Physical stress and catecholamine release.
In both health and disease, noradrenaline and adrenaline concentrations in plasma increase with intensity and duration of exercise (Figure 1). These changes are only to a minor extent due to decreased catecholamine clearance (Figure 2). The increase in sympathoadrenal activity during exercise is primarily elicited by feed-forward stimulation from motor centres in the brain (Figure 3, Table 1), and by afferent impulses from working muscles (Figure 4). During continued exercise, changes in internal milieu may enhance the catecholamine response. Of particular interest from a metabolic point of view is the fact that during exercise a decrease in plasma glucose causes a relatively large increase in plasma adrenaline (Figure 5). Sympathoadrenal activity is of major importance for exercise capacity. By depressing insulin secretion, as well as by direct effects on target tissues, sympathoadrenal activity enhances mobilization of glycogen as well as triglyceride from both extra- and intramuscular depots. After training, noradrenaline responses to given absolute work loads are reduced, while responses to given relative loads, i.e. work load in percent of individual work capacity, VO2/VO2max%, are unchanged. Prolonged endurance training may increase the size and secretory capacity of the adrenal medulla (Figure 7, Table 2), an adaptation which may improve exercise capacity. Differences in catecholamine levels cannot explain the fact that physically-active individuals have a lower cardiac mortality than inactive ones.


Timing matters: A protective role of astrocyte reactivity in neurodegeneration.
Sheehan and Nadarajah et al.1 identified that Bmal1 loss from astrocytes induces the expression of BAG3, a macroautophagy chaperone enriched in Alzheimer's disease patients and in disease-associated astrocytes, enhancing the phagocytosis of misfolded proteins and preventing tau and alpha-synuclein pathologies.


[Construction of cDNA library from human colorectal cancer cell HRT-18].
To construct a cDNA library from human colorectal cancer cell HRT-18. The total RNA was extracted from human CRC (colorectal cancer) cell HRT-18 and the mRNA was isolated from the total RNA by MagneSphere technique, and then the first-strand cDNA was synthesized with oligo (dT) primer containing sfi I site while the double-strand cDNA was amplified through LD-PCR (long-distance PCR) by SMART technique. The double strand cDNA was digested by sfi I ( I A & I B) restriction enzyme before cDNA size fractionation, and the double-strand cDNA fractionated was ligated into the lambdaTripIEX2 vector and then was packaged into lambda phage in vitro. The unamplified human CRC cell HRT-18 cDNA library consisted of 6. 5 x 10(6) independent clones, recombinants clones was more than 96%. The titer of the amplified cDNA library was 1.1 x 10(9) pfu/ml and the average insert of the recombinants was 1.1 kb. The quality of the constructed cDNA library from human CRC cell HRT-18 is excellent and it is helpful to screen CRC specific antigen.


Exactly solving the Kitaev chain and generating Majorana-zero-modes out of noisy qubits.
Majorana-zero-modes (MZMs) were predicted to exist as edge states of a physical system called the Kitaev chain. MZMs should host particles that are their own antiparticles and could be used as a basis for a qubit which is robust-to-noise. However, all attempts to prove their existence gave inconclusive results. Here, the Kitaev chain is exactly solved with a quantum computing methodology and properties of MZMs are probed by generating eigenstates of the Kitev Hamiltonian on 3 noisy qubits of a publicly available quantum computer. After an ontological elaboration I show that two eigenstates of the Kitaev Hamiltonian exhibit eight signatures attributed to MZMs. The results presented here are a most comprehensive set of validations of MZMs ever conducted in an actual physical system. Furthermore, the findings of this manuscript are easily reproducible for any user of publicly available quantum computers, solving another important problem of research with MZMs-the result reproducibility crisis.


Prevention of hepatic steatosis and hepatic insulin resistance in mitochondrial acyl-CoA:glycerol-sn-3-phosphate acyltransferase 1 knockout mice.
In order to investigate the role of mitochondrial acyl-CoA:glycerol-sn-3-phosphate acyltransferase 1 (mtGPAT1) in the pathogenesis of hepatic steatosis and hepatic insulin resistance, we examined whole-body insulin action in awake mtGPAT1 knockout (mtGPAT1(-/-)) and wild-type (wt) mice after regular control diet or three weeks of high-fat feeding. In contrast to high-fat-fed wt mice, mtGPAT1(-/-) mice displayed markedly lower hepatic triacylglycerol and diacylglycerol concentrations and were protected from hepatic insulin resistance possibly due to a lower diacylglycerol-mediated PKC activation. Hepatic acyl-CoA has previously been implicated in the pathogenesis of insulin resistance. Surprisingly, compared to wt mice, mtGPAT1(-/-) mice exhibited increased hepatic insulin sensitivity despite an almost 2-fold elevation in hepatic acyl-CoA content. These data suggest that mtGPAT1 might serve as a novel target for treatment of hepatic steatosis and hepatic insulin resistance and that long chain acyl-CoA's do not mediate fat-induced hepatic insulin resistance in this model.


Fracturing of melamine-embedded cells and tissues: a new technique for studying cell membranes.
A new technique is presented for studying cell membranes by scanning electron microscopy. It is based on the observation that cells and tissues, embedded in a water-compatible melamine resin, are as hard as glass and consequently can be fractured with ease. Fracture faces so exposed are either sputter-coated for studying the surface topography or re-embedded for thin-sectioning, or both. Scanning electron microscopy shows that the fracture faces of a variety of tissues reveal cell membranes and associated structures with remarkable detail. Re-embedding and thin-sectioning of fractured frog retina, mycoplasma and red blood cells indicate that membranes become divided into their exo- and protoplasmic leaflets during fracturing. In this respect, the results reported here must be compared with conventional freeze-fracture techniques.


Preparation of anti-polysaccharide antiserum using liposomes as immunological adjuvant.
Bovine serum albumin (BSA) was coupled to dextran by controlled periodate oxidation followed by sodium borohydride reduction. The conjugate was entrapped in negatively charged, multilamellar phosphatidylcholine (lecithin) liposomes in which the polysaccharide remained surface-exposed, at least partially. Liposome-entrapped conjugate elicited in rabbits an appreciable anti-dextran response when compared with the sera raised in saline or in Freund's adjuvant. The anti-dextran antibodies belonged to both the IgM and IgG classes. The precipitin reaction of dextran with the antiserum raised in liposomes was determined.


Conservative management of a myxoid endometrial stromal sarcoma in a 16-year-old nulliparous woman.
Sarcomas comprise less than 1% of all gynecological cancers and 2% to 5% of all uterine malignancies, of which endometrial stromal sarcoma accounts for approximately 15%. Surgery is fundamental in sarcoma management and a total hysterectomy is performed in the majority of cases. Presented is a case of low-grade myxoid endometrial stromal sarcoma in a nulliparous adolescent female managed by local resection and uterine reconstruction. In selected cases, the initial management of a localized and well defined low-grade endometrial stromal sarcoma could potentially be conservative (uterine-sparing) surgical resection.


The effect of pill mill legislation on suicides.
To examine the effect of pill mill legislation on suicides and drug-related suicides in the United States. We use state-level restricted use mortality data from the National Vital Statistics System for the period 2000-2016, along with state level sociodemographic data from the US Census Bureau and Bureau of Labor Statistics and opioid-related state health policy data from publicly available sources for the analysis. The analyses use a difference-in-differences regression approach. Publicly available secondary data were collected and merged with restricted use mortality data files from the National Vital Statistics System for the analysis. Our results show that pill mill legislation is associated with an 8.5% (p < 0.01) reduction in the drug related suicide rate, a 4.9% (p < 0.05) reduction in suicides among females, and a 4.7% (p < 0.05) reduction in suicides among individuals between age 45 and 64 years. The findings indicate that pill mill legislation has been effective in reducing total suicides among females in the age group 45-64, and drug-related suicides in the population resulting in 658 fewer drug-related suicides for a given year if pill mill laws are adopted by every state.


Assessment of the measurement methods in midshaft clavicle fracture.
Clavicle fractures account for approximately 5% of all fractures in adults and 75% of clavicle fractures occur in the midshaft. Shortening greater than two centimeters is an indicative of surgical treatment. Radiographic exams are often used to diagnose and evaluate clavicle fractures but computed tomography (CT) scan is currently considered the best method to assess these deformities and shortening. 1- To investigate whether different methods of performing the radiographic exam interfere on the measurement of the fractured clavicle length. 2- Compare the clavicle length measurements obtained by the different radiographic exam methods with the CT scan measurements, used as a reference. Twenty-five patients with acute (< 3 weeks) midshaft clavicle fracture were evaluated. Patients underwent six radiographic images: PA Thorax (standing and lying), AP Thorax (standing and lying) and at 10° cephalic tilt (standing and lying), and the computed tomography was used as reference. The mean length (cm) obtained were: 14,930 on CT scan, 14,860 on PA Thorax Standing, 14,955 on PA Thorax Lying, 14,896 on AP Thorax Standing, 14,960 AP Thorax Lying, 15,098 on 10° cephalic tilt Standing and 15,001 on 10° cephalic tilt Lying, (p > 0,05). 1- There is no significant statistical difference in the clavicle fracture length measurement among the variety of radiographic exam performances. 2- The method that comes closest to computed tomography results is the PA thorax incidence, with the patient in the lying position.


A chest pain clinic to improve the follow-up of patients released from an urban university teaching hospital emergency department.
During a 12-month period, 1,045 of 1,554 patients (67%) over age 30 seen in an urban teaching hospital emergency department with acute chest pain were released based on the clinical judgment of the examining physician. Patients who were released were offered follow-up within 24 to 72 hours in a hospital-based chest pain clinic. Of these 1,045 patients, 772 (74%) returned or were contacted by phone, and 29 were directly admitted; 14 had unstable angina, and eight had new myocardial infarctions. Because of its positive impact on the quality of care at an acceptable cost, the Chest Pain Clinic, which was originally instituted as part of a research protocol, has now become part of the routine spectrum of care provided at the University of Cincinnati Medical Center.


The "Authoritarian Personality" Reconsidered: the Phantom of "Left Fascism".
This article explores the question of "Left fascism," which emerged in relation to discussions around the Student Movement in the German Federal Republic in the crucial decade between 1967-1977. The term was originally coined by Jürgen Habermas in a lecture entitled "The Phantom Revolution and its Children" in which he suggests that the extreme voluntarism of the students could not but be characterized as "Left fascist." Such a characterization becomes the basis for a vitally important exchange of letters between Herbert Marcuse and Theodor W. Adorno from January to August of 1969 on the relation between theory and praxis. After first sketching Adorno's conception of the "authoritarian personality," with the help of Sándor Ferenczi's concept of the "identification with the aggressor," the article proceeds to examine the exchange of the letters between Adorno and Marcuse, illustrating Adorno's changed orientation: that "fascism" or "authoritarianism" maybe either left or right. Finally, some conclusions are drawn about the authoritarian tendencies of the contemporary Left.


