause Autosomal Dominant Hypocalcemia Type 1 (ADH1), the most common genetic cause of isolated hypoparathyroidism. Subjects have increased calcium sensitivity in the renal tubule, leading to increased urinary calcium excretion, nephrocalcinosis and nephrolithiasis when compared with other causes of hypoparathyroidism. The traditional approach to treatment includes activated vitamin D but this further increases urinary calcium excretion. In this case series, we describe the use of recombinant human parathyroid hormone (rhPTH)1-84 to treat subjects with ADH1, with improved control of serum and urinary calcium levels. We describe two children and one adult with ADH1 due to heterozygous CASR mutations who were treated with rhPTH(1-84). Case 1 was a 9.4-year-old female whose 24-h urinary calcium decreased from 7.5 to 3.9 mg/kg at 1 year. Calcitriol and calcium supplementation were discontinued after titration of rhPTH(1-84). Case 2 was a 9.5-year-old male whose 24-h urinary calcium decreased from 11.7 to 1.7 mg/kg at 1 year, and calcitriol was also discontinued. Case 3 was a 24-year-old female whose treatment was switched from multi-dose teriparatide to daily rhPTH(1-84). All three subjects achieved or maintained target serum levels of calcium and normal or improved urinary calcium levels with daily rhPTH(1-84) monotherapy. We have described three subjects with ADH1 who were treated effectively with rhPTH(1-84). In all cases, hypercalciuria improved by comparison to treatment with conventional therapy consisting of calcium supplementation and calcitriol.


Quantitative analysis of volatile methylsiloxanes in waste-to-energy landfill biogases using direct APCI-MS/MS.
Landfill-biogas utilization is a win-win solution as it creates sources of renewable energy and revenue while diminishing greenhouse gas emissions. However, the combustion of a siloxane-containing biogas produces abrasive microcrystalline silica that causes severe and expensive damages to power generation equipment. Hence, the importance of siloxane analysis of the biogas has increased with the growth of the waste-to-energy market. We have investigated an improved method for the analysis of octamethylcyclotetrasiloxane (D4) and decamethylcyclopentasiloxane (D5) in biogas using deuterated hexamethyldisiloxane (HMDS-d(18)) as an internal standard with direct atmospheric pressure chemical ionization/tandem mass spectrometry (APCI-MS/MS). The use of HMDS-d(18) as a single internal standard provided effective signal compensation for both D4 and D5 in biogas and improved the sensitivity and reliability for the direct APCI-MS/MS quantification of these compounds in biogas. Low detection limits ( approximately 2 microg/m(3)) were achieved. The method was successfully applied for the determination of D4 and D5 contents in various samples of biogas recovered for electrical power generation from a landfill site in Montreal. Concentrations measured for D4 and D5 were in the ranges of 131-1275 and 250-6226 microg/m(3), respectively. Among the various landfill zones sampled, a clear trend of decreasing D4 and D5 concentrations was observed for older landfill materials.


Exploring the Potential Mechanism of Shufeng Jiedu Capsule for Treating COVID-19 by Comprehensive Network Pharmacological Approaches and Molecular Docking Validation.
Shufeng Jiedu capsule (SFJDC) is a well-known Chinese patent drug that is recommended as a basic prescription and applied widely in the clinical treatment of COVID-19. However, the exact molecular mechanism of SFJDC remains unclear. The present study aims to determine the potential pharmacological mechanisms of SFJDC in the treatment of COVID-19 based on network pharmacology. The network pharmacology-based strategy includes collection and analysis of active compounds and target genes, network construction, identification of key compounds and hub target genes, KEGG and GO enrichment, recognition and analysis of main modules, as well as molecule docking. A total of 214 active chemical compounds and 339 target genes of SFJDC were collected. Of note, 5 key compounds (β -sitosterol, luteolin, kaempferol, quercetin, and stigmasterol) and 10 hub target genes (TP53, AKT1, NCOA1, EGFR, PRKCA, ANXA1, CTNNB1, NCOA2, RELA and FOS) were identified based on network analysis. The hub target genes mainly enriched in pathways including MAPK signaling pathway, PI3K-Akt signaling pathway and cAMP signaling pathway, which could be the underlying pharmacological mechanisms of SFJDC for treating COVID-19. Moreover, the key compounds had high binding activity with three typical target proteins including ACE2, 2OFZ, and 1SSK. By network pharmacology analysis, SFJDC was found to effectively improve immune function and reduce inflammatory responses based on its key compounds, hub target genes, and the relevant pathways. These findings may provide valuable evidence for explaining how SFJDC exerting the therapeutic effects on COVID-19, providing a holistic view for further clinical application.


