Origins of food reinforcement in infants.
Rapid weight gain in infancy is associated with a higher risk of obesity in children and adults. A high relative reinforcing value of food is cross-sectionally related to obesity; lean children find nonfood alternatives more reinforcing than do overweight/obese children. However, to our knowledge, there is no research on how and when food reinforcement develops. This study was designed to assess whether the reinforcing value of food and nonfood alternatives could be tested in 9- to 18-mo-old infants and whether the reinforcing value of food and nonfood alternatives is differentially related to infant weight status. Reinforcing values were assessed by using absolute progressive ratio schedules of reinforcement, with presentation of food and nonfood alternatives counterbalanced in 2 separate studies. Two nonfood reinforcers [Baby Einstein-Baby MacDonald shows (study 1, n = 27) or bubbles (study 2, n = 30)] were tested against the baby's favorite food. Food reinforcing ratio (FRR) was quantified by measuring the reinforcing value of food (Food Pmax) in proportion to the total reinforcing value of food and a nonfood alternative (DVD Pmax or BUB Pmax). Greater weight-for-length z score was associated with a greater FRR of a favorite food in study 1 (FRR-DVD) (r = 0.60, P < 0.001) and FRR of a favorite food in study 2 (FRR-BUB) (r = 0.49, P = 0.006), primarily because of the strong association between greater weight-for-length z score and lower DVD Pmax (r = -0.71, P < 0.0001) and BUB Pmax (r = -0.53, P = 0.003). Infant monthly weight gain was positively associated with FRR-DVD (r = 0.57, P = 0.009) and FRR-BUB (r = 0.37, P = 0.047). Our newly developed paradigm, which tested 2 different nonfood alternatives, demonstrated that lean infants find nonfood alternatives more reinforcing than do overweight/obese infants. This observation suggests that strengthening the alternative reinforcers may have a protective effect against childhood obesity.


Spectral characterization of ciliary beating: variations of frequency with time.
Ciliary beating frequency in tissue culture from frog palate and isolated lung was optically examined using instrumentation that was adjusted to measure a fraction of the surface area of a single ciliary cell. Consecutive 1-s segments of the analogue signal were fast Fourier transformed (FFT) to obtain a power spectrum. At room temperature, these power spectra changed over time from 1 s to the next. Each spectrum contained several dominant frequencies of similar intensities. Cooling the preparation resulted in a single-peak spectrum that was constant over time. A mathematical model is proposed to simulate these findings. The results and the mathematical model support the hypothesis that ciliary beating frequency fluctuates over short periods of time.


Increased epithelial cell proliferation in nasal polyps.
To detect, quantify, and compare respiratory epithelial cell proliferation in nasal mucosa and polyps from patients with nasal polyposis. Cohort study. Patients and samples were selected at the Hôpital Intercommunal de Créteil (France). Flow cytofluorometry and immunohistochemistry were performed at Hôpitaux Tenon and Mondor (Université Paris [France] VI et XII). Twenty-one patients undergoing endoscopic ethmoidectomy for treatment of nasal polyposis. In 10 cases, epithelial cells were removed from frozen inferior turbinate mucosa and polyps by mechanical disaggregation and were then analyzed by flow cytofluorometry, providing the cell DNA content (propidium iodide labeling) and the percentage of S-phase cells. In 11 cases, inferior turbinate mucosa and polyps were fixed in formaldehyde and embedded in paraffin. Proliferating cell nuclear antigen expression in the epithelium was quantified by immunohistochemistry; a proliferating cell nuclear antigen index was calculated for each sample in the basal area, suprabasal area, and full height of the epithelium. All cell populations studied were diploid, and percentages of S-phrase cells were significantly higher in nasal polyps than in mucosa. Proliferating cell nuclear antigen indexes were significantly higher in nasal polyps than in the suprabasal area and full height of the mucosal epithelium. Cell proliferation is increased in epithelium from nasal polyps. Epithelial damage caused by inflammatory mediators could induce this increased cell proliferation via epithelial repair processes. Inflammatory cells could up-regulate epithelial cell proliferation by secreting growth factors.


Effects of intensity of repetitive acoustic stimuli on neural adaptation in the ventral cochlear nucleus of the rat.
To study neural adaptation as a function of stimulus intensity, auditory near-field evoked potentials were recorded from the ventral cochlear nucleus in awake Long Evans rats. Responses to 250-ms trains of repetitive clicks (pulse rates ranging from 100 to 1000 pulses per second) were collected at stimulus intensities of 5, 10, 30, 50 and 70 dB SPL. The amplitude of the first negative (N1) component of the average evoked potentials to individual pulses in the train was measured by using a subtraction method. The N1 responses were normalized with respect to the highest cochlear nucleus potential observed in the train, and then plotted as a function of click position in the train. As expected, the general trend of the curves was an exponential decay reaching a plateau more or less rapidly as a function of both intensity and rate of stimulation. Fitting these curves with exponential decay equations revealed that the rapid time constant decreased for increasing stimulus intensities whereas the short-term time constant is relatively independent of intensity. The amount of adaptation (expressed as the ratio of the plateau to the first peak amplitude) was substantially less prominent at low intensities (5-10 dB SPL) and low rates (100-200 pulses per second) than at higher intensities and high rates. These results indicate that adaptation patterns obtained in the ventral cochlear nucleus by using near-field evoked potentials exhibit properties comparable to those already present at the level of the auditory nerve.


Shellfish and public health: a Swedish perspective.
Bivalves are ancient animals that feed by filtering large volumes of water. In this way, phytoplankton, bacteria and viruses from the water column are greatly concentrated in the mussels. The hazards associated with the consumption of mussels are thus dependent on the occurrence and composition of toxic algae and human microbial pathogens in the areas where shellfish are grown. Diarrheic shellfish toxins have occurred regularly in Sweden during the past 27 years. Peaks of toxins in mussels are mostly recorded from October to December, but the pattern can differ significantly due to location and year, making it hard to predict toxin levels in mussels. With an expansion of aquaculture and a subsequent increase in seafood consumption, better risk management is needed to minimize the effects on humans of algal toxins and human pathogens. New control strategies that have to be implemented are: i) proper site selection of culture installations; ii) regular and cost-efficient monitoring of algae, bacteria and viruses; iii) new indicators for fecal contamination, suitable for the specific locations where shellfish grow; iv) rapid dissemination of information to the industry and public, including risk assessment and advice on how to cope with the situation.


Significance and measurability of the phase of a spatially coherent optical field.
In usual measurements of the phase of an optical field it is generally assumed that the field is monochromatic. In reality this assumption is never justified. The distinction between monochromaticity and complete spatial coherence is first discussed, and it is then shown that with every spatially coherent field (e.g., a laser mode) one can associate a monochromatic wave that, in a well-defined sense, represents the average behavior of the field. Its phase can be measured by standard interferometric techniques and also by techniques developed in recent years for the measurement of the spectral degree of coherence of fields of arbitrary states of coherence.


Pollinator preferences for Nicotiana alata, N. forgetiana, and their F1 hybrids.
The role of pollinators in plant speciation and maintenance of species boundaries is dubious because most plant species are visited by several types of pollinators, and most pollinator species visit several species of plants. We investigated pollinator preferences and their efficacy as ethological isolation mechanisms between two interfertile species, Nicotiana alata and N. forgetiana and their F1 hybrids. Hawkmoths pollinate N. alata, while primarily hummingbirds and occasionally small hawkmoths visit N. forgetiana. F1 hybrids are easily produced in the greenhouse and although the species grow in similar habitats, hybrids have not been found in nature. In Rio Grande do Sul, Brazil, near where both species are found, experimental plots were studied containing both species, and both species plus F1 hybrids. In the mixed-species plots, hawkmoths showed a strong preference for N. alata. Hummingbirds were less common and only visited N. forgetiana. Hybrid seed was produced but plants made significantly fewer hybrid offspring than predicted by the frequency of interspecific pollinator movements. Nicotiana forgetiana was the seed parent of 97% of the F1 offspring, suggesting an asymmetry in pollen delivery or postpollination processes. In plots containing F1 hybrids plus both parental species, hawkmoths preferred N. alata and undervisited the other two phenotypes, except that in the third plot they visited hybrids in proportion to the hybrid frequency. Hummingbirds strongly preferred N. forgetiana in all plots but also visited F1 hybrids in proportion to their frequency in the third plot. Overall, F1 hybrids were well pollinated and were frequently visited immediately before or after one of the parental species. Thus hybrids could facilitate gene flow between the parental species. We conclude that pollinator discrimination among species is strong but is an imperfect isolation mechanism, especially if hybrids are present.


Minimally Invasive Versus Open Esophagectomy for Esophageal Cancer: A Comparison of Early Surgical Outcomes From The Society of Thoracic Surgeons National Database.
Open esophagectomy results in significant morbidity and mortality. Minimally invasive esophagectomy (MIE) has become increasingly popular at specialized centers with the aim of improving perioperative outcomes. Numerous single-institution studies suggest MIE may offer lower short-term morbidity. The two approaches are compared using a large, multiinstitutional database. The Society of Thoracic Surgeons (STS) National Database (v2.081) was queried for all resections performed for esophageal cancer between 2008 and 2011 (n = 3,780). Minimally invasive approaches included both transhiatal (n = 214) and Ivor Lewis (n = 600), and these were compared directly with open transhiatal (n = 1,065) and Ivor Lewis (n = 1,291) procedures, respectively. Thirty-day outcomes were examined using nonparametric statistical testing. Both open and MIE groups were similar in terms of preoperative risk factors. Morbidity and all-cause mortality were equivalent at 62.2% and 3.8%. MIE was associated with longer median procedure times (443.0 versus 312.0 minutes; p < 0.001), but a shorter median length of hospital stay (9.0 versus 10.0 days; p < 0.001). Patients who underwent MIE had higher rates of reoperation (9.9% versus 4.4%; p < 0.001) and empyema (4.1% versus 1.8%; p < 0.001). Open technique led to an increased rate of wound infections (6.3% versus 2.3%; p < 0.001), postoperative transfusion (18.7% versus 14.1%; p = 0.002), and ileus (4.5% versus 2.2%; p = 0.002). Propensity score-matched analysis confirmed these findings. High- and low-volume centers had similar outcomes. Early results from the STS National Database indicate that MIE is safe, with comparable rates of morbidity and mortality as open technique. Longer procedure times and a higher rate of reoperation following MIE may reflect a learning curve.