A quantitative histochemical study of sulphydryl and disulphide content during normal epidermal keratinization.
A quantitative histochemical study was carried out on the distribution of protein thiol and disulphide groups in normal human plantar epidermal tissue. Histochemical demonstration of reactive groups was achieved by addition of N-(4-aminophenyl) maleimide, subsequent diazotization and final coupling with a Nitro Red or chromotropic acid label as first described by Sippel. The quantitative reliability of the method was tested by absorption cytophotometry, and evaluated on the basis of the internal consistency of the results reported. Our histological observations and histophotometric data support accepted views on epidermal keratinization. A limited, though reproducible, amount of disulphide bonds was observed near the basement membrane. The free thiol concentration in basal and prickle cells was low and almost constant, but was higher in the granular cells, where deposition of sulphur-containing proteins on cell membranes is initiated. In Malpighian layers, disulphide cross-links only occurred just beneath the transition zone in thickened cell membranes. The staining pattern of the inner stratum corneum resembled a mosaic and was characterized by a Sharp rise of the disulphide content, which exceeded the decrease in free thiol groups. The free thiol concentration decreased further throughout the cornified layers whilst the disulphide content remained fairly constant. Staining of thiol and disulphide groups together corresponded, within the limits of the standard error, to the sum of the thiol and disulphide concentrations when they were assayed separately in living ahd horny cells. These results confirm that living cells are the main site of free thiol groups, while horny cells are the most prominent of site of disulphide cross-links.


Detection of herpes simplex virus-1 by nested PCR. An experimental model.
Nested polymerase chain reaction (nested PCR) was performed using a reaction mix batch-prepared and kept frozen in single reaction tubes at -20 degrees C until use. Twenty-one New Zealand white rabbits were infected with herpes simplex virus type 1 (HSV-1). Eleven animals were killed on day seven and the other ten were sacrificed on day 21. Viral culture and nested PCR was used to determine the presence of HSV-1 in samples from the tongue, HSV-1 was detected in 90.47% of the animals; in 84.21% by nested PCR and in 52.63% by culture. Nested PCR assay had greater sensitivity than culture in animals sacrificed on day seven with significative difference (p < 0.05). Higher sensitivity and faster results were obtained with this method, so we found it reliable and useful in the setting of a clinical laboratory dealing with diagnosis of herpes virus infections.


The roles of MTHFR (C677T, A1298C) and MGP (G-7A, T-138C) gene variations in development of diabetic nephropathy in patients with type 2 diabetes mellitus.
The goal of this study is to determine the role of MTHFR (C677T, A1298C) and MGP (G-7A, T-138C) gene variations in DN development. There were 61 DN patients and 55 healthy controls in this study. The genotype distributions of these gene variations were determined using PCR and RFLP methods. According to our study, there was no significant relationship between these gene variations and DN (p > 0.05). The allele frequencies of the MTHFR C677T gene variation in the control group were found significantly different from the Hardy-Weinberg distribution (p < 0.05). According to combined genotype analysis, GA-TT combined genotype of MGP (G-7A/T-138C) gene variations was observed significantly more in the patient group with DN. The GA-TT combined genotype of MGP (G-7A/T-138C) gene variations was differ significantly between these groups (OR: 2.359, %95 CI: 1.094-5.087, p = 0.028). In our study, although MTHFR and MGP gene variations were not risk factors, the GA-TT combined genotype of the MGP (G-7A/T-138C) gene variation was detected as an important risk factor for DN.


How do geriatricians feel about managing older people living with HIV? A scoping review.
The proportion of people living with HIV being older adults is increasing and due to high rates of multimorbidity and frailty within this group geriatricians are well placed to contribute to their care. However, little is known about how geriatricians feel about this new opportunity. A scoping review was performed following the Arksey & O'Malley's methodological framework with nine databases searched in December 2021 for studies reporting the experiences or views of geriatricians on caring for people living with HIV. Study inclusion was not limited by language or year of publication. Narrative reviews were excluded. Two reviewers independently performed the extraction using predetermined criteria. A descriptive analysis of extracted information was performed. Six publications reporting four studies, all conducted in the USA, were identified. The current barriers to geriatricians being involved in the care of older people living with HIV are: their current experience in managing people living with HIV, their knowledge of HIV, specific issues related to older people living with HIV and screening for HIV in older people as well as their attitudes to people living with HIV and experience of managing older LGBTQ + people. Prior to geriatricians being routinely involved in the care of older people living with HIV further research outside of the USA is required. Geriatricians will also require specific training which should be incorporated into geriatric medicine training curricula as well as the creation of learning tools and quality clinical practice guidelines ideally created in collaboration with HIV organisations.


TP53, BCL-2 and BAX analysis in 199 ovarian cancer patients treated with taxane-platinum regimens.
In cell line studies, BCL-2 and BAX proteins interfere with cancer response to taxanes. This issue has not received much attention with regard to taxane-platinum (TP)-treated ovarian cancer patients. We evaluated prognostic/predictive significance of BCL-2 and BAX with regard to TP53 status. Immunohistochemical analysis was performed on 199 ovarian carcinomas FIGO stage IIB-IV treated with TP; the results were analyzed by the Cox and logistic regression models. Clinicopathological parameters (residual tumor size, FIGO stage and/or tumor grade, but not patient's age) were the only or the strongest predictors of patient's outcome. Platinum highly sensitive response showed a positive association with TP53 accumulation (p=0.045). As in our previously published analysis on platinum-cyclophosphamide-treated group, complete remission showed a borderline negative (paradoxic) association with high BAX expression in the whole group (p=0.058) and with BCL-2 expression in the TP53(-) group (p=0.058). Our results suggest that TP53, BCL-2 and BAX proteins carry some predictive potential in taxane-platinum-treated ovarian cancer patients, auxiliary to clinicopathological factors. We have confirmed on another patient group that clinical importance of BCL-2 may depend on TP53 status.


The endocannabinoid system: a revolving plate in neuro-immune interaction in health and disease.
Studies of the last 40 years have brought to light an important physiological network, the endocannabinoid system. Endogenous and exogenous cannabinoids mediate their effects through activation of specific cannabinoid receptors. This modulatory homoeostatic system operates in the regulation of brain function and also in the periphery. The cannabinoid system has been shown to be involved in regulating the immune system. Studies examining the effect of cannabinoid-based drugs on immunity have shown that many cellular and cytokine mechanisms are modulated by these agents, thus raising the hypothesis that these compounds may be of value in the management of chronic inflammatory diseases. The special properties of endocannabinoids as neurotransmitters, their pleiotropic effects and the impact on immune function show that the endocannabinoid system represents a revolving plate of neural and immune interactions. In this paper, we outline current information on immune effects of cannabinoids in health and disease.


Evidence for a bifurcation of the mitogenic signaling pathway activated by Ras and phosphatidylcholine-hydrolyzing phospholipase C.
NIH 3T3 cells stably transfected with the gene encoding phosphatidylcholine-hydrolyzing phospholipase C (PC-PLC) from Bacillus cereus display a chronic elevation of intracellular diacylglycerol levels and a transformed phenotype. We have used such PC-PLC-transformed cells to evaluate the roles of the cytoplasmic serine/threonine kinases Raf-1, zeta protein kinase C (zeta PKC) and protein kinase A (PKA) in oncogenesis and mitogenic signal transduction elicited by phosphatidylcholine hydrolysis. We demonstrate here that stable expression of dominant negative mutants of both zeta PKC and Raf-1 lead to reversion of PC-PLC-transformed cells. Interestingly, expression of kinase defective zeta PKC also reverted NIH 3T3 cells transformed by the v-Ha-ras oncogene. Activation of PKA in response to elevation of cAMP levels also lead to reversion of PC-PLC-induced transformation, implicating PKA as a negative regulator acting downstream of PC-PLC. On the other hand, inhibition or depletion of phorbol ester responsive PKCs attenuated but did not block the ability of PC-PLC-transformed cells to induce DNA synthesis in the absence of growth factors. These results clearly implicate both Raf-1 and zeta PKC as necessary downstream components for transduction of the mitogenic/oncogenic signal generated by PLC-mediated hydrolysis of phosphatidylcholine and suggest, together with other recent evidence, a bifurcation in the signaling pathway downstream of PC-PLC.


Acute small bowel obstruction secondary to intestinal endometriosis, an elusive condition: a case report.
Endometriosis is a benign condition affecting females of reproductive age. Although intestinal endometriosis is common it is rare for the condition to manifest as an acute bowel obstruction secondary to ileocaecal and appendicular endometriosis. This case is important to report as it highlights the diagnostic difficulty this particular condition presents to an emergency surgeon. We present the case of a 33 year old female of Asian origin who presented with symptoms and signs of an acute small bowel obstruction. A right hemicolectomy for suspected malignancy was performed with an ileocolic anastomosis. Histological examination demonstrated extensive endometriosis of the appendix and ileocaecal junction. Enteric endometriosis should be considered as a differential diagnosis when assessing females of reproductive age with acute small bowel obstruction. A high index of suspicion is required to arrive at a diagnosis of this elusive condition.


Use of the parenting stress index in mothers of preterm infants.
This report describes parenting stress experienced by mothers of preterm infants following hospital discharge. Twenty-nine mothers and their preterm infants were included in the analysis. The study was conducted using a descriptive and exploratory single group design. The analysis included 29 mothers of preterm infants, mean gestational age 33.14 weeks, mean postnatal age 78.59 days, 6 to 10 weeks after discharge. Mothers were administered the Parenting Stress Index (PSI), a 101-item questionnaire that includes a total score and Parent and Child Domains. It also includes the following 13 scales: Adaptability, Acceptability, Demandingness, Mood, Distractibility/Hyperactivity, Reinforces Parent, Depression, Attachment, Restriction of Role, Sense of Competence, Social Isolation, Relationship with Spouse, and Parent Health. A high rate of missing items was noted on the PSI. In particular, missing items occurred predominantly in the Child Domain. By following guidelines for scoring the PSI when items are missing, summary scores were calculated for 16 of the 29 participants. Total scores demonstrate the stress experienced by parents of preterm infants. Parent Domain scores were comparable with normative samples; however, Child Domain scores were above the 50th percentile for all child scales. Mothers of preterm infants experience stress that is largely attributable to the particular characteristics of low gestation infants. The PSI may provide insight into parenting stress; however, future research should examine missing items more closely.