Nicotine Exposure Along with Oral Contraceptive Treatment in Female Rats Exacerbates Post-cerebral Ischemic Hypoperfusion Potentially via Altered Histamine Metabolism.
Smoking-derived nicotine (N) and oral contraceptives (OCs) synergistically exacerbate ischemic brain damage in the female, and the underlying mechanisms remain elusive. Our published study showed that N toxicity is exacerbated by OC via altered mitochondrial electron transport chain function. Because mitochondria play an important role in cellular metabolism, we investigated the global metabolomic profile of brains of adolescent and adult female Sprague-Dawley rats exposed to N with or without OC (N+/-OC). Rats were randomly exposed to saline or N+/-OC for 16-21 days followed by random allocation into two cohorts. The first cohort was used to characterize the cortical metabolome. Pathway enrichment analysis showed a significant increase in several histamine metabolites including 1-methylhistamine, 1-methyl-4-imidazoleacetate, and 1-ribosyl-imidazleacetate, along with carnosine and homocarnosine in adolescent and adult animals treated with N and N+OC in relation to respective saline controls, which may be reflective of altered histamine metabolism with nicotine treatment. We also observed reduced levels of the neurotransmitters N-acetyl-aspartyl-glutamate (NAAG), gamma-aminobutyrate (GABA), and N-methyl-GABA in N+OC treatment in adolescent animals. The second cohort underwent bilateral carotid artery occlusion and hypotension followed by cerebral blood flow (CBF) assessment a day later. Autoradiographic images of the brain 24 h after ischemic episodes showed severe reduction in cortical and hippocampal local CBF in N+/-OC-exposed rats compared with saline treated. Because GABA and histamine are critical for CBF maintenance, altered metabolism of these neurotransmitters may be responsible for observed severe post-ischemic hypoperfusion, which in turn exacerbates ischemic brain damage.


The magnitude and characteristics of the population of cancer survivors: using population-based estimates of cancer prevalence to inform service planning for survivorship care.
Rising cancer incidence and survival mean that the number of cancer survivors is growing. Accumulating evidence suggests many survivors have long-term medical and supportive care needs, and that these needs vary by survivors' socio-demographic and clinical characteristics. To illustrate how cancer registry data may be useful in survivorship care service planning, we generated population-based estimates of cancer prevalence in Ireland and described socio-demographic and clinical characteristics of the survivor population. Details of people diagnosed with invasive cancer (ICD10 C00-C96) during 1994-2011, and who were still alive on 31/12/2011, were abstracted from the National Cancer Registry, and tabulated by cancer site, sex, current age, marital status, initial treatment, and time since diagnosis. Associations were investigated using chi-square tests. After excluding non-melanoma skin cancers, 17-year cancer prevalence in Ireland was 112,610 (females: 58,054 (52%) males: 54,556 (48%)). The four most prevalent cancers among females were breast (26,066), colorectum (6,598), melanoma (4,593) and uterus (3,505) and among males were prostate (23,966), colorectum (8,207), lymphoma (3,236) and melanoma (2,774). At the end of 2011, 39% of female survivors were aged <60 and 35% were ≥70 compared to 25% and 46% of males (p < 0.001). More than half of survivors of bladder, colorectal and prostate cancer were ≥70. Cancers with the highest percentages of younger (<40) survivors were: testis (50%); leukaemia (females: 28%; males: 22%); cervix (20%); and lymphoma (females: 19%; males: 20%). Fewer female (57%) than male (64%) survivors were married but the percentage single was similar (17-18%). More female (25%) than male survivors (18%; p < 0.001) were ≥10 years from diagnosis. Overall, 69% of survivors had undergone cancer-directed surgery, and 39%, 32% and 18% had received radiotherapy, chemotherapy and hormone therapy, respectively. These frequencies were higher among females than males (surgery: 82%, 54%; radiotherapy: 42%, 35%; chemotherapy: 40%, 22%; hormone therapy: 23%, 13%). These results reveal the socio-demographic and clinical heterogeneity of the survivor population, and highlight groups which may have specific medical and supportive care needs. These types of population-based estimates may help decision-makers, planners and service providers to develop follow-up and after-care services to effectively meet survivors' needs.


