Haemostatic management for oral surgery in patients supported with left ventricular assist device--a preliminary retrospective study.
We investigated haemostatic management, frequency of postoperative bleeding, and prognosis of patients who had left ventricular assist devices, and who were having oral surgical procedures between April 2002 and March 2014, to identify risk factors for bleeding and find out which were the best methods of haemostasis. Medical records were examined retrospectively and we recorded details of the patients, and frequency of bleeding together with factors associated with it. Twenty-nine patients had 39 oral operations, and there were 17 bleeds (44%). The first procedure for each patient was used for statistical calculations. Duration of bleeding tended to be longer for patients with implantable devices (median (interquartile range, IQR) 12.0 (3-18) days) than for those with extracorporeal devices (median (IQR) 3.0 (1-4) days; p=0.079). There was a significantly greater difference in prothrombin time-international normalised ratio (PT-INR) before and after operation in patients who bled, whose median (range) was 0.85 (0.2-1.81), than in those who did not (median (IQR) 0.16 (-0.09-0.31) (p=0.015). There were moderate correlations with postoperative bleeding were seen for the difference between preoperative and postoperative PT-INR (r=0.479, p=0.012) and PT-INR value when bleeding (r=0.407, p=0.035). In conclusion, postoperative bleeding occurred after oral operations in 17/29 patients with left ventricular assist devices by a median (IQR) of 0.85 (0.2-1.81) of the preoperative value.


Response to Pulp Sensibility Tests after Full Pulpotomy in Permanent Mandibular Teeth with Symptomatic Irreversible Pulpitis: A Retrospective Data Analysis.
This retrospective study analyzed the 12-month pulp sensibility (cold and electric) test response after mineral trioxide aggregate (MTA) full pulpotomy in mature permanent teeth with symptomatic irreversible pulpitis. The records of 120 subjects from 3 completed and 1 ongoing clinical study on MTA full pulpotomy were retrieved. Ninety-six first and second mandibular molar teeth with a diagnosis of symptomatic irreversible pulpitis that underwent a single-visit MTA full pulpotomy and had completed a 12-month clinical, radiographic, and pulp sensibility (cold and electric) test follow-up were included. The data were analyzed using the Fisher exact test, the Pearson chi-square test, and the McNemar test. The significance level was predetermined at P < .05. A higher percentage of teeth (94.7%) responded to the electric pulp test in comparison with the cold test (13.5%) (P < .05). Sex-based responses to the electric pulp test (P > .05) and the cold test were similar (P > .05). The age-based response was similar for the electric pulp test (P > .05) but was significant for the cold test (P < .05). The tooth quadrant (left and right), the tooth (mandibular first and second molar), and the location of restoration (proximal or occlusal) did not influence the response of either the electric pulp test (P > .05) or the cold test (P > .05). At the 1-year follow-up, all the teeth that were classified as clinically and radiographically successful responded to the electric pulp test; however, only 13 teeth responded to the cold test (P = .00). The majority (94.7%) of the teeth that underwent MTA full pulpotomy responded to the electric pulp test at a 1-year time interval.


Effect of PCB 126 on aryl hydrocarbon receptor 1 (AHR1) and AHR1 nuclear translocator 1 (ARNT1) mRNA expression and CYP1 monooxygenase activity in chicken (Gallus domesticus) ovarian follicles.
The aim of the experiment was to study the in vitro effect of 3,3',4,4',5-pentachlorobiphenyl (PCB 126; a coplanar PCB congener) on aryl hydrocarbon receptor (AHR1) and AHR1 nuclear translocator (ARNT1) mRNA expression and the activity of CYP1 family monooxygenases in chicken ovarian follicles. White (1-4 mm) and yellowish (4-8 mm) prehierarchical follicles as well as fragments of the theca and granulosa layers of the 3 largest preovulatory follicles (F3-F1) were incubated in a medium supplemented with 0 (control group), 1, 10 or 100 nM PCB 126. The incubation was carried out for 6 h or 24 h for determination of mRNA expression of AHR1 and ARNT1 genes (real-time qPCR) and CYP1 monooxygenase activity (EROD and MROD fluorometric assays), respectively. It was found that chicken ovarian follicles express mRNA of AHR1 and ARNT1 genes. A modulatory effect of PCB 126 on AHR1 and ARNT1 expression depended not only on the biphenyl concentration but also on the follicular layer and the maturational state of the follicle. EROD and MROD activities appeared predominantly in the granulosa layer of the yellow preovulatory follicles. PCB 126 induced these activities in a dose-dependent manner in all ovarian follicles. The obtained results suggest that ovarian follicles, especially the granulosa layer, are involved in the detoxification process of PCBs in the laying hen. Taking this finding into consideration it can be suggested that the granulosa layer of the yellow hierarchical follicles plays a key role in the protective mechanism which reduces the amount of transferred dioxin-like compounds into the yolk of the oocyte.


Caring for the individual.
People do not lose their individuality as they grow older. With the use of a moving case history Carolyn Best describes how a lifetime's experiences and personality should be taken into account when dealing with older people.


Rapid isolation and characterization of native mouse complement components C3 and C5.
A rapid, 1 day procedure for the purification of mouse complement factors C3 and C5 is described. The method is based on fractionated precipitation by polyethylene glycol 6000, followed by Mono Q anion exchange chromatography on a system for fast protein liquid chromatography (FPLC). For C3 isolation, an additional FPLC separation step using Superose 12 (gel filtration) was used. C3 was purified 71-fold with a yield of 32% as measured by biological activity; the preparation contained no detectable contaminants as judged by SDS-PAGE. A comparable procedure for the isolation of C5 resulted in a preparation with a considerable contamination which could be easily removed by affinity chromatography using antibodies directed against these contaminants. With this combined procedure C5 was purified 536-fold with a yield of 28% based on biological activity. SDS-polyacrylamide gel electrophoresis revealed that mouse C3 and C5 had apparent Mrs of 170,000 and 190,000, respectively. Under reducing conditions the alpha and beta chains showed Mrs of 107,000 and 62,000 for C3, and 104,000 and 85,000 for C5.


Effects of magnesium pyrophosphate on mechanical properties of skinned smooth muscle from the guinea pig taenia coli.
Effects of the non-hydrolyzable nucleotide analogue magnesium pyrophosphate (MgPPi) on cross-bridge properties were investigated in skinned smooth muscle of the guinea pig Taenia coli. A "high" rigor state was obtained by removing MgATP at the plateau of an active contraction. Rigor force decayed slowly towards an apparent plateau of approximately 25-35% of maximal active force. MgPPi markedly increased the rate of force decay. The initial rate of the force decay depended on [MgPPi] and could be described by the Michaelis-Menten equation with a dissociation constant of 1.6 mM. The decay was irreversible amounting to approximately 50% of the rigor force. Stiffness decreased by 20%, suggesting that the major part of the cross-bridges were still attached. The results can be interpreted as "slippage" of PPi-cross-bridges to positions of lower strain. The initial rate of MgPPi-induced force decay decreased with decreasing ionic strength in the range 45-150 mM and was approximately 25% lower in thiophosphorylated fibers. MgADP inhibited the MgPPi-induced force decay with an apparent Ki of 2 microM. The apparent Km of MgATP for the maximal shortening velocity in thiophosphorylated fibers was 32 microM. This low Km of MgATP suggests that steps other than MgATP-induced detachment are responsible for the low shortening velocity in smooth muscle. No effects were observed of 4 mM MgPPi on the force-velocity relation, suggesting that cross-bridges with bound MgPPi do not constitute an internal load or that binding of MgPPi is weaker in negatively strained cross-bridges during shortening.


Otoadmittance in normal subjects.
Otoadmittance audiometry was performed on a group of young subjects (18-30 years old) with normal hearing. Mean values and standard deviations for static admittance, conductance and susceptance were computed on the basis of the point of maximum compliance, as well as the point of zero cross (drum-free position). In addition, the values of curve width for conductance and susceptance, middle ear pressure and the threshold of the acoustic reflex for pure tones and interrupted tones were evaluated. Subjects presenting an abnormality of the tympanic membrane were studied as a separate group. The results obtained in this study were compared with those reported in the literature.


Detection and elimination profile of cathinone in equine after norephedrine (Propalin®) administration using a validated liquid chromatography-tandem mass spectrometry method.
Cathinone is the principal psychostimulant present in the leaves of khat shrub, which are widely used in East Africa and the Arab peninsula as an amphetamine-like stimulant. Cathinone readily undergoes metabolism in vivo to form less potent cathine and norephedrine as the metabolites. However, the presence of cathine and norephedrine in biological fluids cannot be used as an indicator of cathinone administration. The metabolism of pseudoephedrine and ephedrine, commonly used in cold and allergy medications, also produces cathine and norephedrine, respectively, as the metabolites. Besides, cathine and norephedrine may also originate from the ingestion of nutritional supplemental products containing extracts of Ephedra species. In Canada, ephedrine and norephedrine are available for veterinary use, whereas cathinone is not approved for human or veterinary use. In this article, the detection of cathinone in equine after administration of norephedrine is reported. To the best of our knowledge, this is the first such report in any species where administration of norephedrine or ephedrine generates cathinone as the metabolite. This observation is quite significant, because in equine detection of cathinone in biological fluids could be due to administration of the potent stimulant cathinone or the nonpotent stimulant norephedrine. A single oral dose of 450 mg norephedrine was administered to four Standardbred mares. Plasma and urine samples were collected up to 120 h after administration. The amount of cathinone and norephedrine detected in post administration samples was quantified using a highly sensitive, specific, and validated liquid chromatography-tandem mass spectrometry method. Using these results, we constructed elimination profiles for cathinone and norephedrine in equine plasma and urine. A mechanism that generates a geminal diol as an intermediate is postulated for this in vivo conversion of norephedrine to cathinone. Cathinone was also detected in samples collected after a single intramuscular administration of 200 mg ephedrine and oral administration of 300 mg ephedrine in equine.


Lumbar spinal fluid collections in children treated with intrathecal chemotherapy: elevated CSF protein as a diagnostic clue.
Subdural fluid collections can interfere with the effective intrathecal administration of chemotherapy by lumbar puncture (LP). We detected this complication in six children who were treated for acute lymphoblastic leukemia (ALL) and presented with an elevated protein concentration of the cerebrospinal fluid (CSF) during routine LP. Contrary to expectation the lumbar fluid collections persisted in two cases and in one case required the insertion of an Ommaya reservoir to continue intrathecal chemotherapy. Awareness and detection of this complication by imaging is important because of its potential to interfere with effective CNS-directed chemotherapy of ALL.


