Bird-livestock interactions associated with increased cattle fecal shedding of ciprofloxacin-resistant Escherichia coli within feedlots in the United States.
This research study was conducted to determine if bird depredation in feedlots is associated with the prevalence of ciprofloxacin-resistant Escherichia coli in cattle and to determine if removal of invasive bird species could be an effective management strategy to help reduce ciprofloxacin-resistant E. coli in cattle within the United States. European starlings (Sturnus vulgaris) were collected from feedlots within multiple geographic regions within the United States and European starlings within all regions tested positive for ciprofloxacin-resistant E. coli, but prevalence differed by region. Total number of birds on feedlots were positively associated with increased cattle fecal shedding of ciprofloxacin-resistant E. coli. Targeted control of invasive European starlings reduced bird numbers on feedlots by 70.4%, but decreasing populations of European starlings was not associated with corresponding reductions in bovine fecal prevalence of ciprofloxacin-resistant E. coli. These data provide evidence for the role of wild bird depredation in feedlots contributing to fecal shedding of ciprofloxacin-resistant E. coli, but a single month of European starling control in feedlots was not sufficient to impact the fecal carriage of this organism in cattle.


A Randomized, Placebo-Controlled Clinical Trial of Bamlanivimab and Etesevimab Together in High-Risk Ambulatory Patients With COVID-19 and Validation of the Prognostic Value of Persistently High Viral Load.
Based on interim analyses and modeling data, lower doses of bamlanivimab and etesevimab together (700/1400 mg) were investigated to determine optimal dose and expand availability of treatment. This Phase 3 portion of the BLAZE-1 trial characterized the effect of bamlanivimab with etesevimab on overall patient clinical status and virologic outcomes in ambulatory patients ≥12 years old, with mild-to-moderate coronavirus disease 2019 (COVID-19), and ≥1 risk factor for progressing to severe COVID-19 and/or hospitalization. Bamlanivimab and etesevimab together (700/1400 mg) or placebo were infused intravenously within 3 days of patients' first positive COVID-19 test. In total, 769 patients were infused (median age [range]; 56.0 years [12, 93], 30.3% of patients ≥65 years of age and median duration of symptoms; 4 days). By day 29, 4/511 patients (0.8%) in the antibody treatment group had a COVID-19-related hospitalization or any-cause death, as compared with 15/258 patients (5.8%) in the placebo group (Δ[95% confidence interval {CI}] = -5.0 [-8.0, -2.1], P < .001). No deaths occurred in the bamlanivimab and etesevimab group compared with 4 deaths (all COVID-19-related) in the placebo group. Patients receiving antibody treatment had a greater mean reduction in viral load from baseline to Day 7 (Δ[95% CI] = -0.99 [-1.33, -.66], P < .0001) compared with those receiving placebo. Persistently high viral load at Day 7 correlated with COVID-19-related hospitalization or any-cause death by Day 29 in all BLAZE-1 cohorts investigated. These data support the use of bamlanivimab and etesevimab (700/1400 mg) for ambulatory patients at high risk for severe COVID-19. Evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants will require continued monitoring to determine the applicability of this treatment. NCT04427501.


Synchronous Electrocatalytic Design of Architectural and Electronic Structure Based on Bifunctional LDH-Co3 O4 /NF toward Water Splitting.
The rational design of highly efficient bifunctional electrocatalysts for water splitting is extremely urgent for application in sustainable energy conversion processes to alleviate the energy crisis and environmental pollution. In this work, through simple deposition of layered double hydroxides (LDH) on Co3 O4 /NF (NF=nickel foam) nanosheets arrays, hierarchical Co3+ -rich materials based on LDH-Co3 O4 /NF are prepared as highly active and stable electrocatalysts for water splitting. The NiFe-LDH-Co3 O4 /NF demonstrates excellent electrochemical activity with an overpotential of 214 mV for the OER and an overpotential of 162 mV for the HER at 10 mA cm-2 . Such a performance is attributed to the optimized electronic states with a high concentration of Co3+ , which improves the intrinsic activity, and the sheet-on-sheet hierarchical structure, which increases the number of active sites. The unique synchronous design of both the architectural and electronic structure of nanomaterials can simultaneously accelerate the reaction kinetics and provide a more convenient charge transfer path. Therefore, the strategy reported herein may open a new pathway for the design of excellent electrocatalysts for water splitting.


Usefulness of [18F]-DA and [18F]-DOPA for PET imaging in a mouse model of pheochromocytoma.
To evaluate the usefulness of [(18)F]-6-fluorodopamine ([(18)F]-DA) and [(18)F]-L-6-fluoro-3,4-dihydroxyphenylalanine ([(18)F]-DOPA) positron emission tomography (PET) in the detection of subcutaneous (s.c.) and metastatic pheochromocytoma in mice; to assess the expression of the norepinephrine transporter (NET) and vesicular monoamine transporters 1 and 2 (VMAT1 and VMAT2), all important for [(18)F]-DA and [(18)F]-DOPA uptake. Furthermore, to compare tumor detection by micro-computed tomography (microCT) to magnetic resonance imaging (MRI) in individual mouse. SUV(max) values were calculated from [(18)F]-DA and [(18)F]-DOPA PET, tumor-to-liver ratios (TLR) were obtained and expression of NET, VMAT1 and VMAT2 was evaluated. [(18)F]-DA detected less metastatic lesions compared to [(18)F]-DOPA. TLR values for liver metastases were 2.26-2.71 for [(18)F]-DOPA and 1.83-2.83 for [(18)F]-DA. A limited uptake of [(18)F]-DA was found in s.c. tumors (TLR = 0.22-0.27) compared to [(18)F]-DOPA (TLR = 1.56-2.24). Overall, NET and VMAT2 were expressed in all organ and s.c. tumors. However, s.c. tumors lacked expression of VMAT1. We confirmed [(18)F]-DA's high affinity for the NET for its uptake and VMAT1 and VMAT2 for its storage and retention in pheochromocytoma cell vesicles. In contrast, [(18)F]-DOPA was found to utilize only VMAT2. MRI was superior in the detection of all organ tumors compared to microCT and PET. [(18)F]-DOPA had overall better sensitivity than [(18)F]-DA for the detection of metastases. Subcutaneous tumors were localized only with [(18)F]-DOPA, a finding that may reflect differences in expression of VMAT1 and VMAT2, perhaps similar to some patients with pheochromocytoma where [(18)F]-DOPA provides better visualization of lesions than [(18)F]-DA.


EOG in a large family with hereditary macular degeneration. (Best's vitelliform macular dystrophy) identification of gene carriers.
A total of 128 descendants from one large family with a history of hereditary macular degeneration (HMD) were examined with EOG. Of these, 42 were affected patients, 48 were healthy offsprings to affected parents, and 38 were normal controls. Affected subjects had a light peak/dark trough ratio smaller than 1.40. In the group of offspring of affected parents the Lp/DT ratios showed a bimodal distribution dividing the group into two parts, one with values less than 1.40 and another with values larger than 1.70. Thus carriers of the HMD gene can apparently be identified by use of EOG. The affected subjects and the carriers had a lower base value of the standing potential than the controls.


An analysis of clinicopathological features and prognosis by comparing hepatoid adenocarcinoma of the stomach with AFP-producing gastric cancer.
To investigate the differences between alpha-fetoprotein-producing gastric cancer (AFPPGC) and hepatoid adenocarcinoma of the stomach (HAS), and the clinicopathologic features and prognosis of HAS. From 1996 to 2007, there were 111 patients with elevated serum level of alpha-fetoprotein (AFP) preoperatively in Fudan University Shanghai Cancer Center. Primary lesions of 104 patients were stained positively for AFP. Among these patients, 45 patients were diagnosed as HAS. The clinicopathologic characteristics and prognostic factors of AFPPGC and HAS were analyzed. Additionally, 208 stage-matched AFP-negative gastric cancer patients were selected as control. Immunohistochemically, the tumor cells were positive for AFP in AFPPGC. Histologically, the polygonal tumor cells were arranged in trabecular fashion or solid nests separated by narrow fibrous stroma composed of sinusoid-like capillaries in HAS. The survival rates of the three groups were statistically different (P < 0.01). AFP-producing gastric cancer and HAS had more aggressive behavior than that of common gastric cancer. The prognosis of HAS was poorer than that of AFPPGC, therefore it should be distinguished from the latter.


Bioequivalence study of a valsartan tablet and a capsule formulation after single dosing in healthy volunteers using a replicated crossover design.
Two formulations of valsartan (Diovan), 320 mg tablets and marketed 160 mg capsules, were evaluated for bioequivalence after single dosing. The study was designed as a single-center, open-label, 2-treatment, 3-period, repeated-measure (replicated), randomized crossover comparison in 40 healthy volunteers, all of whom completed the study successfully. Valsartan was determined in plasma by HPLC with fluorescence detection after solid-phase extraction. Comparing the new 320 mg tablet with 2 x 160 mg of the marketed valsartan capsules taken at the same time, the ratios of the least square means for AUC(0-t), AUC(all), AUC(0-infinity) and Cmax were 1.11, 1.10, 1.10 and 1.09, respectively. The 90% confidence intervals of the AUC and Cmax parameters were within the range of 0.80-1.25. Bioequivalence of the new 320 mg tablet with 2 marketed 160 mg capsules was demonstrated.


Management of Nipple Discharge.
Nipple discharge is the third most common breast-related complaint but is rarely the presenting symptom of breast cancer. Distinguishing patients with physiologic versus pathologic nipple discharge, and treating the later according to the underlying pathologic condition is of utmost importance. Nipple discharge is categorized as lactational, physiologic, or pathologic. Physiologic nipple discharge (galactorrhea) is typically caused by hyperprolactinemia due to medications (ie, antipsychotics), pituitary tumors, and endocrine disorders. When a suspicious radiologic lesion is identified, pathologic assessment of the lesion is indicated. Patients with pathologic nipple discharge should be referred to a breast surgeon for definitive treatment and follow-up.