Evidentiary, extraevidentiary, and deliberation process predictors of real jury verdicts.
In contrast to the extensive literature based on mock jurors, large-sample studies of decision making by real juries are relatively rare. In this field study, we examined relationships between jury verdicts and variables representing 3 classes of potential determinants-evidentiary, extraevidentiary, and deliberation process-using a sample of 114 criminal jury trials. Posttrial data were collected from 11 presiding judges, 31 attorneys, and 367 jurors using a Web-based questionnaire. The strength of the prosecution's evidence was strongly related to the occurrence of a conviction, whereas most extraevidentiary and deliberation process variables were only weakly to modestly related in bivariate form and when the prosecution's evidence strength was controlled. Notable exceptions to this pattern were jury demographic diversity as represented by the number of different race-gender subgroups (e.g., Black males) present in the jury, and several deliberation process variables reflecting advocacy for acquittal (e.g., presence of an identifiable proacquittal faction within the jury and proacquittal advocacy by the foreperson). Variables reflecting advocacy for conviction were essentially unrelated to jury verdict. Sets of extraevidentiary and deliberation variables were each able to modestly improve the explanation of jury verdicts over prosecution evidence strength in multivariate models. This study highlights the predictive efficacy of prosecution evidence strength with respect to jury verdicts, as well as the potential importance of jury demographic diversity and advocacy for acquittal during deliberation. (PsycINFO Database Record


Egg-White Proteins Have a Minor Impact on the Bactericidal Action of Egg White Toward Salmonella Enteritidis at 45°C.
Salmonella enterica serovar Enteritidis is noted for its ability to survive the harsh antibacterial activity of egg white which is presumed to explain its occurrence as the major food-borne pathogen associated with the consumption of eggs and egg products. Liquid egg white is a major ingredient for the food industry but, because of its thermal fragility, pasteurization is performed at the modest temperature of 57°C (for 2-6 min). Unfortunately, such treatment does not lead to sufficient reduction in S. Enteritidis contamination, which is a clear health concern when the product is consumed without cooking. However, egg white is able to limit S. Enteritidis growth due to its alkaline pH, iron deficiency and multiple antimicrobial proteins. This anti-Salmonella activity of egg white is temperature dependent and becomes bactericidal once the incubation temperature exceeds 42°C. This property is exploited in the highly promising pasteurization treatment (42-45°C for 1-5 days) which achieves complete killing of S. Enteritidis. However, the precise mechanism and the role of the egg-white proteins are not fully understood. Here, the impact of exposure of S. Enteritidis to egg white-based media, with or without egg-white proteins (>10 kDa), under bactericidal conditions (45°C) was explored by measuring survival and global expression. Surprisingly, the bactericidal activity of egg white at 45°C was only slightly affected by egg-white proteins indicating that they play a minor role in the bactericidal activity observed. Moreover, egg-white proteins had minimal impact on the global-gene-expression response to egg white such that very similar, major regulatory responses (20% genes affected) were observed both with and without egg-white proteins following incubation for 45 min at 45°C. Egg-white proteins caused a significant change in expression for just 64 genes, including the psp and lysozyme-inhibitor responses genes which is suggestive of an early membrane perturbation effect. Such damage was supported by disruption of the proton motive force by egg-white proteins. In summary, the results suggest that low-mass components of egg white are largely responsible for the bactericidal activity of egg white at 45°C.


Are fructophilic lactic acid bacteria (FLAB) beneficial to humans?
Fructophilic lactic acid bacteria (FLAB) are heterofermentative and related to the genera Fructilactobacillus, Convivina, Leuconostoc, Oenococcus and Weissella. Although they generally prefer fructose above glucose, obligate heterofermentative species will ferment glucose in the presence of external electron acceptors such as pyruvate and fructose. Little is known about the presence of FLAB in the human gut, let alone probiotic properties. In this review we discuss the possible role FLAB may have in the human gastro-intestinal tract (GIT) and highlight the advantages and disadvantages these bacteria may have in individuals with a diet high in fructose.


Management of Malignant Pleural Effusion: A Cost-Utility Analysis.
Malignant pleural effusion (MPE) is associated with a significant impact on health-related quality of life. Palliative interventions abound, with varying costs and degrees of invasiveness. We examined the relative cost-utility of 5 therapeutic alternatives for MPE among adults. Original studies investigating the management of MPE were extensively researched, and the most robust and current data particularly those from the TIME2 trial were chosen to estimate event probabilities. Medicare data were used for cost estimation. Utility estimates were adapted from 2 original studies and kept consistent with prior estimations. The decision tree model was based on clinical guidelines and authors' consensus opinion. Primary outcome of interest was the incremental cost-effectiveness ratio for each intervention over a less effective alternative over an analytical horizon of 6 months. Given the paucity of data on rapid pleurodesis protocol, a sensitivity analysis was conducted to address the uncertainty surrounding its efficacy in terms of achieving long-term pleurodesis. Except for repeated thoracentesis (RT; least effective), all interventions had similar effectiveness. Tunneled pleural catheter was the most cost-effective option with an incremental cost-effectiveness ratio of $45,747 per QALY gained over RT, assuming a willingness-to-pay threshold of $100,000/QALY. Multivariate sensitivity analysis showed that rapid pleurodesis protocol remained cost-ineffective even with an estimated probability of lasting pleurodesis up to 85%. Tunneled pleural catheter is the most cost-effective therapeutic alternative to RT. This, together with its relative convenience (requiring neither hospitalization nor thoracoscopic procedural skills), makes it an intervention of choice for MPE.