Neuropsychiatric disorders associated with recreational nitrous oxide use.
Recreational nitrous oxide use has grown in popularity among young people and has become a serious public health problem. Chronic use of nitrous oxide can lead to a functional vitamin B12 deficiency and neuropsychiatric complications. This study aimed to investigate the characteristics of neuropsychiatric complications associated with nitrous oxide use and to enhance clinicians' awareness of this public health problem. We retrospectively reviewed 16 patients with neuropsychiatric disorders related to nitrous oxide use who were treated in our hospital from June 2021 to October 2022. Their demographics, clinical features, investigations, treatments and outcomes were analyzed. There were ten males and six females between the ages of 17 and 25 with a mean age of 20.5 ± 2.6 years. Thirteen patients sought medical help from the neurology clinic. Two patients presented to the psychiatric department and one patient presented to the emergency department with acute cognitive impairment. All 16 patients presented with neurological symptoms, such as paresthesia in four limbs or the lower limbs, unsteady gait and weakness. Twelve patients developed psychiatric symptoms, such as hallucinations, agitation, depression, emotional indifference and personality changes. Twelve patients had vitamin B12 deficiency. All 16 patients had hyperhomocysteinemia. Fourteen patients showed abnormal high signal on T2-weighted imaging and an inverted "V" sign in axial view, mainly involving the cervical cord. Neuropsychiatric symptoms improved with vitamin B12 treatment and cessation of nitrous oxide use in all cases. Young adults are predominately involved in recreational use of nitrous oxide, which can cause neuropsychiatric complications. The clinical response to vitamin B12 supplementation and cessation of nitrous oxide use is generally good. Clinicians should recognize nitrous oxide use as a public health problem and a cause of a wide range of neuropsychiatric symptoms, particularly in younger patients.


The 76-gene signature defines high-risk patients that benefit from adjuvant tamoxifen therapy.
To assess the benefit from adjuvant systemic tamoxifen therapy in breast cancer risk groups identified by the previously established prognostic 76-gene signature. In 300 lymph node-negative (LNN), estrogen receptor-positive (ER+) breast cancer patients (136 treated with adjuvant tamoxifen, 164 having received no systemic adjuvant therapy), distant metastasis-free survival (DMFS) as a function of the 76-gene signature was determined in a multicenter fashion. In 136 tamoxifen-treated patients, the 76-gene signature identified a group of patients with a poor prognosis [hazard ratio (HR), 4.62; P = 0.0248]. These patients showed a 12.3% absolute benefit of tamoxifen in 10-year DMFS (HR, 0.52; P = 0.0318) compared with untreated high-risk patients. This represented a 71% increase in relative benefit compared with the 7.2% absolute benefit observed for all 300 patients without using the gene signature. In the low-risk group there was no significant 10-year DMFS benefit of tamoxifen. The 76-gene signature defines high-risk patients who benefit from adjuvant tamoxifen therapy. Although we did not study the value of chemotherapy in this study, low-risk patients identified by the 76-gene signature have a prognosis good enough that chemotherapy would be difficult to justify. The prognosis of these patients is sufficiently good, in fact, that a disease-free benefit for tamoxifen therapy is difficult to prove, though benefits in terms of loco-regional relapse and a reduction in risk for contralateral breast cancer might justify hormonal therapy in these patients.


Melanocytes determine angiogenesis gene expression across human tissues.
Several angiogenesis-dependent diseases, including age-related macular degeneration and infantile hemangioma, display differential prevalence among Black, as compared to White individuals. Although socioeconomic status and genetic architecture have been suggested as explaining these differences, we have recently shown that pigment production per se might be involved. For example, we have shown that the extracellular protein fibromodulin is a pro-angiogenic factor highly secreted by melanocytes in White but not Black individuals. Still, additional pigment-dependent angiogenic factors and their molecular mechanisms remain to be identified. Understanding the contribution of pigmentation to angiogenesis in health and disease is essential for precision medicine of angiogenesis-dependent diseases with racial disparity. Toward that goal, we compared the transcriptomes of Black and White individuals in three tissues with angiogenic activity, namely artery, whole blood, and skin. We identified several differentially expressed angiogenesis pathways, including artery morphogenesis, regulation of endothelial cell chemotaxis, and cellular response to vascular endothelial growth factor stimulus. We then demonstrated that the expression of key genes in these pathways is directly modulated by the degree of pigmentation. We further identified the precise pigment production pathway controlling the expression of these genes, namely melanocortin 1 receptor (MC1R) signaling. These results demonstrate pigment-mediated regulation of angiogenesis-related pathways and their driver genes across human tissues.


ACTH response in rats during biphasic fever induced by interleukin-1.
Injection of a low concentration (0.3 micrograms/kg iv) of interleukin-1 beta (IL-1 beta) produced monophasic fever, but high concentrations (15 micrograms/kg iv) produced biphasic fever in rats. Treatment with IL-1 beta caused dose-dependent rises in the plasma concentration of adrenocorticotropic hormone (ACTH) 30 min after injection. Moreover, significant increases in plasma levels of ACTH were observed 90 and 180 min after injection of the high dose of IL-1 beta. ACTH response induced by IL-1 beta (15 micrograms/kg iv) was suppressed by pretreatment with injection of indomethacin (Indo), a potent inhibitor of prostaglandin (PG) synthesis, in a dose-dependent manner (1 and 10 mg/kg iv). Also, biphasic fever induced by the high dose of IL-1 beta was completely abolished by pretreatment with the intravenous injection of Indo. Intracerebroventricular (icv) injection of Indo (50 micrograms) did not affect febrile and ACTH responses induced by intravenous IL-1 beta, whereas those responses induced by IL-1 beta (2 ng icv) were significantly suppressed by injection of Indo (50 micrograms icv). Although it is possible that intracerebroventricular Indo does not reach the site of intravenous IL-1 beta action within the brain, these results suggest that in rats febrile and ACTH responses induced by intravenous IL-1 beta are caused by IL-1 beta-acting structures outside the blood-brain barrier. It is likely that these structures subsequently synthesize and release PGE2, which in turn induces ACTH and febrile responses in rats.


Antagonism against Vibrio cholerae by diffusible substances produced by bacterial components of the human faecal microbiota.
Cholera vibrios sometimes survive, probably in low-level silent populations, in the small intestine of chronic carriers or pass through the gastrointestinal tract of a few individuals without causing diarrhoea or colonisation. To understand these situations, the present study used plate cultures (ex-vivo test) to investigate the frequency of appearance of an inhibitory halo against Vibrio cholerae produced by faecal specimens from 92 healthy volunteers (40 females, 52 males) aged 4-61 years. The frequency of inhibitory halo was 20.6% in the whole group. An apparently higher percentage (27.3%) was observed in the age range 20-40 years when compared with the range 4-19 years (10.7%), but not the range 41-61 years (20.0%). Frequency was significantly higher in males (30.8%) than females (7.5%). The dominant microbiota of a volunteer whose faeces produced an inhibitory halo was isolated by plate culture of decimal dilutions in an anaerobic chamber. Potential isolates of 26 apparently different morphologies were associated with germ-free NIH mice. One week later, the inhibitory test showed an antagonistic halo around the faeces from the associated animals, but not from the axenic mice. Of the 26 bacteria isolated, two (Lactobacillus sp. and Peptostreptococcus sp.) produced a compound antagonistic against V. cholerae in an in-vitro assay. When bi-associated with germ-free mice those strains eliminated the vibrio from the intestinal ecosystem in c. 5 days.


Measuring the quality of provided services for patients with chronic kidney disease.
The healthcare organizations need to develop and implement quality improvement plans for their survival and success. Measuring quality in the healthcare competitive environment is an undeniable necessity for these organizations and will lead to improved patient satisfaction. This study aimed to measure the quality of provided services for patients with chronic kidney disease in Kerman in 2014. This cross-sectional, descriptive-analytic study was performed from 23 January 2014 to 14 February 2014 in four hemodialysis centers in Kerman. All of the patients on chronic hemodialysis (n = 195) who were referred to these four centers were selected and studied using census method. The required data were collected using the SERVQUAL questionnaire, consisting of two parts: questions related to the patients' demographic characteristics, and 28 items to measure the patients' expectations and perceptions of the five dimensions of service quality, including tangibility, reliability, responsiveness, assurance, and empathy. The collected data were analyzed using SPSS 21.0 through some statistical tests, including independent-samples t test, one-way ANOVA, and paired-samples t test. The results showed that the means of patients' expectations were more than their perceptions of the quality of provided services in all dimensions, which indicated that there were gaps in all dimensions. The highest and lowest means of negative gaps were related to empathy (-0.52 ± 0.48) and tangibility (-0.29 ± 0.51). In addition, among the studied patients' demographic characteristics and the five dimensions of service quality, only the difference between the patients' income levels and the gap in assurance were statistically significant (P < 0.001). Overall, the results of the present study showed that the expectations of patients on hemodialysis were more than their perceptions of provided services. The healthcare providers and employees should pay more attention to the patients' opinions and comments and use their feedback to solve the workplace problems and improve the quality of provided services. In addition, training the health staff to meet the patients' emotional needs and expectations is suggested.


[Effect of a constant magnetic field on biological systems].
The effect of magnetic field on biological systems is discussed. A number of existing theories are evaluated, and a conclusion is made that it is difficult to explain from the standpoint of physics, neglecting the specifies of the living cell, the effect of the constant magnetic field on biological systems at the microscopic level.


Adipocyte Glucocorticoid Receptor Deficiency Attenuates Aging- and HFD-Induced Obesity and Impairs the Feeding-Fasting Transition.
Glucocorticoids (GCs) are important regulators of systemic energy metabolism, and aberrant GC action is linked to metabolic dysfunctions. Yet, the extent to which normal and pathophysiological energy metabolism depend on the GC receptor (GR) in adipocytes remains unclear. Here, we demonstrate that adipocyte GR deficiency in mice significantly impacts systemic metabolism in different energetic states. Plasma metabolomics and biochemical analyses revealed a marked global effect of GR deficiency on systemic metabolite abundance and, thus, substrate partitioning in fed and fasted states. This correlated with a decreased lipolytic capacity of GR-deficient adipocytes under postabsorptive and fasting conditions, resulting from impaired signal transduction from β-adrenergic receptors to adenylate cyclase. Upon prolonged fasting, the impaired lipolytic response resulted in abnormal substrate utilization and lean mass wasting. Conversely, GR deficiency attenuated aging-/diet-associated obesity, adipocyte hypertrophy, and liver steatosis. Systemic glucose tolerance was improved in obese GR-deficient mice, which was associated with increased insulin signaling in muscle and adipose tissue. We conclude that the GR in adipocytes exerts central but diverging roles in the regulation of metabolic homeostasis depending on the energetic state. The adipocyte GR is indispensable for the feeding-fasting transition but also promotes adiposity and associated metabolic disorders in fat-fed and aged mice.