Pericapillary rosettes in the human spinal cord.
We have found large eosinophilic bodies in the pericapillary regions of the gray and white matter in the human spinal cord. These are entirely different from the previously reported pericapillary inclusion bodies (PIB). We have designated them pericapillary rosettes (PR), since they consist of clusters of round or ovoid structures of various sizes which form rosettes around the transversely sectioned capillaries. Positive staining with silver impregnation and anti-neurofilament antibody, the presence of the myelin around the bodies and the accumulation of neurofilaments within them indicate that axonal swelling is associated with the formation of PR. These bodies are not observed in individuals aged less than 30 years, and afterwards they increase in proportion to age. Over the age of 80, they are almost always found in the spinal cord, particularly in the gray matter of both the anterior and posterior horns at the thoracic and lumbar levels. Thus, the development of PR is closely related to the aging process.


Metabolism of (-)-cis- and (-)-trans-rose oxide by cytochrome P450 enzymes in human liver microsomes.
The in vitro metabolism of (-)-cis- and (-)-trans-rose oxide was investigated using human liver microsomes and recombinant cytochrome P450 (P450 or CYP) enzymes for the first time. Both isomers of rose oxide were incubated with human liver microsomes, and the formation of the respective 9-oxidized metabolite were determined using gas chromatography-mass spectrometry (GC-MS). Of 11 different recombinant human P450 enzymes used, CYP2B6 and CYP2C19 were the primary enzymes catalysing the metabolism of (-)-cis- and (-)-trans-rose oxide. CYP1A2 also efficiently oxidized (-)-cis-rose oxide at the 9-position but not (-)-trans-rose oxide. α-Naphthoflavone (a selective CYP1A2 inhibitor), thioTEPA (a CYP2B6 inhibitor) and anti-CYP2B6 antibody inhibited (-)-cis-rose oxide 9-hydroxylation catalysed by human liver microsomes. On the other hand, the metabolism of (-)-trans-rose oxide was suppressed by thioTEPA and anti-CYP2B6 at a significant level in human liver microsomes. However, omeprazole (a CYP2C19 inhibitor) had no significant effects on the metabolism of both isomers of rose oxide. Using microsomal preparations from nine different human liver samples, (-)-9-hydroxy-cis- and (-)-9-hydroxy-trans-rose oxide formations correlated with (S)-mephenytoin N-demethylase activity (CYP2B6 marker activity). These results suggest that CYP2B6 plays important roles in the metabolism of (-)-cis- and (-)-trans-rose oxide in human liver microsomes.


Hepatic decompensation in antiretroviral-treated patients co-infected with HIV and hepatitis C virus compared with hepatitis C virus-monoinfected patients: a cohort study.
The incidence and determinants of hepatic decompensation have been incompletely examined among patients co-infected with HIV and hepatitis C virus (HCV) in the antiretroviral therapy (ART) era, and few studies have compared outcome rates with those of patients with chronic HCV alone. To compare the incidence of hepatic decompensation between antiretroviral-treated patients co-infected with HIV and HCV and HCV-monoinfected patients and to evaluate factors associated with decompensation among co-infected patients receiving ART. Retrospective cohort study. Veterans Health Administration. 4280 co-infected patients who initiated ART and 6079 HCV-monoinfected patients receiving care between 1997 and 2010. All patients had detectable HCV RNA and were HCV treatment-naive. Incident hepatic decompensation, determined by diagnoses of ascites, spontaneous bacterial peritonitis, or esophageal variceal hemorrhage. The incidence of hepatic decompensation was greater among co-infected than monoinfected patients (7.4% vs. 4.8% at 10 years; P < 0.001). Compared with HCV-monoinfected patients, co-infected patients had a higher rate of hepatic decompensation (hazard ratio [HR] accounting for competing risks, 1.56 [95% CI, 1.31 to 1.86]). Co-infected patients who maintained HIV RNA levels less than 1000 copies/mL still had higher rates of decompensation than HCV-monoinfected patients (HR, 1.44 [CI, 1.05 to 1.99]). Baseline advanced hepatic fibrosis (FIB-4 score >3.25) (HR, 5.45 [CI, 3.79 to 7.84]), baseline hemoglobin level less than 100 g/L (HR, 2.24 [CI, 1.20 to 4.20]), diabetes mellitus (HR, 1.88 [CI, 1.38 to 2.56]), and nonblack race (HR, 2.12 [CI, 1.65 to 2.72]) were each associated with higher rates of decompensation among co-infected patients. Observational study of predominantly male patients. Despite receiving ART, patients co-infected with HIV and HCV had higher rates of hepatic decompensation than HCV-monoinfected patients. Rates of decompensation were higher for co-infected patients with advanced liver fibrosis, severe anemia, diabetes, and nonblack race. National Institutes of Health.


Epithelioid angiomyolipoma of the kidney: pathological features and clinical outcome in a series of consecutively resected tumors.
The 2004 World Health Organization classification of tumors defines epithelioid angiomyolipoma of kidney as a potentially malignant mesenchymal neoplasm with reported metastasis in approximately one-third of the cases. However, this conclusion was based primarily on individual case reports and small retrospective series. More recently reported larger series have shown varying results. We reviewed 437 consecutive renal angiomyolipomas with primary resection at three tertiary-care institutions with high nephrectomy volumes. Only tumors showing >80% epithelioid histology were included in this study. Tumors resected elsewhere and reviewed in consultation were not included. Twenty of these 437 (4.6%) were classified as epithelioid angiomyolipoma. The female to male ratio was 11:9, mean age 49.7 (range, 30-80) years, and mean tumor size 8.7 (range, 1-25) cm. Microscopic tumor necrosis was present in 10 (50%) tumors and mitotic activity (range, <1-5/10 high power fields) in 8 (40%); atypical mitoses were seen in only 1 (5%) tumor. Pleomorphic ganglion-like or multinucleated giant cells were seen in 18 (90%) tumors. With a mean follow-up of 82.5 (range, 1-356) months, seventeen patients were alive with no-evidence-of-disease at the time of last follow-up; two patients died of unrelated causes with no-evidence-of-disease, and one patient (5%) developed distant metastases. Our data, based on consecutively resected angiomyolipomas with long clinical follow-up, suggests that epithelioid angiomyolipomas constitute a small proportion of all angiomyolipomas, and the rate of aggressive behavior among epithelioid angiomyolipomas, even when showing morphologic features previously reported to portend aggressive clinical behavior, is very low.


Thiophene and butadiene-thiolate complexes of molybdenum: observations relevant to the mechanism of hydrodesulfurization.
Mo(PMe3)6 reacts with thiophene to give the eta5-thiophene complex (eta5-C4H4S)Mo(PMe3)3 and the eta5-butadiene-thiolate complex (eta5-C4H5S)Mo(PMe3)2(eta2-CH2PMe2), which are the first examples of (i) eta5-thiophene coordination and (ii) C-S cleavage and hydrogenation by a molybdenum compound. Deuterium labeling studies suggest that the hydrogenation of thiophene may involve an alkylidene intermediate, an observation that has ramifications for the mechanisms of hydrodesulfurization.


Philosophy, medicine and healthcare: insights from the Italian experience.
To contribute to our understanding of the relationship between philosophical ideas and medical and healthcare models. A diachronic analysis is put in place in order to evaluate, from an innovative perspective, the influence over the centuries on medical and healthcare models of two philosophical concepts, particularly relevant for health: how Man perceives his identity and how he relates to Nature. Five epochs are identified--the Archaic Age, Classical Antiquity, the Middle Ages, the Modern Age, the 'Postmodern' Era--which can be seen, à la Foucault, as 'fragments between philosophical fractures'. From a historical background perspective, up to the early 1900s progress in medical and healthcare models has moved on a par with the evolution of philosophical debate. Following the Second World War, the Health Service started a series of reforms, provoked by anti-positivistic philosophical transformations. The three main reforms carried out however failed and the medical establishment remained anchored to a mechanical, reductionist approach, perfectly in line with the bureaucratic stance of the administrators. In this context, future scenarios are delineated and an anthropo-ecological model is proposed to re-align philosophy, medicine and health care.


Fungicide Management of Pasmo Disease of Flax and Sensitivity of Septoria linicola to Pyraclostrobin and Fluxapyroxad.
Among the diseases that have the potential to cause damage to flax (Linum usitatissimum L.) every year, the fungal disease pasmo, caused by Septoria linicola, is the most important. Fungicide application and a diverse crop rotation are the most important strategies to control this disease because there is little variation in resistance among flax cultivars. However, few fungicide products are available to flax growers. Field studies were conducted at four locations in Western Canada in 2014, 2015, and 2016 to determine the effect of two fungicide active ingredients applied singly and in combination: pyraclostrobin, fluxapyroxad, and fluxapyroxad + pyraclostrobin; and two application timings (early-flower, mid-flower, and at both stages) on pasmo disease severity, seed yield, and quality of flaxseed. The results indicated that among the three fungicide treatments, both pyraclostrobin and fluxapyroxad + pyraclostrobin controlled pasmo effectively; however, fluxapyroxad + pyraclostrobin was the most beneficial to improve the quality and quantity of the seed for most of the site-years. Disease severity in the fungicide-free control was 70%, and application of fluxapyroxad + pyraclostrobin decreased disease severity to 18%, followed by pyraclostrobin (23%) and fluxapyroxad (48%). Application of fluxapyroxad + pyraclostrobin also improved seed yield to 2,562 kg ha-1 compared with 1,874 kg ha-1 for the fungicide-free control, followed by pyraclostrobin (2,391 kg ha-1) and fluxapyroxad (2,340 kg ha-1). Fungicide application at early and mid-flowering stage had the same effects on disease severity and seed yield; however, seed quality was improved more when fungicide was applied at mid-flowering stage. Continuous use of the same fungicide may result in the development of fungicide insensitivity in the pathogen population. Thus, sensitivity of S. linicola isolates to pyraclostrobin and fluxapyroxad fungicides was determined by the spore germination and microtiter assay methods. Fungicide insensitivity was not detected among the 73 isolates of S. linicola tested against either of these fungicides.