Hypercalcemia, hypercalciuria, and kidney stones in long-term studies of vitamin D supplementation: a systematic review and meta-analysis.
Vitamin D supplementation is increasingly being used in higher doses in randomized controlled trials (RCTs). However, adverse events from very large annual doses of vitamin D have been shown in 2 RCTs, whereas in a third RCT, low-dose vitamin D, with calcium supplements, was shown to increase kidney stone risk. We analyzed the side effects related to calcium metabolism in RCTs, specifically hypercalcemia, hypercalciuria, and kidney stones, in participants who were given vitamin D supplements for ≥24 wk compared with in subjects in the placebo arm. The following 3 main online databases were searched: Ovid Medline (PubMed), EMBASE, and the Cochrane Library. Software was used for the meta-analysis. A total of 48 studies with 19,833 participants were identified, which reported ≥1 of the following side effects: hypercalcemia, hypercalciuria, or kidney stones. Of these studies, kidney stones were reported in only 9 trials with a tendency for fewer subjects reporting stones in the vitamin D arm than in the placebo arm (RR: 0.66, 95% CI: 0.41, 1.09; P = 0.10). In 37 studies, hypercalcemia was shown with increased risk shown for the vitamin D group (RR: 1.54; 95% CI: 1.09, 2.18; P = 0.01). Similar increased risk of hypercalciuria was shown in 14 studies for the vitamin D group (RR: 1.64; 95% CI: 1.06, 2.53; P = 0.03). In subgroup analyses, it was shown that the effect of vitamin D supplementation on risk of hypercalcemia, hypercalciuria, or kidney stones was not modified by baseline 25-hydroxyvitamin D, vitamin D dose and duration, or calcium co-supplementation. Long-term vitamin D supplementation resulted in increased risks of hypercalcemia and hypercalciuria, which were not dose related. However, vitamin D supplementation did not increase risk of kidney stones. Additional large RCTs of long-term vitamin D supplementation are required to confirm these findings.


Capturing SCL and HR changes to win and loss events during gambling on electronic machines.
The role of physiological arousal is central to theories about the onset and maintenance of gambling behaviours including problem gambling. The range of possibilities suggested include tonic underarousal and phasic abnormalities such as hypersensitivity to reward and/or reduced sensitivity to negative consequences associated with losses. Among the various types of gambling, electronic gambling machines (EGMs) are associated with the large majority of gambling related problems. The demonstration that physiological changes associated with rapidly occurring win and loss events during electronic gambling can be reliably captured is fundamental to further progress in the psychophysiology of gambling. The current study monitored electrodermal and cardiac activities of twenty-four healthy participants to event outcomes (losses, fake wins, small wins and big wins) during a task on a real EGM. The results demonstrated that it is possible to reliably capture the profile of physiological changes as they occurred in real time to the many different win and loss events during electronic gambling. Relative to baseline levels, win events produced significant increases in skin conductance levels, (but not in HR) whereas loss events produced no significant changes. The study has important applications for further experimental and clinical research.


Neurocysticercosis involving the pituitary stalk : case report and literature review.
Neurocysticercosis (NCC) is the most common parasitic infestation of the central nervous system. Most cases of NCC are to related and/or associated with inflammation within the cerebral parenchyma. A 71-year-old woman presented with a 4-year history of visual disturbance. This symptom had become aggravated 4 weeks earlier. Her visual acuity gradually decreased and superior hemianopsia was noted. Magnetic resonance imaging (MRI) revealed an enhanced and thickened pituitary stalk accompanying a suspicious mass. The provisional diagnoses were lymphoma, glioma, or other inflammatory conditions. Laboratory studies, including blood and hormonal studies, showed normal findings. Surgical resection was performed. In the pathological examination, degenerated parasitic wall structure was seen and its contents were composed of completely degenerated focal globular structures suggesting the scolex of cysticercus. We report an unusual case of NCC involving the pituitary stalk which was presented with a juxtasellar tumor. The possible underlying mechanisms are discussed with a review of pertinent literature.