Habitat selection of larval brook lampreys (Lampetra planeri, Bloch) in a South Swedish stream.
The burrowing larvae of the brook lamprey Lampetra planeri (Bloch) were shown by discriminant analysis to inhabit stream sites having certain qualities. Although a few larvae occurred in far-from-optimal habitats, most larvae selected those with low current velocity, low water depth, a low number of particles in the 0.5-1 mm range, and with low chlorophyll α content. Other factors normally positively attributed to larval lamprey distribution such as organic content, shade, and presence of algae did not improve the discriminant model. The last factor even showed a negative correlation. Stream bed stability was considered to be of great importance although it was not possible to estimate quantitatively.


Comparative study of spinal motoneuron axon collaterals.
Numerous spinal motoneurons in mammals possess recurrent axon collaterals included in a feedback loop for controlling motoneuron activity. For nonmammalian vertebrates, the data concerning the existence of collaterals and their intraspinal branching are fragmentary and contradictory. We focused on axonal branching of motoneurons in lampreys, frogs, turtles and young rats, using light microscopic analysis of HRP- or neurobiotin-labeled motoneurons. In lampreys, only a restricted portion of spinal motoneurons, related to the dorsal fins, showed recurrent collaterals. In frogs, a great complexity and high total length of collateral branches as well as a great number of axon swellings were found. In turtles, axon collateralization of spinal motoneurons was much more restricted, and present in particular in lumbar motoneurons innervating proximal hindlimb muscles. Young rat spinal motoneurons have rather abundant recurrent axon collaterals. It is likely that the presence of axon collaterals from spinal motoneurons is related to the level of complexity of locomotion.


Using structural equation model to explore occupational lead exposure pathways.
The aim of the present study was to demonstrate the use of a structural equation model to explore the complicated lead exposure pathways in a lead battery plant. A total of 96 out of 113 assembly workers were recruited in this study. Lead measurements included blood lead, respirable airborne lead, and body surface lead loadings. Latent variables of inadvertent contact of lead on fingers and ingested lead had indirect and direct effects on the blood lead levels, respectively, and so did the variables of respirable airborne lead, smoking, and the working-place clothes being washed. A model chi(22)2 value of 31.1 (P=0.094) for a goodness of fit test indicates that the derived structural equation model appropriately accounted for the variation of blood lead levels. It is concluded that lead loadings on fingers and lips had significant effects on occupational lead uptake, and, after-work hours and break times at work were the critical time periods for inadvertent lead exposure.


Uncommon but Clinically Significant: Bacillus Calmette-Guerin (BCG) Infection of the Urinary Tract and its Impact on Quality of Life.
BACKGROUND The intravesical administration of bacillus Calmette-Guerin (BCG), an attenuated live strain of Mycobacterium bovis, is an immunotherapy given for superficial bladder cancer and is generally well tolerated and widely used. However, BCG sometimes causes local infections, such as cystitis and prostatitis or systemic infection. Because BCG infection is a rare complication of intravesical BCG instillation, the combination of an anti-tuberculous regimen and its duration of are unknown. CASE REPORT We describe 2 cases of BCG infection localized to the urinary tract. Case 1 was a 77-year-old man with BCG infection of the bladder and prostate. Combination therapy of anti-tuberculous agents with isoniazid, rifampicin, and ethambutol did not improve his symptoms, and his quality of life was significantly impaired from the symptoms of BCG infection; therefore, he underwent total resection of the bladder and prostate. Case 2 was an 84-year-old man with BCG infection of the bilateral ureter and bladder. It took 15 months for his symptoms to improve, but combination therapy with isoniazid, rifabutin, and ethambutol improved his condition completely. CONCLUSIONS Although BCG infection of the urinary tract is a rare complication, it is clinically important because it directly affects the quality of life of patients and requires a longer duration of treatment, depending on the symptoms. Tissue cultures are also difficult to culture, making a definitive diagnosis challenging. If the symptoms of BCG infection are not controlled, surgery can be necessary even if it is not a complication of a vital organ.


Elemental analysis of serum and hair from pre-eclamptic South African women.
Pre-eclampsia is a hypertensive disorder that is associated with adverse maternal and perinatal outcomes. It has been proposed that specific trace and macro elements associated with antioxidant activities may also play a contributory role in aetiology of pre-eclampsia. The aim of this study was to measure the concentrations of thirteen different elements in hair and serum samples from women with a diagnosis of pre-eclampsia and compare them with normotensive controls. Venous blood and pubic hair samples were collected from forty-three pre-eclamptic and twenty-three normotensive pregnant women. In each sample, the concentration of arsenic (As); calcium (Ca); cadmium (Cd); chromium (Cr); cobalt (Co); magnesium (Mg); manganese (Mn); iron (Fe); copper (Cu); lead (Pb); selenium (Se); nickel (Ni); zinc (Zn) were measured using inductively coupled plasma-optical emission spectrometry. Cobalt concentration in hair was significantly lower in the pre-eclampsia group (1.56±0.74μg/g) compared to the normotensive group (2.89±4.99μg/g) (p=0.02). The concentrations of Zn and Cr were significantly higher in hair samples from the pre-eclamptic group, compared to the normotensive control group (Zn, 395.99±48.60 vs 330.88±29.70μg/g; Cr, 13.31±2.67 vs 11.05±7.62μg/g: p≤0.05). There were no significant differences in the hair levels of other elements between groups. Serum Zn was significantly higher in the pre-eclamptic group (0.16-253.4mg/L) compared to the normotensive group (0.2-48.4mg/L) (p=0.01). Serum Ca, Co, Cu, Mg, Mn and Se levels were found to be significantly lower in the pre-eclamptic group compared to the normotensive group (p<0.05). This study confirms the association between pre-eclampsia and maternal trace as well as macro element levels.


Arisugacins A and B, novel and selective acetylcholinesterase inhibitors from Penicillium sp. FO-4259. I. Screening, taxonomy, fermentation, isolation and biological activity.
An in vitro screening method for selective acetylcholinesterase (AChE) inhibitors was established. Inhibitory activity of AChE and butyrylcholinesterase (BuChE) was measured and the culture broths of microorganisms that showed selective inhibition against AChE were characterized. By using this method, a strain producing the novel and selective inhibitors of AChE, arisugacins A and B, was picked out among over seven thousand microorganisms tested. Arisugacins were obtained as white powders from the culture broth together with three known compounds, territrems B and C and cyclopenin that also showed selective inhibition against AChE. Arisugacins and territrems are members of the meroterpenoid compounds. They showed potent inhibitory activities against AChE with IC50 values in range of 1.0 approximately 25.8 nM. Furthermore, they showed greater than 2,000-fold more potent inhibition against AChE than BuChE.


The influence of harvest time on total phenolic and flavonoid contents, antioxidant, antibacterial and cytotoxicity of Rheum khorasanicum root extract.
For many centuries, medicinal herbs and their derivatives have been used to treat or prevent various diseases. However, environmental factors such as the season for collection of plant may change the therapeutic efficacy. The present work investigates seasonal variations of phenolic, flavonoid content, antioxidant, antibacterial, and cytotoxic potential of hydroalcoholic extract of Rheum khorasanicum (HER). R. khorasanicum was collected in three different months: December, February, and April. The Folin-Ciocalteu assay was applied to measure the total phenolic content of HER. Antioxidant activities (DPPH and FRAP) were also determined. Next, the extracts were evaluated for antibacterial potential against some Gram-positive and Gram-negative strains. The minimal inhibitory concentration (MIC) was determined by the microdilution method. Finally, the effect of extracts on the viability of C6, A549, and HT-29 cells was evaluated via the MTT assay. All three extracts contained considerable phenolic and flavonoid contents and showed desirable antioxidant activity. The April sample exhibited the greatest phenolic and flavonoid content and significant antioxidant activity potential in the FRAP test. In addition, the April sample had the highest antibacterial activity and cytotoxic effect on the cancerous cell lines. The April extract showed more antioxidant, antibacterial and cytotoxic effect, probably because of its higher phenolic and flavonoid contents than other samples. These results demonstrate that the harvest timing of R. khorasanicum affects the plant's phenolic content and its antioxidant and cytotoxicity activities.


Electron-microscopic evidence for particles smaller than 250 A in very low density lipoproteins of human plasma.
Particle size distributions of very low density lipoproteins (VLDL) in man were examined by electron microscopy. A comparison was made between normolipidemic and hyperlipidemic subjects. The results showed that the VLDL fraction frequently contained particles between 100--250 A in diameter and in some cases particles less than 100 A were observed.


Visual stimulation increases regional cerebral blood flow and metabolism in the goldfish.
Studies with radioactive antipyrene and deoxyglucose indicated that both blood flow and metabolism are enhanced in the goldfish optic tectum following a brief visual stimulation. It is concluded that the brain of cold-blooded animals demonstrates regionally regulated physiological alterations, previously reported only in warm-blooded species.


Differentiation between complicated and uncomplicated appendicitis: diagnostic model development and validation study.
Differentiating complicated appendicitis has become important, as multiple trials showed that non-operative management of uncomplicated appendicitis is feasible. We developed and validated a diagnostic model to differentiate complicated from uncomplicated appendicitis. This retrospective study included 1153 patients (mean age ± standard deviation, 30 ± 8 years) with appendicitis on CT (804 patients for development, and 349 for validation). Complicated appendicitis was confirmed in 300 and 121 patients in the development and validation datasets, respectively. The reference standard was surgical or pathological report except in 7 patients who underwent percutaneous abscess drainage. We developed a model using multivariable logistic regression and Bayesian information criterion. We assessed calibration and discriminatory performance of the model in the validation dataset via calibration plot and the area under the curve (AUC), respectively. We measured sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and proportion of false- and true-negatives of the model in the validation dataset, targeting 95% sensitivity. Five CT features (contrast-enhancement defect of the appendiceal wall, abscess, moderate or severe periappendiceal fat stranding, appendiceal diameter, and extraluminal air) and percentage of segmented neutrophil were included in our model. The calibration slope was 1.03, and AUC was 0.81 (95% CI 0.77-0.85) in the validation dataset. The sensitivity, specificity, PPV, NPV, and proportion of false- and true-negatives were 93.4% (91.8-99.1), 28.1% (13.6-24.1), 40.8% (35.0-46.8), 88.9% (79.3-95.1), 2.3%, and 18.3%, respectively. Our model may identify patients with unequivocally uncomplicated appendicitis, who may benefit from non-operative management with low risk of failure.