Association between presence of the metabolic syndrome and its components with carotid intima-media thickness and carotid and femoral plaque area: a population study.
We aimed to explore the association between presence and number of components of the Metabolic Syndrome (MetS) and subclinical atherosclerosis outcomes (common carotid intima media thickness, plaque presence and sum of plaque area) in both the carotid and femoral bifurcations. Cross-sectional analysis of 771 volunteers from the ongoing epidemiological Cyprus Study (46% male; mean age = 60.1 ± 9.8). (a) Carotid intima-media thickness (IMTcc), (b) sum of plaque area in the carotid bifurcations (sum of the largest plaques in each carotid bifurcation-SPAcar), (c) sum of plaque area in the femoral bifurcations (sum of the largest plaques in each femoral bifurcation-SPAfem) and (d) sum of plaque area in both carotid and femoral bifurcations (sum of the areas of the largest plaques present in each of the four bifurcations-SPA) were measured at baseline using ultrasound. Presence and number of components of the MetS was ascertained using the National Cholesterol Education Program ATPIII definition and their association tested using multivariable regression models. MetS was present in 259 (33.6%) individuals and was associated with a 0.02 mm increase in IMTcc (95% CI: 0.00 to 0.04, p = 0.047) after adjustment for age, sex, family history of CVD, alcohol consumption (BU/week) and smoking (pack-years). Each additional component of the MetS was associated with a 16% higher SPA (95% CI: 6.8% to 25.2%, pfor trend = 0.001), a 10% higher SPAcar (95% CI: 5% to 24%, pfor trend = 0.003) and a 14% higher SPAfem in the adjusted model. We confirm an association between the MetS and IMTcc as well as report for the first time an association between the MetS and its components and femoral plaque area, in a general population over 40 years of age. Having any risk factors for the MetS increases the risk for subclinical atherosclerosis, with the risk increasing with each additional component. Using the dichotomous definition of the MetS may be overlooking the risk for subclinical atherosclerosis -and by inference future cardiovascular events- associated with having less than 3 risk factors.


Belgian Fertility Clinic Staff Value Healthy Lifestyle Promotion but Lack Access to a Structured Lifestyle Modification Programme: An Observational Study.
Guidelines advise promoting a healthy lifestyle among patients with fertility problems as the lifestyle of women and men proved to be associated with their fertility. Australian fertility nurses were shown to lack access to structured lifestyle modification programmes, although they value healthy lifestyle promotion. This study aimed to examine whether gynaecologists also value promoting a healthy lifestyle and whether structured lifestyle modification programmes are available in Belgian fertility clinics. An observational study was conducted among health care professionals (HCPs) working in Belgian fertility clinics. An Australian questionnaire on attitudes and practices related to promoting a healthy lifestyle among patients with fertility problems was reciprocally back-to-back translated and three open-ended questions were added. All HCPs of Belgian fertility clinics, including gynaecologists, fertility nurses/midwives, psychologists, and embryologists, were invited by e-mail to complete the questionnaire online. Responses to closed and open-ended questions were analysed with, respectively, descriptive statistics and qualitative thematic analysis. Finally, differences in perspectives between different groups of HCPs were explored. A total of 50 fertility nurses/midwives, 42 gynaecologists, and 19 other HCPs completed the survey (n = 111). Regarding attitudes, all respondents valued informing patients about the impact of lifestyle on fertility. The vast majority of HCPs (n = 96; 86%) stated that fertility clinics have the responsibility to address unhealthy lifestyles prior to offering fertility treatment. Fertility nurses/midwives were significantly more likely than gynaecologists to state that fertility clinics have this responsibility (p = 0.040). Regarding practices, the patient's lifestyle was most commonly discussed by the gynaecologist (n = 107; 96%) during the first appointment (n = 105; 95%). The lifestyle factors that were being addressed, according to the vast majority of respondents, were smoking, weight, age, alcohol, and recreational drugs. Only three HCPs (from three different clinics) stated that their clinic offered a structured lifestyle modification programme. HCPs explained that they lacked the resources and expertise for offering a structured lifestyle modification programme. Response rates were limited, but the responding Belgian gynaecologists and fertility nurses/midwives confirmed the findings of the previous study in Australian fertility nurses. HCPs working in Belgian fertility clinics value healthy lifestyle promotion but lack access to structured lifestyle modification programmes to implement in their daily clinical practice. Future studies should focus on developing and evaluating structured lifestyle modification programmes for patients with fertility problems.


Impact of clinical presentations on lipid core plaque assessed by near-infrared spectroscopy intravascular ultrasound.
Near-infrared spectroscopy-intravascular ultrasound (NIRS-IVUS) studies have demonstrated that lipid core plaque (LCP) is frequently observed in the culprit segment of myocardial infarction (MI). However, little is known about the impact of clinical presentations such as chronic coronary syndrome (CCS) and acute coronary syndrome (ACS) including unstable angina (UA), non ST-segment elevation MI (NSTEMI), and ST-segment elevation MI (STEMI) on LCP. The present prospective single-center registry included a total of 178 patients who underwent percutaneous coronary intervention under NIRS-IVUS guidance. Patients were divided into CCS and ACS groups, and ACS patients were further sub-divided into the 3 groups according to the clinical presentation. The primary endpoint was coronary LCP in the target lesion assessed by NIRS-IVUS with maximal lipid core burden index over any 4 mm segment (maxLCBI4mm). The study population included 124 and 54 patients with CCS and ACS. MaxLCBI4mm in the target lesion was significantly higher in the ACS group than in the CCS group (503 [284-672] vs. 406 [250-557], p = 0.046). Among ACS patients, MaxLCBI4mm in the target lesion was also significantly different in those with UA (n = 18), NSTEMI (n = 21), and STEMI (n = 15) (288 [162-524] vs. 518 [358-745] vs. 646 [394-848], p = 0.021). In conclusion, LCP assessed by NIRS-IVUS, a surrogate of coronary plaque vulnerability, was significantly different according to the clinical presentations such as CCS, UA, NSTEMI, and STEMI.


Mimotopes identify conformational epitopes on parvalbumin, the major fish allergen.
Parvalbumin, the major fish allergen, is recognized by allergen-specific IgE of more than 90% of all fish-allergic patients. A detailed knowledge of allergenic structures is crucial for developing a vaccine inducing blocking antibodies specifically directed towards the IgE binding epitopes. In the present study we aimed to use the phage display technique to generate mimotopes, which mimic epitopes on parvalbumin. Parvalbumin-specific IgE was purified from sera of fish-allergic patients and used for screening of a constrained decamer phage library. After four rounds of biopanning using parvalbumin-specific IgE, five phage clones were selected which were specifically recognized by parvalbumin-specific IgE as well as IgG. DNA sequencing and peptide alignment revealed a high degree of sequence similarities between the mimotopes. Interestingly, on the surface of natural parvalbumin three regions could be defined by computational mimotope matching. In accordance, previously defined allergenic peptides of cod parvalbumin highlighted areas in close proximity or overlapping with the mimotope matching sites. From the presented data we conclude that our approach identified conformational epitopes of parvalbumin relevant for IgE and IgG binding. We suggest that these mimotopes are suitable candidates for an epitope-specific immunotherapy of fish-allergic patients.


Biosynthesis, intracellular processing and secretion of haptoglobin in cultured rat hepatocytes.
Biosynthesis, intracellular processing and secretion of the hetero-tetrameric (alpha 2 beta 2) glycoprotein, haptoglobin, were studied in primary cultured rat hepatocytes. The results obtained from pulse-chase experiments demonstrated that haptoglobin was initially synthesized as a larger precursor (pro-form), a single polypeptide chain comprising both the alpha- and beta-subunits, and immediately cleaved into subunits during intracellular transport, although about 8% of the newly synthesized haptoglobin was secreted as a pro-form. Monensin which impedes the secretory process at the Golgi complex blocked the complete glycosylation of beta-subunit but rather accelerated the conversion of the pro-form to subunits. These results indicate that the proteolytic processing of the haptoglobin precursor takes place at an early stage before the Golgi complex of the intracellular transport.


Production of zearalenone, nivalenol, moniliformin, and wortmannin from toxigenic cultures ofFusarium obtained from pasture soil samples collected in New Zealand.
One culture ofF avenaceum, 4 cultures ofF oxysporum, and 11 cultures of Fsambucinum were isolated from soil samples of pasture in New Zealand in 1987. All cultures, when grown on rice media and fed to rats caused a weight loss in rats as well as toxic signs including hemorrhaging and congestion, uterine enlargement, and hematuria. 6 out of 16 cultures caused death in rat feeding tests.F oxysporum #1 killed rats (feeding test) within 5-12hrs. 10 cultures produced zearalenone (19 to 8,849 ppm), 8 cultures produced nivalenol (32 to 117 ppm), 1 culture,F sambucinum #8, produced wortmannin (40 ppm), and 5 cultures produced moniliformin (19 to 9,000ppm). We report for the first time the co-occurrence of zearalenone, nivalenol, and moniliformin produced byF sambucinum #3 in culture.F avenaceum #1 andF oxysporum cultures (nos 1, 2, and 3) produced moniliformin alone.F oxysporum #4 produced zearalenone alone as well.F sambucinum #5 caused erythema in the small intestine of rats and 100% mortality and did not produce any known toxin(s). Nivalenol when administered to the stomach of rats orally at levels 10, 20, and 40mg/kg body weight caused inflammation in the intestines, coma, and death. The mycotoxins T-2 toxin, HT-2 toxin, T-2 tetraol, diacetoxyscirpenol (DAS), monoacetoxyscirpenol (MAS), deoxynivalenol (DON), 3-acetyl-and 15-acetyldeoxynivalenol, depoxynivalenol, fusarenon-X, alpha-and beta-zearalenone, and fusarochromanone (TDP-1) were not detected in the extracts of these cultures.


Effect of heat treatment on the performance of tryptose-sulfite-cycloserine agar for enumeration of Clostridium perfringens.
Dissolving dehydrated tryptose-sulfite-cycloserine agar by only boiling or microwaving was found to inhibit Clostridium perfringens colony development in pour plates when compared with C. perfringens recovery in tryptose-sulfite-cycloserine agar prepared by autoclaving.


Evaluation of groEL gene analysis for identification of Borrelia burgdorferi sensu lato.
The nucleotide sequences of the groEL genes, the flagellin genes, and the 16S rRNA genes from 22 reference strains of Borrelia were compared. groEL sequence analysis is useful not only in interspecies differentiation but also in intraspecies differentiation of Borrelia afzelii and Borrelia garinii isolates.