Oral metronomic vinorelbine combined with endocrine therapy in hormone receptor-positive HER2-negative breast cancer: SOLTI-1501 VENTANA window of opportunity trial.
The biological effect of oral metronomic vinorelbine (mVNB) alone or in combination with endocrine therapy in patients with hormone receptor-positive (HR+)/HER2-negative breast cancer has been scarcely addressed. Postmenopausal women with untreated stage I-III HR+/HER2-negative breast cancer were randomized (1:1:1) to receive 3 weeks of letrozole (LTZ) 2.5 mg/day, oral mVNB 50 mg 3 days/week, or the combination. The primary objective was to evaluate, within PAM50 Luminal A/B disease, if the anti-proliferative effect of LTZ+mVNB was superior to monotherapy. An anti-proliferative effect was defined as the mean relative decrease of the PAM50 11-gene proliferation score in combination arm vs. both monotherapy arms. Secondary objectives included the evaluation of a comprehensive panel of breast cancer-related genes and safety. An unplanned analysis of stromal tumor-infiltrating lymphocytes (sTILs) was also performed. PAM50 analyses were performed using the nCounter®-based Breast Cancer 360™ gene panel, which includes 752 genes and 32 signatures. Sixty-one patients were randomized, and 54 paired samples (89%) were analyzed. The main patient characteristics were mean age of 67, mean tumor size of 1.7 cm, mean Ki67 of 14.3%, stage I (55.7%), and grades 1-2 (90%). Most baseline samples were PAM50 Luminal A (74.1%) or B (22.2%). The anti-proliferative effect of 3 weeks of LTZ+mVNB (- 73.2%) was superior to both monotherapy arms combined (- 49.9%; p = 0.001) and mVNB (- 19.1%; p < 0.001). The anti-proliferative effect of LTZ+mVNB (- 73.2%) was numerically higher compared to LTZ (- 65.7%) but did not reach statistical significance (p = 0.328). LTZ+mVNB induced high expression of immune-related genes and gene signatures, including CD8 T cell signature and PDL1 gene and low expression of ER-regulated genes (e.g., progesterone receptor) and cell cycle-related and DNA repair genes. In tumors with ≤ 10% sTILs at baseline, a statistically significant increase in sTILs was observed following LTZ (paired analysis p = 0.049) and LTZ+mVNB (p = 0.012). Grade 3 adverse events occurred in 3.4% of the cases. Short-term mVNB is well-tolerated and presents anti-proliferative activity alone and in combination with LTZ. The high expression of immune-related biological processes and sTILs observed with the combination opens the possibility of studying this combination with immunotherapy. Further investigation comparing these biological results with other metronomic schedules or drug combinations is warranted. NCT02802748 , registered 16 June 2016.


Sequential merocyanine product isomerization following femtosecond UV excitation of a spiropyran.
The ring-opening dynamics of the photochromic switch 1',3'-dihydro-1',3',3'-trimethyl-6-nitrospiro[2H-1-benzopyran-2,2'-(2H)-indole] in tetrachloroethene is studied with both femtosecond time-resolved ultraviolet (UV)/visible and UV/mid-infrared (IR) pump-probe spectroscopy. During the first picosecond we identify two new transient features in the UV/vis experiments, the first of which we assign to spiropyran S1 --> S(n) absorption (lifetime < or = 0.2 ps). The second feature (lifetime 0.5 +/- 0.2 ps) we tentatively assign to the merocyanine T2 state. After 1 ps both probing methods show biexponential merocyanine formation kinetics, with average time constants of 17 +/- 3 and 350 +/- 20 ps. In the UV/IR experiments, the initial dynamics show more dispersion in formation times than in the UV/vis measurements, whereas the slower time constant is the same in both. A weak transient IR signal at approximately 1360 cm(-1) demonstrates that this biexponentiality is caused by a sequential isomerization between two merocyanine species. Lifetimes provide evidence that the merocyanine S1 state is not involved in the photochemical reaction.


The role of autologous blood transfusion in joint replacement surgery.
The efficacy of predeposited autologous blood transfusion (PABT) with and without intra/postoperative blood salvage to reduce or eliminate the need for homologous blood transfusion (HBT) in primary total hip or knee replacement surgery was investigated by retrospective and prospective studies. Depending on the type of surgery, one to three units of PABT eliminated the need for HBT in 50 to 78% of patients, but, intra/postoperative blood salvage alone reduced the need only in 11 to 29%. In contrast, blood salvage, when combined with three units of PABT, eliminated the need for HBT in all patients undergoing primary joint replacement surgery. A cost comparison analysis showed that blood salvage was more expensive than PABT, and therefore it should be limited to patients who had predeposited fewer than three units of autologous blood.