Neuropathic Symptoms in World Trade Center Disaster Survivors and Responders.
The objective of this research is to determine whether responders and survivors of the World Trade Center (WTC) disaster experience symptoms of neuropathy at a rate higher than those not exposed. A survey of neuropathic symptoms in patients who were and were not exposed at the WTC based upon the Michigan Neuropathy Screening Instrument (MNSI). Even after correction for medical comorbidities, age, and depression, neuropathic symptoms are much more common in those exposed to WTC dust and increase with increasing exposure. This study provides evidence that exposure to WTC dust is associated with neuropathic symptoms.


Noninvasive localization of human atherosclerotic lesions with indium 111-labeled monoclonal Z2D3 antibody specific for proliferating smooth muscle cells.
Targeting exclusive antigens in atherosclerotic plaques with antibodies may provide a noninvasive means to detect rapidly proliferative atherosclerotic lesions. 111In-labeled negative charge-modified Z2D3 F(ab')2 (Z2D3) specific for an antigen expressed exclusively by proliferating smooth muscle cells has been shown to accumulate in rabbit atherosclerotic plaques. The safety, biodistribution, accumulation, and elimination of Z2D3 were assessed in 11 patients who were candidates for carotid endarterectomy. The presence of atheromas in these patients was confirmed by angiography and Doppler ultrasound. Z2D3 (250 microg) labeled with 5 mCi of 111In was administered by slow intravenous injection. Planar and single photon emission computed tomography (SPECT) images were obtained 4, 24, 48, and 72 hours later. Carotid endarterectomy was performed and the surgical specimens were imaged, weighed, gamma-counted, and analyzed by immunostaining. Uptake of Z2D3 at the site of the carotid plaques was observed in the planar and SPECT views at 4 hours in all subjects. In addition, antibody uptake was noted in the contralateral vessel in 5 subjects. SPECT images identified the atherosclerotic plaques with focal uptake. The antibody uptake corresponded with the angiographic location of the disease. Immunohistochemical studies of the endarterectomy specimens confirmed the localization of Z2D3 into the plaque areas containing smooth muscle cells. Adverse drug reactions were not observed. This study demonstrates the feasibility of targeting atherosclerotic lesions with negative charge-modified antibody. It also proposes the possibility of selective identification of various components of atherosclerotic plaque, which may contribute to determining strategies of intervention in future.


Lignin isolated from primary walls of hybrid aspen cell cultures indicates significant differences in lignin structure between primary and secondary cell wall.
Hybrid aspen (Populus tremula x tremuloides) cell cultures were grown for 7, 14 and 21 days. The cell cultures formed primary cell walls but no secondary cell wall according to carbohydrate analysis and microscopic characterization. The primary walls were lignified, increasingly with age, according to Klason lignin analysis. Presence of lignin in the primary walls, with a higher content in 21-day old cells than in 7-day old cells, was further supported by phloroglucinol/HCl reagent test and confocal microscopy after both immunolocalization and staining with acriflavin. Both laccase and peroxidase activity were found in the cultures and the activity increased during lignin formation. The lignin from the cell culture material was compared to lignin from mature aspen wood, where most of the lignin originates in the secondary cell wall, and which served as our secondary cell wall control. Lignin from the cell walls was isolated and characterized by thioacidolysis followed by gas chromatography and mass spectrometry. The lignin in the cell cultures differed from lignin of mature aspen wood in that it consisted exclusively of guaiacyl units, and had a more condensed structure. Five lignin structures were identified by mass spectrometry in the cell suspension cultures. The results indicate that the hybrid aspen cell culture used in this investigation may be a convenient experimental system for studies of primary cell wall lignin.


A Student-Led Global Shared Medical Curriculum.
Students can be change agents in transforming medical education. The Medical Student Alliance for Global Education (MeSAGE) aims to establish a worldwide shared medical curriculum through open-access content focused on emerging global health issues. MeSAGE modules are novel tools for integration of ideas and topics important to medical students.


Desvenlafaxine As the Main Possible Culprit in Triggering Reversible Cerebral Vasoconstriction Syndrome: A Case Report.
Reversible cerebral vasoconstriction syndrome (RCVS) is not an uncommon condition. It should be suspected in young patients with new onset headaches and neurologic deficits. We report a 38-year-old male patient with a history of depression on desvenlafaxine for two years and no other triggering factor who was diagnosed with RCVS confirmed by cerebral angiogram. Discontinuation of the medication and calcium channel blockers initiation led to rapid clinical improvement. The diagnosis was further confirmed by angiographic improvement two months later. Although the association of selective serotonin reuptake inhibitors (SSRI)/ serotonin norepinephrine reuptake inhibitors (SNRI) with RCVS has been reported frequently, desvenlafaxine is a much less reported trigger, with only nine cases in total. In contrast to prior reported cases where the time from exposure to onset of RCVS was weeks to months, the time interval, in this case, was two years. This case report aims to support previous literature in suggestion of this association.


Intestinal absorption, excretion, and biotransformation of hyodeoxycholic acid in man.
Five patients fitted with a biliary T-tube after cholecystectomy were given orally a tracer dose of [14C]hyodeoxycholic acid and 500 mg of the same unlabeled acid. Intestinal absorption and biotransformation, liver metabolism, bile secretion, fecal and urinary excretions of this acid or of its metabolites were studied. Hyodeoxycholic acid was well absorbed by the human intestine. It was not subjected to intestinal transformations and, particularly, did not produce a significant amount of lithocholic acid, which does not support the existence of intestinal bacterial 6 alpha-dehydroxylases. The percentage of hyodeoxycholic acid and of its metabolites recovered in bile varied from 11.5 to 31%. Two major metabolites were isolated from bile: glycohyodeoxycholic acid and hyodeoxycholic acid glucuronide. Analysis of urinary bile acids showed that a large proportion (30-84%) of the administered hyodeoxycholic acid was excreted by the kidney as a glucuronide. The large extent of both glucuronidation and urinary excretion of hyodeoxycholic acid is a unique example of bile acid metabolism and excretion in man.


Cardiovascular health and target end-organ damage and comorbidities in hypertensive patients from a Spanish primary care urban population.
We hypothesized that a poorer cardiovascular health status is related to a higher risk of hypertension-mediated organ-damage (HMOD) or hypertension-related comorbidities (HRC). We assessed the relationship between cardiovascular health metrics (CVHM) and HMOD-HRC in 243 hypertensive patients from primary care center followed for two years. We recorded the baseline CVHM score (Life's Simple 7) plus clinical data, including prevalent and incident HMOD-HRC, hospitalization and mortality. The prevalence of ideal CVHM scores was very low in both men and women. The patients with healthier CVHM scores were younger, and had a lower prevalence of diabetes, cardiovascular disease and chronic kidney disease. We recorded 264 cases of HMOD-HRC (225 at baseline and 39 during follow-up). Nine patients died and 64 had any-cause hospitalization during follow-up. A lower prevalence of HMOD-HRC and unfavorable outcomes was observed as the number of ideal CVHM increased (P<0.05). Multivariate logistic regression adjusted for confounders showed a lower CVHM score (0-1) was associated with increased odds of HMOD-HRC (4.04, 95% CI 1.26-12.94; P=0.019) and composite endpoint (HMOD-HRC, death or all-cause hospitalization) (3.43, 95% CI 1.19-9.92; P=0.023). Individual components were less predictive than the cumulative CVHM score. Few hypertensive patients in this urban population had ideal CVHM scores. An inverse relationship between scores and outcomes (HMOD-HRC, death or hospitalizations) was observed. Interventions to increase this score may improve prognosis among community-based hypertensive patients.


Spectral Properties of Schrödinger Operators Associated with Almost Minimal Substitution Systems.
We study the spectral properties of ergodic Schrödinger operators that are associated with a certain family of non-primitive substitutions on a binary alphabet. The corresponding subshifts provide examples of dynamical systems that go beyond minimality, unique ergodicity and linear complexity. In some parameter region, we are naturally in the setting of an infinite ergodic measure. The almost sure spectrum is singular and contains an interval. We show that under certain conditions, eigenvalues can appear. Some criteria for the exclusion of eigenvalues are fully characterized, including the existence of strongly palindromic sequences. Many of our structural insights rely on return word decompositions in the context of non-uniformly recurrent sequences. We introduce an associated induced system that is conjugate to an odometer.


Shelf life study of healthy pork liver pâté with added seaweed extracts from Ascophyllum nodosum, Fucus vesiculosus and Bifurcaria bifurcata.
The effect of the addition of seaweed extracts from three brown algae species [Ascophyllum nodosum (AN), Fucus vesiculosus (FV) and Bifurcaria bifurcata (BB)], which are a great source of natural antioxidants, on the oxidative stability of refrigerated low-fat pork liver pâtés was studied. In the studied pâtés, half of pork fat was replaced with a mixture consisting of canola and high-oleic sunflower oil (75:25, v/v), thus improving their fatty acid profile in terms of polyunsaturated fatty acids (PUFA). In order to avoid the oxidation of PUFA in the new samples, seaweed extracts (500 ppm) were added. In addition, some samples were formulated with a synthetic antioxidant (BHT at 50 ppm) (BHT) and a control batch (CON) (without antioxidant) was also prepared, for comparison purposes. Thus, in total, five batches of liver pâté were prepared: CON, BHT, AN, FV and BB. Pâté samples were analyzed at 0, 45, 90, 135 and 180 days of refrigerated storage at 4 °C. The addition of seaweed extracts did not modify significantly (P > 0.05) the chemical composition or microbial characteristics of healthy pork liver pâté, except for the protein content, which resulted in a significant increase (≈2-3%) in the batches manufactured with addition of seaweed extracts compared to control samples. At the end of storage (180 days), L* values were significantly lower in the FV and BB batches than in the other batches. Moreover, the a* and b* values were also significantly lower in CON batches than in the samples with antioxidants added. Differences in oxidative parameters (conjugated dienes, TBARs and carbonyls) among batches were observed at the end of the storage time, showing samples with seaweed extracts a similar degree of protection against oxidation compared to BHT formulated samples. A decline of the volatile compounds was noted in all the batches during storage. The total volatile compounds at the end of the storage were significantly lower in BTH, AN, or BB batches than in control batches.