Efficiency evaluation of the main multiresidue methods used in Europe for the analysis of amitraz and its major metabolites.
This paper compares the performance of the three most widely employed multiresidue methods [quick, easy, cheap, effective, rugged, and safe (QuEChERS), mini-Luke, and ethyl acetate] currently used for the determination of amitraz residues in fruits. A fast and differentiated analysis of amitraz and its two main metabolites, N-2,4-dimethylphenyl-N-methylformamidine and 2,4-dimethylformanilide, was performed by HPLC-electrospray ionization-MS/MS using a triple quadrupole mass spectrometer in the positive mode. A test of the stability of the standard solutions showed a rapid hydrolysis of amitraz to the amide and amidine derivatives in solutions containing water, including QuEChERS extracts of crops that were previously acidified. Two useful mass transitions were used to confirm the presence of each analyte in the sample extracts. LOD values ranging from 0.4 to 2.0 microglkg were obtained. Linearity of response over 2 orders of magnitude was demonstrated (r2 > 0.999) in solvent and pear extract. The recovery studies were performed on pear blanks spiked at two concentration levels, 50 and 500 microg/kg (n = 5). Best recoveries, ranging from 75 to 103%, were obtained by the application of the QuEChERS method with CV < 8% in all cases. The QuEChERS method was applied to a monitoring study carried out by the Chemical and Veterinary Investigation Office Stuttgart laboratory. From the 63 pear samples analyzed, 21 contained amitraz residues (expressed as sum) ranging from 0.02 to 2.9 mg/kg. Amitraz parent was detected only in a few cases at very low concentration levels, with N-2,4-dimethylphenyl-N-methylformamidine being the metabolite almost entirely representing the total residue. These results emphasize that the residue situation is clearly underestimated if only the parent compound is targeted, and they reinforce how important it is to include amitraz in the target scope of pesticide residue laboratories, especially since the concentrations detected exceeded the Acute Reference Dose in the majority of cases and pose a health risk to the consumer.


Impact of anaemia on health-related quality of life and cardiac remodelling in patients with lower risk myelodysplastic syndromes. Results of GlobQoL study.
The aim of this study was to analyse the eventual changes in health-related quality of life (HRQoL) and left ventricular function (LVF) over a 1-year follow-up period in a cohort of patients with lower risk myelodysplastic syndromes (MDS) receiving standard supportive treatment, in order to identify potential clues for early clinical intervention, as well as to analyse how they relate to haemoglobin levels and other aspects of the disease. A total of 39 adult anaemic patients with lower risk MDS were included in a prospective, observational, multi-centre study. Changes in performance status, functional capacity and HRQoL were collected by using standardised measures (ECOG scale; SPPB, Short Physical Performance Battery; SF-36, Short-Form 36 questionnaire; QLQ-C30, Quality of Life Core Questionnaire; FACT-An, Functional Assessment of Cancer Therapy-Anaemia scale questionnaires respectively). Need for transfusion (Linear Analogue Scale Assessment), as perceived independently by the patient and the haematologist, was also recorded. No changes in HRQoL (or LVF) were found, except for slight reductions in SF-36 physical function (P = 0.034), SPPB gait speed (P = 0.038) and FACT-An score (P = 0.029), all without apparent immediate clinical relevance for HRQoL, that were unrelated to changes in haemoglobin level. Periodical evaluation of gait speed may assist the clinician in early detection of patient's occult functional decline before it becomes clinically relevant.


An audit of pattern of patients' presentation at the periodontics clinic of the university college hospital, ibadan.
This study is aimed at assessing the various reasons why patients present at the periodontics clinic of the University College Hospital, Ibadan. A six months retrospective review of patients treated in the periodontics clinic of the University College Hospital, Ibadan was conducted. Case file records were retrieved and information on patients' bio-data, occupation and their various presenting complaint during their first consultation at the clinic were reviewed. Three hundred patients were seen in the clinic during the period under review but records of four of them were incomplete and were therefore excluded from the study. The association between the gender of the patients and their various initial presenting complaints was assessed using chi-square tests, p set at (<0.05). Records of two hundred and ninety-six patients were reviewed comprising of 150 males and 146 female (M/F, 1:1). Out of these patients, only eighty-four (28.4%) had been coming for regular check-up while the remaining 71.6% reported with various complaints. Majority (45.3%) presented with pain of which there were slightly more females than males (M/F =1:1.1). Gum bleeding and poor oral hygiene were other reasons why patients presented at the clinic. The younger age groups were noticed to be more frequent at the clinic on routine basis than the older ones during the period under review. The finding of this study further confirmed that majority of people only seek dental care to alleviate their pain. We therefore suggest that efforts should be intensified towards public enlightenment, as prevention is better and cheaper than cure.


Dogmatism and Happiness.
Happiness is a drive and constructive force of life. A person feels wellbeing under different effective factors. Religious dogmatism that has an influence on the entire world is one of the depreciatory factors of happiness or wellbeing. The current study decided to analyze the relation between dogmatism and wellbeing, and according to a model, answer the following question: how does religious dogmatism decrease wellbeing? This study is a correlation research. Population of study includes all people with 30-50 yr old who live in Tehran, Iran, in 2015. Among all, 180 subjects were selected as in access sample. The Oxford happiness questionnaire and Rokeach dogmatism scale were used. Data were analyzed by Pearson correlation test. There is a significant negative correlation between dogmatism and happiness (α=0.05). Dogmatism is one of the factors that have a negative effect on wellbeing. Religious dogmatism is the most dangerous factor against wellbeing. Dogmatic individuals have an inflexible cognitive system that emerges as a stable personality trait and decreases their adjustment with environment. Affective well-being and cognitive wellbeing are affected by individual adjustment. Therefore, in dogmatic individuals with low adjustment, the decrease of affective well-being and cognitive wellbeing is inevitable. This process will result in decrease of happiness and increase of aggression.


Accurate modeling of dielectric interfaces by the effective permittivities for the fourth-order symplectic finite-difference time-domain method.
The fourth-order finite-difference time-domain (FDTD) method using a symplectic integrator propagator can calculate the propagation of the electromagnetic waves with very low dispersion error in the region of a constant or smoothly varying index profile. An additional technique is required for the problem with the discontinuous dielectric interfaces. We derived the third-order effective permittivities at dielectric interfaces for the fourth-order FDTD method in the case of 2D TE polarization. As the required accuracy level is increased, the memory resources used by the fourth-order FDTD method with the effective permittivities are reduced severalfold or more compared with the standard FDTD method. The accurate performance of the proposed method is demonstrated through numerical examples.


Syntactic gender and semantic expectancy: ERPs reveal early autonomy and late interaction.
This experiment explored the effect of semantic expectancy on the processing of grammatical gender, and vice versa, in German using event-related-potentials (ERPs). Subjects were presented with correct sentences and sentences containing an article-noun gender agreement violation. The cloze probability of the nouns was either high or low. ERPs were measured on the nouns. The low-cloze nouns evoked a larger N400 than the high-cloze nouns. Gender violations elicited a left-anterior negativity (LAN, 300-600 msec) for all nouns. An additional P600 component was found only in high-cloze nouns. The N400 was independent of the gender mismatch variable; the LAN was independent of the semantic variable, whereas an interaction of the two variables was found in the P600. This finding indicates that syntactic and semantic processes are autonomous during an early processing stage, whereas these information types interact during a later processing phase.


Quantitative real-time PCR expression analysis of peripheral blood mononuclear cells in pancreatic cancer patients.
The ability of peripheral blood mononuclear cells (PBMCs) to act as a surrogate window into the presence and physiologic effects of pancreatic cancer is becoming increasingly apparent. In this chapter, we describe the techniques for isolation, lysis, RNA extraction, cDNA synthesis, and Q-RT PCR analysis of PBMCs as well as reasonable alternatives and the advantages and disadvantages of each. We further discuss the noteworthy considerations necessary for successful isolation and conversion of the high-quality PBMC RNA required to acquire interpretable and reproducible results for PBMC genetic expression analysis.


Psoas abscess in inflammatory bowel disease.
The inflammatory bowel disease (IBD) is sometimes complicated by the development of a psoas abscess. We recently encountered three patients of IBD with psoas abscess. Two patients had Crohn's ileocolitis and one with ulcerative colitis. During 1979-1984, 23 patients with psoas abscess due to a variety of underlying disease processes were seen at our institution. At the same time period, 483 cases of Crohn's disease and 283 cases of ulcerative colitis were encountered. Therefore, of 766 patients with IBD only three were complicated by psoas abscess (incidence ratio = 0.6%). Thus, psoas abscess was a very rare complication of IBD in patients seen at our institution. In our series of 23 psoas abscess patients, IBD was not a major causative factor. Additionally, to our knowledge, psoas abscess complicating ulcerative colitis has not been reported previously.


Structure of outer hair cell stereocilia links in the chinchilla.
The structure of side, tip, and "attachment" links of chinchilla outer hair cell (OHC) stereocilia was studied by transmission and scanning electron microscopy using tannic acid and Cuprolinic blue histochemical procedures. Tannic acid, which interacts with many different types of proteins and glycoproteins irrespective of their electrical charge, showed strong reactivity for the central area of the side links and weak reactivity for the marginal area of these links adjacent to the stereocilia membrane. Tannic acid treatment revealed the tip links as thin strands, about 5 nm thick. Attachment links were poorly visualized after tannic acid treatment and appeared as sparse filamentous strands at tips of the tallest OHC stereocilia. Cuprolinic blue, at a high critical electrolyte concentration, reacted with strongly negative, primarily sulfated, carbohydrate residues of glycoconjugate macromolecules. In contrast to the tannic acid treatment, the central portions of the OHC stereocilia side links were unstained after Cuprolinic blue treatment; however, membrane-associated ends of these links were darkly stained. The tip links showed a similar appearance as after tannic acid treatment; however, Cuprolinic blue revealed an electron-dense substructure at both ends of its insertion into the stereocilia. Cuprolinic blue reactive structures were also observed as attachment links only at the tips of the OHC stereocilia of the tallest row in each bundle. These structures formed a crown-like array around the tip of each stereocilium. Their primary function appears to be attachment of type B fibrils of the tectorial membrane to the tallest OHC stereocilia. Cuprolinic blue reactive structures of the side, tip, and attachment links appear to contain acidic, sulfated residues of proteoglycans or glycoproteins. These structures may function as connective elements between the stereocilia links and the hair cell cytoskeleton.