Identification of UV-B light-responsive regions in the promoter of the tryptophan decarboxylase gene from Catharanthus roseus.
The tryptophan decarboxylase (Tdc) gene encodes a key enzyme in the biosynthesis of terpenoid indole alkaloids (TIAs) in Catharanthus roseus. TIAs absorb ultraviolet light (UV) and putative functions in plants include a role as UV protectants. In support of this possible function we demonstrate here that UV light induces accumulation of several TIAs as well as expression of the Tdc gene in C. roseus. In addition, in tobacco a Tdc-gusA construct was found to be specifically induced by UV-B light. Lack of induction by UV-A or other wavelengths of light indicate that Tdc expression is regulated by a specific UV-B receptor and corresponding signal transduction pathway. To identify UV-responsive Tdc promoter elements, a loss-of-function analysis was performed, in which deletion derivatives were fused to the gusA reporter gene and analysed in transgenic tobacco plants. Truncation of the Tdc promoter from -1818 (relative to the start of transcription) to -160 reduced expression levels two-fold without affecting the qualitative UV response. Deletion to -37 further reduced expression levels five-fold, but the delta37 promoter also remained UV-responsive. Subsequently, the -160 to -37 region was further studied by gain-of-function experiments, in which the transcriptional activities of tetramerized subfragments fused to truncated promoters were analysed. Combination of the data identified several functional regions in the -160 to +198 promoter. The - 160 to -99 region acts as the main transcriptional enhancer. UV-responsive elements appeared to be redundant in the -160 Tdc promoter and to reside between -99 and -37 and between -37 and + 198.


Dose emission and aerodynamic characterization of the terbutaline sulphate dose emitted from a Turbuhaler at low inhalation flow.
Previously, dose emission below 30 L min(-1) through DPI has not been routinely determined. However, during routine use some patients do not achieve 30 L min(-1) inhalation flows. Hence, the aim of the present study was to determine dose emission characteristics for low inhalation flows from terbutaline sulphate Turbuhaler. Total emitted dose (TED), fine particle dose (FPD) and mass median aerodynamic diameter (MMAD) of terbutaline sulphate Turbuhaler were determined using inhalation flows of 10-60 L min(-1) and inhaled volume of 4 L. TED and FPD increase significantly with the increase of inhalation flows (p <0.05). Flows had more pronounced effect on FPD than TED, thus, faster inhalation increases respirable amount more than it increases emitted dose. MMAD increases with decrease of inhalation flow until flow of 20L min(-1) then it decreases. In vitro flow dependent dose emission has been demonstrated previously for Turbuhaler for flow rates above 30 L min(-1) but is more pronounced below this flow. Minimal FPD below 30 L min(-1) suggests that during routine use at this flow rate most of emitted dose will impact in mouth. Flow dependent dose emission results suggest that Pharmacopoeias should consider the use variety of inhalation flows rather than one that is equivalent to pressure drop of 4 KPa.


Epidemiology and variability of Malassezia spp.
A short review on Malassezia spp., completed with our experience, is made. The main epidemiological characteristics with particular regard to the diffusion in several animal species, the characteristics of skin colonization (in particular of the dog) and the distribution of the different Malassezia spp. in some hosts are discussed. Lastly the main phenotypic and genotypic characteristics, referred to M. pachydermatis especially, were described, showing their high variability and differentiation.


Not only "nurture", but also "nature", influence the outcome of zygoma repair.
The present study aims to elucidate the relationship between preoperative deviation patterns of fractured zygomas and treatment outcomes. Forty-five randomly selected patients with tri-pod type zygoma fractures were classified into a medial rotation group and a lateral rotation group, depending on preoperative deviation patterns. A minimum of 6 months after the operation, symmetry of the cheek was evaluated by three plastic surgeons using a VAS system. The evaluated scores were compared between the two groups. Furthermore, simulation of postoperative secondary deformity was performed by applying hypothetically defined relapse forces on CAD models produced by referring to the CT data of 20 patients. The deviation values obtained by the simulation were compared between the two groups. The results demonstrate that VAS scores were higher for the lateral rotation group than for the medial rotation group and that the deviation values were higher for the medial rotation group than for the lateral rotation group. It is concluded that treatment outcomes of zygoma fractures are affected by preoperative deviation patterns. Cases with medial rotation are likely to present poorer outcomes than those with lateral rotation.