Population screening of lactate dehydrogenase deficiencies in Fukuoka Prefecture in Japan and molecular characterization of three independent mutations in the lactate dehydrogenase-B(H) gene.
Screening for lactate dehydrogenase (LDH) subunit deficiencies was performed on 2880 blood samples from healthy individuals in the Fukuoka Prefecture in Japan by means of electrophoresis. The frequencies of heterozygotes with either LDH-A or LDH-B deficiency were found to be 0.104% at each locus. These estimated frequencies of either LDH-A or LDH-B deficiencies were slightly lower than, but not significantly different from, those found previously in Shizuoka Prefecture. The genetic mutations in individuals heterozygous for LDH-B deficiency were analyzed by the polymerase chain reaction and DNA conformation polymorphism. Abnormal migration patterns were observed in individuals heterozygous for LDH-B deficiency. Subsequent sequence determination of the mutant alleles revealed three novel mutations: an eight-base duplication in exon 3, a four-base duplication in exon 4, and a one-base deletion in exon 7 of the LDH-B gene. These three mutations result in frame-shift translation and premature termination. In addition, the mutations resulting in the duplication of eight or four nucleotides appear to cause a decrease in the levels of LDH-B mRNA.


Hospital sees success by the dashboard light.
These days, interactive media is all the rage. It seems no business is complete without an online presence. Crouse Hospital has gone one step further, creating an interactive informational Web site that puts its employees in the driver's seat.


Radiological study of two disseminated malignant non-Hodgkin lymphomas affecting only the bones in children.
Malignant non-Hodgkin lymphomas are a neoplastic proliferation of lymphoid cells whose clinical manifestations are extremely variable. All tissues can be affected. There may be localization in lymphoid organs (Waldeyer's ring, spleen, digestive tract), other localizations (lungs, pleura, liver, bone marrow, central nervous system), and unusual localizations. Although bone marrow is often affected, bone involvement is very rare in the early stages of the disease. This report concerns the radiological study of two disseminated malignant non-Hodgkin lymphomas affecting only the bone in children.


Exploring the lived experiences of debilitating period pain management in the UK.
Five to ten percent of women experience period pains that disrupt their lives yet 4 in 5 women believe that their claims for their dysmenorrhea are not taken seriously. Within the process of seeking support and understanding about their pain, they face various barriers that prevent them from finding the answers they deserve. Semi-structured interviews were conducted with 8 women aged 20-28 to discuss their experiences with dysmenorrhea throughout their time since menarche. Using Scheper-Hughes and Lock understanding of the mindful body, this research explores women's experiences of dysmenorrhea through their physical body (relationship with the body and needing control), the social body (cultural concepts and comparisons to others) and the body politic (medicalisation, the medical team and the transvaginal ultrasound). The impact of these aspects of their mindful bodies developed arguments showing how different actors had an impact on preventing them obtaining the patient-centred care they required without resistance. More must be done to honour the experience of pain women have regarding their periods, especially by healthcare professionals. There must be consistency in the way women are approached for their dysmenorrhea to prevent discrepancies of support. This must be done with clearer guidance on what is offered to women with dysmenorrhea, especially in the primary care setting.


Data to model the influence of CSR on consumer behaviors: A process approach.
The aim of this research is to present inferential statistical data on the influence of Corporate Social Responsibility (CSR) perceptions on consumer advocacy behaviors, and to consider when and how that relationship occurs. Data was provided by 252 customers of a food company located in Spain. Structural equation modeling was used to analyze the psychometric proprieties of the measurement scales and to test the proposed direct hypotheses; conditional process analysis was used to test the proposed mediation hypothesis. The data indicate that CSR practices positively influence consumer advocacy behaviors through consumer admiration - the higher the integrity, the stronger the effect. This article provides data related to "Corporate social responsibility and consumer advocacy behaviors: The importance of emotions and moral virtues" [1].


Can sectioning the posterior communicating artery be predicted with computed tomography angiography in the microsurgical clipping of basilar apex aneurysms?
Microsurgical clipping is a viable option for managing high-riding basilar apex aneurysms (BAXs) using a transsylvian approach. Cutting the posterior communicating artery (PCoA) at the perforator-free zone provides sufficient exposure of BAX, although it is not always safe. The aim was to qualitatively predict sectioning of the interfering PCoA by using preoperative computed tomographic angiography (CTA). A virtual trajectory from the lesser sphenoid wing to the neck of the aneurysm was simulated on CTA in 19 consecutive patients operated on BAX aneurysms from 2013 to 2018. The angles on CTA resembled the typical view through the extended pterional craniotomy. Next, the ipsilateral PCoA was tracked from the internal carotid to its end at the posterior cerebral artery in the trajectory. The opticocarotid and carotid-oculomotor window served as the corridors for entering the interpeduncular fossa in 16 patients (84.2%) and in 3 patients (15.8%), respectively. The PCoA was intentionally cut during nine surgeries and preserved in 10 of them. The PCoA was cut more often when positioned toward the cranial base and more medially in the corridor; both the Kernel density analysis and the data points representing the position of the PCoA supported this finding (p < 0.01). The CTA-based position of either ends of the PCoA in the trajectory did not differ between cut and not-cut groups (p = 0.19-0.96). Aneurysm projection, rupture, size, PCoA diameter, length, and other distances on CTA were not related to the sectioning of PCoA (p > 0.05). The probability of PCoA sectioning is higher when the PCoA is positioned medially and closer to the cranial base. If the anatomical course of the PCoA is recognized beforehand, it can contraindicate surgery. Preoperative CTA-based planning facilitates the surgery of BAX aneurysms. Therefore, CTA can make microsurgical clipping planning more predictable for the neurosurgeon and safer for the patient.


Consideration of oral health in rare disease expertise centres: a retrospective study on 39 rare diseases using text mining extraction method.
Around 8000 rare diseases are currently defined. In the context of individual vulnerability and more specifically the one induced by rare diseases, ensuring oral health is a particularly important issue. The objective of the study is to evaluate the pattern of oral health care course for patients with any rare genetic disease. Description of oral phenotypic signs-which predict a theoretical dental health care course-and effective orientation into an oral healthcare were evaluated. We set up a retrospective cohort study to describe the consideration of patient oral health and potential orientation to an oral health care course who have at least been seen once between 1 January 2017 and 1 January 2020 in Necker Enfants Malades Hospital. We recruited patients from this study using the data warehouse, Dr Warehouse® (DrWH), from Necker-Enfants Malades Hospital. The study sample included 39 rare diseases, 2712 patients, with 54.7% girls and 45.3% boys. In the sample studied, 27.9% of patients had an acquisition delay or a pervasive developmental disorder. Among the patient files studied, oral and dental phenotypic signs were described for 18.40% of the patients, and an orientation in an oral healthcare was made in 15.60% of patients. The overall "network" effect was significantly associated with description of phenotypic signs (corrected p = 1.44e-77) and orientation to an oral healthcare (corrected p = 23.58e-44). Taking the Defiscience network (rare diseases of cerebral development and intellectual disability) as a reference for the odd ratio analysis, OSCAR, TETECOU, FILNEMUS, FIMARAD, MHEMO networks stand out from the other networks for their significantly higher consideration of oral phenotypic signs and orientation in an oral healthcare. To our knowledge, no study has explored the management of oral health in so many rare diseases. The expected benefits of this study are, among others, a better understanding, and a better knowledge of the oral care, or at least of the consideration of oral care, in patients with rare diseases. Moreover, with the will to improve the knowledge on genetic diseases, oral heath must have a major place in the deep patient phenotyping. Therefore, interdisciplinary consultations with health professionals from different fields are crucial.


Syntaxin 6-mediated exosome secretion regulates enzalutamide resistance in prostate cancer.
Prostate cancer (PCa) deaths are typically the result of metastatic castration-resistant PCa (mCRPC). Recently, enzalutamide (Enz), an oral androgen receptor inhibitor, was approved for treating patients with mCRPC. Invariably, all PCa patients eventually develop resistance against Enz. Therefore, novel strategies aimed at overcoming Enz resistance are needed to improve the survival of PCa patients. The role of exosomes in drug resistance has not been fully elucidated in PCa. Therefore, we set out to better understand the exosome's role in the mechanism underlying Enz-resistant PCa. Results showed that Enz-resistant PCa cells (C4-2B, CWR-R1, and LNCaP) secreted significantly higher amounts of exosomes (2-4 folds) compared to Enz-sensitive counterparts. Inhibition of exosome biogenesis in resistant cells by GW4869 and dimethyl amiloride strongly decreased their cell viability. Mechanistic studies revealed upregulation of syntaxin 6 as well as its increased colocalization with CD63 in Enz-resistant PCa cells compared to Enz-sensitive cells. Syntaxin 6 knockdown by specific small interfering RNAs in Enz-resistant PCa cells (C4-2B and CWR-R1) resulted in reduced cell number and increased cell death in the presence of Enz. Furthermore, syntaxin 6 knockdown significantly reduced the exosome secretion in both Enz-resistant C4-2B and CWR-R1 cells. The Cancer Genome Atlas analysis showed increased syntaxin 6 expressions associated with higher Gleason score and decreased progression-free survival in PCa patients. Importantly, IHC analysis showed higher syntaxin 6 expression in cancer tissues from Enz-treated patients compared to Enz naïve patients. Overall, syntaxin 6 plays an important role in the secretion of exosomes and increased survival of Enz-resistant PCa cells.


Methotrexate sequestration in an ovarian cyst.
Methotrexate has been documented to accumulate in pleural effusions and ascitic fluid, resulting in severe local and systemic toxicity. In the following case report, we publish results of intraoperative measurements of methotrexate levels in serum and an ovarian cyst and attempt to determine if ovarian cysts similarly act as a depot for methotrexate. After determining intraoperative measurements of serum and ovarian cystic levels of methotrexate, we compared demonstrated pharmacokinetics to those expected by using pharmacokinetic systems analysis software. Intraoperative measurement of methotrexate levels on day 3 of a 5-day methotrexate regimen revealed a serum methotrexate concentration of 1.6 x 10(-7) M and a concentration of 3.1 x 10(-7) M within the 166.4 ml ovarian cyst. The measured levels demonstrate that methotrexate is sequestered within an ovarian cyst resulting in higher local drug levels. Our pharmacokinetic analysis suggests that methotrexate doses less than 100 mg/m2 can be safely administered to patients with small ovarian cysts. However, computed simulations support the possibility of local and systemic toxicity arising from large ovarian cysts when using high doses of methotrexate.