Multi-label zero-shot learning with graph convolutional networks.
The goal of zero-shot learning (ZSL) is to build a classifier that recognizes novel categories with no corresponding annotated training data. The typical routine is to transfer knowledge from seen classes to unseen ones by learning a visual-semantic embedding. Existing multi-label zero-shot learning approaches either ignore correlations among labels, suffer from large label combinations, or learn the embedding using only local or global visual features. In this paper, we propose a Graph Convolution Networks based Multi-label Zero-Shot Learning model, abbreviated as MZSL-GCN. Our model first constructs a label relation graph using label co-occurrences and compensates the absence of unseen labels in the training phase by semantic similarity. It then takes the graph and the word embedding of each seen (unseen) label as inputs to the GCN to learn the label semantic embedding, and to obtain a set of inter-dependent object classifiers. MZSL-GCN simultaneously trains another attention network to learn compatible local and global visual features of objects with respect to the classifiers, and thus makes the whole network end-to-end trainable. In addition, the use of unlabeled training data can reduce the bias toward seen labels and boost the generalization ability. Experimental results on benchmark datasets show that our MZSL-GCN competes with state-of-the-art approaches.


Research productivity of Pakistan in medical sciences during the period 1996-2012.
This study aimed to investigate the degree of research outcome in medical science subjects in Pakistan during the period 1996-2012. In this study, the research papers published in various global science journals during the period 1996-2012 were accessed. We recorded the total number of research documents having an affiliation with a Pakistan. The main source for information was Institute of Scientific Information (ISI) Web of Science, Thomson Reuters and SCI-mago/Scopus. In global science, Pakistan contributed 58133 research papers in all science and social sciences both in ISI and non ISI indexed journals. However, in medical sciences the total number of research papers from Pakistan are 25604, citable documents 23874, citations 128061, mean citations per documents 6.45 and mean Hirsch index is 35.33. In Pakistan, the upward trend of articles published in global medical science was from the period 1996-2008. However, from 2008 the trend is markedly declined. Pakistan significantly improved its international ranking positions in research during the period 2000-2008. However, the upward trend of research papers published in global medical science could not be retained and from the year 2008 the trend started declining. This trend of research papers further declined in year 2012 compared to year 2011. It is suggested that, Pakistan must take strategic steps to enhance the research culture and increase the research and development expenditure in the country.


Unusual features in a case of snakebite, presumably due to a Cape cobra (Naja nigricollis).
A case of snakebite, thought to be due to a Cape cobra, in a young girl is described. Unusual features were a protracted period of paralysis and severe neurological residua in the form of hemiparesis and impaired vision. The ophthalmological features started as a bilateral optic neuritis and progressed to bilateral optic atrophy. It is difficult to ascribe all these effects to the neurotoxins of the Cape cobra as the neurotoxic features usually resolve rapidly if the patient survives. The actions of the neurotoxins, the quantity of antivenom to be administered in cases of cobra bite and the possible use of anticholinesterases such as neostigmine in these cases are also discussed.


Impact of childhood adversities on depression in early adulthood: A longitudinal cohort study of 478,141 individuals in Sweden.
Although the relationship between childhood adversity (CA) and depression is widely accepted, there is little information on what proportion of depression is attributable to CA. We used a Swedish cohort of 478,141 individuals born in 1984-1988 in Sweden. Register-based CA indicators included parental death, parental substance abuse and psychiatric morbidity, parental criminality, parental separation, public assistance recipiency, child welfare intervention, and residential instability. Estimates of risk of depression, measured as retrieval of prescribed antidepressants and/or psychiatric care with a clinical diagnosis of depression, between 2006 and 2012 were calculated as Hazard Ratios (HR) with 95% confidence intervals (CI), using a Cox regression analysis. All CAs predicted depression in early adulthood. Furthermore, the predictive association between the CA indicators and depression was graded, with highest HRs observed for 4+ CAs (HR: 3.05 (95% CI 2.83-3.29)) for a clinical diagnosis for depression and HR: 1.32 (95% CI 1.25-1.41) for antidepressant medication after adjustments were made for important confounding factors. Of the studied CAs, child welfare intervention entailed highest HR for depression. Regardless of causality issues, children and youth with a history of multiple CA should be regarded as a high-risk group for depression by professionals in social, and health services that come into contact with this group.


Treatment outcomes of impaired physicians in Oklahoma.
Data on one hundred twenty impaired physicians were analyzed to determine treatment outcomes from three differing types of chemical dependency treatment. The data showed that long-term (three to four months) treatment geared specifically to health care professionals was the most effective treatment modality, showing higher rates of favorable treatment outcomes measured by abstinence from alcohol and other drugs.


Serum albumin binding of structurally diverse neutral organic compounds: data and models.
Binding to serum albumin has a strong influence on freely dissolved, unbound concentrations of chemicals in vivo and in vitro. For neutral organic solutes, previous studies have suggested a log-log correlation between the albumin-water partition coefficient and the octanol-water partition coefficient (K(ow)) and postulated highly nonspecific binding that is mechanistically analogous to dissolution into solvents. These relationships and concepts were further explored in this study. Bovine serum albumin (BSA)-water partition coefficients (K(BSA/w)) were measured for 83 structurally diverse neutral organic chemicals in consistent experimental conditions. The correlation between log K(BSA/w) and log K(ow) was moderate, with R(2) = 0.76 and SD = 0.43. The log K(BSA/w) of low-polarity compounds including a series of chlorobenzenes and polycyclic aromatic hydrocarbons increased with log K(ow) linearly up to log K(ow) = 4-5, but then the linear relationship apparently broke off, and the increase became gradual. The fitting of polyparameter linear free energy relationship models with five solute descriptors was just comparable to that of the log K(ow) model (R(2) = 0.78-0.79, SD = 0.41-0.42); the relatively high SD obtained suggests that solvent dissolution models are not capable of modeling albumin binding accurately. A size limitation of the binding site(s) of albumin is suggested as a possible reason for the high SD. An equilibrium distribution model indicates that serum albumin generally has high contributions to the binding in the serum of polar compounds and relatively small low-polarity compounds, whereas albumin binding for large low-polarity compounds is outcompeted by the strong partitioning into lipids due to low relative affinity of albumin for these compounds.


Multi-agent modeling of the South Korean avian influenza epidemic.
Several highly pathogenic avian influenza (AI) outbreaks have been reported over the past decade. South Korea recently faced AI outbreaks whose economic impact was estimated to be 6.3 billion dollars, equivalent to nearly 50% of the profit generated by the poultry-related industries in 2008. In addition, AI is threatening to cause a human pandemic of potentially devastating proportions. Several studies show that a stochastic simulation model can be used to plan an efficient containment strategy on an emerging influenza. Efficient control of AI outbreaks based on such simulation studies could be an important strategy in minimizing its adverse economic and public health impacts. We constructed a spatio-temporal multi-agent model of chickens and ducks in poultry farms in South Korea. The spatial domain, comprised of 76 (37.5 km x 37.5 km) unit squares, approximated the size and scale of South Korea. In this spatial domain, we introduced 3,039 poultry flocks (corresponding to 2,231 flocks of chickens and 808 flocks of ducks) whose spatial distribution was proportional to the number of birds in each province. The model parameterizes the properties and dynamic behaviors of birds in poultry farms and quarantine plans and included infection probability, incubation period, interactions among birds, and quarantine region. We conducted sensitivity analysis for the different parameters in the model. Our study shows that the quarantine plan with well-chosen values of parameters is critical for minimize loss of poultry flocks in an AI outbreak. Specifically, the aggressive culling plan of infected poultry farms over 18.75 km radius range is unlikely to be effective, resulting in higher fractions of unnecessarily culled poultry flocks and the weak culling plan is also unlikely to be effective, resulting in higher fractions of infected poultry flocks. Our results show that a prepared response with targeted quarantine protocols would have a high probability of containing the disease. The containment plan with an aggressive culling plan is not necessarily efficient, causing a higher fraction of unnecessarily culled poultry farms. Instead, it is necessary to balance culling with other important factors involved in AI spreading. Better estimations for the containment of AI spreading with this model offer the potential to reduce the loss of poultry and minimize economic impact on the poultry industry.


[Manifest depressive-delusional episodes of juvenile endogenous psychosis].
The structure of the first psychotic episode of juvenile endogenous intermittent psychosis with the dominance of depressive and delusional disorders was studied in a sample of 50 male patients aged 16-25 years. Three types of first episodes were singled out: episodes with homonomous structure - 11 (22%) patients, heteronomous episodes with the dominance of delusional disorders - 20 (40%) patients and heteronomous episodes with the dominance of depressive disorders - 19 (38%) patients. The differences between these types were determined by characteristics of the structure, the ratio of affective to delusional symptomatology, dynamic changes in the status, objective measures of the PANSS and CDSS. The main characteristics of these states due to the pathoplastic effect of the age factor were revealed. The authors suggest that the typological subdivision is significant for the diagnosis and prognosis of an endogenous psychosis with manifest depressive-delusional episodes. This suggestion should be verified in the follow-up study.


Self-expandable metal stents for malignant esophageal obstruction: a comparative study between extrinsic and intrinsic compression.
Self-expandable metal stents (SEMSs) are effective for malignant esophageal obstruction, but usefulness of SEMSs in extrinsic lesions is yet to be elucidated. This study is aimed at evaluating the clinical usefulness of SEMSs in the extrinsic compression compared with intrinsic. A retrospective review was conducted for 105 patients (intrinsic, 85; extrinsic, 20) with malignant esophageal obstruction who underwent endoscopic SEMSs placement. Technical and clinical success rates were evaluated and clinical outcomes were compared between extrinsic and intrinsic group. Extrinsic group was mostly pulmonary origin. Overall technical and clinical success rate was 100% and 91%, respectively, without immediate complications. Extrinsic and intrinsic group did not differ significantly in clinical success rate. The median stent patency time was 131.3 ± 85.8 days in intrinsic group while that of extrinsic was 54.6 ± 45.1 due to shorter survival after stent insertion. The 4-, 8-, and 12-week patency rates were 90.5%, 78.8%, and 64.9% respectively in intrinsic group, while stents of extrinsic group remained patent until death. Uncovered, fully covered, and double-layered stent were used evenly and the types did not influence patency in both groups. In conclusion, esophageal SEMSs can safely and effectively be used for malignant extrinsic compression as well as intrinsic.