An AUV-Aided Cross-Layer Mobile Data Gathering Protocol for Underwater Sensor Networks.
Underwater sensor networks (UWSNs) have recently attracted much attention due to their ability to discover and monitor the aquatic environment. However, acoustic communication has posed some significant challenges, such as high propagation delay, low available bandwidth, and high bit error rate. Therefore, proposing a cross-layer protocol is of high importance to the field to integrate different communication functionalities (i.e, an interaction between data link layer and network layer) to interact in a more reliable and flexible manner to overcome the consequences of applying acoustic signals. In this paper, a novel Cross-Layer Mobile Data gathering (CLMD) scheme for Underwater Sensor Networks (UWSNs) is presented to improve the performance by providing the interaction between the MAC and routing layers. In CLMD, an Autonomous Underwater Vehicle (AUV) is used to periodically visit a group of clusters which are responsible for data collection from members. The communications are managed by using a distributed cross-layer solution to enhance network performance in terms of packet delivery and energy saving. The cluster heads are replaced with other candidate members at the end of each operational phase to prolong the network lifetime. The effectiveness of CLMD is verified through an extensive simulation study which reveals the performance improvement in the energy-saving, network lifetime, and packet delivery ratio with varying number of nodes. The effects of MAC protocols are also studied by studying the network performance under various MAC protocols in terms of packet delivery ratio, goodput, and energy consumption with varying density of nodes.


Treatment of critical bleeding in trauma patients.
Massive haemorrhage after trauma is a big challenge for care-givers, being a leading cause of early in-hospital mortality. Surgical bleeding may be easily controlled with several techniques. Otherwise, consumptive coagulopathy is often extremely difficult to stop. An adjunctive strategy to treat traumatic coagulopathic bleeding is recombinant activated factor VII (rFVIIa) (NovoSeven, Novo Nordisk A/S, Bagsvaerd, Denmark). All major trauma victims haemodinamically unstable (systolic blood pressure < 90 mmHg or > 90 mmHg with massive infusions or vasopressors) admitted to the Emergency Department of the Niguarda Ca' Granda Hospital in Milan from October 2002 to September 2005 were reviewed. Mechanical bleeding was controlled with interventional techniques when indicated. Blood derivatives were administrated to maintain haemoglobin> 7 g/dL, INR < 1.5, fibrinogen > 1 and platelet count > 50 x 109. Off-label administration of rFVIIa was performed in the last year in any coagulopathic salvageable patient when all other strategies failed to control bleeding. Major trauma were 942, mean age 32.49+/-18.44 years, 94% blunt trauma, 25.13% haemodynamically unstable. Deaths occurred in 17.02% of cases before any procedure. Emergency invasive treatments were performed in 72.34% of cases. Infusions restored haemodynamic stability in 10.63% of patients. In average 9.4+/-4.1 units of red blood cells were transfused in unstable patients. rFVIIa (dosing 60-100 mg/kg) was administrated in 12 patients. Mortality occurred in 33.33% of cases. The principal cause of death was brain injury. A femoral artery thrombosis was observed in a mangled leg. No other adverse effects due to rFVIIa were documented. Off-label administration of rFVIIa was able to reverse life-threatening bleeding not manageable with standard strategies in our series of major trauma patients without systemic adverse effects.


Cannabinoid hyperemesis syndrome: literature review and proposed diagnosis and treatment algorithm.
Cannabinoid hyperemesis syndrome (CHS) is characterized by cyclic vomiting and compulsive bathing behaviors in chronic cannabis users. Patients are typically diagnosed with CHS only after multiple and extensive medical evaluations, consequently without a clear etiology of their symptoms or treatment plan leading to symptomatic improvement. Increased healthcare provider awareness of CHS as a cause of nausea, vomiting, and abdominal pain coupled with an attentiveness to focused history taking-especially noting symptomatic improvement with prolonged exposure to hot showers or baths-can lead to effective treatment through cannabis cessation. We propose a diagnosis and treatment algorithm for physicians to follow when evaluating patients presenting with nausea, vomiting, and abdominal pain who are suspected to suffer from CHS.


Bilateral mixed density lesions in the body of the mandible.
A patient with actinomycosis involving the right and left body of the mandible is reported. Such a diagnosis, although not common, should be considered when formulating a differential diagnosis of such mixed radiopaque-radiolucent lesions. Proper collection of a specimen, transplant, and culture under anaerobic conditions is imperative if a laboratory diagnosis is to be made. A biopsy, yielding the characteristic histopathological features of actinomycosis infection, is frequently adequate for diagnosis and treatment.