Demonstration of penetrating intramyocardial coronary arteries with high-frequency transthoracic echocardiography and Doppler in human subjects.
Characterization of intramyocardial coronary artery flow may offer insight into the spectrum of coronary physiology. The purposes of this study were to test the feasibility of detection and measurement of intramyocardial coronary artery flow by using high-frequency transthoracic ultrasound and to evaluate the hemodynamic and morphologic differences in intramyocardial coronary arteries between patients with echocardiographically normal myocardium and patients with diseased myocardium. In 116 subjects (age 58 +/- 19 years; male:female 67:49; 58 normal [control subjects], 40 with left ventricular hypertrophy [LVH], 18 with systolic left ventricular dysfunction [cardiomyopathy, CM]), we examined the myocardium just beneath the apical impulse window at a depth of 3 to 5 cm by using a 6- or 7-MHz centerline frequency transducer. For color Doppler examination, a special preset coronary program with a low Nyquist limit (12 to 20 cm) was used. After obtaining linear color signals, the width and length, peak and mean diastolic pulsed Doppler flow velocities, diastolic velocity time integrals, and percent duration of diastolic Doppler flow were measured. The number of linear color flow signals per square centimeter was counted in 520 different cardiac cycles, and the angles formed by their inner curvature was measured with a graduated protractor. We identified color flow Doppler signals within the myocardium having a mean width of 1.1 +/- 0.4 mm and flow direction from epicardium to endocardium in 104 (89. 7%) subjects and spectral Doppler signals in 74 (63.8%) subjects. In 33 (45.8%) subjects, only diastolic flow was detected and in 39 (54. 2%) subjects, diastolic flow was predominant with systolic reversal. Peak and mean diastolic flow velocities and velocity time integrals of spectral Doppler signal in control subjects were 26.2 +/- 8.6 cm/s, 19.0 +/- 6.3 cm/s, and 9.5 +/- 2.7 cm, respectively. There were no significant differences in width and density of linear color flow signals among the 3 groups. The color flow signals in the LVH and CM groups had a narrower angle of inner curvature (P <.005 for LVH, P <.05 for CM, respectively), and their spectral Doppler signals showed significantly higher diastolic velocities and shorter diastolic flow duration (P <.005 for LVH, P <.05 for CM, respectively) than those of the control subjects. Detection and measurement of flow signals consistent with penetrating intramyocardial coronary arteries are feasible in a high percentage of subjects by use of high-frequency transthoracic ultrasound. The findings in patients with LVH and CM suggest that there are distinct hemodynamic and morphologic departures from those with normal left ventricles that may be a consequence of disordered myocardial perfusion in diseased myocardium.


Alfalfa Weevil (Coleoptera: Curculionidae) Resistance to Lambda-cyhalothrin in the Western United States.
Forage alfalfa (Medicago sativa L. [Fabales: Fabaceae]) is a key agricultural commodity of the western region of the United States. The key insect pest of alfalfa, Hypera postica Gyllenhal (Coleoptera: Curculionidae), has developed resistance to the most common class of insecticide used to manage its damage. Alfalfa weevil samples from 71 commercial alfalfa fields located in Arizona, California, Montana, Oregon, Washington, and Wyoming were assayed for susceptibility to lambda-cyhalothrin during 2020-2022 using a laboratory concentration-response assay. Seventeen field sites representing all six states were highly resistant to lambda-cyhalothrin (resistance ratios > 79.6) and bioassay mortality often did not exceed 50% even at the highest concentration tested (3.30 µg/cm2 in 2020 and 10.00 µg/cm2 in 2021-2022). Field sites assayed with more than one pyrethroid active ingredient indicated likely cross-resistance between lambda-cyhalothrin and zeta-cypermethrin (type II pyrethroids) and variable and/or limited potential cross-resistance to permethrin (type I pyrethroid). Thirty-two field sites representing five states were susceptible to lambda-cyhalothrin (resistance ratios ranging from 1 to 20). While resistance is widespread, integrated resistance management strategies including rotating mode of action groups, applying chemical control tactics only when economic thresholds have been met, and utilizing cultural control tactics can be employed to slow the further development of resistance.


Evaluating the impact of COVID-19 on cancer declarations in Quebec, Canada.
COVID-19 affected healthcare worldwide, limited access to healthcare, and delayed cancer screening and diagnosis. In this study, the effect of the first year of COVID-19 was determined on cancer diagnoses in the province of Quebec, Canada. Data were collected from the 13 Quebec Cancer Registry health institutions. Newly diagnosed cancer declarations in the first year of the COVID-19 (April 2020-March 2021) were compared with the reference periods (averages of 3 previous years). The main focus was on four leading cancers: lung, prostate, colorectal, and breast cancers. Generalized regression models with a poisson approximation and interrupted time series (ITS) analysis were used. Underestimated cases were presented in terms of relative risk (RR) and 95% confidence intervals (CI). The changes in the stage-specific counts were also assessed in each of the four cancers. Results were illustrated separately for the first 4 months of the pandemic (first wave). This study estimated an overall under-reporting of 15.3% (29,019 vs. 24,584) of declarations. This under-reporting was evident across all age groups above 35 years (p < 0.0001), four primary cancers (p < 0.0001), all stages of cancers (p < 0.0001), and both sexes (p < 0.0001). Based on the relative risks, stage-specific lung cancer counts were underestimated by 5%-34% in the first wave (0%-11% in the first year), prostate cancer by 16%-46% in the first wave (0%-25% in the first year), colorectal cancer 15%-45% in the first wave (0%-24% in the first year), and breast cancer 3%-45% in the first wave and (0%-28% in the first year). However, no stage-IV cancers were statically under-reported compared to the pre-pandemic era and not even in the first wave. Cancer diagnosis was underestimated due to the COVID-19 pandemic in the first year; this effect was more evident in the first phase of the pandemic in Quebec. Further research is required to determine the accurate burden of the disease in the long term.


Sulbactam-enhanced cytotoxicity of doxorubicin in breast cancer cells.
Multidrug resistance (MDR) is a major obstacle in breast cancer treatment. The predominant mechanism underlying MDR is an increase in the activity of adenosine triphosphate (ATP)-dependent drug efflux transporters. Sulbactam, a β-lactamase inhibitor, is generally combined with β-lactam antibiotics for treating bacterial infections. However, sulbactam alone can be used to treat Acinetobacter baumannii infections because it inhibits the expression of ATP-binding cassette (ABC) transporter proteins. This is the first study to report the effects of sulbactam on mammalian cells. We used the breast cancer cell lines as a model system to determine whether sulbactam affects cancer cells. The cell viabilities in the present of doxorubicin with or without sulbactam were measured by MTT assay. Protein identities and the changes in protein expression levels in the cells after sulbactam and doxorubicin treatment were determined using LC-MS/MS. Real-time reverse transcription polymerase chain reaction (real-time RT-PCR) was used to analyze the change in mRNA expression levels of ABC transporters after treatment of doxorubicin with or without sulbactam. The efflux of doxorubicin was measures by the doxorubicin efflux assay. MTT assay revealed that sulbactam enhanced the cytotoxicity of doxorubicin in breast cancer cells. The results of proteomics showed that ABC transporter proteins and proteins associated with the process of transcription and initiation of translation were reduced. The mRNA expression levels of ABC transporters were also decreased when treated with doxorubicin and sulbactam. The doxorubicin efflux assay showed that sulbactam treatment inhibited doxorubicin efflux. The combination of sulbactam and doxorubicin enhances the cytotoxicity of doxorubicin in the breast cancer cells by inhibiting the expression of ABC transporter proteins and proteins associated with the process of transcription and initiation of translation, and blocking the efflux of doxorubicin. Co-treatment of doxorubicin and sulbactam can be used in breast cancer treatment to decrease the prescribed dose of doxorubicin to avoid the adverse effects of doxorubicin.


Detection of glycated polypeptides in human aqueous humor by lectin-binding analysis.
The proteins from 30 samples of normal human aqueous humor were separated into major fractions by sodium dodecyl-sulfate polyacrylamide gel electrophoresis, transferred to nitrocellulose, and probed with lectins to characterize the glycated polypeptides. The lectins used were derived from Canavalia ensiformis (concanavalin-A), Phaseolus vulgaris (erythroagglutinin), Arachis hypogaea (peanut agglutinin), and Ulex europaeus agglutinin-I. Using this microanalytical technique, the glycated polypeptides in the aqueous humor were separated into nine major fractions with apparent molecular weights of 17, 41, 50, 55, 61, 77, 80, 120 and 151 kDa. The predominant oligosaccharides detected on these fractions were complex chains usually with sialic acid residues. The possible roles of the glycated polypeptides in the aqueous humor in health and disease are discussed. Our investigation of these molecules in human aqueous humor provides baseline data for a rapid diagnostic analysis of microsamples of this fluid obtained from diseased eyes.


A comparative techno-economic assessment of biochar production from different residue streams using conventional and microwave pyrolysis.
A comparative techno-economic assessment and Monte Carlo risk analysis is performed on large scale (3 tonne/h) biochar production plants for conventional (CPS) and microwave (MWP) pyrolysis using six different residue streams. Both plants are viable with minimum selling prices between € 436/tonne and € 863/tonne for CPS, and between € 564/tonne and € 979/tonne for MWP. The CPS is therefore more viable than MWP as it is a simpler and more established technology. However, a 20% biochar price increase due to higher biochar quality makes the MWP technology more viable. Nevertheless, the discounted payback period remains higher than this of CPS due to the increased CAPEX. Biochar price is the most important determinant of a biochar production plant's feasibility, motivating the need for economic and market research on biochar prices in function of biochar characteristics to reduce fluctuations in widely varying biochar prices.


Raising the bar on cat-friendly care.
A decade after publishing their first feline-friendly handling guidelines, International Cat Care and the International Society of Feline Medicine are poised to launch new guidance to help every veterinary professional to 'think cat'.


The effect of high-dose-rate brachytherapy dwell sequence on cell survival.
During a high-dose-rate (HDR) brachytherapy treatment, as the source steps through different dwell positions, the dose rate at any fixed point within the implant varies, because the distance between the point and the source continually changes. The instantaneous dose rate may vary by a factor of 100 or more, in a complex dwell position sequence. Two different points which receive the same total dose may have received that dose with a very different sequence of dose rates. Any effects due to the complex changes in dose rate, including the sequence of dose delivery, are ignored. We investigated the possible effects of the sequence in which dose is delivered at two different dose rates, representative of dose rates that occur during an HDR treatment. The target consisted of a tube containing a 1.0 cm(3) suspension of V-79 Chinese hamster cells. Two fixed source dwell positions near and far from the target, representing high and intermediate dose rates, were considered. The experiments compared the survival of V-79 cells exposed to an irradiation sequence consisting of either an HDR component followed by an intermediate-dose-rate component (H-I arm), or the reverse (I-H arm). In either case, the total dose and the dose ratio were the same, only the order in which the high- or intermediate-dose-rate components of the dose were delivered was changed. When the intermediate-dose-rate component was given before the HDR component, there was increased survival. All data pairs from three experiments showed greater survival for the I-H arm than the H-I arm by amounts ranging from 4% to 24%. Simple linear-quadratic models such as the Lea-Catchside model, which is invariant to time reversal of irradiation sequence, do not predict these results. These results suggest that targets receiving the same total dose of radiation during an HDR implant may not experience the same biological effect. This may be related to induced radioresistance or sublethal damage repair.