Stabilization of human neutrophil NADPH oxidase activated in a cell-free system by cytosolic proteins and by 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide.
The superoxide-generating respiratory burst oxidase (NADPH oxidase) from human neutrophils can be activated in a cell-free system consisting of plasma membrane and cytosol by anionic amphiphiles such as sodium dodecyl sulfate and arachidonate (McPhail, L. C., Shirley, P. S., Clayton, C. C., and Snyderman, R. (1985) J. Clin. Invest. 75, 1735-1739; Curnutte, J. T. (1985) J. Clin. Invest. 75, 1740-1743; Bromberg, Y., and Pick, E. (1984) Cell. Immunol. 88, 213-221). Herein, the activity thus obtained is shown to be very labile at 37 degrees C. The rate of inactivation varied inversely with cytosol concentration. The stabilizing factor(s) was destroyed by heat and trypsin, indicating that it is protein in nature. Whereas cytosol from normal cells and from a chronic granulomatous disease patient lacking p67phox stabilized the oxidase activity, that from a chronic granulomatous disease patient lacking p47phox did not. Also, dialdehyde NADPH-treated cytosol showed no stabilizing effect, indicating that p47phox and a putative NADPH-binding component both participate in stabilization. The mechanism of inactivation was further explored by examining the stabilizing effect of agents that can act as chemical cross-linkers. Of several tested, 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) was the most effective, but others that utilize different chemical mechanisms were also partially effective. EDC extended the half-life at 37 degrees C from 2 to 120 min, protected against the inactivating effects of Triton X-100 and high salt, and did not affect the Km for NADPH. Stabilization required prior activation in the presence of both cytosol and membrane; and EDC treatment of cytosol, membrane, or a mixture of the two prior to the addition of sodium dodecyl sulfate failed to induce stabilization. EDC eliminated the requirement for the continuous presence of cytosol and activator. Dialysis did not cause a loss in activity, whereas control activity was diminished with dialysis and was largely restored with added sodium dodecyl sulfate. In the absence of EDC, the separation of cytosol from the membrane fraction resulted in a significant loss of activity, which was largely restored by the addition of cytosol. However, EDC treatment allowed the isolation of a nearly fully active oxidase in the membrane fraction, the activity of which was not influenced by added cytosol. These results support a model in which the active NADPH oxidase consists of a dissociable complex among membrane and cytosolic components and indicate that the longevity of the activated state requires continuous association of these components.


Effect of a 48-hour intravenous delta 4-androstenedione infusion on the pregnant rhesus monkey in the last third of gestation: changes in maternal plasma estradiol concentrations and myometrial contractility.
Increased myometrial activity in the pregnant rhesus monkey occurs in situations in which plasma estrogen concentrations are elevated. Examples of such situations are after laparotomy, with or without hysterotomy, and before delivery. The increased activity occurs primarily in the hours of darkness. To investigate the possibility of a causal relationship between the rise in estrogens and myometrial activity, we infused androstenedione intravenously for 48 hours to the rhesus monkey in the last third of gestation. Myometrial activity was quantified either as an increase in the number of individual contraction events or as a change in the power spectrum at high frequencies characteristic of contractions. Androstenedione infusion was followed by increased myometrial activity. Maternal plasma 17 beta-estradiol concentration was significantly elevated at 10 AM on the second day of androstenedione infusion. We conclude that, in the rhesus monkey late in gestation, estradiol may play a role in the regulation of the contraction activity observed during the hours of darkness in several different situations.


[Retrospective study of serological tests for syphilis diagnosis at Nantes University hospital, between 1999 and 2006].
Since 2000, a resurgence of syphilis cases was observed in France and, particularly, in Paris area. The aim of this study was to evaluate the evolution of syphilis prevalence in Nantes area and its impact on our laboratory activity. Between 1999 and 2006, serological tests for syphilis performed at the laboratory were analysed according to the results of these tests, the age and patient sex and the wards. We treated about 32,000 serological tests, over an eight-year period. The number of tests increased by 7.5% per year and patients with a positive result were multiplied by three. These patients were men for 78%, with an average age of 43.4 years. The serological tests providing positive results were in general from two sectors, the anonymous and free detection center and the internal medicine ward and infectious diseases unit. Our study highlighted a strong increase in the number of positive tests, since 2001, with a clear orientation towards a sex male ratio in our area. This inclination currently did not show any decrease, at the opposite to what was observed by the InVS in Paris area.


Current approaches and strategies to identify Hedgehog signaling pathway inhibitors for cancer therapy.
The Hedgehog signaling pathway plays a vital role in embryonic development and tissue patterning. Aberrant regulation of this pathway is commonly associated with the occurrence, development and progression of various types of malignancies. The development of inhibitors targeting Hedgehog pathway has attracted significant interests in cancer therapy and led to the discovery of three drugs Vismodegib, Sonidegib and Glasdegib. However, their clinical application has been hampered due to adverse effects and resistance issues, highlighting the urgent need for new inhibitors. Herein we give a systematic overview of the current status and characteristics of various approaches to developing the Hedgehog pathway inhibitors, including library screening, natural product-oriented approach, analogue approach, drug repositioning, in silico tools and others. The future prospects are also discussed for the discovery and development of next-generation inhibitors.


Airway and ventilation management.
Airway management is fundamental to ACLS. Success with any airway device relies as much on the operator's experience and skill as on the device itself. The purpose of using an airway device is to provide a patent route for ventilating the lungs and to protect against pulmonary aspiration. Training should emphasize the importance of confirming that the airway device is positioned correctly and that the lungs can be ventilated effectively. If airway intervention is to have a positive effect on outcome, the choice of airway device is less important than thorough training, ongoing experience and review, and close attention to complications. Regardless of whether a provider chooses to use the LMA, the combitube, or the tracheal tube, providers must be familiar with more than one method of airway management because of the possibility of failure to insert or ventilate with their primary airway device of choice.


Primary human keratinocytes externalize stratifin protein via exosomes.
Although, stratifin (SFN) is externalized by keratinocytes and stimulates the expression of matrix metalloproteinase-1 (MMP-1) in fibroblasts, its mechanism of externalization is not known. Here, we hypothesize that keratinocytes have a capacity to release stratifin through externalization of exosomes. To test this hypothesis, exosomes were purified from human keratinocyte conditioned medium (KCM) and analyzed for the presence of SFN by Western blot analysis using lysosomal-associated membrane protein 2 (LAMP-2) and heat shock cognate 70 (hsc70) as exosomal markers. The results showed the presence of SFN in keratinocyte lysate, concentrated KCM and exosomes, but not in concentrated unconditioned medium. Transmission electron microscopic examination revealed the presence of unique "saucer-like" structures characteristic of exosomes whose diameters were <100 nm. Similar to the recombinant SFN, the exosomes associated proteins stimulated MMP-1 expression in fibroblasts. Depletion of the exosomes markedly reduced this MMP-1 stimulatory effect. To further statistically confirm these findings, fibroblasts were treated with three different exosome preparations and the finding showed more than 7.4-fold increase in the level of MMP-1 in the treated cells. Furthermore, we found that approximately 1% of the total proteins contained in exosomes correspond to SFN. In conclusion, this study is the first report showing that keratinocytes have the capacity to produce exosomes through which some intracellular proteins such as SFN, with MMP-1 stimulating activity for fibroblasts, is externalized into keratinocyte microenvironment.


A new diatom growth inhibition assay using the XTT colorimetric method.
Marine biofouling, which leads to significant operational stress and economic damage on marine infrastructures, is a major problem in marine related industries. Currently, the most common way to avoid marine biofouling involves the use of biocidal products in surface coatings. However, the need for environmentally friendly antibiofouling compounds has increased rapidly with the recent global prohibition of harmful antifoulants, such as tributyltin (TBT). In particular, periphytic diatoms have been shown to contribute significantly to biofilms, which play an important role in biofouling. Therefore, inhibiting the proliferation of fouling diatoms is a very important step in the prevention of marine biofouling. In this study, we developed a new, rapid, accurate, and convenient growth inhibition assay using the XTT colorimetric method to prevent the growth of the fouling periphytic diatom, Nitzschia amabilis Hidek. Suzuki (replaced synonym, Nitzschia laevis Hustedt). The feasibility of this method was verified by determining the growth inhibition activities of two standard photosynthetic inhibitors, DCMU and CuSO4. However, neither inhibitor had any cytotoxic activities at the range of concentrations tested. Moreover, this method was applied by screening and purification of herbicidic but non-cytotoxic compounds from cyanobacteria extracts. Our results demonstrate the utility of this newly established growth inhibition assay for the identification of marine anti-biofouling compounds.


Role of Ca2(+)-calmodulin and protein kinase C in the secretory action of heat-labile enterotoxin of Escherichia coli in mice.
The mucosal-to-serosal and serosal-to-mucosal fluxes of Na+ and Cl- were carried out in control and heat-labile enterotoxin treated mice in the presence or absence of Ca2(+)-ionophore A23187, the activator of Ca2(+)-calmodulin or Phorbol-12-myristate-13-acetate (PMA), the activator of Protein kinase C (PKC) or 1-(5-isoquinolinyl sulphonyl)-2-methyl piperazine (H-7), an inhibitor of PKC. There was net secretion of Na+ and Cl- in experimental group in comparison to net absorption in control group. The addition of ionophore or PMA resulted in net secretion of Na+ and Cl- in control group. In experimental group ionophore increased the net secretion of Na+ and Cl- while, PMA could not cause any change in Na+ and Cl- fluxes in experimental group. Calmodulin activity remained unaltered in heat-labile enterotoxin treated mice as compared to control. H-7, reversed the effects of PMA and heat-labile enterotoxin. These studies demonstrate that heat-labile enterotoxin primarily involves PKC in its action.