Designing an optimization model for green closed-loop supply chain network of heavy tire by considering economic pricing under uncertainty.
The conditions of global competition and environmental sensitivities have made organizations and factories to collect returned products, in such a way that these organizations have tried to rehabilitate, recycle, or destroy these products in order to protect the environment. This paper propose a mathematical model for the green closed-loop supply chain network of heavy tire by considering the economic pricing of its products under conditions of uncertainty, which economically determines the price and leads to more profitability. In addition, the relevant model is a two-objective fuzzy model, the first objective of which is to minimize costs and maximize profits, and the second objective is to minimize environmental issues. The proposed model can also determine the optimal location of each center based on potential locations, the optimal amount of production, distribution, collection, recycling, as well as the reproduction of products. The ε-constraint method is used to solve the model with two objective functions; this method ensures strong Pareto optimal answers and prevents weak Pareto answers. Independent two-sample t-test is used to verify the results of certain and uncertain models in the studied model. In order to evaluate the effectiveness and profitability of the proposed method, a case study in the field of heavy tires is finally used, through which very useful results are obtained.


Development of the MEDOS/HIA DeltaStream extracorporeal rotary blood pump.
The DeltaStream blood pump has been developed for extracorporeal circulation with one focus on potential integration into simplified bypass systems (SBS). Its small size and an embedded electric motor are the basic pump properties. A variation of the impeller design has been performed to optimize hydraulic and hematologic characteristics. A simple impeller design was developed which allows flow and pressure generation for cardiopulmonary bypass applications. The option of a pulsatile flow mode for ventricular assist device applications also was demonstrated in vitro. Impeller washout holes were implemented to improve nonthrombogenicity. The pump was investigated for potential thermal hazards for blood caused by the integrated electric motor. It could be demonstrated that there is no thermal risk associated with this design. Durability tests were performed to assess the lifetime of the pump especially with regard to the incorporated polymeric seal. Seal lifetimes of up to 28 days were achieved using different blood substitutes. In animal tests using either the pump as a single device or in an SBS setup, biocompatibility, low hemolysis, and nonthrombogenicity were demonstrated. In summary, the DeltaStream pump shows great potential for different extracorporeal perfusion applications. Besides heart-lung machine and SBS applications, ventricular assist and extracorporeal membrane oxygenation up to several days also appear promising as potential applications.


Relationship between Cottonseed Malate Synthase Aggregation Behavior and Suborganellar Location in Glyoxysomes and Endoplasmic Reticulum.
Malate synthase (EC 220.127.116.11) (MS), an enzyme unique to the glyoxylate cycle, was studied in cotyledons of dark-grown cotton (Gossypium hirsutum, L.) seedlings. MS has generally been regarded as a peripheral membrane protein in glyoxysomes and believed by some to be synthesized on rough ER. Immunocyto-chemical localization of MS in both in situ and isolated cottonseed glyoxysomes, however, showed that MS was located throughout the matrix of glyoxysomes, not specifically associated with their membranes. Biochemical data also supported matrix localization. Isolated glyoxysomes were diluted in variously-buffered salt solutions (200 millimolar KCl or 100 millimolar K-phosphate) or detergents (0.1% Triton X-100, 10 millimolar deoxycholate, or 1.0% Triton X-114) and centrifuged to pellet membranes. Greater than 70% of the MS was recovered in supernatants after treatment with salt solutions, whereas generally less than 30% was released following detergent treatments. MS in pellets derived from glyoxysomes burst in low ionic strength buffer solutions was aggregated (observed on rate-zonal gradients). MS released following salt treatments was the 20S nonaggregated form indicating that salt solutions either disaggregated (or prevented aggregation of) glyoxysomal MS rather than releasing it from membranes. We confirmed reports by others that MS comigrated with ER (NADH: cytochrome c reductase) in sucrose (20-40% w/w) gradients buffered with 100 millimolar Tricine (pH 7.5) after 3 hours centrifugation. However, cottonseed MS did not comigrate with ER in gradients buffered with 10 millimolar Hepes (pH 7.0) or 20 millimolar K-phosphate (pH 7.2) after 3 hours centrifugation, or after 22 hours centrifugation in Tricine or Hepes. Collectively, our data with cotton seeds indicate that MS is not a peripheral membrane protein, and that the aggregation behavior of MS (in various buffers) very likely has led to misinterpretations of its putative associations with ER and glyoxysomal membranes.