Low back pain and osteoarthritis pain: a perspective of estrogen.
Low back pain (LBP) is the world's leading cause of disability and is increasing in prevalence more rapidly than any other pain condition. Intervertebral disc (IVD) degeneration and facet joint osteoarthritis (FJOA) are two common causes of LBP, and both occur more frequently in elderly women than in other populations. Moreover, osteoarthritis (OA) and OA pain, regardless of the joint, are experienced by up to twice as many women as men, and this difference is amplified during menopause. Changes in estrogen may be an important contributor to these pain states. Receptors for estrogen have been found within IVD tissue and nearby joints, highlighting the potential roles of estrogen within and surrounding the IVDs and joints. In addition, estrogen supplementation has been shown to be effective at ameliorating IVD degeneration and OA progression, indicating its potential use as a therapeutic agent for people with LBP and OA pain. This review comprehensively examines the relationship between estrogen and these pain conditions by summarizing recent preclinical and clinical findings. The potential molecular mechanisms by which estrogen may relieve LBP associated with IVD degeneration and FJOA and OA pain are discussed.


Enzymatic extraction of chondroitin sulfate from skate cartilage and concentration-desalting by ultrafiltration.
Skate cartilage is a fishery by-product, which contains chondroitin sulfate (CS), a glycosaminoglycan well known for its chondroprotective effect. Here described is a low-cost two-step process producing CS in non-denaturing conditions, consisting of an enzymatic extraction followed by tangential filtration to concentrate and purify CS. The performances of UF and MF membranes were compared in terms of flux and selectivity. The 0.1 microm-pore size membrane appeared to be the most efficient to separate CS from the other compounds.


Maternal and Perinatal Outcomes in Singleton Nulliparous Spontaneous Preterm Birth with and without Preterm Premature Rupture of Membranes-A National Population-Based Cohort Study.
Preterm birth (PTB, birth before 37 gestational weeks) is the leading cause of neonatal death and a major challenge for obstetric and neonatal care. About two-thirds of PTBs are spontaneous PTB (sPTB), of which approximately 30% start with preterm premature rupture of membranes (PPROM). The aim of the study was to investigate risk factors and maternal and perinatal outcomes in sPTB with and without PPROM. This is a national population-based cohort study including all singleton pregnancies in nulliparous women with spontaneous onset of labor and vaginal births (n = 266,968) registered in the Swedish Medical Birth Register 2005 to 2014. sPTB with PPROM (sPTB-PPROM) and sPTB without PPROM were compared regarding risk factors and maternal and perinatal outcomes. Logistic regression was used to estimate adjusted odds ratios (aORs) with 95% confidence intervals (CIs). Adjustments were made for maternal age, body mass index, country of birth, smoking, chronic hypertension, pregestational and gestational diabetes, and gestational length. sPTB-PPROM (n = 5,037), compared with sPTB without PPROM (n = 8,426), was more common in women with previous spontaneous abortions, prepregnancy urinary tract infections, chronic hypertension, and gestational diabetes and had a higher risk of postpartum endometritis (aOR: 2.78, 95% CI: 1.55-5.00). Infants born to women with sPTB-PPROM had a lower risk of birth asphyxia (aOR: 0.60, 95% CI: 0.43-0.83), respiratory distress syndrome (aOR: 0.86, 95% CI: 0.70-1.00), retinopathy of prematurity (aOR: 0.93, 95% CI: 0.92-0.94), necrotizing enterocolitis (aOR: 0.95, 95% CI: 0.94-0.96), and higher risk of hypoglycemia (aOR: 1.14, 95% CI: 1.01-1.28), and hyperbilirubinemia (aOR: 1.28, 95% CI: 1.19-1.38) compared with infants born to sPTB without PPROM. Our findings of risk factors and distinct differences in adverse outcomes after sPTB-PPROM compared with sPTB without PPROM are of vital importance and might serve as a basis when elaborating programs for the prevention and management of PPROM. · This is a large cohort study of spontaneous preterm birth (sPTB).. · Singleton nulliparous sPTB with/without preterm premature rupture of membrane (PPROM) were studied.. · Distinct differences in adverse perinatal outcomes in sPTB with and without PPROM were observed..


Differences in the detection of highly pathogenic avian influenza H5N1 virus in feather samples from 4-week-old and 24-week-old infected Pekin ducks (Anas platyrhynchos var. domestica).
Previous studies have reported the detection of H5N1 HPAI virus in feathers from ducks naturally and experimentally infected and suggested that feather calami (FC) could be used as diagnostic samples for the early detection of H5N1 HPAI infections. Ducks are readily infected with H5N1 HPAI viruses although the development of clinical signs and deaths were reported as age-related with younger birds being more susceptible. The correlation between age and virus localisation in FC of infected ducks has not been studied to date. In the present study juvenile (4-week-old) and adult (24-week-old) Pekin ducks (Anas platyrhynchos var. domestica) were infected experimentally with a clade 2.2 H5N1 HPAI virus (A/duck/Nigeria/1071-23/2007). Tracheal (Tr) and cloacal (Cl) swabs and FC were collected at 3, 5, 7 and 10 days post infection and tested by RRT-PCR and a double antibody sandwich-ELISA (DAS-ELISA) developed in house. Virus was detected in swabs and FC of challenged ducks with a higher rate of detection in juvenile ducks. In this age group virus was detected over a longer period of time in FC compared to swabs. Our study showed that FC samples collected from young ducks are a valid diagnostic specimen for H5N1 HPAI virus detection. The DAS-ELISA on FC proved to be a suitable alternative diagnostic test when molecular and/or virus isolation techniques are not available therefore it could be useful in the diagnosis of H5N1 HPAI infections in under-resourced countries.


Topical anesthesia: modulation of the monosynaptic reflexes by desensitization of the skin.
Skin desensitization by topical anesthesia was studied for its effect on the motoneuron excitability of the soleus muscle. Skin areas overlying calf, tibial, quadriceps and hamstrings muscles and skin dermatomes (L2, L3, L4, L5, S1 and S2) were studied separately. Motoneuron excitabilities were measured by the H-reflex and Achilles tendon reflex (for alpha and gamma motoneurons). It was shown that anesthesia applied to all skin areas and dermatomes, except those overlying the antagonist muscles, resulted in significant facilitation of the soleus H-reflex. In these cases, the ATR showed either slight inhibition or no significant changes. Anesthesia to the skin overlying the anterior tibial antagonistic muscle produced varied and inconsistent modifications in the amplitude of the H-reflex. In these cases the ATR was either slightly facilitated or showed no significant changes. These results appear to indicate the existence of on-going excitatory and inhibitory effects from the skin on the alpha and gamma motoneuron pool probably via segmental and suprasegmental levels. A possible clinical application of these results to modulate the motoneuron pool excitability is proposed.


Assessment of variables contributing to cyclosporine distribution in blood.
Factors which can account for the poor correlation between whole blood and plasma Cyclosporine (CsA) levels in patients on CsA prophylaxis are evaluated. The study took account of the influence of plasma separation procedures, and the sample haematocrit on CsA distribution in the blood of renal transplant patients (n = 35). CsA was measured using both specific and non-specific CsA radioimmunoassays. Significant negative correlations occurred between CsA distribution and the haematocrit, independently of the plasma separation procedure or the specificity of the assay. All results were lower when using the specific assay but a significantly higher percentage of CsA was measured in the plasma by specific assay compared to nonspecific assay when plasma was separated at both 22 degrees C (t-test, p less than 0.02) and at 37 degrees C, p less than 0.01). This may relate to the selective binding of CsA and its analogues by blood cells. This study is a prelude to the development of more consistent plasma separation procedures in the monitoring of this drug.


Manganese-cerium composite oxide pyrolyzed from metal organic framework supporting palladium nanoparticles for efficient toluene oxidation.
Manganese-cerium metal oxide with flocculent structure prepared via the pyrolysis of Mn/Ce-MOF and supported Pd were applied for the catalytic oxidation of toluene. The Pd/Mn3Ce2-300 catalyst could completely oxidize toluene at 190 °C, which presented excellent catalytic performance. Moreover, Pd/Mn3Ce2-300 possessed great reusability, stability and water resistance even under 10 vol% water vapors. A series of characterizations including X-ray diffraction (XRD), N2 adsorption-desorption, scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS) and H2 temperature programmed reduction (H2-TPR) were used to investigate the physicochemical properties of the samples. It was found that Pd/Mn3Ce2-300 possessed a better reduction ability at low temperature, more surface absorbed oxygen and surface Pd species, and a strong interaction between Pd and Mn3Ce2-300, resulting in great catalytic performance for toluene degradation.


Factors Affecting Success of New Drug Clinical Trials.
Clinical trials are an essential process in the development of new drugs. In spite of time-consuming processes and high costs, the overall success rate of clinical trials is only 7.9%, which is a high risk for biopharmaceutical companies. However, despite these huge risks, research on finding factors affecting clinical trials to overcome and manage to risks has been insufficient. Considering these characteristics of the pharmaceutical industry, this study investigated the factors affecting the success of sponsor-initiated clinical trials. The success factors investigated were categorized into four factors: quality of clinical trials, speed of clinical trials, relationship type, and communication. Logistic regression was performed to measure each factor by analyzing 24,295 cases of Phase 1 to 4 trials from ClinicalTrials.gov. Because of the analysis, the factors affecting the success of the clinical trials were varied according to each clinical phase and the drug types: New Molecular Entity (NME)/Biologics, and the success ratio in the quality variable affected the overall clinical trial phases. Additionally, the experience, speed, relationship type, and communication variables were also found to be statistically significant for the success of each phase and drug type.


Technical and economic effects of an inline progesterone indicator in a dairy herd estimated by stochastic simulation.
For several years progesterone in milk or blood has been recognized as an indicator of different cow states related to reproduction. For this study, an existing simulation model was modified in order to analyze the technical and economic effects of including information on progesterone status in an automatic inline monitoring system. Implementation of an inline progesterone indicator was assumed to directly affect the estrus detection rate, the period until treatment for post-partum anestrus and the number of mistimed AIs. Different implementations of an inline progesterone indicator were simulated in a typical Danish dairy herd with 120 cows and in other herd situations represented by: a herd with poor reproduction efficiency, a herd with a high estrus detection rate and a herd using a 9 week postponed AI period for primiparous cows. It was concluded that implementation of an inline progesterone indicator in a dairy herd previously using visual estrus detection has a break-even price of 3-81 euros per cow-year depending on differences in implementation type and herd reproduction management. The highest break-even price was found using the assumptions that simulated a herd with initially poor reproductive efficiency. With the assumptions that simulated a typical Danish herd the break-even price was 46 euros per cow-year. Attributable effects of using the indicator, including effects of labor time, are discussed.