Effect of salt concentration on immunoglobulin G structure.
An effect of salt concentration on the human myeloma immunoglobulin G structure was studied by means of circular dichroism, thermal perturbation difference spectroscopy and isoelectric focusing in a pH gradient created by a concentration gradient of glucose in borate buffer solution. Immunoglobulin G (K) Iva showed a significant shift of isoelectric point to the alkaline region as a result of the increase in salt concentration. The difference spectra indicated a change in the exposure of tyrosine residues as a result of increase in salt concentration. No changes in the circular dichroic spectra with salt concentration were observed between 205 and 250 nm. Spectral changes observed for the undigested immunoglobulin G molecule are more marked than those observed for the isolated Fab fragments.


Scaling of Berry-curvature monopole dominated large linear positive magnetoresistance.
The linear positive magnetoresistance (LPMR) is a widely observed phenomenon in topological materials, which is promising for potential applications on topological spintronics. However, its mechanism remains ambiguous yet, and the effect is thus uncontrollable. Here, we report a quantitative scaling model that correlates the LPMR with the Berry curvature, based on a ferromagnetic Weyl semimetal CoS2 that bears the largest LPMR of over 500% at 2 K and 9 T, among known magnetic topological semimetals. In this system, masses of Weyl nodes existing near the Fermi level, revealed by theoretical calculations, serve as Berry-curvature monopoles and low-effective-mass carriers. Based on the Weyl picture, we propose a relation [Formula: see text], with B being the applied magnetic field and [Formula: see text] the average Berry curvature near the Fermi surface, and further introduce temperature factor to both MR/B slope (MR per unit field) and anomalous Hall conductivity, which establishes the connection between the model and experimental measurements. A clear picture of the linearly slowing down of carriers, i.e., the LPMR effect, is demonstrated under the cooperation of the k-space Berry curvature and real-space magnetic field. Our study not only provides experimental evidence of Berry curvature-induced LPMR but also promotes the common understanding and functional designing of the large Berry-curvature MR in topological Dirac/Weyl systems for magnetic sensing or information storage.


Factors associated with elevated rates of adverse outcomes after cyclodestructive procedures versus drainage device procedures.
To identify factors associated with an increased risk of adverse outcomes after cyclodestructive or drainage device procedures. Retrospective, cohort analysis. A total of 5570 Medicare patients who were older than 65 years of age and who underwent cyclodestructive or drainage device procedures in 1994 participated. The authors identified cyclodestructive and drainage device procedures from claims to the Health Care Finance Administration (HCFA) by International Classification of Diseases (ICD-9) procedure codes, Current Procedural Terminology procedure codes, and HCFA Common Procedural Classification System codes. The authors analyzed adverse outcome rates using hierarchical logistic regression. Race, age group, gender, length of observed follow-up, state in which surgery took place, ocular procedures performed before and at the same time as the index surgery, and ocular diagnosis were included as covariates in the model. The authors defined an adverse outcome as the occurrence after the index surgery of at least one of the following: repeat cyclodestructive or drainage device procedure, retinal hole-tear repair, retinal detachment repair, surgery for endophthalmitis, vitrectomy, enucleation, evisceration, surgery for ocular hypotony, and/or extrusion or revision of drainage device. Adverse outcomes were also defined without the inclusion of repeat cyclodestructive or drainage device procedures. When repeat cyclodestructive or drainage device procedures were not included in the definition of an adverse outcome, eyes with a drainage device procedure were 3.8 times more likely to have an adverse outcome than eyes with a cyclodestructive procedure (odds ratio [OR], 3.8; 95% confidence interval [CI], 3.07, 4.67). Subjects with concurrent corneal transplant had increased odds of an adverse outcome compared to subjects without a concurrent corneal transplant (OR, 2.00; 95% CI, 1.27, 3.15). When the definition of an adverse outcome included repeat cyclodestructive or drainage device procedures, the odds of an adverse outcome were similar for both cyclodestructive and drainage device procedures (OR, 0.94; 95% CI, 0.79, 1.13). Cyclodestructive procedures need to be repeated more frequently than drainage device procedures. However, if the patient has a drainage device procedure, then that patient is more likely to have other types of adverse ophthalmic events than if he or she had a cyclodestructive procedure. Because the average follow-up of subjects in this study is 5 months (range, 0-12 months), outcomes that might take longer to manifest themselves would be excluded from this study.


Effects of hemiretinal form deprivation on central refractive development and posterior eye shape in chicks.
We determined effects of hemiretinal form deprivation (i.e., form-depriving half of the retina) on central refractive development and posterior eye shape in chicks. Seventy-seven White Leghorn chicks were randomly assigned to receive superior (SRD, "Superior Retinal Deprivation" or inferior visual field deprivation, same principle applies for the following abbreviations, n=17), inferior (IRD, n=14), temporal (TRD, n=23) or nasal hemiretinal (NRD, n=23) form deprivation monocularly from day 5 to day 26. Central refractive errors, expressed as interocular difference in spherical equivalent (M), J0 and J45 astigmatic components, were measured using Hartinger refractometer at the beginning and weekly after treatment for 3weeks. At the end of the treatment period, eyes of a subset of birds were enucleated and eye shape profile was photographed along four different meridians. These digital images were later processed to extract axial length (AL), equatorial diameter (ED), and AL/ED. For comparison purposes, the eye shape profile was also acquired from a separate group of birds reared with monocular full-retinal form deprivation (FRD, n=10). The four hemiretinal form deprivations altered central ametropia and posterior eye shape to different degrees. The biggest contrast in M was found between SRD and IRD groups (mean±SE after 3weeks: SRD=-4.14±0.71 D vs. IRD=+1.24±0.36 D; p<0.05), whereas subtle differences in J0 and J45 components were found across the four treatment groups (both p⩽0.03). SRD group also showed significantly higher AL/ED ratio compared to IRD and NRD groups (0.76±0.05 vs. 0.74±0.07 and 0.75±0.04; both p⩽0.03). Furthermore, M was significantly correlated with AL/ED ratio in the treated eyes of hemiretinal treated chicks (r=-0.55, p<0.001). Our results suggest that mechanism regulating central ametropia can be influenced by selectively interrupting the visual experience at different parts of visual field.


Assessment of cardiovascular risk in patients with rheumatoid arthritis using the SCORE risk index.
Rheumatoid arthritis is an autoimmune disease that causes systemic involvement and is associated with increased risk of cardiovascular disease. To analyze the prediction index of 10-year risk of a fatal cardiovascular disease event in female RA patients versus controls. Case-control study with analysis of 100 female patients matched for age and gender versus 100 patients in the control group. For the prediction of 10-year risk of a fatal cardiovascular disease event, the SCORE and modified SCORE (mSCORE) risk indexes were used, as suggested by EULAR, in the subgroup with two or more of the following: duration of disease ≥10 years, RF and/or anti-CCP positivity, and extra-articular manifestations. The prevalence of analyzed comorbidities was similar in RA patients compared with the control group (p>0.05). The means of the SCORE risk index in RA patients and in the control group were 1.99 (SD: 1.89) and 1.56 (SD: 1.87) (p=0.06), respectively. The means of mSCORE index in RA patients and in the control group were 2.84 (SD=2.86) and 1.56 (SD=1.87) (p=0.001), respectively. By using the SCORE risk index, 11% of RA patients were classified as of high risk, and with the use of mSCORE risk index, 36% were at high risk (p<0.001). The SCORE risk index is similar in both groups, but with the application of the mSCORE index, we recognized that RA patients have a higher 10-year risk of a fatal cardiovascular disease event, and this reinforces the importance of factors inherent to the disease not measured in the SCORE risk index, but considered in mSCORE risk index.


Demographic and clinical profile of microspodial keratitis in North India: an underreported entity.
Ocular microsporidiosis was first described in immunocompromised subjects but recent reports have also shown cases in immunocompetent hosts. The database of existing clinical studies is very limited. The aim of present study was to analyse demographic profile, clinical features, microbiological profile, treatment and outcome of ocular microsporidiosis in northern India. The present study was carried out in the Department of Medical Parasitology, Advanced Eye Center, Postgraduate Institute of Medical Education and Research, and Bharat Vikas Parishad Charitable trust, Chandigarh. A total of 250 patients during year 2013-17 and suspected of microsporidial keratitis (either clinically or after exclusion of bacterial, viral or fungal agents). Corneal scraping were taken and subjected for various staining methods and PCR. 8 patients of microsporidial keratitis were confirmed, based on positivity by at least any two of the above mentioned techniques. None of the patients had history of contact lens wear or exposure to swimming pool. All these patients were systemically healthy and HIV serology was negative except one had history of diabetes mellitus. This study is a reminder to clinicians that when multifocal diffuse epithelial keratitis and culture-negative keratoconjunctivitis not responding to medical therapy, regardless of immune status are found in patients with symptoms suggesting an infectious keratitis, microsporidial keratoconjunctivitis should be included in the differential diagnosis.