Fertility regulation in nursing women: VII. Influence of NORPLANT levonorgestrel implants upon lactation and infant growth.
The objective of this study was to test the influence of NORPLANT implants upon lactation and infant growth. The results obtained during the first postpartum year are reported. One-hundred women were enrolled in the implant group. The control group was formed by 100 women who received a Copper T IUD. Treatments were administered at day 55 +/- 3. At admission all subjects were in exclusive breastfeeding with an adequate weight increase of the infant. No significant differences were found between the treated and control groups in the percentage of women in full nursing at different postpartum intervals, except for the 12th month postpartum where a lower percentage of cases from the NORPLANT group was in the full nursing category. No difference was found in the time of weaning. The infants showed a normal weight gain rate in both groups although the girls from the NORPLANT group showed a significantly lower daily weight increase during the 4th month than the girls from the IUD group. No pregnancies were diagnosed. No women asked for implant removal during the first year. No serious side effects related to treatment were detected. Bleeding irregularities were rare during breastfeeding which is in contrast with what occurs in non-nursing women treated with NORPLANT implants. Levonorgestrel concentrations found in milk were variable and individual values ranged from 23 to 311 pg/ml. The dose received by the infant can be estimated around 15 to 18 ng/Kg/day during the first month of treatment when the higher plasma values of levonorgestrel are observed. These levels is conjunction with the clinical observations reported here minimize the potential problems associated with levonorgestrel transference through maternal milk. Nevertheless, long-term studies are required to settle this matter and until more information is available, NORPLANT implant use in lactating women should be limited to cases who require a highly effective contraceptive method and where non-hormonal methods of similar effectiveness are contraindicated or unacceptable.


Costs associated with invasive Scedosporium and Lomentospora prolificans infections: a case-control study.
Little is known about the short- and long-term healthcare costs of invasive Scedosporium/Lomentospora prolificans infections, particularly in patient groups without haematological malignancy. This study investigated excess index hospitalization costs and cumulative costs of these infections. The predictors of excess cost and length of stay (LOS) of index hospitalization were determined. These estimates serve as valuable inputs for cost-effectiveness models of novel antifungal agents. A retrospective case-control study was conducted at six Australian hospitals. Cases of proven/probable invasive Scedosporium/L. prolificans infections between 2011 and 2021 (n = 34) were matched with controls (n = 66) by predefined criteria. Cost data were retrieved from activity-based costing systems and analysis was performed from the Australian public hospital perspective. All costs were presented in 2022 Australian dollars (AUD). Median regression analysis was used to adjust excess costs of index hospitalization whereas cumulative costs up to 1.5 years follow-up were estimated using interval-partitioned survival probabilities. Invasive Scedosporium/L. prolificans infections were independently associated with an adjusted median excess cost of AUD36 422 (P = 0.003) and LOS of 16.27 days (P < 0.001) during index hospitalization. Inpatient stay was the major cost driver (42.7%), followed by pharmacy cost, of which antifungal agents comprised 23.8% of the total cost. Allogeneic haematopoietic stem cell transplant increased the excess cost (P = 0.013) and prolonged LOS (P < 0.001) whereas inpatient death within ≤28 days reduced both cost (P = 0.001) and LOS (P < 0.001). The median cumulative cost increased substantially to AUD203 292 over 1.5 years in cases with Scedosporium/L. prolificans infections. The economic burden associated with invasive Scedosporium/L. prolificans infections is substantial.


BGDB: a database of bivalent genes.
Bivalent gene is a gene marked with both H3K4me3 and H3K27me3 epigenetic modification in the same area, and is proposed to play a pivotal role related to pluripotency in embryonic stem (ES) cells. Identification of these bivalent genes and understanding their functions are important for further research of lineage specification and embryo development. So far, lots of genome-wide histone modification data were generated in mouse and human ES cells. These valuable data make it possible to identify bivalent genes, but no comprehensive data repositories or analysis tools are available for bivalent genes currently. In this work, we develop BGDB, the database of bivalent genes. The database contains 6897 bivalent genes in human and mouse ES cells, which are manually collected from scientific literature. Each entry contains curated information, including genomic context, sequences, gene ontology and other relevant information. The web services of BGDB database were implemented with PHP + MySQL + JavaScript, and provide diverse query functions. Database URL: http://dailab.sysu.edu.cn/bgdb/


Expert statement on the ICU management of patients with thrombotic thrombocytopenic purpura.
Thrombotic thrombocytopenic purpura (TTP) is fatal in 90% of patients if left untreated and must be diagnosed early to optimize patient outcomes. However, the very low incidence of TTP is an obstacle to the development of evidence-based clinical practice recommendations, and the very wide variability in survival rates across centers may be partly ascribable to differences in management strategies due to insufficient guidance. We therefore developed an expert statement to provide trustworthy guidance about the management of critically ill patients with TTP. As strong evidence was difficult to find in the literature, consensus building among experts could not be reported for most of the items. This expert statement is timely given the recent advances in the treatment of TTP, such as the use of rituximab and of the recently licensed drug caplacizumab, whose benefits will be maximized if the other components of the management strategy follow a standardized pattern. Finally, unanswered questions are identified as topics of future research on TTP.


[Omeprazole (20 mg daily) compared to ranitidine (150 mg twice daily) in the treatment of esophagitis caused by reflux. Results of a double-blind randomized multicenter trial in France and Belgium].
We report the results of a trial of omeprazole 20 mg daily versus ranitidine 150 mg b.i.d. in the short-term management of erosive or ulcerative esophagitis. The principal aim of the trial was to assess the healing rates of the esophageal lesions. The trial was conducted in 19 centers (16 in France and 3 in Belgium). The lesions of the esophageal mucosa were defined as follows: grade 2 (n = 112), round or linear erosions; grade 3 (n = 33), confluent erosions affecting the total esophageal circumference; or grade 4 (n = 11), erosions as described above plus deep ulcerations or peptic stenosis which did not need endoscopic dilatation. The main criterion was the complete healing of esophageal lesions after 4 weeks of treatment. Patients were randomly allocated to double-blind treatment with omeprazole or ranitidine. Clinical and endoscopic examinations were done on inclusion in the trial and at day 29 +/- 6, and again at day 57 +/- 6 if esophagitis was unhealed. No patient was excluded from the analysis on an "intention-to-treat" basis, and 25 patients were excluded from the "per protocol" analysis, mainly because of poor compliance with the trial protocol. The healing rate at weak 4 was 50 of 62 patients (81 p. 100) treated with omeprazole and 31 of 69 patients (45 p. 100) with ranitidine (p less than 0.001). The corresponding figures at week 8 were 58 of 61 (95 p. 100) and 40 of 61 (65 p. 100) (p less than 0.001).


Charge association. A case report and short annotation.
A premature female infant was noted to have an unusual combination of abnormalities, consistent with the CHARGE ASSOCIATION. 1. Left (L) choanal stenosis 2. Fallot's Tetralogy 3. Esophageal atresia with distal TOF (Tracheo-Oesophageal Fistula) 4. Duodenal stenosis 5. Annular pancreas with ectopic pancreatic tissue in the proximal jejunum. Baby had surgery for the gastrointestinal tract abnormalities. She lived for only 19 days.


Comparison of estrogenic components used for hormonal contraception.
Attempts have been made over the years to replace ethinyl estradiol (EE) in combined oral contraceptives (COCs) with the less potent natural estrogen estradiol (E2), or its prodrug, E2 valerate (E2V), to improve their safety and tolerability. Recently, a COC incorporating a novel weak natural estrogen, estetrol (E4), combined with drospirenone, has become available. We present a comparative analysis of the three prevailing estrogens used in COCs, focusing on their structure-function relationships, receptor-binding affinity, potency, metabolism, pharmacokinetic parameters, and pharmacodynamics. The binding affinity of EE to estrogen receptor (ER)α is twice that of E2, whereas its affinity for ERβ is about one-half that of E2. E4 has a lower binding affinity for the ERs than E2. The high potency of EE is notable in its dramatic increase in estrogen-sensitive hepatic globulins and coagulation factors. EE and E2 undergo extensive and comparable metabolism, while E4 produces only a very limited number of metabolites. E4 has the highest bioavailability among the three estrogens, with E2 having <5%. Studies demonstrate consistent ovulation inhibition, although a higher dose of E4 (15 mg) in COCs is required to achieve follicular suppression compared to E2 (1-3 mg) and EE (0.01-0.035 mg). E2 and E4 in COCs may be less stimulatory of coagulant proteins than EE. Studies with E2/dienogest suggest a comparable risk of venous thromboembolism to EE/levonorgestrel, while data assessing risk with an E4-based COC are insufficient. Nevertheless, the E4-based formulation shows promise as a potential alternative to EE and E2 due to its lower potency and possibly fewer side effects.


[Design of antisense oligodeoxynucleotide targeting at bcl-2 mRNA and observation on its effect on the sensitivity of leukemia cells to arabinosyl cytosine].
The effective target sites for antisense oligodeoxynucleotides (AS-ODN) on bcl-2 mRNA, except its start region, were looked for and their effects on the sensitivity of HL-60 and K562 leukemia cells to arabinosyl cytosine (Ara-C) were observed. The secondary structure of bcl-2 mRNA was simulated with RNAstructure microsoftware, and AS-ODNs, targeting at some sites, were designed and synthesizd with phosphorothioate modifying. The median inhibitory concentration (IC(50)) of Ara-C for HL-60 and K562 cells was determined with MTT method; the apoptosis rate and bcl-2 protein expression level were assayed by flow cytometry. The results showed that 10 micro mol/L bcl-2 AS-ODN combined with Ara-C inhibited the expression of bcl-2 protein, increased apoptosis in HL-60 and K562 cells and decresed IC(50) of Ara-C significantly. The AS-ODN targeting the coding region of bcl-2 mRNA had stronger effect than AS-ODN targeting the translation initiation region. In conclusion, the much more effective sites for antisense oligodeoxynucleotides to target, except translation start region, might provide a new useful way for antisense drug design.