Significant association of interleukin 8 -251T/A polymorphism with smoking behavior in a Japanese population.
Accumulating evidence indicates that the genotype may impact on smoking behavior and a deeper understanding of the molecular basis could lead to more effective strategies for preventing initiation of the habit and to help smokers to quit. Since individual variation in airway responsiveness to cigarette smoke might have an important influence, we have focused on associations between smoking behavior and polymorphisms affecting the inflammatory cytokine, IL-8. In the present study, 453 Japanese non-cancer outpatients (191 males and 262 females) who visited Aichi Cancer Center Hospital were genotyped for the IL8 -251T/A polymorphism, and age- and sex-adjusted odds ratios (aORs) for smoking were estimated using a logistic regression model. The aORs for IL8 251-TA and AA combined, genotypes associated with high production of IL-8, were 0.52 (95% CI 0.33-0.82, P=0.004) for ever having smoked and 0.55 (0.33-0.92, P=0.023) for being a current smoker. Our results suggest that the inflammatory-prone genotype of IL8 may act to deter initiation or characteristics of the smoking habit.


Prevalence of Deep Vein Thrombosis and Pulmonary Embolism Treated with Mechanical Compression Device After Total Knee Arthroplasty in Asian Patients.
The purpose of this study was: (1) to determine the prevalence of deep vein thrombosis (DVT) after the use of a mechanical compression device only, without pharmacological thromboprophylaxis; (2) to investigate the factors associated with DVT; and (3) to investigate the natural course of DVT and PE. We reviewed consecutive series of 874 patients (1434 knees) who received treatment with a mechanical compression device only for prevention of DVT after primary TKA. The prevalence of DVT was 6.6% (94 of 1434 knees). Proximal thrombi were found in 6 of 1434 knees (0.4%). No patient had PE on perfusion lung scans. Further sonograms and venograms for the patients with thrombi at 6 months after the operation revealed that all thrombi were resolved.


Dual-design expandable colorectal stent for a malignant colorectal obstruction: preliminary prospective study using new 20-mm diameter stents.
To evaluate the safety and effectiveness of a 20-mm diameter dual-design expandable colorectal stent for malignant colorectal obstruction. The study series included 34 patients with malignant colorectal obstruction who underwent implantation of a 20-mm dual-design expandable colorectal stent in our department between March 2009 and June 2010. The 20-mm dual-design expandable colorectal stent was placed by using a 3.8-mm delivery system that had 28-mm diameter proximal and distal ends. Among the 34 patients, stent placement for palliation was performed in 20 patients, while stent placement for bridge to surgery was performed in 14 patients. A 97% (33 of 34) success rate was achieved for the stent placement. The perforation rate in the bridge to surgery group was 7% (1 of 14), compared to 0% (0 of 19) in palliative group. Migration occurred in one of 33 patients (3%) at 30 days after stent placement. The placement of a 20-mm diameter dual-design stent appears to be clinically safe and effective for the management of colorectal obstruction, with low perforation and migration rates.


Deep learning predicts extreme preterm birth from electronic health records.
Models for predicting preterm birth generally have focused on very preterm (28-32 weeks) and moderate to late preterm (32-37 weeks) settings. However, extreme preterm birth (EPB), before the 28th week of gestational age, accounts for the majority of newborn deaths. We investigated the extent to which deep learning models that consider temporal relations documented in electronic health records (EHRs) can predict EPB. EHR data were subject to word embedding and a temporal deep learning model, in the form of recurrent neural networks (RNNs) to predict EPB. Due to the low prevalence of EPB, the models were trained on datasets where controls were undersampled to balance the case-control ratio. We then applied an ensemble approach to group the trained models to predict EPB in an evaluation setting with a nature EPB ratio. We evaluated the RNN ensemble models with 10 years of EHR data from 25,689 deliveries at Vanderbilt University Medical Center. We compared their performance with traditional machine learning models (logistical regression, support vector machine, gradient boosting) trained on the datasets with balanced and natural EPB ratio. Risk factors associated with EPB were identified using an adjusted odds ratio. The RNN ensemble models trained on artificially balanced data achieved a higher AUC (0.827 vs. 0.744) and sensitivity (0.965 vs. 0.682) than those RNN models trained on the datasets with naturally imbalanced EPB ratio. In addition, the AUC (0.827) and sensitivity (0.965) of the RNN ensemble models were better than the AUC (0.777) and sensitivity (0.819) of the best baseline models trained on balanced data. Also, risk factors, including twin pregnancy, short cervical length, hypertensive disorder, systemic lupus erythematosus, and hydroxychloroquine sulfate, were found to be associated with EPB at a significant level. Temporal deep learning can predict EPB up to 8 weeks earlier than its occurrence. Accurate prediction of EPB may allow healthcare organizations to allocate resources effectively and ensure patients receive appropriate care.


Diffusion tensor MRI of chemotherapy-induced cognitive impairment in non-CNS cancer patients: a review.
Patients with non-central nervous system cancers often experience subtle cognitive deficits after treatment with cytotoxic agents. Therapy-induced structural changes to the brain could be one of the possible causes underlying these reported cognitive deficits. In this review, we evaluate the use of diffusion tensor imaging (DTI) for assessing possible therapy-induced changes in the microstructure of the cerebral white matter (WM) and provide a critical overview of the published DTI research on therapy-induced cognitive impairment. Both cross-sectional and longitudinal DTI studies have demonstrated abnormal microstructural properties in WM regions involved in cognition. These findings correlated with cognitive performance, suggesting that there is a link between reduced "WM integrity" and chemotherapy-induced impaired cognition. In this paper, we will also introduce the basics of diffusion tensor imaging and how it can be applied to evaluate effects of therapy on structural changes in cerebral WM. The review concludes with considerations and discussion regarding DTI data interpretation and possible future directions for investigating therapy-induced WM changes in cancer patients. This review article is part of a Special Issue entitled: Neuroimaging Studies of Cancer and Cancer Treatment.


[Hematopoietic indices in rats with sarcoma 45 in the process of treatment with cytostatics and diuretic agents].
Sarcoma 45 growth in rats was noted to be followed by the development of anemia and leucocytosis. Sessional use of 6-mercaptopurine and cyclophosphane resulted in the enhancement of anemia, the development of leucopenia, and suppression of bone marrow hemopoiesis. The suppression of hemopoiesis was much less manifested, if cytostatics were used together with diuretics (diacarbe or furocemid).


ABO hemolytic disease of the newborn: a need for clarity and consistency in diagnosis.
The diagnosis of ABO hemolytic disease of the newborn (ABO HDN) has been the subject of considerable debate and clinical confusion. Its use as an overarching default diagnosis for hyperbilirubinemia in all ABO incompatible neonates regardless of serological findings is problematic and lacks diagnostic precision. Data on hemolysis indexed by carbon monoxide (CO) levels in expired air (ETCOc) and blood (COHbc) support an essential role for a positive direct antiglobulin test (DAT) in making a more precise diagnosis of ABO HDN. A working definition that includes ABO incompatibility, significant neonatal hyperbilirubinemia, and a positive DAT is needed to gain clarity and consistency in the diagnosis of ABO HDN. Absent a positive DAT, the diagnosis of ABO HDN is suspect. Instead, a negative DAT in a severely hyperbilirubinemic ABO incompatible neonate should trigger an exhaustive search for an alternative cause, a search that may require the use of targeted gene panels.


Image Pretreatment Tools I: Algorithms for Map Denoising and Background Subtraction Methods.
One of the critical steps in two-dimensional electrophoresis (2-DE) image pre-processing is the denoising, that might aggressively affect either spot detection or pixel-based methods. The Median Modified Wiener Filter (MMWF), a new nonlinear adaptive spatial filter, resulted to be a good denoising approach to use in practice with 2-DE. MMWF is suitable for global denoising, and contemporary for the removal of spikes and Gaussian noise, being its best setting invariant on the type of noise. The second critical step rises because of the fact that 2-DE gel images may contain high levels of background, generated by the laboratory experimental procedures, that must be subtracted for accurate measurements of the proteomic optical density signals. Here we discuss an efficient mathematical method for background estimation, that is suitable to work even before the 2-DE image spot detection, and it is based on the 3D mathematical morphology (3DMM) theory.


Abnormal dynamic brain activity and functional connectivity of primary motor cortex in blepharospasm.
Accumulating evidence indicates that dynamic amplitude of low-frequency fluctuations (dALFF) or dynamic functional connectivity (dFC) can provide complementary information, distinct from static amplitude of low-frequency fluctuations (sALFF) or static functional connectivity (sFC), in detecting brain functional abnormalities in brain diseases. We aimed to examine whether dALFF and dFC can offer valuable information for the detection of functional brain abnormalities in patients with blepharospasm. We collected resting-state functional magnetic resonance imaging data from 46 patients each of blepharospasm, hemifacial spasm (HFS), and healthy controls (HCs). We examined intergroup differences in sALFF and dALFF to investigate abnormal regional brain activity in patients with blepharospasm. Based on the dALFF results, we conducted seed-based sFC and dFC analyses to identify static and dynamic connectivity changes in brain networks centered on areas showing abnormal temporal variability of local brain activity in patients with blepharospasm. Compared with HCs, patients with blepharospasm displayed different brain functional change patterns characterized by increased sALFF in the left primary motor cortex (PMC) but increased dALFF variance in the right PMC. However, differences were not found between patients with HFS and HCs. Additionally, patients with blepharospasm exhibited decreased dFC strength, but no change in sFC, between right PMC and ipsilateral cerebellum compared with HCs; these findings were replicated when patients with blepharospasm were compared to those with HFS. Our findings highlight that dALFF and dFC are complementary to sALFF and sFC and can provide valuable information for detecting brain functional abnormalities in blepharospasm. Blepharospasm may be a network disorder involving the cortico-ponto-cerebello-thalamo-cortical circuit.


Squeeze-film lubrication of the human ankle joint with synovial fluid filtrated by articular cartilage with the superficial zone worn out.
A squeeze-film lubrication model of the human ankle joint in standing that takes into account the fluid transport across the articular surface is presented. Articular cartilage is a biphasic mixture of the ideal interstitial fluid and an elastic permeable isotropic homogeneous intrinsically incompressible matrix. The simple homogeneous model for articular cartilage models the case of early osteoarthritis, when the intact superficial zone of the normal articular cartilage, much stiffer in tension than the bulk material, has been already disrupted or worn out. The calculations indicate for this case that in normal approach motion the lubricating fluid film is quickly depleted and turned into a synovial gel film that is supposed to serve as a boundary lubricant if sliding motion follows


Indirect relativistic bridge and substituent effects from the 'heavy' environment on the one-bond and two-bond (13)C-(1)H spin-spin coupling constants.
Indirect relativistic bridge effect (IRBE) and indirect relativistic substituent effect (IRSE) induced by the 'heavy' environment of the IV-th, V-th and VI-th main group elements on the one-bond and geminal (13)C-(1)H spin-spin coupling constants are observed, and spin-orbit parts of these two effects were interpreted in terms of the third-order Rayleigh-Schrödinger perturbation theory. Both effects, IRBE and IRSE, rapidly increase with the total atomic charge of the substituents at the coupled carbon. The accumulation of IRSE for geminal coupling constants is not linear with respect to the number of substituents in contrast to the one-bond couplings where IRSE is an essentially additive quantity.