Redistribution of hepatocyte chloride during L-alanine uptake.
We used ion-sensitive, double-barrel microelectrodes to measure changes in hepatocyte transmembrane potential (Vm), intracellular K+, Cl-, and Na+ activities (aiK, aiCl and aiNa), and water volume during L-alanine uptake. Mouse liver slices were superfused with control and experimental Krebs physiological salt solutions. The experimental solution contained 20 mM L-alanine, and the control solution was adjusted to the same osmolality (305 mOsm) with added sucrose. Hepatocytes also were loaded with 50 mM tetramethylammonium ion (TMA+) for 10 min. Changes in cell water volume during L-alanine uptake were determined by changes in intracellular, steady-state TMA+ activity measured with the K+ electrode. Hepatocyte control Vm was -33 +/- 1 mV. L-alanine uptake first depolarized Vm by 2 +/- 0.2 mV and then hyperpolarized Vm by 5 mV to -38 +/- 1 mV (n = 16) over 6 to 13 min. During this hyperpolarization, aiNa increased by 30% from 19 +/- 2 to 25 +/- 3 mM (P < 0.01), and aiK did not change significantly from 83 +/- 3 mM. However, with added ouabain (1 mM) L-alanine caused only a 2-mV increase in Vm, but now aiK decreased from 61 +/- 3 to 54 +/- 5 mM (P < 0.05). Hyperpolarization of Vm by L-alanine uptake also resulted in a 38% decrease of aiCl from 20 +/- 2 to 12 +/- 3 mM (P < 0.001). Changes in Vm and VCl-Vm voltage traces were parallel during the time of L-alanine hyperpolarization, which is consistent with passive distribution of intracellular Cl- with the Vm in hepatocytes.(ABSTRACT TRUNCATED AT 250 WORDS)


Clinical impact of stress dose steroids in patients with septic shock: insights from the PROWESS-Shock trial.
The aim of our study was to evaluate the clinical impact of the administration of intravenous steroids, alone or in conjunction with drotrecogin-alfa (activated) (DrotAA), on the outcomes in septic shock patients. We performed a sub-study of the PROWESS-Shock trial (septic shock patients who received fluids and vasopressors above a predefined threshold for at least 4 hours were randomized to receive either DrotAA or placebo for 96 hours). A propensity score for the administration of intravenous steroids for septic shock at baseline was constructed using multivariable logistic regression. Cox proportional hazards model using inverse probability of treatment weighting of the propensity score was used to estimate the effect of intravenous steroids, alone or in conjunction with DrotAA, on 28-day and 90-day all-cause mortality. A total of 1695 patients were enrolled of which 49.5% received intravenous steroids for treatment of septic shock at baseline (DrotAA + steroids N = 436; DrotAA + no steroids N = 414; placebo + steroids N = 403; placebo + no steroids N = 442). The propensity weighted risk of 28-day as well as 90-day mortality in those treated vs. those not treated with steroids did not differ among those randomized to DrotAA vs. placebo (interaction p-value = 0.38 and p = 0.27, respectively) nor was a difference detected within each randomized treatment. Similarly, the course of vasopressor use and cardiovascular SOFA did not appear to be influenced by steroid therapy. In patients with lung infection (N = 744), abdominal infection (N = 510), Gram-positive sepsis (N = 420) and Gram-negative sepsis (N = 461), the propensity weighted risk of 28-day as well as 90-day mortality in those treated vs. those not treated with steroids did not differ among those randomized to DrotAA vs. placebo nor was a difference detected within each randomized treatment. In the present study of septic shock patients, after adjustment for treatment selection bias, we were unable to find noticeable positive impact from intravenous steroids for treatment of septic shock at baseline either in patients randomized for DrotAA or placebo. Clinicaltrials.gov NCT00604214 . Registered 24 January 2008.


Hashimoto's thyroiditis - an independent risk factor for papillary carcinoma.
The link between Hashimoto's thyroiditis and thyroid carcinoma has long been a topic of controversy. The aim of our study was to determine the prevalence of thyroid carcinoma and Hashimoto's thyroiditis coexistence in histopathologic material of thyroidectomized patients. In a retrospective study, the clinicohistopathologic data of 2117 patients (1738 females/379 males), who underwent total or partial thyroidectomy for thyroid gland disorder at a single institution from the 1st of January 2005 to the 31st of December 2014 were analyzed. Thyroid carcinoma was detected in 318 cases (15%) and microcarcinoma (thyroid cancer ≤10mm in diameter) was found in permanent sections in 169 cases (8%). Hashimoto's thyroiditis was detected in 318 (15%) patients. Hashimoto's thyroiditis was significantly more often associated with thyroid carcinoma and microcarcinoma compare to benign condition (p=0.048, p=0.00014, respectively). Coexistence of Hashimoto's thyroiditis and thyroid carcinoma/thyroid microcarcinoma did not affect tumor size (p=0.251, p=0.098, respectively), or tumor multifocality (p=0.831, p=0.957, respectively). Bilateral thyroid microcarcinoma was significantly more often detected when Hashimoto's thyroiditis was also diagnosed (p=0.041), but presence of Hashimoto's thyroiditis did not affect bilateral occurrence of thyroid carcinoma (p=0.731). Hashimoto's thyroiditis is associated with significantly increased risk of developing thyroid carcinoma, especially thyroid microcarcinoma.


Transgenerational inheritance of metabolic disease.
Metabolic disease encompasses several disorders including obesity, type 2 diabetes, and dyslipidemia. Recently, the incidence of metabolic disease has drastically increased, driven primarily by a worldwide obesity epidemic. Transgenerational inheritance remains controversial, but has been proposed to contribute to human metabolic disease risk based on a growing number of proof-of-principle studies in model organisms ranging from Caenorhabditis elegans to Mus musculus to Sus scrofa. Collectively, these studies demonstrate that heritable risk is epigenetically transmitted from parent to offspring over multiple generations in the absence of a continued exposure to the triggering stimuli. A diverse assortment of initial triggers can induce transgenerational inheritance including high-fat or high-sugar diets, low-protein diets, various toxins, and ancestral genetic variants. Although the mechanistic basis underlying the transgenerational inheritance of disease risk remains largely unknown, putative molecules mediating transmission include small RNAs, histone modifications, and DNA methylation. Due to the considerable impact of metabolic disease on human health, it is critical to better understand the role of transgenerational inheritance of metabolic disease risk to open new avenues for therapeutic intervention and improve upon the current methods for clinical diagnoses and treatment.


Blood pressure and adipose tissue linoleic acid.
In a natural, "free-living population" of 650 men, surveyed with the purpose of health assessment within an epidemiological design, a strongly significant negative correlation between the relative linoleic acid composition of adipose tissue and blood pressures was found (P less than 0.001). This correlation remained significant when age and weight were statistically controlled for. Thus, dietary, lipid-lowering linoleic acid seems to effect blood pressures as well in a favorable way.


The MAL Family of Proteins: Normal Function, Expression in Cancer, and Potential Use as Cancer Biomarkers.
The MAL family of integral membrane proteins consists of MAL, MAL2, MALL, PLLP, CMTM8, MYADM, and MYADML2. The best characterized members are elements of the machinery that controls specialized pathways of membrane traffic and cell signaling. This review aims to help answer the following questions about the MAL-family genes: (i) is their expression regulated in cancer and, if so, how? (ii) What role do they play in cancer? (iii) Might they have biomedical applications? Analysis of large-scale gene expression datasets indicated altered levels of MAL-family transcripts in specific cancer types. A comprehensive literature search provides evidence of MAL-family gene dysregulation and protein function repurposing in cancer. For MAL, and probably for other genes of the family, dysregulation is primarily a consequence of gene methylation, although copy number alterations also contribute to varying degrees. The scrutiny of the two sources of information, datasets and published studies, reveals potential prognostic applications of MAL-family members as cancer biomarkers-for instance, MAL2 in breast cancer, MAL2 and MALL in pancreatic cancer, and MAL and MYADM in lung cancer-and other biomedical uses. The availability of validated antibodies to some MAL-family proteins sanctions their use as cancer biomarkers in routine clinical practice.


Clinical outcomes and resource utilisation in patients with major burns treated with NovoSorb® BTM.
Patients with major burns can undergo temporary coverage while skin graft donor sites heal, where dermal templates have an emerging role. The aim of this study was to evaluate the clinical outcomes and resource utilisation in patients with major burns treated with a bilayer biodegradable synthetic matrix (NovoSorb BTM). This retrospective cohort study included patients admitted to the Royal Brisbane and Women's Hospital Adult Burn Unit with burns to at least 40 % TBSA who survived their acute admission. Patients treated from July 2017 to June 2022 with BTM were compared with patients with similar injuries treated using cadaveric allograft as temporising full thickness wound coverage between January 2013 and June 2017. Outcomes measures included number of operations, total operative time, hospital and intensive care unit (ICU) length of stay (LOS), cadaveric allograft and BTM use, and blood product use. Unadjusted comparisons were made with Wilcoxon Rank-Sum tests and Fisher's exact tests. Multivariate linear regression was used to adjust for the effect of TBSA on each outcome. Fifty-five patients were included (78 % male), 22 of whom were treated with BTM. We found no significant differences in age, sex, or TBSA between groups. One patient had half of the BTM removed due to infection and replaced with allograft. Patients treated with BTM had significantly less operative theatre time (median 1361.5 min [BTM] vs 1768 min [no BTM], P = 0.044). Number of operations, allograft use, hospital and ICU LOS, and blood product use were similar between groups. Adjusted models accounting for TBSA supported unadjusted models. Resource utilisation and clinical outcomes were similar in patients with at least 40 % TBSA treated with BTM and those who were treated with allograft before the introduction of BTM. Patients treated with BTM had significantly less total operative time and no difference in number of operations, allograft use and ICU LOS.


Environment-dependent morphology in plasmodium of true slime mold Physarum polycephalum and a network growth model.
Branching network growth patterns, depending on environmental conditions, in plasmodium of true slime mold Physarum polycephalum were investigated. Surprisingly, the patterns resemble those in bacterial colonies even though the biological mechanisms differ greatly. Bacterial colonies are collectives of microorganisms in which individual organisms have motility and interact through nutritious and chemical fields. In contrast, the plasmodium is a giant amoeba-like multinucleated unicellular organism that forms a network of tubular structures through which protoplasm streams. The cell motility of the plasmodium is generated by oscillation phenomena observed in the partial bodies, which interact through the tubular structures. First, we analyze characteristics of the morphology quantitatively, then we abstract local rules governing the growing process to construct a simple network growth model. This model is independent of specific systems, in which only two rules are applied. Finally, we discuss the mechanism of commonly observed biological pattern formations through comparison with the system of bacterial colonies.