Candida albicans stimulates endothelial cell eicosanoid production.
The response of human umbilical vein endothelial cells to invasion by Candida species was examined in vitro. Live Candida albicans caused significant endothelial release of eicosanoids, mainly prostaglandins. Since prostaglandin I2 (PGI2) is an important prostaglandin produced by endothelial cells, factors influencing its release were studied. The ability of different strains and species of Candida to induce endothelial PGI2 release was closely related to their capacity to injure the endothelium (r = .99). C. albicans was the only species tested that either stimulated PGI2 release or damaged the endothelial cells; only this organism possessed detectable phospholipase activity. Candida glabrata and Candida tropicalis had no phospholipase activity and neither increased PGI2 release nor caused significant endothelial damage. Close proximity with germinated C. albicans was required for endothelial injury and PGI2 release. The ability of C. albicans to stimulate endothelial cells may have important implications in regulating neutrophil activities against organisms that interact with endothelial cells.


Phosphorylation of chemoattractant receptors regulates chemotaxis, actin reorganization and signal relay.
Migratory cells, including mammalian leukocytes and Dictyostelium, use G-protein-coupled receptor (GPCR) signaling to regulate MAPK/ERK, PI3K, TORC2/AKT, adenylyl cyclase and actin polymerization, which collectively direct chemotaxis. Upon ligand binding, mammalian GPCRs are phosphorylated at cytoplasmic residues, uncoupling G-protein pathways, but activating other pathways. However, connections between GPCR phosphorylation and chemotaxis are unclear. In developing Dictyostelium, secreted cAMP serves as a chemoattractant, with extracellular cAMP propagated as oscillating waves to ensure directional migratory signals. cAMP oscillations derive from transient excitatory responses of adenylyl cyclase, which then rapidly adapts. We have studied chemotactic signaling in Dictyostelium that express non-phosphorylatable cAMP receptors and show through chemotaxis modeling, single-cell FRET imaging, pure and chimeric population wavelet quantification, biochemical analyses and TIRF microscopy, that receptor phosphorylation is required to regulate adenylyl cyclase adaptation, long-range oscillatory cAMP wave production and cytoskeletal actin response. Phosphorylation defects thus promote hyperactive actin polymerization at the cell periphery, misdirected pseudopodia and the loss of directional chemotaxis. Our data indicate that chemoattractant receptor phosphorylation is required to co-regulate essential pathways for migratory cell polarization and chemotaxis. Our results significantly extend the understanding of the function of GPCR phosphorylation, providing strong evidence that this evolutionarily conserved mechanism is required in a signal attenuation pathway that is necessary to maintain persistent directional movement of Dictyostelium, neutrophils and other migratory cells.


Graft copolymer nanoparticles with pH and reduction dual-induced disassemblable property for enhanced intracellular curcumin release.
Nanoparticle (NP)-assisted drug delivery systems with disassemblable behaviors in response to intracellular microenvironment are urgently demanded in systemic cancer chemotherapy for enhanced intracellular drug release. Curcumin (CUR), an effective and safe anticancer agent, was limited by its water insolubility and poor bioavailability. Herein, pH and reduction dual-induced disassemblable NPs for high loading efficiency and improved intracellular release of CUR were developed based on an acid degradable cyclic benzylidene acetal groups (CBAs)-functionalized poly(2,4,6-trimethoxybenzylidene-1,1,1-tris(hydroxymethyl)ethane methacrylate)-g-SS-poly(ethylene glycol) (PTTMA-g-SS-PEG) graft copolymer, which was readily prepared via RAFT copolymerization and coupling reaction. The NPs self-assembled from PTTMA-g-SS-PEG copolymers were stable at physiological pH, and quickly disassembled in mildly acidic and reductive environments because of the hydrolysis of CBAs in hydrophobic PTTMA core and the cleavage of disulfide-linked detachable PEG shell. PTTMA-g-SS-PEG NPs exhibited excellent CUR loading capacity with drug loading content up to 19.2% and entrapment efficiency of 96.0%. Within 20 h in vitro, less than 15.0% of CUR was released from the CUR-loaded NPs in normal physiological conditions, whereas 94.3% was released in the presence of reductive agent and mildly acidic conditions analogous to the microenvironment in endosome/lysosome and cytoplasm. Confocal fluorescence microscopies revealed that the CUR-loaded PTTMA-g-SS-PEG NPs exhibited more efficiently intracellular CUR release for EC-109 cells than that of CUR-loaded reduction-unresponsive PTTMA-g-PEG NPs and free CUR. In vitro cytotoxicity studies displayed blank PTTMA-g-SS-PEG NPs showed low toxicity at concentrations up to 1.0 mg/mL, whereas CUR-loaded PTTMA-g-SS-PEG NPs demonstrated more efficient growth inhibition toward EC-109 and HepG-2 cells than reduction-unresponsive controls and free CUR. Therefore, the above results indicated that pH and reduction dual-induced disassemblable PTTMA-g-SS-PEG NPs may have emerged as superior nanocarriers for active loading and promoted intracellular drug delivery in systemic cancer chemotherapy.


Soil hydrology drives ecological niche differentiation in a native prairie microbiome.
While the impacts of soil moisture on soil microbiome diversity and composition are well characterized, the influence of hydrological regime has been overlooked. As precipitation patterns are altered by climate change, understanding the impact of soil hydrology on community structure and function is critical. In this work, water level was continuously monitored for over a year in a Midwestern prairie-wetland at 10 cm depth increments up to a depth of 120 cm in 10 locations. We analyzed microbiome composition and edaphic factors in soil cores collected from this unique spatially distributed, longitudinal data set. We demonstrate that the fraction of time that each sample was inundated explains more variability in diversity and composition across this site than other commonly assessed edaphic factors, such as soil pH or depth. Finally, we show that these compositional changes influence abundance of ammonia oxidizers. The observed patterns in community composition and diversity are fundamentally regulated by the interaction of water with a structured landscape, particularly an elevated sand ridge characterized by drier conditions and a lower-lying wetland with more clayey soils. Similar processes are generally expected to influence the biogeography of many terrestrial environments, as morphology, hydrology and soil properties generally co-vary.


Defective lysosomal release of glycoprotein-derived sialic acid in fibroblasts from patients with sialic acid storage disease.
Fibroblasts from patients with sialic acid storage disease (SASD), sialidosis, mucolipidosis II, and from normal controls, were incubated in the presence of the glycoprotein fetuin that was tritium-labelled in its sialic acid residues by the periodate/[3H]borohydride reduction method, and the fate of the intracellular radioactive sialic acid (C7-sialic acid) followed in pulse-chase experiments. The model glycoprotein was readily endocytosed and degraded, more than 90% of the radioactivity being trichloroacetic acid (TCA)-soluble after 4 days of incubation. In all of the patients' fibroblasts, there was an increased accumulation of TCA-soluble radioactivity and, upon chase, a much lower rate of elimination than in normal controls. Gel chromatography of the material from the chase experiment showed that, in normal cells, most of the radioactivity at zero time behaved as free C7-sialic acid. This, as well as material of larger size (sialyloligosaccharides), was very much diminished by 48 h. In cells from two patients with SASD, there were large peaks both in the sialic acid and oligosaccharide positions; whereas the oligosaccharides were somewhat decreased by the end of the chase period, the sialic acid was essentially unchanged. In sialidosis fibroblasts, the radioactive material consisted of oligosaccharides, but very little C7-sialic acid; the elimination of the oligosaccharides was retarded. In normal cells, about 80% of the radioactivity released into the medium after 48 h chase behaved as free C7-sialic acid upon gel chromatography and t.l.c. Subcellular fractionation in Percoll gradients showed that the radioactive C7-sialic acid remaining in normal cells after 48 h of chase was mainly localized in the cytosol. In SASD cells, on the other hand, it was associated with lysosomal fractions which, unexpectedly, exhibited an abnormally low density. Our findings demonstrate that SASD fibroblasts degrade the sialoglycoprotein but, unlike normal cells, accumulate the liberated C7-sialic acid along with sialyloligosaccharides in their lysosomes. The results therefore support the concept of a defective transport system for sialic acid in the lysosomal membrane of patients with SASD.


Penile Cancer: Contemporary Lymph Node Management.
In penile cancer, the optimal diagnostics and management of metastatic lymph nodes are not clear. Advances in minimally invasive staging, including dynamic sentinel lymph node biopsy, have widened the diagnostic repertoire of the urologist. We aimed to provide an objective update of the recent trends in the management of penile squamous cell carcinoma, and inguinal and pelvic lymph node metastases. We systematically reviewed several medical databases, including the Web of Science® (with MEDLINE®), Embase® and Cochrane databases, according to PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analyses) guidelines. The search terms used were penile cancer, lymph node, sentinel node, minimally invasive, surgery and outcomes, alone and in combination. Articles pertaining to the management of lymph nodes in penile cancer were reviewed, including original research, reviews and clinical guidelines published between 1980 and 2016. Accurate and minimally invasive lymph node staging is of the utmost importance in the surgical management of penile squamous cell carcinoma. In patients with clinically node negative disease, a growing body of evidence supports the use of sentinel lymph node biopsies. Dynamic sentinel lymph node biopsy exposes the patient to minimal risk, and results in superior sensitivity and specificity profiles compared to alternate nodal staging techniques. In the presence of locoregional disease, improvements in inguinal or pelvic lymphadenectomy have reduced morbidity and improved oncologic outcomes. A multimodal approach of chemotherapy and surgery has demonstrated a survival benefit for patients with advanced disease. Recent developments in lymph node management have occurred in penile cancer, such as minimally invasive lymph node diagnosis and intervention strategies. These advances have been met with a degree of controversy in the contemporary literature. Current data suggest that dynamic sentinel lymph node biopsy provides excellent sensitivity and specificity for detecting lymph node metastases. More robust long-term data on multicenter patient cohorts are required to determine the optimal management of lymph nodes in penile cancer.