Mental health in people with Parkinson's disease during the COVID-19 pandemic: potential for targeted interventions?
The COVID-19 pandemic has introduced a myriad of challenges to the social life and care of people with Parkinson's disease (PD), which could potentially worsen mental health problems. We used baseline data of the PRIME-NL study (N = 844) to examine whether the association between COVID-19 stressors and mental health is disproportionately large in specific subgroups of people with PD and to explore effects of hypothetical reductions in COVID-19 stressors on mental health and quality of life. The mean (SD) age of the study population was 70.3 (7.8) years and 321 (38.0%) were women. The linear regression effect estimate of the association of COVID-19 stressors with mental health was most pronounced in women, highly educated people, people with advanced PD and people prone to distancing or seeking social support. Smaller effect estimates were found in people scoring high on confrontive coping or planful problem solving. The parametric G-formula method was used to calculate the effects of hypothetical interventions on COVID-19 stressors. An intervention reducing stressors with 50% in people with above median MDS-UPDRS-II decreased the Beck Depression Inventory in this group from 14.7 to 10.6, the State-Trait Anxiety Inventory from 81.6 to 73.1 and the Parkinson's Disease Quality of Life Questionnaire from 35.0 to 24.3. Insights from this cross-sectional study help to inform tailored care interventions to subgroups of people with PD most vulnerable to the impact of COVID-19 on mental health and quality of life.


A method for staining actin-containing structures in thick plastic sections for medium voltage electron microscopy.
A staining procedure has been developed for imaging actin-containing structures in thick plastic sections in the electron microscope. The stress fibres of a fibroblastic cell line were used as a model system, and were first characterized immunocytochemically. After fixation of cells in formaldehyde, mordanting in a solution of gadolinium chloride allows stress fibres to be stained for light microscopy with haematoxylin. A brief exposure to a solution of ammonium paramolybdate renders haematoxylin-stained structures sufficiently electron-dense to be imaged in 1 micron thick plastic sections in a JEOL 200CX electron microscope, operating at 200 kV, and possibly in conventional instruments operating at 100 kV, particularly if equipped with a lanthanum hexaboride source.


Supplemental Nutrition Assistance Program (SNAP)-Authorized Grocery, Convenience, Dollar, and Restaurant or Delivery Service Settings Are Associated With Increased Obesity Prevalence in Virginia.
United States Department of Agriculture Supplemental Nutrition Assistance Program (SNAP) participants use SNAP-authorized stores for dietary purchases. Relationships between obesity prevalence and access to grocery and varied nontraditional (eg, dollar, drug, and convenience) SNAP settings are underexplored. This research aimed to determine the association of a full range of SNAP-authorized stores with obesity prevalence in Virginia. The SNAP Retailer Locator was used to cross-sectionally identify authorized stores, and county health ranking information was applied based on store location. Virginia, United States. The SNAP-authorized stores, classified among store categories: grocery or supermarket; drug; mass merchandiser; supercenter; convenience; dollar; club; other; nonfood store; farmers markets; and independent grocery stores. County-level obesity prevalence with income and rurality as potential confounders. Multiple linear regression was used to determine associations between county-level adult obesity prevalence and available SNAP-authorized store formats (P < .05 a priori). Store format was a predictor of obesity prevalence in Virginia in simple and adjusted models (R2 = 0.035, P < .0001 and R2 = 0.434, P < .0001, respectively). Grocery store or supermarket access was associated with obesity. The SNAP-authorized convenience, dollar, and nonfood stores were associated with a 0.3, 0.5, and 1.3 increase in county obesity prevalence, respectively (P < .05). Research, practice, and health policy approaches to improve grocery, convenience, dollar, and restaurant or delivery service settings may favorably influence community obesity prevalence in Virginia.


A Simulation-Based Cost-Effectiveness Analysis of Severe Acute Respiratory Syndrome Coronavirus 2 Infection Prevention Strategies for Visitors of Healthcare Institutions.
The aim is to quantitatively evaluate different infection prevention strategies in the context of hospital visitor management during pandemics and to provide a decision support system for strategic and operational decisions based on this evaluation. A simulation-based cost-effectiveness analysis is applied to the data of a university hospital in Southern Germany and published COVID-19 research. The performance of different hospital visitor management strategies is evaluated by several decision-theoretic methods with varying objective functions. Appropriate visitor restrictions and infection prevention measures can reduce additional infections and costs caused by visitors of healthcare institutions by >90%. The risk of transmission of severe acute respiratory syndrome coronavirus 2 by visitors of terminal care (ie, palliative care) patients can be reduced almost to 0 if appropriate infection prevention measures are implemented. Antigen tests do not seem to be beneficial from both a cost and an effectiveness perspective. Hospital visitor management is crucial and effectively prevents infections while maintaining cost-effectiveness. For terminal care patients, visitor restrictions can be omitted if appropriate infection prevention measures are taken. Antigen testing plays a subordinate role, except in the case of a pure focus on additional infections caused by visitors of healthcare institutions. We provide decision support to authorities and hospital visitor managers to identify appropriate visitor restriction and infection prevention strategies for specific local conditions, incidence rates, and objectives.


Monitoring ADO dependent proteolysis in cells using fluorescent reporter proteins.
2-Aminoethanethiol dioxygenase (ADO) is the mammalian orthologue of the plant cysteine oxidases and together these enzymes are responsible for catalysing dioxygenation of N-terminal cysteine residues of certain proteins. This modification creates an N-degron motif that permits arginylation and subsequent proteasomal degradation of such proteins via the Arg-branch of the N-degron pathway. In humans 4 proteins have been identified as substrates of ADO; regulators of G-protein signalling (RGS) 4, 5 and 16, and interleukin-32 (IL-32). Nt-cysteine dioxygenation of these proteins occurs rapidly under normoxic conditions, but ADO activity is very sensitive to O2 availability and as such the stability of substrate proteins is inversely proportional to cellular O2 levels. Much is still to understand about the biochemistry and physiology of this pathway in vitro and in vivo, and Cys N-degron targeted fluorescent proteins can provide a simple and effective tool to study this at both subcellular and high-throughput scales. This chapter describes the design, production and implementation of a fluorescent fusion protein proteolytically regulated by ADO and the N-degron pathway.


The influence of different nutrients on plasma cholecystokinin levels in the rat.
Isocaloric and isovolemic amounts of protein (casein), fat (intralipid) and carbohydrate (saccharose) and an isovolemic control solution of water were administered intragastrically to conscious rats. The plasma CCK levels, determined by a sensitive and specific radioimmunoassay, showed an increment of 6.3 +/- 0.6, 2.7 +/- 0.5, 1.7 +/- 0.4 and -0.9 +/- 0.4 pM, respectively (basal value 2.5 +/- 0.3 pM). The threshold increment of plasma CCK to stimulate pancreatic enzyme secretion by exogenous CCK was found to be 1.5 pM. It is therefore concluded that casein is a potent stimulus for CCK secretion and pancreatic secretion, but that fat and even carbohydrate, although less potent, also produce a CCK increment above the threshold for pancreatic secretion.


The crystal structure of exonuclease RecJ bound to Mn2+ ion suggests how its characteristic motifs are involved in exonuclease activity.
RecJ, a 5' to 3' exonuclease specific for single-stranded DNA, functions in DNA repair and recombination systems. We determined the crystal structure of RecJ bound to Mn(2+) ion essential for its activity. RecJ has a novel fold in which two domains are interconnected by a long helix, forming a central groove. Mn(2+) is located on the wall of the groove and is coordinated by conserved residues characteristic of a family of phosphoesterases that includes RecJ proteins. The groove is composed of residues conserved among RecJ proteins and is positively charged. These findings and the narrow width of the groove indicate that the groove binds single- instead of double-stranded DNA.


Rifampicin drug resistance and host immunity in tuberculosis: more than meets the eye.
Tuberculosis (TB) is the leading cause of death due to an infectious agent, with more than 1.5 million deaths attributed to TB annually worldwide. The global dissemination of drug resistance across Mycobacterium tuberculosis (Mtb) strains, causative of TB, resulted in an estimated 450 000 cases of drug-resistant (DR) TB in 2021. Dysregulated immune responses have been observed in patients with multidrug resistant (MDR) TB, but the effects of drug resistance acquisition and impact on host immunity remain obscure. In this review, we compile studies that span aspects of altered host-pathogen interactions and highlight research that explores how drug resistance and immunity might intersect. Understanding the immune processes differentially induced during DR TB would aid the development of rational therapeutics and vaccines for patients with MDR TB.


Positron emission tomography in amyotrophic lateral sclerosis: Towards targeting of molecular pathological hallmarks.
During the past decades, extensive efforts have been made to expand the knowledge of amyotrophic lateral sclerosis (ALS). However, clinical translation of this research, in terms of earlier diagnosis and improved therapy, remains challenging. Since more than 30% of motor neurons are lost when symptoms become clinically apparent, techniques allowing non-invasive, in vivo detection of motor neuron degeneration are needed in the early, pre-symptomatic disease stage. Furthermore, it has become apparent that non-motor signs play an important role in the disease and there is an overlap with cognitive disorders, such as frontotemporal dementia (FTD). Radionuclide imaging, such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT), form an attractive approach to quantitatively monitor the ongoing neurodegenerative processes. Although [18F]-FDG has been recently proposed as a potential biomarker for ALS, active targeting of the underlying pathologic molecular processes is likely to unravel further valuable disease information and may help to decipher the pathogenesis of ALS. In this review, we provide an overview of radiotracers that have already been applied in ALS and discuss possible novel targets for in vivo imaging of various pathogenic processes underlying ALS onset and progression.