A polypeptide conjugate of bilirubin from human bile.
An alkali-stable bilirubin conjugate has been obtained from human T-tube bile as its phenylazo derivative. The conjugate consists of a polypeptide probably of molecular weight 7000 to which the azo pigment of bilirubin is linked covalently through its carboxyl group. It thus constitutes the first biliprotein found in mammals. It is not known whether both carboxyl groups of native bilirubin participate in the binding of the conjugating protein, nor has it been possible to determine the number of pigment moieties occurring on a single polypeptide chain. The isolation makes use of the tendency of the conjugate to form large aggregates and involves the following steps: azo coupling of the native bile, (NH4)2S04 precipitation of macromolecules and aggregates, removal of low molecular weight contaminants by dialysis and gel filtration (first on Sepharose 6B IN 6 M guanidine, then on Sephadex LH-20 in 50% acqueous 2-chloroethanol) and a concluding purification by chromatography on p-aminobenzyl cellulose using a PH gradient. The final preparation appeared to be homogeneous on polyacrylamide electrophoresis.


[Series: Education and the dentist in 2025. Evidence-based clinical practice guidelines for an academic learning line 'quality and safety in oral care'].
Education in the field of quality and safety in oral care still needs further development, both for students and teachers. Based on the current development of clinical practice guidelines in the field of oral care in the Netherlands, this article describes a proposal for implementing this as a 'quality of oral care' learning line in the dental school curricula. Within clinical educational practice and scientific training, students should become familiar with the development, assessment and application of clinical practice guidelines. Some proposals for embedding this new learning line in the curriculum are given. In order to further shape the learning line, close cooperation between the three dental schools and the Kennisinstituut Mondzorg (Institute for Knowledge Translation in Oral Care) in the Netherlands is recommended.


The benefit of early-stage diagnosis: A registry-based survey evaluating the quality of life in patients with melanoma.
The morbidity associated with advanced stage melanoma is an important consideration in the dialog surrounding early detection and overdiagnosis. Few studies have stratified melanoma patient quality of life (QoL) by stage at diagnosis. We sought to investigate if melanoma stage is independently associated with changes in QoL within a large, community-based melanoma registry. Secondarily, we investigated whether demographic factors such as age, geographic location or level of education are associated with changes in QoL in the same population. 1108 melanoma patients were surveyed over a three-month period using the QoL in Adult Cancer Survivors Survey, consisting of 47 items on a 7-point frequency scale. Data were analysed using both descriptive statistical models and adjusted multivariate logistic regression. There were 677 respondents generating a 61% response rate. Overall, higher stage at diagnosis correlated with the largest decreases in QoL as it pertained to both general (p = 0.001) and Cancer-Specific stressors (p < 0.001). Education level (p = 0.020), age (p < 0.001), rural area code designation (p = 0.020) and family history of melanoma (p = 0.017) were also independently associated with changes in QoL. Earlier stage at melanoma diagnosis is associated with better QoL and thus represents a crucial intervention in patient care. Given our findings and the growing body of evidence surrounding morbidity in late-stage melanoma, it is essential that QoL be included in assessing the benefits of early detection.


A new G protein-coupled receptor from a primitive metazoan shows homology with vertebrate aminergic receptors and displays constitutive activity in mammalian cells.
Biogenic amine receptors mediate wide-ranging hormonal and modulatory functions in vertebrates, but are largely unknown in primitive invertebrates. In a representative of the most basal multicellular animals possessing a nervous system, the cnidarian Renilla koellikeri, aminergic-like receptors were previously characterized pharmacologically and found to engender control of the animal's bioluminescent and peristaltic reactions. Using degenerate oligonucleotides in a RT-PCR strategy, we obtained a full-length cDNA encoding a polypeptide with typical G protein-coupled receptor (GPCR) characteristics and which displayed a significant degree of sequence similarity (up to 45%) to biogenic amine receptors, particularly dopamine and adrenergic receptors. The new receptor, named Ren1, did not resemble any one specific type of amine GPCR and thus could not be identified on the basis of sequence. Ren1 was expressed transiently and stably in cultured mammalian cells, as demonstrated by immunocytochemistry and western blotting. Functional analysis of transfected HEK293, LTK- and COS-7 cells, based on both cAMP and Ca2+ signalling assays, revealed that Ren1 was not activated by any of the known biogenic amines tested and several related metabolites. The results indicated, however, that cells stably expressing Ren1 contained, on average, an 11-fold higher level of cAMP than the controls, in the absence of agonist stimulation. The high basal cAMP levels were shown to be specific for Ren1 and to vary proportionally with the level of Ren1 expressed in the transfected cells. Taken together, the data suggested that Ren1 was expressed as a constitutively active receptor. Its identification provides a basis for examination of the early evolutionary emergence of GPCRs and their functional properties.


Increased resistance to influenza as a possible source of heterozygote advantage in cystic fibrosis.
Cystic fibrosis is the most common lethal or semi-lethal genetic disease in Caucasians of Central European origin, among whom it is inherited as an autosomal recessive trait at a frequency approximately 10 times that expected from recurrent mutation alone. A decreased sialic acid content has been observed in cell surface glycoproteins on cystic fibrosis fibroblasts and in numerous soluble glycoprotein preparations from cystic fibrosis homozygotes. Sialic acid residues on cell surface glycoconjugates play an essential role in the binding and infectivity of myxoviruses and paramyxoviruses, including those causing pandemic influenza. It is suggested that increased resistance to these viruses conferred by similar but quantitatively smaller alterations in sialoglycoconjugate structure in cystic fibrosis heterozygotes may have provided a selective advantage to maintain the high frequency of the cystic fibrosis gene in Caucasian populations.


Classification of rheumatoid arthritis: the importance of including data from the siblings.
A discriminant analysis has been applied to physical and laboratory data on a series of 37 patients with rheumatoid arthritis (RA). Good discrimination was found between RA when it was associated with organ-specific autoimmune phenomena and when it was not. When data from other members of the families was included there was consistently better discrimination than when using data from the patients alone. The results suggest that future studies of classification of variable diseases should include study of relatives.


Artificial Intelligence-Based PTEN Loss Assessment as an Early Predictor of Prostate Cancer Metastasis After Surgery: A Multicenter Retrospective Study.
Phosphatase and tensin homolog (PTEN) loss is associated with adverse outcomes in prostate cancer and can be measured via immunohistochemistry. The purpose of the study was to establish the clinical application of an in-house developed artificial intelligence (AI) image analysis workflow for automated detection of PTEN loss on digital images for identifying patients at risk of early recurrence and metastasis. Postsurgical tissue microarray sections from the Canary Foundation (n = 1264) stained with anti-PTEN antibody were evaluated independently by pathologist conventional visual scoring (cPTEN) and an automated AI-based image analysis pipeline (AI-PTEN). The relationship of PTEN evaluation methods with cancer recurrence and metastasis was analyzed using multivariable Cox proportional hazard and decision curve models. Both cPTEN scoring by the pathologist and quantification of PTEN loss by AI (high-risk AI-qPTEN) were significantly associated with shorter metastasis-free survival (MFS) in univariable analysis (cPTEN hazard ratio [HR], 1.54; CI, 1.07-2.21; P = .019; AI-qPTEN HR, 2.55; CI, 1.83-3.56; P < .001). In multivariable analyses, AI-qPTEN showed a statistically significant association with shorter MFS (HR, 2.17; CI, 1.49-3.17; P < .001) and recurrence-free survival (HR, 1.36; CI, 1.06-1.75; P = .016) when adjusting for relevant postsurgical clinical nomogram (Cancer of the Prostate Risk Assessment [CAPRA] postsurgical score [CAPRA-S]), whereas cPTEN does not show a statistically significant association (HR, 1.33; CI, 0.89-2; P = .2 and HR, 1.26; CI, 0.99-1.62; P = .063, respectively) when adjusting for CAPRA-S risk stratification. More importantly, AI-qPTEN was associated with shorter MFS in patients with favorable pathological stage and negative surgical margins (HR, 2.72; CI, 1.46-5.06; P = .002). Workflow also demonstrated enhanced clinical utility in decision curve analysis, more accurately identifying men who might benefit from adjuvant therapy postsurgery. This study demonstrates the clinical value of an affordable and fully automated AI-powered PTEN assessment for evaluating the risk of developing metastasis or disease recurrence after radical prostatectomy. Adding the AI-qPTEN assessment workflow to clinical variables may affect postoperative surveillance or management options, particularly in low-risk patients.


Facilitation and inhibition of male rat ejaculatory behaviour by the respective 5-HT1A and 5-HT1B receptor agonists 8-OH-DPAT and anpirtoline, as evidenced by use of the corresponding new and selective receptor antagonists NAD-299 and NAS-181.
1. Ejaculatory problems and anorgasmia are well-known side-effects of the SSRI antidepressants, and a pharmacologically induced increase in serotonergic neurotransmission inhibits ejaculatory behaviour in the rat. In the present study the role of 5-HT1A and 5-HT1B receptors in the mediation of male rat ejaculatory behaviour was examined by use of selective agonists and antagonists acting at these 5-HT receptor subtypes. 2. The 5-HT1A receptor agonist 8-OH-DPAT (0.25-4.00 micromol kg(-1) s.c.) produced an expected facilitation of the male rat ejaculatory behaviour, and this effect was fully antagonized by pretreatment with the new selective 5-HT1A receptor antagonist (R)-3-N,N-dicyclobutylamino-8-fluoro-3,4-dihydro-2H-1-benzopyran-5 -carboxamide hydrogen (2R,3R) tartrate monohydrate (NAD-299) (1.0 micromol kg(-1) s.c.). NAD-299 by itself (0.75-3.00 micromol kg(-1) s.c.) did not affect the male rat ejaculatory behaviour. 3. The 5-HT1B receptor agonist anpirtoline (0.25-4.00 micromol kg(-1) s.c.) produced a dose-dependent inhibition of the male rat ejaculatory behaviour, and this effect was fully antagonized by pretreatment with the 5-HT1B receptor antagonist isamoltane (16 micromol kg(-1) s.c.) as well as by the new and selective antagonist (R)-(+)-2-(3-morpholinomethyl-2H-chromene-8-yl)oxymethylmorphol ino methansulphonate (NAS-181) (16 micromol kg(-1) s.c.). Isamoltane (1.0-16.0 micromol kg(-1) s.c.) and NAD-181 (1.0-16.0 micromol kg(-1) s.c.) had no, or weakly facilitatory effects on the male rat ejaculatory behaviour. The non-selective 5-HT1 receptor antagonist (-)-pindolol (8 micromol kg(-1) s.c.), did not antagonize the inhibition produced by anpirtoline. 4. The present results demonstrate opposite effects, facilitation and inhibition, of male rat ejaculatory behaviour by stimulation of 5-HT1A and 5-HT1B receptors, respectively, suggesting that the SSRI-induced inhibition of male ejaculatory dysfunction is due to 5-HT1B receptor stimulation.