Electrophysiology of human colon motility in health and disease.
Recent years have seen a number of studies measuring electrical activities of the human colon muscle layers. In vitro studies have enhanced our understanding of myogenic control of colon motility. In vivo studies have suggested a relationship between patterns of electrical activities and the transport of colon contents. This chapter describes the patterns of electrical and motor activity that the human colon can perform depending on the nature and intensity of the stimulus, using recent in vitro and in vivo data. In vitro studies with human tissue have shown differences between the electrical activity of the longitudinal and circular muscles. They have also revealed the unique nature of the electrical control activity of the circular muscle of human colon. The electrical oscillatory activity of this layer is variable in frequency from 1 to 60 cpm, variable in amplitude, and not omnipresent. Furthermore, the activity is sensitive to stretch and markedly altered by excitatory and inhibitory substances. In vivo data, especially spike action potential recordings for 24 h, have revealed patterns of electrical activity related to intake of meals, sleep, and also constipation. The limitations of some intraluminal techniques to record electrical activity are discussed. Further studies are needed to accurately relate in vivo activities to cellular events recorded in vitro, and to relate these to altered patterns of activity in disease. The suggestion is made that a relevant in vivo assessment of the colonic motility of a patient can only be achieved by long-lasting (24-h) studies, because of the large variability in the hour-to-hour colonic activity. Timing of experimental drug intervention is important since colonic motility undergoes diurnal changes. Recent studies into profiles of electrical and motor activity in irritable bowel syndrome (IBS) suggest that there is not a typical IBS myogenic activity. Rather, patterns of electrical activity can be related to the symptoms of IBS: diarrhea and constipation. Recent electrophysiologic data on Hirschsprung's disease reveal absence of intrinsic inhibitory innervation in the aganglionic segment. In vitro studies on tissue from diverticular disease patients show abnormal myogenic activity.


[The relationship between experiential avoidance and posttraumatic symptoms following war trauma--a brief report].
A large body of literature stresses the role of experiential avoidance as a developmental and maintenance factor of many forms of psychopathology including post-traumatic stress disorder. For the first time, the current study examined the relationship between experiential avoidance and war-related post-traumatic symptoms. 123 students in Kosovo who reported war-related experiences took part in this study. Results show that experiential avoidance was significantly correlated with post-traumatic symptoms above and beyond the number of traumatic experiences.


A SWATH-MS analysis of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome peripheral blood mononuclear cell proteomes reveals mitochondrial dysfunction.
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a serious and complex physical illness that affects all body systems with a multiplicity of symptoms, but key hallmarks of the disease are pervasive fatigue and 'post-exertional malaise', exacerbation after physical and/or mental activity of the intrinsic fatigue and other symptoms that can be highly debilitating and last from days to months. Although the disease can vary widely between individuals, common symptoms also include pain, cognitive deficits, sleep dysfunction, as well as immune, neurological and autonomic symptoms. Typically, it is a very isolating illness socially, carrying a stigma because of the lack of understanding of the cause and pathophysiology. To gain insight into the pathophysiology of ME/CFS, we examined the proteomes of peripheral blood mononuclear cells (PBMCs) by SWATH-MS analysis in a small well-characterised group of patients and matched controls. A principal component analysis (PCA) was used to stratify groups based on protein abundance patterns, which clearly segregated the majority of the ME/CFS patients (9/11) from the controls. This majority subgroup of ME/CFS patients was then further compared to the control group. A total of 60 proteins in the ME/CFS patients were differentially expressed (P < 0.01, Log10 (Fold Change) > 0.2 and < -0.2). Comparison of the PCA selected subgroup of ME/CFS patients (9/11) with controls increased the number of proteins differentially expressed to 99. Of particular relevance to the core symptoms of fatigue and post-exertional malaise experienced in ME/CFS, a proportion of the identified proteins in the ME/CFS groups were involved in mitochondrial function, oxidative phosphorylation, electron transport chain complexes, and redox regulation. A significant number were also involved in previously implicated disturbances in ME/CFS, such as the immune inflammatory response, DNA methylation, apoptosis and proteasome activation. The results from this study support a model of deficient ATP production in ME/CFS, compensated for by upregulation of immediate pathways upstream of Complex V that would suggest an elevation of oxidative stress. This study and others have found evidence of a distinct pathology in ME/CFS that holds promise for developing diagnostic biomarkers.


Photochemical reaction dynamics of 2,2'-dithiobis(benzothiazole): direct observation of the addition product of an aromatic thiyl radical to an alkene with time-resolved vibrational and electronic absorption spectroscopy.
The photochemical reaction dynamics of the benzothiazole-2-thiyl (BS) radical, produced by 330 nm ultraviolet photolysis of 2,2'-dithiobis(benzothiazole) (BSSB), are examined on the picosecond time scale. The initial addition product of a thiol-ene reaction between the BS radical and styrene is directly observed by transient vibrational absorption spectroscopy (TVAS). Transient electronic absorption spectroscopy (TEAS) in the ultraviolet and visible spectral regions reveals rapid formation of the ground state BS radical with a time constant of ∼200 fs. The photolytically generated BS radical decays through geminate recombination to the parent molecule BSSB and competitive formation of a BS radical dimer with a rate coefficient of (3.7 ± 0.2) × 10(10) M(-1) s(-1) in methanol, and thereafter (36 ± 1)% of the initially formed BS radicals survive at the longest time delay (1.3 ns). In styrene solution, in contrast to methanol and toluene solutions, kinetic traces of the BS radical show an additional decay with a time constant of 305 ± 13 ps, and a broad band at 345-500 nm grows with the same time constant, suggesting a bimolecular reaction of the BS radical with styrene. The TVAS measurements reveal an absorption band of the ground state BS radical at 1301 cm(-1) in toluene solution, and the band decays with a time constant of 294 ± 32 ps in styrene solution. Two product bands grow at 1239 cm(-1) and 1429 cm(-1) with respective time constants of 312 ± 68 ps and 325 ± 33 ps, and are attributed to the addition product BS-St radical formed from the BS radical and styrene. A bimolecular reaction rate coefficient of kreact = (3.8 ± 0.2) × 10(8) M(-1) s(-1) is deduced and 22 ± 1% of the initially formed BS radicals are converted to the BS-St radical in neat styrene solution.


Agreement between scales in the measurement of breast cancer risk perceptions.
The objective of this article is to compare the accuracy and numeric responses of breast cancer risk perception as measured by a frequency scale and percentage scale. A cross-sectional survey was conducted. Perceptions of five-year and lifetime breast cancer risk were measured using a frequency and a percentage scale. Estimation error was calculated as the absolute difference between actual breast cancer risk as determined by the Gail model and perceived risk. Agreement between scales was determined by calculating the mean and standard deviation of the difference between numeric responses. The study was conducted among women enrolled in two primary care clinics associated with an academic medical center. Two-hundred-fifty-four participants were recruited from one of the two participating internal medicine clinics. Inclusion criteria included female gender and age 40-84 years. Exclusion criteria included a history of breast cancer, dementia, or a life expectancy of less than two years. The frequency scale was more accurate than the percentage scale in estimating lifetime risk (p= 0.05), but less accurate in estimating five-year risk (p < 0.02). Only 79 participants (31%) were considered consistent scale users, providing identical responses when using the frequency and percentage scale for a given risk estimate. Although the mean difference (percentage-frequency scale) for estimates of breast cancer lifetime risk was only 2.4, the empirically determined 90% limits of agreement between the frequency and percentage scale for lifetime risk were wide, from -30 to 40. Higher numeracy was associated with consistent use of scales (OR 1.61, 95% CI; 1.09-2.37). We report disagreement in breast cancer risk perceptions when measured by a frequency and a percentage scale. The accuracy and direction of bias associated with each scale varies according to the time frame of risk being assessed.


Artemisinin induces apoptosis in human cancer cells.
Artemisinin is a chemical compound extracted from the wormwood plant, Artemisia annua L. It has been shown to selectively kill cancer cells in vitro and retard the growth of implanted fibrosarcoma tumors in rats. In the present research, we investigated its mechanism of cytotoxicity to cancer cells. Molt-4 cells, in complete RPMI-1640 medium, were first incubated with 12 microM of human holotransferrin at 37 degrees C in a humid atmosphere of 5% CO2 for one hour. This enhanced the iron supply to the cells. The cells were then pelleted and transferred to a complete RPMI-1640 containing 200 microM of an analog dihydroartemisinin (DHA) and incubation was started (0 h). In addition, some culture samples were treated with holotransferrin alone and some (controls) were assayed without neither holotransferrin nor DHA treatment. Cells were counted and DNA diffusion assay was used to evaluate apoptosis and necrosis in each sample at 0 h and at 1, 2, 4 and 8 h of incubation. DHA treatment significantly decreased cell counts and increased the proportion of apoptosis in cancer cells compared to controls (chi2=4.5, df=1, p<0.035). Addition of holotransferrin significantly further decreased cell counts (chi2=4.5, df=1, p<0.035) and increased apoptosis (chi2=4.5, df=1, p<0.035). No necrotic cells were observed. This rapid induction of apoptosis in cancer cells after treatment with DHA indicates that artemisinin and its analogs may be inexpensive and effective cancer agents.


Patterns of flight behavior and capacity of unmated navel orangeworm (Lepidoptera: Pyralidae) adults related to age, gender, and wing size.
The navel orangeworm, Amyelois transitella (Walker) (Lepidoptera: Pyralidae), is a key pest of almond, pistachio, and walnut tree crops in California. Understanding dispersal of adults between orchards is important to improving management options. Laboratory flight behavior of unmated navel orangeworm of ages 1, 2, 3, 5, and 7 d posteclosion was examined using flight mills. As a group, females flew farther and longer than males, but the differences were not statistically significant. Flight speed did not differ between sexes. Flight duration and distance did not differ with age, except that 7-d-old adults performed worse for these parameters than did 1- and 2-d-old adults. Females began their flights ≍1.5 h after the onset of dusk, and ≍1.5 h earlier in the night than males. Flight capacity and propensity were substantial for both sexes and all age classes tested. At least 20% of adults (except 7-d-old males) made a continuous flight ≥5.5 h, and median total distances flown during the 10.5-h night ranged from 7 to 15 km depending on age class. Thus navel orangeworm flight mill performance was greater than that of most pests tested from the families Pyralidae and Tortricidae. Surface area and length of forewings and hindwings were greater in females than males, but had little effect on flight performance. The results are generally consistent with field observations of navel orangeworm dispersal, but it will be important to characterize the effects of mating on flight, and flight on fecundity.