Listeria Infected Pseudoaneurysm of the Superficial Femoral Artery.
We present a unique case of listeria-infected pseudoaneurysm of the superficial femoral artery. Listeria monocytogenes, a gram positive, intracellular bacterium, is widespread in the environment. The manifestation of infection in humans ranges from mild gastroenteritis to life-threatening listeriosis. The incidence in the healthy population is low (0.7 per 100,000) but rises sharply in pregnancy, the immunocompromised and patients with malignancy. Listeria rarely causes mycotic aneurysm formation, with fewer than 40 cases reported in the literature. Further investigation revealed the patient to be diagnosed with a hepatocellular carcinoma. It is likely that the two pathologies were linked. Hence, we would advocate investigation for underlying malignancy in patients presenting with a mycotic aneurysm, particularly those resulting from Listeria infection.


Age-related brain trajectories in schizophrenia: a systematic review of structural MRI studies.
Using the Pubmed database, we performed a detailed literature search for structural magnetic resonance imaging studies on patients with schizophrenia, investigating the relationship between macroscopic and microscopic structural parameters and age, to delineate an age-related trajectory. Twenty-six studies were considered for the review, from January 2000 to June 2012. Research results are heterogeneous because of the multifactorial features of schizophrenia and the multiplicity of the methodological approaches adopted. Some areas, within the amygdala-hippocampus complex, which are affected early in life by schizophrenia, age in a physiological way. Other regions, such as the superior temporal gyrus, appear already impaired at the onset of symptoms, undergo a worsening in the acute phase but later stabilize, progressing physiologically over years. Finally, there are regions, such as the uncinate fasciculus, which are not altered early in life, but are affected around the onset of schizophrenia, with their impairment continuously worsening over time. Further extensive longitudinal studies are needed to understand the timing and the possible degenerative characteristics of structural impairment associated with schizophrenia.


Targeted inhibition of protein synthesis renders cancer cells vulnerable to apoptosis by unfolded protein response.
Cellular stress responses including the unfolded protein response (UPR) decide over the fate of an individual cell to ensure survival of the entire organism. During physiologic UPR counter-regulation, protective proteins are upregulated to prevent cell death. A similar strategy induces resistance to UPR in cancer. Therefore, we hypothesized that blocking protein synthesis following induction of UPR substantially enhances drug-induced apoptosis of malignant cells. In line, upregulation of the chaperone BiP was prevented by simultaneous arrest of protein synthesis in B cell malignancies. Cytotoxicity by immunotoxins-approved inhibitors of protein synthesis-was synergistically enhanced in combination with UPR-inducers in seven distinct hematologic and three solid tumor entities in vitro. Synergistic cell death depended on mitochondrial outer membrane permeabilization via BAK/BAX, which correlated with synergistic, IRE1α-dependent reduction of BID, accompanied by an additive fall of MCL-1. The strong synergy was reproduced in vivo against xenograft mouse models of mantle cell lymphoma, Burkitt's lymphoma, and patient-derived acute lymphoblastic leukemia. In contrast, synergy was absent in blood cells of healthy donors suggesting a tumor-specific vulnerability. Together, these data support clinical evaluation of blocking stress response counter-regulation using inhibitors of protein synthesis as a novel therapeutic strategy.


Thermodynamic stability of cisplatin-loaded polymeric micelles and the phenotypic switching of the tumor-associated macrophages induced by combination of cisplatin-loaded micelles and Anti-PD-L1 antibody.
Chemotherapy is an effective anti-tumor treatment. Some anticancer chemotherapeutic drugs can not only induce cell death, but can also elicit antitumor immune responses. Here, the stability of cisplatin-loaded polymeric micelles (CDDP-PMs), pharmacokinetic drug-drug interactions of CDDP and anti-PD-L1 antibody (aPD-L1) in vivo and the alteration of the tumor microenvironment by combination of CDDP-PMs and aPD-L1 were evaluated. CDDP-PMs were fabricated by coordinated complexation and self-assembly method for tumor targeting. CDDP-PMs with higher mass ratio of copolymer have higher thermodynamic stability. The pharmacokinetic study showed that the CDDP and aPD-L1 were metabolized and cleared by two different pathways, suggesting that there is almost no risk of potential drug interactions between CDDP and aPD-L1 and the combination of aPD-L1 and CDDP- PMs may not alter the tissue distribution of CDDP. In vivo antitumor test showed that the tumor growth inhibition rates of CDDP-PMs combined with medium-dose aPD-L1 and CDDP-PMs combined with high-dose PD-L1 were 89.41% and 93.16%, respectively and therapeutic efficacy can be further increased by increasing the dose of aPD-L1 in co-administration group. This therapeutic system by combining chemotherapy and immunotherapy further increases the link between them and holds great potential to offer better safety and antitumor efficacy profiles.


A new electrocardiographic classification for post-myocardial infarction clinical trials.
A new electrocardiographic code was developed for clinical trials involving patients with acute myocardial infarction (AMI). In the Multicenter Post-Infarction Program (MPIP), the electrocardiogram, classified by the Minnesota code, was not useful as a clinical predictor and played almost no role in subsequent analysis. To test its value the new code was applied to the electrocardiograms of 653 of the 866 patients in the MPIP data base who had sustained a first AMI. The MPIP code identifies AMI by region and severity. The 4 regions are anterior, lateral, inferior and posterior, defined by traditional criteria. Severity codes include Q-wave and non-Q-wave AMI, ST depression and no ischemic changes. The interpretation for each of 4 regions results in a 4-digit location severity code that is amenable to sorting and analysis. Fourteen separate and mutually exclusive groups were identified. Mortality gradients were found within the inferior AMI groups, but not within the anterior AMI groups. Mean ejection fraction was 50% for patients with isolated anterior infarction and decreased progressively (p less than 0.0003) as the extent of lateral wall involvement increased. For isolated inferior AMI, mean ejection fraction was 53%; lateral or posterior involvement did not significantly change this. The MPIP code is easy to apply, correlates acceptably well with clinically relevant variables of left ventricular function and permits the electrocardiogram to be used as a clinical predictor in large clinical trials.


The effects of binge alcohol exposure on tooth movement and associated root resorption in rats.
Considering the increasing prevalence of alcohol use and the growing number of orthodontic patients, some orthodontic patients might engage in binge drinking during treatment. Nevertheless, little is known about the effect of alcohol use on orthodontic treatment. Male Wistar rats were divided into ethanol and control groups (n = 32). The rats received a single daily intraperitoneal injection of 20% (vol/vol) ethanol/saline solution at a dose of 3 g/kg of ethanol or saline for three consecutive days, and no injection was given during the remaining four days each week. All rats received orthodontic appliances to draw the maxillary first molar mesially. The rats were sacrificed at days 14 and 28, respectively. The amount of tooth movement was measured. Root resorption area was evaluated by scanning electron microscope. Hematoxylin and eosin (H&E) staining and tartrate-resistant acid phosphatase (TRAP) staining were conducted. Immunohistochemistry staining was performed to evaluate the expressions of nuclear factor kappa B ligand (RANKL), osteoprotegerin (OPG), and inducible nitric oxide synthase (iNOS). There were no significant differences in tooth movement and root resorption between ethanol and control groups. The number of TRAP-positive cells was significantly higher in the ethanol group. The expression of RANKL was statistically increased in the ethanol group. In contrast, the expression of OPG was remarkably decreased in rats injected with ethanol. Moreover, the iNOS level was significantly up-regulated in the ethanol group. The tooth movement and root resorption in rats were not affected by binge alcohol exposure.


Human-animal-environment interactions as a context for youth social-emotional health and wellbeing: Practitioners' perspectives on processes of change, implementation, and challenges.
Human-animal-environment interactions (HAEIs) are increasingly used in interventions for youth with psychosocial challenges, yet research is limited. Staff from an exemplary program that use HAEIs have unique perspectives on the processes involved in youth outcomes. The aim of this study was to elucidate processes of change that may underly HAEIs and key implementation considerations. A phenomenological approach was used to ascertain HAEI staff perspectives of how they have seen HAEIs impact youth. Semi-structured interviews were completed with 24 staff at a mental health treatment program that utilizes HAEIs. Six themes were identified, including views that HAEIs had challenges, afforded youth with valuable opportunities, improved mood, facilitated relationships and self-regulation, and strengthened self-conception. Findings will inform program development; and future research to assess mediating variables and best practices in implementation of HAEIs.


Epidural abscess, discitis and vertebral osteomyelitis caused by Neiserria subflava.
Neisseria subflava is generally regarded as commensal flora of the oropharyngeal tract and usually non-pathogenic. There are, however, reports of invasive disease such as bacteremia, endocarditis, sepsis, meningitis, septic arthritis and discitis caused by this organism. This paper presents the first reported case of an epidural abscess caused by Neiserria subflava.


Retinitis pigmentosa. A mimic of neurologic disease.
Six patients with various forms of retinitis pigmentosa who were misdiagnosed as having neurologic disease are presented. In five of the patients, visual field defects were misinterpreted as being secondary to a neurologic rather than a retinal problem. In two patients, optic nerve drusen, which accompanied the retinal degeneration, were mistaken for papilledema. Since the diagnosis of retinitis pigmentosa is not always obvious on ophthalmoscopy, the clinician must be aware of the various manifestations of this disorder and be able to distinguish visual field defects on a retinal from a neurologic basis.


Evidence map of recommendations on diabetic foot ulcers care:A systematic review of 22 guidelines.
Diabetic foot ulcers (DFUs) are one of the major complications of diabetes, representing a leading cause of hospitalization and non-traumatic lower limb amputations. Clinical practice guidelines (CPGs) are statements that include recommendations intended to improve patients' outcomes by providing recommendations for key clinical issues with alternative care options. The aim of this study is to systematically review CPGs on DFUs care and generate an evidence-map for visualizing research trends and gaps in the CPGs. A search of the PubMed, Embase, and Web of Science, guideline databases and website of diabetes society was performed to include the diabetic CPGs. We exacted the basic information, methodological quality and reporting quality of CPGs, recommendations for DFUs care by the Excel 2016. Four researchers evaluated the methodological and reporting quality of diabetic foot CPGs by AGREE Ⅱ instrument and RIGHT checklist. The bubble plot format of evidence map was reduced by R (3.5.1) software. 22 CPGs proved eligible, which included 10 diabetic foot guidelines and 12 comprehensive diabetes guidelines. According to the recommendations of diabetic CPGs, current standard of care for DFUs care mainly involves offloading of pressure, wound care, choice of shoes and adjunctive treatment. Recommendations on offloading of pressure and wound care were consistent in 22 CPGs. However, there were some conflicts on adjunctive treatment recommendations and recommendations for choice of shoes were not accurate. There is mixed quality evidence of CPGs for DFUs care, and some recommendations are inconsistent. This evidence map could provide new perspectives in presentation of evidence and help us know the need for future research to address the current gaps, as well as areas of opportunity for CPG development.