Enantioselective monoreduction of 2-alkyl-1,3-diketones mediated by chiral ruthenium catalysts. dynamic kinetic resolution.
The reduction of 2-alkyl-1,3-diketones using (R,R)- or (S,S)-RuCl[N-(tosyl)-1,2-diphenylethylenediamine](p-cymene) in the presence of formic acid and triethylamine affords syn-2-alkyl-3-hydroxy ketones as the major products with high enantioselectivity. [reaction: see text]


Dysregulation of the mammalian target of rapamycin pathway in chromophobe renal cell carcinomas.
Targeted therapy in advanced clear cell renal cell carcinomas (RCC) is now an established modality. The latter is in stark contrast to non-clear cell subtypes. We explored the translational support for the use of antagonists of the mammalian target of rapamycin (mTOR) and the vascular endothelial growth factor pathways in chromophobe RCC. The immunoexpression of PTEN, phos-AKT, phosphorylated S6 (phos-S6), 4EBP1, p27, c-MYC, and HIF-1α was evaluated in 33 patients with chromophobe RCC who were treated by partial/radical nephrectomy without adjuvant therapy. PTEN was lower in tumor than in normal kidney (P<.001), and loss of PTEN expression was found in 67% of the tumors. In tumor tissues, phos-S6 and 4EBP1 were higher than in normal kidney (P≤.005). Conversely, scores of p27 were lower in tumor than in normal kidney (P<.001). Finally, scores of phos-AKT, c-MYC, and HIF-1α were not significantly different in tumor and in normal kidney. Overall mortality and cancer-specific mortality were 9% and 0%, respectively. Multifocal tumors had higher levels of PTEN, phos-AKT, and HIF-1α (P≤.01). None of the clinicopathologic variables (age, ethnicity, gender, pT stage, tumor size, multifocality, and positive surgical margins) was associated with outcome. Similarly, none of the tested biomarkers predicted overall mortality, either in unadjusted or adjusted Cox regression models. In summary, our study provides new evidence of dysregulation of the mTOR pathway in chromophobe RCC. Immunohistochemistry for mTOR pathway and hypoxia-induced pathway members lacked prognostic significance in our cohort.


Paediatric laryngeal tuberculosis presenting with stridor.
A rare case of laryngeal tuberculosis in a 15-month-old Indian child is described. The unusual mode of presentation with stridor, suspicious radiological signs and papillomatous nature of the laryngeal lesion are highlighted.


Effects of ethanol hangover on the operant self-administration of cocaine in rats.
To assess the interaction of experimentally induced ethanol hangover and cocaine self-administration, rats maintained to self-administer cocaine (0.5 mg/kg/inj) were given either saline or 2 or 4 g/kg ethanol (10% w/v, IP) 15 h prior to cocaine access (dose range tested 0.03-1.0 mg/kg/inj). Cocaine was shown to be dose-dependently self-administered in a significant inverted U-shaped function. EtOH hangover had a significant effect on the dose-dependent effects of cocaine, resulting in a general flattening of the inverted U-shaped function with increasing intensity of hangover. A significant dose-dependent reduction in the number of reinforcer deliveries occurred at the peak of the cocaine dose-response function (0.06 mg/kg/inj) following the 2 and 4 g/kg EtOH pretreatment doses when compared to saline pretreatment. These data suggest that hangover may alter the ability for moderate doses of cocaine to "prime" and maintain stable self-administration behavior.


Biologic effect of 5-fluoro-2'-deoxyuridine incorporation in L1210 deoxyribonucleic acid.
Recent studies have demonstrated that 5-fluoro-2'-deoxyuridine (FdUrd) misincorporates in eukaryotic DNA. We have extended these findings and studied the relationship between DNA incorporation of FdUrd and cell lethality. This required an approach that would distinguish the DNA and RNA effects of this agent. The specific effect of (FdUrd)DNA formation on L1210 clonogenic survival was, therefore, monitored using deoxyuridine (dUrd) to inhibit the metabolism and subsequent incorporation of FdUrd into RNA. The results demonstrated that misincorporation of FdUrd in DNA resulted in lethal cellular events. These observations suggest a new mechanism of action for this cytotoxic and mutagenic agent.


In vitro and in vivo survival of bisected sheep embryos derived from frozen-thawed unsorted, and frozen-thawed sex-sorted and refrozen-thawed ram spermatozoa.
Ovine IVP embryos were derived from frozen-thawed unsorted and frozen-thawed sex-sorted spermatozoa that had been refrozen and thawed. The embryos were bisected and cultured in vitro, or transferred to recipient ewes to determine their survival in vitro and in vivo. Oocyte progression to the blastocyst stage was similar for unsorted (97/232, 41.8%) and sex-sorted spermatozoa (113/286, 39.5%; P > 0.05). Embryo survival in vitro post-bisection was similar for demi-embryos derived from unsorted and sex-sorted sperm, and embryos bisected at the blastocyst and expanded blastocyst stage (P > 0.05). A higher proportion of recipient ewes were pregnant at Day 63 after transfer of two intact embryos derived from unsorted (17/21, 80.9%) than two demi-embryos derived from unsorted (5/15, 33.3%) or sex-sorted spermatozoa (7/17, 41.2%). The number of fetuses per original embryo at Day 63 did not differ among groups (unsorted intact: 23/42, 54.8%; unsorted demi: 7/15, 46.7%; sex-sorted demi: 10/17, 58.8%) and twin pregnancies were observed in all groups. Embryo survival to term was high, and was not significantly different among intact (unsorted: 22/42, 52.4%) and demi-embryos (unsorted: 4/15, 26.7%; sex-sorted spermatozoa: 7/17, 41.2%; P > 0.05). Dizygotic twins (n = 6 sets) were born after the transfer of two intact embryos derived from unsorted spermatozoa, but only singleton lambs resulted from the transfer of demi-embryos. In conclusion, bisected IVP embryos successfully developed into morphologically normal lambs. However, embryo survival to term was neither increased nor decreased by embryo bisection.


Global burden of blood-pressure-related disease, 2001.
Few studies have assessed the extent and distribution of the blood-pressure burden worldwide. The aim of this study was to quantify the global burden of disease related to high blood pressure. Worldwide burden of disease attributable to high blood pressure (> or =115 mm Hg systolic) was estimated for groups according to age (> or =30 years), sex, and World Bank region in the year 2001. Population impact fractions were calculated with data for mean systolic blood pressure, burden of deaths and disability-adjusted life years (DALYs), and relative risk corrected for regression dilution bias. Worldwide, 7.6 million premature deaths (about 13.5% of the global total) and 92 million DALYs (6.0% of the global total) were attributed to high blood pressure. About 54% of stroke and 47% of ischaemic heart disease worldwide were attributable to high blood pressure. About half this burden was in people with hypertension; the remainder was in those with lesser degrees of high blood pressure. Overall, about 80% of the attributable burden occurred in low-income and middle-income economies, and over half occurred in people aged 45-69 years. Most of the disease burden caused by high blood pressure is borne by low-income and middle-income countries, by people in middle age, and by people with prehypertension. Prevention and treatment strategies restricted to individuals with hypertension will miss much blood-pressure-related disease.


Fertility rate and subsequent pregnancy outcomes after conservative surgical techniques in postpartum hemorrhage: 15 years of literature.
To investigate the most appropriate surgical technique for optimizing hemostasis and preservation of subsequent fertility after postpartum hemorrhage (PPH). Systematic review of the literature. Not applicable. None. Review of MEDLINE, EMBASE, ScienceDirect, and the Cochrane Library. Comparison of the effectiveness of conservative surgical techniques, separately or together, with respect to success rate (ability to stop bleeding and preserve the uterus), fertility rate (subsequent pregnancies or the return of regular menstrual cycles), complication rate of the procedure, and the outcomes of subsequent pregnancies in terms of type of delivery and eventual delivery complications. Compressive sutures and vessel embolization may be considered life-saving procedures by achieving the best hemostatic efficacy. Data on restoration of menses and pregnancy rates after these procedures are limited by short-term follow-up and by the paucity of studies, especially for vascular ligation. Pelvic vessel embolization and compressive sutures are associated with high rates of restoration of regular menses and successive pregnancies, even if the former is burdened by an increased rate of placental disorders and fetal growth restriction and the latter by an increased risk of cesarean deliveries and PPH recurrence. Randomized trials would be desirable to define the best management of PPH.


Randomized Controlled Trial for Paclitaxel-coated Balloon versus Plain Balloon Angioplasty in Dysfunctional Hemodialysis Vascular Access: 12-month Outcome from a Nonsponsored Trial.
Plain balloon angioplasty is regarded as the mainstay of treatment for failing vascular access with high success rate, but the poor treatment durability creates significant workload and increases patient morbidity. The study aims to compare target lesion primary patency rate at 12 months between paclitaxel-coated balloon (DCB) versus plain old balloon angioplasty (POBA) for treatment of dysfunctional vascular access. This nonsponsored-randomized trial enrolled 40 patients with dysfunctional dialysis access at a single center. Patients were randomized into In.Pact Admiral Paclitaxel DCB or POBA after lesion crossing regardless of lesion type. Patients are followed up under surveillance protocol. Patients, hemodialysis staff, and sonographer are blinded to the treatment arms. Twelve-month primary patency rate in both arms are evaluated. 40 patients were recruited since June 2016 and were allocated to the DCB or POBA group. The mean age is 58 and 57 years with comparable demographic parameters. The locations of target lesion were comparable in both groups (juxta and arteriovenous anastomosis, cannulation site, and fistula/graft), with similar mean target lesion stenosis 69.8 +/- 15.8% for DCB and 69.5 +/- 13.6% for POBA (P = 0.95), and the lesion length for DCB is 45.8 +/- 38.4 mm and 50.2 +/- 33.5 mm for POBA (P = 0.70). Patients in DCB performed significantly better in terms of primary patency at 6 months 85% versus 55% (P = 0.007). The superiority in primary patency in DCB group exists at 12 months 65% versus 30% (P = 0.007). Paclitaxel balloon angioplasty approach provides significant better primary patency in dysfunctional arteriovenous access at 12 months in our nonsponsored-randomized trial.


The association between perioperative frailty and ability to complete a web-based geriatric assessment among older adults with cancer.
The aim of this study was to assess the degree to which patient frailty is associated with both need for assistance and time required to complete the eRFA, a web-based GA tool. We retrospectively identified patients who underwent surgery for cancer from 2015 to 2020, had a hospital length of stay ≥1 day, and completed the eRFA before surgery. Frailty was assessed using two methods: the MSK-FI (score 0-11) and the AGD (score 0-13). Time to complete the eRFA was automatically recorded by a web-based tool; assistance with eRFA completion was self-reported by the patient. In total, 3456 patients were included (median age, 78 years). Overall, 58% of surveys were completed without assistance, 30% were completed with assistance, and 12% were completed by someone other than the patient. Younger age (median age: without assistance, 77 years; with assistance, 80 years; completed by someone else, 80 years) and lower frailty score (median AGD: 4, 6, and 8, respectively; median MSK-FI: 2, 3, and 3, respectively) were associated with independency (all p < 0.001). Higher frailty score was associated with longer time to complete the eRFA (all nonlinear association p < 0.001). Frail patients are more likely to benefit from completion of GA to determine appropriate treatment. Given that not all cancer patients have a caregiver who can assist completing a digital questionnaire, innovative solutions are needed to help frail patients complete the eRFA without assistance.