Protease-Activated Receptor-1 Supports Locomotor Recovery by Biased Agonist Activated Protein C after Contusive Spinal Cord Injury.
Thrombin-induced secondary injury is mediated through its receptor, protease activated receptor-1 (PAR-1), by "biased agonism." Activated protein C (APC) acts through the same PAR-1 receptor but functions as an anti-coagulant and anti-inflammatory protein, which counteracts many of the effects of thrombin. Although the working mechanism of PAR-1 is becoming clear, the functional role of PAR-1 and its correlation with APC in the injured spinal cord remains to be elucidated. Here we investigated if PAR-1 and APC are determinants of long-term functional recovery after a spinal cord contusive injury using PAR-1 null and wild-type mice. We found that neutrophil infiltration and disruption of the blood-spinal cord barrier were significantly reduced in spinal cord injured PAR-1 null mice relative to the wild-type group. Both locomotor recovery and ability to descend an inclined grid were significantly improved in the PAR-1 null group 42 days after injury and this improvement was associated with greater long-term sparing of white matter and a reduction in glial scarring. Wild-type mice treated with APC acutely after injury showed a similar level of improved locomotor recovery to that of PAR-1 null mice. However, improvement of APC-treated PAR-1 null mice was indistinguishable from that of vehicle-treated PAR-1 null mice, suggesting that APC acts through PAR-1. Collectively, our findings define a detrimental role of thrombin-activated PAR-1 in wound healing and further validate APC, also acting through the PAR-1 by biased agonism, as a promising therapeutic target for spinal cord injury.


SAVOR-TIMI to DECLARE-TIMI: A Review on Cardiovascular Outcome Trials of Incretin-modulators and Gliflozins.
Since 2008 United State (US) food drug administration mandate, several newer anti-diabetic drugs (ADD) have undergone a mandatory cardiovascular (CV) outcome trial (CVOT) in type diabetes (T2DM) patients with high CV risk. These includes CVOT done with dipeptidyl-peptidase-4 inhibitors, sodium-glucose co-transporter-2 inhibitors and glucagon-like peptide-1 receptor agonist (GLP-1RAs). Several double-blind, randomized, placebo-controlled CVOT have been presented and published in the last decade (2008-2018). We systematically searched the database of PubMed and ClinicalTrials.gov from January 1, 2008 to December 31, 2018 using specific key words. Subsequently, we pooled the data of different cardiovascular endpoints and made a comparative forest plot using GraphPad software Inc. Prism Version 8, US. Saxagliptin, alogliptin, sitagliptin and linagliptin are CV neutral drugs. Saxagliptin showed a significantly higher hospitalization due to heart failure (HHF). Empagliflozin and canagliflozin have shown a significant reduction in composite of 3-point major cardiac adverse events (3P-MACE). Additionally, empagliflozin, canagliflozin and dapagliflozin significantly reduced the HHF and the composite of CV death or HHF. Moreover, empagliflozin showed significant reduction in CV- and all-cause death in patients with T2DM with established CV disease. While both exendin-backbone-based GLP-1RAs such as lixisenatide and extended-release exenatide were CV neutral; GLP-1-backbone-based GLP-1RAs such as liraglutide, semaglutide and albiglutide shown a significant reduction in the composite of 3-P MACE. Additionally, liraglutide shown a significant reduction in CV- and all-cause death. Moreover, semaglutide reduced non-fatal stroke and albiglutide reduced myocardial infarction, while extended-release exenatide reduced all-cause death; however, P value of significance for these outcomes should be considered nominal.


Experimental investigation of the concept of a 'breathing zone' using a mannequin exposed to a point source of inertial/sedimenting particles emitted with momentum.
An inhaling mannequin, CALTOOL, was used in a specially ventilated room to compare the concentrations inhaled with those sampled by samplers mounted across the breathing zone. The CALTOOL is made from metal sheets and consists of a cylindrical torso (42 x 24 x 54 cm) with a circular cylinder as head. A circular nozzle simulates the mouth. This nozzle is part of a cassette that holds a filter. The inhalation rate is not periodic but kept constant at nominally 20 l min(-1). The CALTOOL was placed in a horizontal air stream ( approximately 10 cm s(-1)) either facing or back to the wind. In front of the lower chest of the CALTOOL, a particle source was mounted which emitted particles with a momentum directed upwards at an angle of 45 degrees towards the CALTOOL. Five monodisperse aluminium oxide powders were used as test aerosols. The mass median aerodynamic diameters of the test aerosols ranged approximately 10 to 95 mum. Six conically shaped aerosol samplers were mounted horizontally and over the breathing zone of the CALTOOL, one on each shoulder, three across the upper torso, and one at the lower torso centre. Four to six runs per test aerosol and CALTOOL orientation in the airflow were conducted. The samples were analysed gravimetrically. The concentration ratio aerosol sampler to the CALTOOL cassette was determined for the investigated mounting positions. The results showed that when the CALTOOL was exposed to particles emitted with momentum from a point source in front of the lower chest, the variation in concentration over the breathing zone was large. The ratio of the concentration sampled by an aerosol sampler mounted somewhere within the breathing zone to the CALTOOL cassette concentration, would, for specific particle sizes, easily differ by a factor of 3, but may extend up to 10-100, depending on the particular conditions. The basic concept of a breathing zone consisting of a hemisphere of radius 25-30 cm is therefore not well suited for workers handling a point source emitting large particles. For such sampling situations, it is suggested that the radius of the breathing zone is reduced to 10 cm, which may be achieved by a head-mounted sampler.


The impact of nonsteroidal anti-inflammatory drug-induced gastropathy.
Gastric and duodenal injury related to nonsteroidal anti-inflammatory drug (NSAID) use is extremely common, and a variety of strategies can be employed to reduce this frequent side effect of an otherwise useful category of medications. Although the best approach may be to discontinue NSAID treatment, this is not always possible for patients with arthritis pain or for those who require low-dose aspirin therapy for underlying cardiovascular disease. In arthritis cases, one of the new cyclooxygenase-2 specific inhibitors can be used to replace a traditional NSAID, but the addition of another drug to treat and heal ulcers is normally still needed. Patients taking aspirin are also candidates for additional treatment.


Rat annexin V crystal structure: Ca(2+)-induced conformational changes.
Annexins are a family of calcium- and phospholipid-binding proteins implicated in mediating membrane-related processes such as secretion, signal transduction, and ion channel activity. The crystal structure of rat annexin V was solved to 1.9 angstrom resolution by multiple isomorphous replacement. Unlike previously solved annexin V structures, all four domains bound calcium in this structure. Calcium binding in the third domain induced a large relocation of the calcium-binding loop regions, exposing the single tryptophan residue to the solvent. These alterations in annexin V suggest a role for domain 3 in calcium-triggered interaction with phospholipid membranes.


Diffuse duodenal nodular lymphoid hyperplasia: a large cohort of patients etiologically related to Helicobacter pylori infection.
Nodular lymphoid hyperplasia of gastrointestinal tract is a rare disorder, often associated with immunodeficiency syndromes. There are no published reports of its association with Helicobacter pylori infection. From March 2005 till February 2010, we prospectively followed all patients with diffuse duodenal nodular lymphoid hyperplasia (DDNLH). Patients underwent esophagogastroduodenoscopy with targeted biopsies, colonoscopy, and small bowel video capsule endoscopy. Duodenal nodular lesions were graded from 0 to 4 based on their size and density. Patients were screened for celiac sprue (IgA endomysial antibody), immunoglobulin abnormalities (immunoglobulin levels & serum protein electrophoresis), small intestine bacterial overgrowth (lactulose hydrogen breath test), and Helicobacter pylori infection (rapid urease test, and histological examination of gastric biopsies). Patients infected with Helicobacter pylori received sequential antibiotic therapy and eradication of infection was evaluated by 14C urea breath test. Follow up duodenoscopies with biopsies were performed to ascertain resolution of nodular lesions. Forty patients (Males 23, females 17; mean age ± 1SD 35.6 ± 14.6 years) with DDNLH were studied. Patients presented with epigastric pain, vomiting, and weight loss. Esophagogastroduodenoscopy showed diffuse nodular lesions (size varying from 2 to 5 mm or more) of varying grades (mean score ± 1SD 2.70 ± 0.84) involving postbulbar duodenum. Video capsule endoscopies revealed nodular disease exclusively limited to duodenum. None of the patients had immunoglobulin deficiency or small intestine bacterial overgrowth or positive IgA endomysial antibodies. All patients were infected with Helicobacter pylori infection. Sequential antibiotic therapy eradicated Helicobacter pylori infection in 26 patients. Follow up duodenoscopies in these patients showed significant reduction of duodenal nodular lesions score (2.69 ± 0.79 to 1.50 ± 1.10; p < 0.001). Nodular lesions showed complete resolution in 5 patients and significant resolution in remaining 21 patients. Patients with resistant Helicobacter pylori infection showed no significant reduction of nodular lesions score (2.71 ± 0.96 to 2.64 ± 1.15; p = 0.58). Nodules partially regressed in score in 2 patients, showed no interval change in 10 patients and progressed in 2 patients. We report on a large cohort of patients with DDNLH, etiologically related to Helicobacter pylori infection.


Exploring the influence of meteorological conditions on the performance of a waste stabilization pond at high altitude with structural equation modeling.
Algal photosynthesis plays a key role in the removal mechanisms of waste stabilization ponds (WSPs), which is indicated in the variations of three parameters, dissolved oxygen, pH, and chlorophyll a. These variations can be considerably affected by extreme climatic conditions at high altitude. To investigate these effects, three sampling campaigns were conducted in a high-altitude WSP in Cuenca (Ecuador). From the collected data, the first application of structure equation modeling (SEM) on a pond system was fitted to analyze the influence of high-altitude characteristics on pond performance, especially on the three indicators. Noticeably, air temperature appeared as the highest influencing factors as low temperature at high altitude can greatly decrease the growth rate of microorganisms. Strong wind and large diurnal variations of temperature, 7-20 °C, enhanced flow efficiency by improving mixing inside the ponds. Intense solar radiation brought both advantages and disadvantages as it boosted oxygen level during the day but promoted algal overgrowth causing oxygen depletion during the night. From these findings, the authors proposed insightful recommendations for future design, monitoring, and operation of high-altitude WSPs. Moreover, we also recommended SEM to pond engineers as an effective tool for better simulation of such complex systems like WSPs.