[The effect of composition and ionic strength of external solution on the aspartate-ammonia lyase and fumarate hydratase activity in Escherichia coli cells].
It was found that the nonspecific effect of ionic strength of the external solution on the enzymatic activity of E. coli cells consists in rapid changes in the permeability of cell membranes interacting with the substrate. This effect depends on the initial substrate concentration, i.e., ionic strength of the external solution, and is maintained for some time as the substrate concentration decreases. Chloramphenicol, a protein synthesis inhibitor, and sodium azide, a respiration inhibitor (300 micrograms/ml and 200 microM, respectively) do not change the enzymatic activity of E. coli cells during the synthesis of L-aspartic and L-malic acids from fumaric acid. The kinetic equations of L-aspartate and L-malate synthesis are described by equations of zero and intermediate (between zero and first) order, respectively.


Empathic Responses to Mother's Emotions Predict Internalizing Problems in Children of Depressed Mothers.
Recent theories posit that empathy, typically an adaptive characteristic, may be associated with internalizing problems when children are chronically exposed to mother's depression. We tested this postulation in a sample of children (N = 82, M age = 5 years). Children witnessed their mothers express sadness, anger, and happiness during a simulated phone conversation, and researchers rated children's negative affective empathy, positive affective empathy, and information-seeking (cognitive empathy) in response to their mother's emotions. The chronicity of mother's depression during the child's lifetime moderated associations between children's empathy and internalizing problems. As predicted, all three empathy measures were related to greater mother-rated internalizing problems in children of chronically (i.e., 2-3 years) depressed mothers. Greater positive empathy was related to lower internalizing problems in children of nondepressed mothers. Positive empathy may contribute to adaptive processes when mothers are not depressed, and positive, negative, and cognitive empathy may contribute to maladaptive processes when mothers are chronically depressed.


Gene transfer after subarachnoid hemorrhage: a tool and potential therapy.
This mini-review describes steps towards gene therapy to prevent vasospasm after subarachnoid hemorrhage, and summarizes some remaining obstacles. With recombinant adenoviruses, it is now possible to prevent vasospasm in experimental animals. If an adenoviral or other effective vector is demonstrated to be safe, it is likely that gene therapy will be used in patients to prevent vasospasm.


Anatomy and surgery of pure neuroendoscopic infratentorial supracerebellar approach for resection of pineal region tumor.
The pineal region tumors are surrounded by important structures. Neuroendoscopy has been increasingly used at home and abroad. This study is to simulate pure neuroendoscopic infratentorial supracerebellar approach for resection of pineal region tumor from the cadaveric head, and discuss the advantages and safety through this corridor. The anatomical structure for resection of pineal region tumor was visualized through pure neuroendoscopic infratentorial supracerebellar approach in three cadaveric heads. Three cases with pineal region tumors were retrospectively analyzed and summarized between June 2017 and December 2017. All cases were operated through pure neuroendoscopic infratentorial supracerebellar approach in the first affiliated hospital of Fujian medical university. The anatomical structures of pineal region can be completely visualized by pure neuroendoscopic infratentorial supracerebellar corridor in the cadaveric head. Among the three cases, the first case was total resection, the second case was subtotal resection and the last case was partial resection. The postoperative pathology revealed cavernous hemangioma, germinoma and yolk sac tumor, respectively. The patients were followed-up for 1-6 months and had normal life.The KPS (karnofsky performance status) score was 100. The anatomical structure of the pineal region can be completely visualized and the tumor can be safely removed through pure neuroendoscopic infratentorial supracerebellar approach.


Fast adaptive alpha-particle spectrum fitting algorithm based on genetically estimated initial parameters.
This work presents a high performance procedure for the unfolding of alpha particle spectra based on genetically estimated initial parameters. The process starts with the search for a globally optimized set of fitting parameters from a population of randomly generated solutions. The solution found with the genetic algorithm is then transferred to a Levenberg-Marquardt procedure in order to calculate the covariance matrix for the fit. The proposed method provides the set of final parameters and their associated standard deviation. Several fitted spectra demonstrate the effectiveness of the proposed method in searching for and finding initial conditions in a fast and automated process.


Safety of endoscopic retrograde cholangiopancreatography (ERCP) in pregnancy: A systematic review and meta-analysis.
Endoscopic retrograde cholangiopancreatography (ERCP) is a technically challenging procedure rarely associated with severe postprocedure complications. Hormonal changes during pregnancy promote cholelithiasis, but there are limited clinical data available on the outcomes of ERCP in pregnant women. ERCP techniques without irradiation were recently introduced as potential alternative. We performed a systematic review and meta-analysis to assess the safety of ERCP in pregnancy and to compare outcomes of radiation versus nonradiation ERCP. A systematic search of PubMed, Medline/Ovid, Web of Science, and Google Scholar through April 18th, 2018 using PRISMA and MOOSE guidelines identified 27 studies reporting the outcomes of ERCP in pregnancy. Random effects pooled event rate and 95% confidence intervals (CIs) were estimated. Heterogeneity was measured by I2, and meta-regression analysis was conducted. Adverse outcomes were divided into fetal, maternal pregnancy-related, and maternal nonpregnancy-related. In all, 27 studies reporting on 1,307 pregnant patients who underwent ERCP were identified. Median age was 27.1 years. All results were statistically significant (P < 0.01). The pooled event rate for overall adverse outcomes was 15.9% (95% CI = 0.132-0.191) in all studies combined, 17.6% (95% CI = 0.109-0.272) in nonradiation ERCP (NR-ERCP) subgroup and 21.6% (95% CI = 0.154-0.294) in radiation ERCP subgroup. There was no significant difference in the pooled event rate for fetal adverse outcomes in NR-ERCP 6.2% (95% CI = 0.027-0.137) versus 5.2% (95% CI = 0.026-0.101) in radiation ERCP group. There was no significant difference in maternal pregnancy-related adverse outcome event rate between NR-ERCP (8.4%) (95% CI = 0.038-0.173) and radiation ERCP (7.1%) (95% CI = 0.039-0.125). Maternal nonpregnancy-related adverse outcome event rate in NR-ERCP was 7.6% (95% CI = 0.038-0.145), which was half the event rate in radiation ERCP group of 14.9% (95% CI = 0.102-0.211). ERCP done by experienced endoscopists is a safe procedure during pregnancy. Radiation-free techniques appear to reduce the rates of nonpregnancy-related complications, but not of fetal and pregnancy-related complications.


FAM83A promotes the progression and metastasis of human pancreatic neuroendocrine tumors by inducing the epithelial-mesenchymal transition via the PI3K/AKT and ERK pathways.
Family with sequence similarity 83, member A (FAM83A) has been reported to play an important role in cancer progression and metastasis. The purpose of this study was to clarify the role and mechanism of FAM83A in pancreatic neuroendocrine tumors (PanNETs). PanNET specimens and adjacent nontumor pancreatic tissues obtained from 68 patients who underwent curative surgery for PanNETs were assessed for FAM83A expression using immunochemical staining. The relationships between FAM83A expression, clinicopathological parameters and prognosis were statistically analyzed. PanNET cell lines were used to study the role of FAM83A in the progression and metastasis of PanNETs in vitro and in vivo. FAM83A was overexpressed in PanNET specimens compared with adjacent nontumor tissues. Furthermore, FAM83A expression was closely associated with lymph node metastasis (P = 0.02), perineural invasion (P = 0.001), WHO classification (P = 0.039), AJCC stage (P = 0.01) and shorter disease-free survival in patients with PanNETs (P < 0.001). FAM83A overexpression effectively promoted PanNET cell proliferation, migration, invasion and growth both in vitro and in vivo, whereas FAM83A inhibition exerted the opposite effects. Subsequent mechanistic investigations revealed that FAM83A promotes the progression and metastasis of PanNETs by inducing epithelial-mesenchymal transition (EMT) via the PI3K/AKT and ERK pathways. FAM83A plays an important role in the progression and metastasis of PanNET by inducing the EMT via the activation of the ERK and PI3K/AKT pathways and may serve as a valuable molecular target in PanNET treatment.


Carmustine infusion reactions are more common with rapid administration.
Carmustine is a nitrosurea alkylating agent predominantly used at Peter MacCallum Cancer Centre as part of the autologous stem cell transplant induction regimens Stanford BCNU and BEAM. Acute infusion reactions were anecdotally reported to be higher than the reported rates of 10%, and it was suggested that the rate of infusion being employed was excessive. Some references suggest maximum infusion rates of 3 mg/m(2)/min for carmustine, a rate which is exceeded in the 2-h infusions used for Stanford BCNU, but not with BEAM. A retrospective audit was conducted in 64 patients (57 Stanford BCNU, 7 BEAM) who had received these regimens between January 2009 and November 2010. Rates of infusion reaction to carmustine were higher than literature values, with reactions in Stanford BCNU (94.7%) being significantly higher than for BEAM (28.6%; P = 0.0003). These findings have resulted in a change of administration of carmustine in Stanford BCNU from 2 to 3 h. Further studies plan to compare the incidence of infusion reactions before and after the change in administration rates. Patients receiving rapid infusion of carmustine in the Stanford BCNU regimen for stem cell conditioning have a high rate of infusion reaction. A maximum rate of 3 mg/m(2)/min is recommended.


Indirect effects of apomorphine on serotoninergic neurons in rats.
We have studied the effects of apomorphine on central serotoninergic system by using fluorescence histochemistry and high performance liquid chromatography coupled with electrochemical detection. Apomorphine has been shown selectively to elevate intracellular serotonin fluorescence in dorsal raphe neurons and serotonin and/or 5-hydroxyindoleacetic acid concentrations in the major terminal area of the dorsal raphe, the striatum. Apomorphine has no effect on serotonin neurons in the median raphe or its corresponding projection site, the hippocampus. In the present study, intraventricular 6-hydroxydopamine, when administered together with desimipramine and pargyline, antagonized the apomorphine-induced elevations of serotonin fluorescence in the dorsal raphe and serotonin and 5-hydroxyindoleacetic acid levels in the striatum. This antagonism was found when 6-hydroxydopamine was given either 3 or 10 days before 3 mg/kg apomorphine. Apomorphine also elevated extraperikaryal serotonin fluorescence and catecholamine fluorescence in the dorsal raphe selectively and these effects were also blocked by 6-hydroxydopamine. Additionally, 6-hydroxydopamine accelerated striatal serotonin turnover when it was given 10 days prior to death. This phenomenon probably reflects some compensatory change of mesostriatal serotonin neurons in response to the prolonged depletion of brain dopamine. The above results suggest that the observed effects of apomorphine on the serotoninergic system are mediated indirectly through dopaminergic neurons and that postsynaptic dopamine receptors are probably not responsible for apomorphine's effects.


A pictorial presentation of 3.0 Chicago Classification for esophageal motility disorders.
High resolution manometry changed several esophageal motility paradigms. The 3.0 Chicago Classification defined manometric criteria for named esophageal motility disorders. We present a pictorial atlas of motility disorders. Achalasia types, esophagogastric junction obstruction, absent contractility, distal esophageal spasm, hypercontractile esophagus (jackhammer), ineffective esophageal motility, and fragmented peristalsis are depicted with high-resolution manometry plots. RESUMO A manometria de alta resolução mudou vários paradigmas da motilidade digestiva. A Classificação de Chicago, na versão 3.0, definiu critérios manométricos para as doenças da motilidade esofagiana. O presente artigo é um atlas das dismotilidades descritas. Tipos de acalásia, obstrução ao nível da junção esofagogástrica, contrações ausentes, espasmo esofagiano distal, esôfago hipercontrátil, motilidade esofagiana ineficaz e peristalse fragmentada são mostradas em traçados de manometria de alta resolução.


Novel Platforms for Biomedical HIV Prevention Delivery to Key Populations - Community Mobile Clinics, Peer-Supported, Pharmacy-Led PrEP Delivery, and the Use of Telemedicine.
A gap exists between PrEP interest and PrEP uptake in key populations (KP) for HIV prevention that may be ascribed to PrEP delivery services not being acceptable. This review summarizes novel platforms for HIV prevention outside of the traditional health facilities environment. Mobile health clinics provide highly acceptable integrated, KP-focused services at convenient locations with the potential of high PrEP uptake. Telemedicine and health apps decongest health systems and allow for personal agency and informed decision-making on personal health. Pharmacy-led PrEP delivery provides de-medicalized, confidential PrEP services at extended hours in community locations, from trusted medical professionals. Peer-supported delivery encourages continued PrEP use. Community-based, differentiated and de-medicalized PrEP delivery can address uptake and continued use barriers in key populations. Future research should assess scalability, cost-effectiveness and sustainability of these PrEP delivery platforms, as well as focus on ways to simplify PrEP provision.


Decentralized Brain Age Estimation Using MRI Data.
Recent studies have demonstrated that neuroimaging data can be used to estimate biological brain age, as it captures information about the neuroanatomical and functional changes the brain undergoes during development and the aging process. However, researchers often have limited access to neuroimaging data because of its challenging and expensive acquisition process, thereby limiting the effectiveness of the predictive model. Decentralized models provide a way to build more accurate and generalizable prediction models, bypassing the traditional data-sharing methodology. In this work, we propose a decentralized method for biological brain age estimation using support vector regression models and evaluate it on three different feature sets, including both volumetric and voxelwise structural MRI data as well as resting functional MRI data. The results demonstrate that our decentralized brain age regression models can achieve similar performance compared to the models trained with all the data in one location.


Local calcification as a determinant of the outcome of excimer laser coronary angioplasty: an in vitro study.
Calcification influences the outcome of various angioplasty techniques in the treatment of coronary artery disease. During angioscopic in vitro studies, we observed that dissections and perforations not caused by vessel bending frequently occurred at the boundary areas of plaque and adjacent vessel wall. This study investigated whether this is related to the distribution of calcific deposits. Postmortem excimer laser coronary angioplasty (308-nm XeCl) was performed in 51 stenotic coronary arteries. Twenty-three segments were further examined; these consisted of 11 perforations, six dissections, three segments with no ablative effect after the application of 20,000 laser impulses, and three successfully passed stenoses without complications. X-ray diffraction analysis and scanning electron microscopy were performed to detect calcium deposits and their spatial relationship to perforations and dissections. X-ray diffractions analysis detected calcifications in 21 of 23 specimens. Postmortem angiography revealed calcifications only on 11 of 23 segments. Three of 11 perforations were located at the plaque border, as were three of six dissections. In all six complications at the plaque border, x-ray diffraction analysis revealed that the plaque border was identical with a border of calcium deposits. Eight of 11 perforations and three of six dissections could be explained by axis divergence between the laser catheter and the vessel orientation. Contributing factors for perforations and dissections during excimer laser coronary angioplasty are axis divergence and the distribution of plaque calcification. More sensitive methods are needed to detect local vessel wall calcium in vivo.


Modulation of aluminum sensing properties of a sulphone group containing chemosensor and its biological applications.
A chemosensor with two binding pockets facilitates binding of one metal ion in either of the pockets providing a better chance for the interaction and hence recognition of the cation. We report here a chemosensor, namely 2,2'-(1E)-(5,5'-sulfonylbis(2-hydroxy-5,1-phenylene))bis(azan-1-yl-1-ylidene)bis(methan-1-yl-1-ylidene)dinaphthalen-1-ol (H4L-naph), for selective sensing of Al3+ in DMF- HEPES buffer (1:4, v/v, pH 7.4). It shows almost 100-fold fluorescence enhancement at 532 nm (λex = 482 nm) in the presence of Al3+. Its quantum yield and excited state lifetime enhances significantly with the cations. H4L-naph forms a 1:2 complex with Al3+ with an association constant value of 2.18 × 104 M-2. Fluorescence enhancement may be attributed to CHEFF mechanism and restriction of >CN isomerization. Effect of the presence of naphthyl rings instead phenyl ring of a previously reported probe has resulted shifting of excitation/emission peak towards longer wavelength. The probe has been applied to image Al3+ in L6 cells with no significant cytotoxicity.


Intraoperative radiotherapy in the multimodality approach to bone and soft tissue cancers.
IORT is a powerful tool for the management of cancer and has been shown to improve local control in the treatment of sarcomas in one prospective, randomized, controlled trial. IORT allows dose escalation in areas where escalation with EBRT would cause potentially excessive acute or late normal tissue toxicity. It has a unique toxicity profile but remains safe and effective when used in appropriately selected patients. In addition, IORT is becoming more widely available at different cancer centers and offers great flexibility in treatment planning for a wide variety of malignancies. As IORT use becomes more common, special care will be required to ensure that it is used by a multidisciplinary team of radiation oncologists and surgeons to ensure the best results for patients.


Prevalence of hand dermatitis in inpatient nurses at a United States hospital.
Hand dermatitis is a significant problem among inpatient nurses. Accurate population-based data on the prevalence and risk factors for hand dermatitis in this group are lacking. To determine the prevalence of hand dermatitis in inpatient nurses at a US hospital. Each nursing unit in a single hospital was visited twice by a single physician. All nurses working at the time of each visit were questioned and examined. No nurses were enrolled twice. Fifty-five percent (92 of 167) of the nurses had hand dermatitis. Among intensive care unit (ICU) nurses, the prevalence was 65% (35 of 54); among non-ICU nurses, the prevalence was 50% (57 of 113). In nurses with self-reported atopic dermatitis, the prevalence was 71% (12 of 17); in nurses without self-reported atopic dermatitis, it was 53% (80 of 150). Data collection on variables such as hand hygiene and glove use relied on subject recall and was considered unreliable. There was a low prevalence of atopic patients. Hand dermatitis affects over 50% of inpatient nurses. Hand dermatitis appears to be more common in the ICU setting and in nurses with a self-reported history of atopy.


Malignant mixed müllerian tumors of the uterus. A clinicopathologic assessment of 34 cases.
We have analyzed clinical and pathologic features of a series of 34 patients with malignant mixed müllerian tumors of the uterus. This study includes 17 homologous and 17 heterologous lesions. The most significant prognostic indicator in our patients was tumor extent (stage) at diagnosis. Of lesser importance were the presence of heterologous elements, especially chondrosarcoma, high grade of carcinoma and tumor size. Survival rates were 52% at 2 years and 36% at 5 years for homologous tumors; and 47% and 14%, respectively, for the heterologous variety.


Neutrophil lymphocyte ratio as a predictor of stroke.
The aim of this study is to investigate the relationship of the neutrophil to lymphocyte ratio (NLR) with short-term mortality in acute stroke. This retrospective study included 255 patients with acute cerebral infarction who presented within 24 hours of symptom onset. A hemogram from peripheral venous blood samples was taken at the time of admission. The NLR was calculated as the ratio of neutrophils to lymphocytes. Duration of follow-up was defined as 60 days. Seventy-one of 255 patients died during the follow-up period. The median NLR was significantly increased among the mortality group compared with the survival group (median 11.50, interquartile ratio [IQR] 10.40 vs median 3.79, IQR 4.72; P = .001). In our multivariate Cox regression model, NLR >5.0 (hazard ratio [HR] 3.30; 95% confidence interval [CI] 1.35-8.07), National Institutes of Health Stroke Scale score (HR 1.11; 95% CI 1.07-1.16), glucose values at admission (HR 1.007; 95% CI 1.002-1.011), and history of coronary artery disease (HR 2.49; 95% CI 1.26-4.92) were predictors of short-term mortality. The sensitivity for short-term mortality when the NLR was >5 was 83.10%, and the specificity was 62.00%. The positive predictive value of a NLR >5 was 45.7%, and negative predictive value was 90.50%. A strong linear association between NLR and National Institutes of Health Stroke Scale score was also observed (r = 0.64; P = .001). In addition, the NLR was higher in both the atherosclerotic and cardioembolic stroke subgroups than the lacunar infarct subgroup (6.5 [IQR 7.2], 7.5 [IQR 8.9], and 3.20 [IQR 3.50], respectively; P = .001). The NLR at the time of hospital admission may be a predictor of short-term mortality in acute stroke patients. Because of the routine use and inexpensive nature of hemogram analysis, the NLR should be investigated in future prospective, randomized controlled trials investigating acute stroke.


Renal hemodynamic effects of somatostatin are not related to inhibition of endogenous insulin release.
Somatostatin inhibits endocrine and exocrine secretions and exerts renal vasoconstriction. The mechanism underlying somatostatin's vascular effects is unknown. Since insulin can cause vasodilation, we hypothesized that removal of basal insulin release by somatostatin may contribute to somatostatin-induced renal vasoconstriction. The study was conducted in different protocols comprising forty-six healthy male volunteers. Randomized studies were performed to compare the effects of somatostatin alone (0.1 microg/kg/min) to the effects of somatostatin + low dose insulin (0.1 mU/kg/min), the effects of somatostatin + low dose insulin to the effects of somatostatin + high dose insulin (1.5 mU/kg/min), and the effects of insulin (1.5 mU/kg/min) + somatostatin. Renal plasma flow (RPF) and glomerular filtration rate (GFR) were measured with the para-aminohippurate (PAH) and the inulin clearance technique, respectively. Blood pressure and pulse rate were measured non-invasively. Somatostatin alone decreased GFR (-14 +/- 6%, P < 0.001) and RPF (-16 +/- 7%, P < 0.001) whereas systemic hemodynamics were unchanged. Preceding or concomitant infusion of insulin at high doses (insulin plasma concentration of 127 +/- 25 or 144 +/- 17 microU/mL) but not co-infusion with low dose insulin (insulin plasma concentration of 11 +/- 3 microU/mL) mitigated or reversed the vasoconstrictive actions of somatostatin on GFR and RPF. Somatostatin induces marked renal vasoconstriction and exogenous restoration of fasting insulin concentrations does not influence the renal vascular effects. Therefore, it is unlikely that somatostatin-induced vasoconstriction is due to removal of basal insulin. Plasma insulin concentrations in the high postprandial range can reverse somatostatin-induced renal vasoconstriction, suggesting functional antagonism.


Lignin degradation potential and draft genome sequence of Trametes trogii S0301.
Trametes trogii is a member of the white-rot fungi family, which has a unique ability to break down recalcitrant lignin polymers to CO2 and water, and they have enormous potential to biodegrade a wide range of toxic environmental pollutants. Because of its industrial potential, the identification of lignin-degrading enzyme systems in Trametes is an important area of research. Development and utilization of industrial value genes are suffering due to deficiency knowledge of genome available for their manipulation. In the present study, Homokaryotic strains of T. trogii S0301 were screened and sequencing by PacBio Sequel II platform. The final draft genome is ~ 39.88 Mb, with a contig N50 size of 2.4 Mb, this was the first genome sequencing and assembly of T. trogii species. Further analyses predicted 14,508 protein-coding genes. Results showed that T. trogii S0301 contains 602 genes encoding CAZymes, include 211 glycoside hydrolase and 117 lignin-degrading family genes, nine laccases related genes. Small subunit ribosomal RNA gene (18S rRNA) sequencing confirms its phylogenetic position. Moreover, T. trogii S0301 has the largest number of cytochromes P450 (CYPs) superfamily genes compare to other fungi. All these results are consistent with enzymatic assays and transcriptome analysis results. We also analyzed other genome characteristics in the T. trogii S0301genome. Here, we present a nearly complete genome for T. trogii S0301, which will help elucidate the biosynthetic pathways of the lignin-degrading enzyme, advancing the discovery, characterization, and modification of novel enzymes from this genus. This genome sequence will provide a valuable reference for the investigation of lignin degradation in the Trametes genus.


Safety and immunogenicity of a single administration of live-attenuated Japanese encephalitis vaccine in previously primed 2- to 5-year-olds and naive 12- to 24-month-olds: multicenter randomized controlled trial.
Safe and effective Japanese encephalitis (JE) vaccines are needed to protect populations living in or visiting endemic areas. A live-attenuated JE-chimeric virus vaccine (JE-CV) has been developed with a single-dose regimen. In an open-label, crossover study, 100 children aged 2 to 5 years with a history of 2-dose primary vaccination with mouse-brain derived inactivated JE vaccine according to the Thai Expanded Program for Immunization schedule, and 200 JE vaccination-naive 12- to 24-month-old toddlers were randomized 1:1 to receive JE-CV, containing ≥4 log10 plaque forming units, 1 month before or after hepatitis A control vaccine. Neutralizing antibody titers were assessed using PRNT50 (titers expressed in inverse of dilution) before and 28 days after JE-CV, and at months 7 and 12. All 2- to 5-year-olds and 96% of 12- to 24-month-olds were seroprotected (titer ≥10) 28 days after JE-CV administration, and geometric mean titers (GMT) (95% confidence interval) in these age groups were 2634 (1928-3600) and 281 (219-362), respectively. One year later, seroprotection rates in the 2 age groups were 97% and 84% and GMTs were 454 and 62.3, respectively. Vaccine-induced antibodies neutralized a panel of wild-type JE isolates. There were no vaccine-related serious adverse events. Reactogenicity of JE-CV was comparable with that of the inactivated hepatitis A vaccine. A single administration of JE-CV has a good safety profile and elicits a protective immune response in both JE-naive toddlers and JE-primed young children.


[L-DOPA test for evaluating in vivo catecholamine biosynthesis in normal persons and persons with different diseases].
Administration of 1-DOPA into healthy persons increased its excretion with urine and elevated the adrenaline secretion. The increase of catecholamines excretion was not observed in aged patients with hypertension; the data obtained suggest that the synthesis of catecholamines with utilization of DOPA was inhibited. In patients with ulcerous disease excretion of 1-DOPA was not increased after its administration, but secretion of catecholamines was decreased during the day time. Under ulcerous disease 1-DOPA appears to be used in process unrelated to synthesis of catecholamines.


Structure-function-property-design interplay in biopolymers: spider silk.
Spider silks have been a focus of research for almost two decades due to their outstanding mechanical and biophysical properties. Recent advances in genetic engineering have led to the synthesis of recombinant spider silks, thus helping to unravel a fundamental understanding of structure-function-property relationships. The relationships between molecular composition, secondary structures and mechanical properties found in different types of spider silks are described, along with a discussion of artificial spinning of these proteins and their bioapplications, including the role of silks in biomineralization and fabrication of biomaterials with controlled properties.


Tear proteins in health, disease, and contact lens wear.
Although well known as manifestations of sorrow, emotions, frustration, and blackmail, tears have a more prosaic and important function as a lubricant and as a blood substitute for the cornea. Tears transport oxygen and carbon dioxide and play a central role in the cellular economy of the ocular surface and conjunctiva. In addition to proteins, tears contain lipids and glycoproteins, which increase the wetting effect of the aqueous component and delay evaporation. The total protein concentration of tears is about 10% of that of the plasma. About 80 proteins and polypeptide components have been detected by electrophoresis. Among 30 proteins identified in tears, about 50% are enzymes. Some of the tear enzymes are secreted by the lacrimal glands; others are produced by or released from epithelial cells of the cornea and the conjunctiva. Finally, a few enzymes originate from plasma and appear in tears only in cases with increased permeability of the conjunctival vessels. The aim of this review is to provide clinical and biochemical information about tear enzymes both for ophthalmologists and for biochemists interested in clinical and experimental tear enzymology.


Highly homologous proteins exert opposite biological activities by using different interaction interfaces.
We present a possible molecular basis for the opposite activity of two homologues proteins that bind similar ligands and show that this is achieved by fine-tuning of the interaction interface. The highly homologous ASPP proteins have opposite roles in regulating apoptosis: ASPP2 induces apoptosis while iASPP inhibits it. The ASPP proteins are regulated by an autoinhibitory interaction between their Ank-SH3 and Pro domains. We performed a detailed biophysical and molecular study of the Pro - Ank-SH3 interaction in iASPP and compared it to the interaction in ASPP2. We found that iASPP Pro is disordered and that the interaction sites are entirely different: iASPP Ank-SH3 binds iASPP Pro via its fourth Ank repeat and RT loop while ASPP2 Ank-SH3 binds ASPP2 Pro via its first Ank repeat and the n-src loop. It is possible that by using different moieties in the same interface, the proteins can have distinct and specific interactions resulting in differential regulation and ultimately different biological activities.


Simultaneous assessment of cerebral hemodynamics and contrast agent uptake in lesions with disrupted blood-brain-barrier.
The purpose of this study was to develop a method that eliminates the influence of the T1 relaxation time upon the signal-time course in perfusion-weighted imaging of cerebral lesions with blood-brain-barrier (BBB) disruption. On a 1.5 T whole body clinical magnetic resonance (MR) imager, we implemented a dual-echo RF-spoiled FLASH sequence (TE=6/23.6 ms). We developed a postprocessing routine that allowed to calculate a signal-time course representing only the change in T2* and another one representing only the change in T1. Using this method, we examined 7 patients with various brain lesions showing evidence of BBB disruption. In the signal-time-curves obtained from the early echo we found a distinct signal drop due to the T2* effect. These effects could be eliminated by the correction algorithm yielding a 67% higher signal increase. Correction of the signal-time curve of the late echo yielded a more pronounced maximum signal drop and a decrease in postcontrast signal intensity. We found that without this correction the relative regional cerebral blood volume and the first moment of the concentration-time curve were underestimated by 72% and 22%, respectively. The dual echo-sequence combined with the postprocessing algorithm separates T1 and T2* effects and thus allows to assess cerebral hemodynamics and contrast agent kinetics simultaneously. This method may be a useful tool for characterizing, staging, and therapy monitoring of brain tumors.


Selective therapeutic embolization of renal cell carcinoma in solitary kidneys.
We report 3 cases of renal cell carcinoma in a solitary kidney treated by selective tumor embolization. Embolization resulted in occlusion of the majority of the vascular supply of the tumor, with preservation of normal renal parenchyma and sufficient renal function. Selective tumor embolization is a good therapeutic alternative in patients in whom partial nephrectomy cannot be performed. Owing to the limited availability of bucrylate, absolute ethanol is recommended as the preferred embolic agent.


The association between midlife cardiorespiratory fitness and later life chronic kidney disease: The Cooper Center Longitudinal Study.
Chronic kidney disease (CKD) is a major public health problem, particularly in older age and in those with diabetes mellitus (DM), with high comorbidity and treatment costs. Prospective observational cohort study. 17,979 participants, 22% women with a mean age of 50.0 (SD 8.8), in the Cooper Center Longitudinal Study (CCLS) seen initially between 1971 to 2009 who also received Medicare coverage from 1999 to 2009. Age, body mass index, blood pressure, cholesterol, glucose levels, current tobacco use, and cardiorespiratory fitness. Incident CKD and DM were determined from Medicare administrative claims data. During 116,973person-years of observation, 2022 cases of incident CKD occurred. Multivariable-adjusted proportional hazards models revealed a 24% lower risk of CKD among moderate fit (hazards ratio[HR] 0.76, 95% CI 0.67-0.85 compared to low fit) and a 34% lower risk of CKD among high fit (HR 0.66, 95% CI 0.58-0.76 compared to low fit). Even following the development of DM, fitness was associated with lower risk of CKD (HR 0.94, 95% CI 0.89-0.99) per 1-MET increment. Relatively homogeneous population of well-educated Caucasians. Results of the present study suggest that higher fitness is associated with lower risk of CKD decades later even in at-risk populations such as diabetics. The findings support a role for enhancing fitness through regular physical activity in preventive strategies for CKD including those who may develop DM in later life.


Health Advocacy and Training Perceptions: a Comparison of Medical Student Opinions.
The American Medical Association considers health advocacy to be a core aspect of a physician's responsibility, which has sparked medical schools to institutionalize training. However, there is little information regarding student perspectives on advocacy education. To evaluate medical student opinions on advocacy education and to determine similarities and differences across classes. In this qualitative study, four focus groups were conducted with five to eight students from each medical school class. Students were randomly selected from rosters and received an email to participate. Sessions were audiotaped and transcribed, and demographic data was obtained. Investigators reviewed transcripts independently and identified important items in each transcript then consolidated common themes into groups. These themes were integrated into concept map representations. Of those contacted, 25 (16%) students chose to participate in focus group sessions. All participants who responded to questionnaires (n = 24) identified advocacy in medicine as very important. Definitions of advocacy varied among students and classes. Common themes in all focus groups included feeling overwhelmed by advocacy due to lack of time, lack of perceived prioritization in medical education, feelings of imposter syndrome, and inability to align individual views with healthcare systems. Another common theme was frustration that students learned of advocacy through didactic sessions rather than engagement in advocacy work. All participating students identified advocacy as an important aspect of medicine, yet students felt inadequately prepared to participate in advocacy work. This reveals an opportunity to improve upon the formal education needed to engage in advocacy.


Na+/K+-ATPase Activity in Smolts of Pink Salmon Oncorhynchus gorbuscha (Walbaum, 1792) from the White Sea Exposed to Fresh, Estuarine, and Sea Water.
The Na+/K+-ATPase (NKA) activity in smolts of pink salmon Oncorhynchus gorbuscha (a salmon species introduced in 1959 into the rivers of the Kola Peninsula) was studied in a ten-day cage experiment with fresh, estuarine, and sea water; the fish were caught during seaward migration in the Indera River of the White Sea basin. The development of tolerance to increased salinity in pink salmon smolts was accompanied by NKA activation. In estuarine water characterized by salinity fluctuations (from fresh to sea water) and in the marine environment (28‰), the NKA activity in pink salmon smolts was significantly higher than in the individuals kept in the cages installed in fresh water. The hypoosmoregulatory ability of pink salmon fry was registered, these data indicated that smoltification in this fish species took place in early ontogenesis. The changes in NKA activity evidenced the readiness of migrating pink salmon fry for the marine phase of their life cycle.


On the opportunity cost of the photosynthate invested in stem elongation reactions mediated by phytochrome.
Seedlings of shade-intolerant species react to alterations of the light climate caused by their neighbors with morphological changes that may influence the pattern of resource acquisition and utilization at the whole-canopy level. One such change, the increased stem elongation rate that is triggered by low red (R, 660 nm) to far-red (FR, 730 nm) ratios (R:FR) in dense canopies, might reduce the amount of assimilates available for leaf area expansion or root growth, and in that way affect resource capture by the canopy. We have tested this hypothesis by comparing the growth of both isolated individuals and canopies of the weed Amaranthus quitensis under conditions differing only in the spectral distribution of the incident light. When canopies received the full spectrum of sunlight, the stems were a large proportion (40-57%) of total biomass. Filtering the FR waveband (and hence raising the R:FR ratio to eliminate the neighbors' proximity-signal) resulted in shorter canopies with lighter stems. However, the growth of leaves and roots was not promoted by this treatment, indicating that the opportunity cost of the assimilates invested in the stems was nil or very small. Filtering the FR had no effect on biomass accumulation when plants were grown as isolated individuals. The higher growth of the canopics under full spectrum could be due to a higher light interception or to a higher efficiency of light conversion into biomass. The first possibility is weakened by the observation that filtering the FR had no effect on the dynamics of soil covering by the crops. The second is indirectly strengthened by results of an experiment with isolated plants showing that stem elongation, stem growth, and total plant biomass can be increased by reducing the flux of R light received by the stems without affecting the light climate of the leaves. Further work is needed to distinguish between these two possibilities; whatever the cause, our results show that the elongation responses to decreased R:FR may lead to a net increase in canopy productivity, and do not necessarily have a negative impact on the growth of resource-harvesting organs.


Effect of xenon on brain injury, neurological outcome, and survival in patients after aneurysmal subarachnoid hemorrhage-study protocol for a randomized clinical trial.
Aneurysmal subarachnoid hemorrhage (aSAH) is a neurological emergency, affecting a younger population than individuals experiencing an ischemic stroke; aSAH is associated with a high risk of mortality and permanent disability. The noble gas xenon has been shown to possess neuroprotective properties as demonstrated in numerous preclinical animal studies. In addition, a recent study demonstrated that xenon could attenuate a white matter injury after out-of-hospital cardiac arrest. The study is a prospective, multicenter phase II clinical drug trial. The study design is a single-blind, prospective superiority randomized two-armed parallel follow-up study. The primary objective of the study is to explore the potential neuroprotective effects of inhaled xenon, when administered within 6 h after the onset of symptoms of aSAH. The primary endpoint is the extent of the global white matter injury assessed with magnetic resonance diffusion tensor imaging of the brain. Despite improvements in medical technology and advancements in medical science, aSAH mortality and disability rates have remained nearly unchanged for the past 10 years. Therefore, new neuroprotective strategies to attenuate the early and delayed brain injuries after aSAH are needed to reduce morbidity and mortality. ClinicalTrials.gov NCT04696523. Registered on 6 January 2021. EudraCT, EudraCT Number: 2019-001542-17. Registered on 8 July 2020.


Vibrio vulnificus.
V vulnificus is a halophilic or salt-requiring vibrio that has been isolated repeatedly from seawater and shellfish in coastal waters. This vibrio, first described by Hollis et al in 1976, can be differentiated from other similar vibrios by its ability to ferment lactose and by its lower tolerance for sodium chloride. V vulnificus, unlike most other vibrios, has seldom been incriminated as a cause of gastroenteritis but is a particularly virulent organism that causes severe wound infections in mostly healthy persons, or causes primary septicemia in persons with an underlying chronic disease, particularly chronic liver disease. Wound infections may range from relatively mild to severe and rapidly progressive cellulitis and myositis. Approximately 50% of patients with wound infections have some type of chronic underlying disease and the mortality rate is in the range of 15%. Wound infections are almost always associated with contact with seawater or the handling or cleaning of shellfish. Patients with primary septicemia have fever, chills, and prostration, and rapidly become hypotensive. Over 70% have distinctive bullous skin lesions that can strongly suggest the diagnosis in a patient with the appropriate history. The mortality rate is over 50%. There is a striking association between eating raw oysters and primary septicemia, with patients usually reporting having eaten raw oysters (or other shellfish) 24 to 48 hours before onset of symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)


Inhaled nebulized sodium nitrite decreases pulmonary artery pressure in β-thalassemia patients with pulmonary hypertension.
Pulmonary hypertension is a life-threatening complication in β-thalassemia. Inhaled sodium nitrite has vasodilatory effect on pulmonary vasculature. However, its effect on pulmonary artery pressure (PAP) in β-thalassemia subjects with pulmonary hypertension has never been reported. In this study, we investigated the change in PAP during inhalation of sodium nitrite in 5 β-thalassemia patients. We demonstrated that sodium nitrite administered by nebulization rapidly decreased PAP as measured by echocardiography and right heart catheterization. The effect of nitrite was short as PAP returned to baseline at end of inhalation. Our findings support acute pulmonary vasodilation effect of nitrite in β-thalassemia with pulmonary hypertension.


Sex Differences in Genomic Drivers of Adipose Distribution and Related Cardiometabolic Disorders: Opportunities for Precision Medicine.
This review focuses on the human genetics, epidemiology, and molecular pathophysiology of sex differences in central obesity, adipose distribution, and related cardiometabolic disorders. Distribution of fat is important for cardiometabolic health, with peripheral fat depots having a protective effect and central visceral fat depots conferring a detrimental effect on health. There are important sex differences in fat distribution that are masked when studying body mass index as a measure of obesity. From epidemiological, murine, and in vitro studies, several mechanisms have been proposed to explain the sex differences in adipose distribution, including sex hormonal effects, cell-intrinsic properties, and the microenvironment in fat depots. More recently, human genetics have revealed hundreds of loci for central obesity providing disruptive opportunities for mechanistic discoveries and clinical translation. A striking feature is that over one-third of these loci have reproducible but poorly understood sexual dimorphic associations with central obesity, most having stronger effects in women. Understanding the genetic and molecular mechanisms of adipose distribution and its sexual dimorphism in humans provides a unique opportunity to promote the use of precision medicine for early identification of at-risk individuals, and the development of novel therapeutic strategies for central obesity and related cardiometabolic disorders.


Isolation and characterization of a Chinese hamster ovary cell mutant which accumulates UDP glucuronic acid and requires uridine for growth.
The isolation and characterization of a new pyrimidine requiring mutant of Chinese hamster ovary cells (CHO-Kl, pro-) is described. This mutant (P192) shows an absolute requirement for uridine for growth but is fully capable of pyrimidine nucleotide synthesis. P192 cells accumulate exceedingly large amounts of a compound identified by a variety of chromatographic, chemical, and labelling criteria as UDP glucuronic acid (UDPglcUA). This compound comprises approximately 60% of the acid-soluble nucleotides of P192 cells. Possible genetic mechanisms leading to the phenotype of P192 are examined, and the role of UDPglcUA in cellular metabolism is discussed.


Normotensive ischemic acute kidney injury as a manifestation of intra-abdominal hypertension.
Intra-abdominal hypertension (IAH), leading to abdominal compartment syndrome (ACS), is a frequent cause of acute kidney injury (AKI) in surgical and trauma intensive care units not commonly recognized by nephrologists. Multiple organ systems are often affected and frequently culminate in disastrous outcomes. The diagnosis of AKI as a manifestation of IAH requires a high index of clinical suspicion, especially, because laboratory and imaging studies are unreliable. Early recognition and treatment of the condition is associated with good clinical outcome. We report a typical case of normotensive ischemic AKI as a manifestation of IAH following abdominal surgery.