[Superinfection of Libman-Sacks endocarditis in a lupus patient: a case report].
Libman-Sacks endocarditis is an uncommon cardiac manifestation of lupus, characterized by noninfective heart valve vegetations. Most patients are asymptomatic. However, clinical manifestations of acute forms can mimic infectious endocarditis and complicate both differential diagnosis and treatment. We here report the case of a 28-year-old female patient with lupus erythematosus followed up from 2018. She had signs and symptoms supporting the diagnosis of infective endocarditis. Assessments allowed for the diagnosis of superinfection Libman-Sacks endocarditis. The patient died despite the combination of bi-antibiotic therapy and corticosteroids.


Corrected cast for implant-supported prosthesis: segmental matrix pickup.
A modification of a segmental framework matrix technique for fabrication of an implant-supported prosthesis is presented. A direct "pickup" procedure creates a master cast with intraorally verified accuracy. Proximal contacts and interocclusal relationships are also recorded.


Automated machine learning-based prediction of microplastics induced impacts on methane production in anaerobic digestion.
Microplastics as emerging pollutants have been heavily accumulated in the waste activated sludge (WAS) during biological wastewater treatment, which showed significantly diverse impacts on the subsequent anaerobic sludge digestion for methane production. However, a robust modeling approach for predicting and unveiling the complex effects of accumulated microplastics within WAS on methane production is still missing. In this study, four automated machine learning (AutoML) approach was applied to model the effects of microplastics on anaerobic digestion processes, and integrated explainable analysis was explored to reveal the relationships between key variables (e.g., concentration, type, and size of microplastics) and methane production. The results showed that the gradient boosting machine had better prediction performance (mean squared error (MSE) = 17.0) than common neural networks models (MSE = 58.0), demonstrating that the AutoML algorithms succeeded in predicting the methane production and could select the best machine learning model without human intervention. Explainable analysis results indicated that the variable of microplastic types was more important than the variable of microplastic diameter and concentration. The existence of polystyrene was associated with higher methane production, whereas increasing microplastic diameter and concentration both inhibited methane production. This work also provided a novel modeling approach for comprehensively understanding the complex effects of microplastics on methane production, which revealed the dependence relationships between methane production and key variables and may be served as a reference for optimizing operational adjustments in anaerobic digestion processes.


Retracted: Application of Artificial Intelligence Computing in the Universal Design of Aging and Healthy Housing.
[This retracts the article DOI: 10.1155/2022/4576397.].


Results of re-operation on the deviated eye in patients with sensory heterotropia.
To evaluate the result of re-operation on the deviated eye of recurred, consecutive or undercorrected sensory strabismus after surgery. The medical records of 11 patients who had received second strabismus operation on the deviated eye due to recurred, consecutive or undercorrected sensory strabismus were studied retrospectively. Among the 11 patients, five patients were operated for recurred exotropia after surgery of sensory exotropia (group 1), two for consecutive exotropia after surgery of sensory esotropia (group 2), and four for undercorrected esotropia after surgery of sensory esotropia (group 3). Re-operation was performed 19.2+/-12.6 years after the first operation and the mean preoperative deviation before re-operation was 30.0+/-8.66 prism diopters (PD), 32.5+/-10.6PD, and 32.5+/-8.66PD, respectively. In all cases, a small amount of recession or resection compared with the usual surgical dosage was applied in re-operation on the deviated eye. The mean follow-up period after re-operation was 12.3+/-14.2 (1-48 months). Among the 11 patients, postoperative deviations less than 10PD were achieved postoperatively in 8 (72.7%) at 1 month and of the 8 patients with follow-up data beyond 6 months, 5 (62.5%) showed orthotropia within 10PD at 6 months or later. The surgical result of re-operation on the deviated eye of recurred, consecutive or undercorrected sensory strabismus after the first surgery was satisfactory in spite of the reduced amount of surgical correction compared with the surgical dosage recommended for the non-operated eye.


Lipid composition and de novo lipid biosynthesis of human palmar fat in Dupuytren's disease.
Seventy-two surgically obtained Dupuytren's disease palmar-fat (DDPF) specimens and 18 location-matched specimens from patients not suffering from this disease (controls) were studied for their total lipid composition and de novo lipogenic activity. Incubation of "DDPF" with 1-[14C]acetate in oxygen produced [14C]palmitate and [14C]stearate in approximately equal yields as those obtained from "controls." No [14C]octanate was formed in any of the palmar-fat preparations. The lipids and fatty acid analysis revealed differences: (a) DDPF specimens were richer in free fatty acids, methyl esters of fatty acids and free-cholesterol than specimens of controls. (b) DDPF specimens contained less phospholipids. (c) DDPF specimens showed a significantly higher content of octanoate and other short-chain fatty acids than specimens of controls. The above findings are not incompatible with the results expected if some mild hypoxia occurred in DDPF; this has been suggested in the statistical correlations observed for this disease and alcoholism with liver involvement.


Tamoxifen treatment for precocious puberty in McCune-Albright syndrome: a multicenter trial.
We undertook a 1-year multicenter trial of tamoxifen treatment for precocious puberty in girls with McCune-Albright syndrome (MAS). Girls < or =10 years with classic or atypical MAS were recruited. Pretreatment history was collected for 6 months. Patients received 20 mg tamoxifen daily. Diaries were used to record bleeding. Evaluations included physical examination, bone age, pelvic ultrasound, hormone levels, and safety assessments. A total of 28 girls (2.9-10.9 years of age) were enrolled from 20 centers, of whom 25 completed 12 months of tamoxifen treatment. Compared with before the study, vaginal bleeding episodes decreased (3.42+/-3.36/year vs 1.17+/-1.41/year), growth velocity slowed (SDS 1.22+/-2.65 vs -0.59+/-3.06, P=.005), and rate of bone maturation decreased (1.21+/-0.78 vs 0.72+/-0.36, P=.02). Ovarian volumes were enlarged and asymmetric throughout the study, and uterine volumes were increased. No adverse events occurred. Tamoxifen treatment of precocious puberty in MAS results in a reduction of vaginal bleeding and significant improvements in growth velocity and rate of skeletal maturation.


Proteus mirabilis urease. Partial purification and inhibition by boric acid and boronic acids.
Urease was purified 800-fold and partially characterized from Proteus mirabilis, the predominant microorganism associated with urinary stones. Boric acid is a rapid reversible competitive inhibitor of urease. The pH-dependence of inhibition exhibited pKa values of 6.25 and 9.3, where the latter value is probably due to the inherent pKa of boric acid. Three boronic acids also were shown to inhibit urease competitively.


Binding of 11-cis retinaldehyde to the partially purified cellular retinaldehyde binding protein from bovine retinal pigment epithelium.
11-cis retinaldehyde binding analysis was performed on a bovine retinal pigment epithelium preparation of cellular retinaldehyde binding protein (CRALBP), whose purity degree was estimated as 75%. Equilibrium binding studies were carried out measuring the replacement of tritium-labeled with unlabeled 11-cis retinaldehyde at 25 degrees C. Analysis of the experimental data both by a direct curve-fitting procedure utilizing a non linear least square regression analysis and by a conventional Scatchard plot revealed a single non-interacting binding site with an apparent equilibrium constant of 0.9 X 10(-7) M. A binding stoichiometry of approximately 1 mol of 11-cis retinaldehyde/mol of binding protein can be calculated from the experimental data. Competition studies carried out in the presence of unlabeled 'trans' and 'cis' isomers of vitamin A derivatives confirm the high degree of specificity of the 11-cis retinaldehyde binding.


Subcellular calcium and magnesium mobilization in rat liver stimulated in vivo with vasopressin and glucagon.
The total Ca2+ content of the endoplasmic reticulum and the total Ca2+ and Mg2+ content of mitochondria were determined by electron probe microanalysis of rat liver rapidly frozen in vivo following brief (5-15 s) stimulation with vasopressin or prolonged (10-12 min) stimulation with vasopressin + glucagon. Brief vasopressin injection into the anterior mesenteric vein released 1.8 +/- 0.3 (S.D.) mmol of Ca2+/kg dry weight, from the rough endoplasmic reticulum (p less than 0.01), reducing Ca2+ content of the endoplasmic reticulum from 4.4 +/- 0.2 (S.E.) (controls) to 2.6 +/- 0.2 mmol of Ca2+/kg dry weight. Following vasopressin injection, endoplasmic reticulum Ca2+ was also significantly (p less than 0.025) lower than that in brief sham injected animals (3.5 +/- 0.2 mmol/kg dry weight). Mitochondrial Ca2+ was between 1.0 and 2.3 (+/-0.2) mmol/kg dry weight of mitochondrion, under all conditions studied, and no significant differences were observed. Both hormonal and brief sham injection into the anterior mesenteric vein increased mitochondrial Mg2+ from 42 (+/-0.8) to 49 (+/-1.8) mmol/kg dry weight (p less than 0.05). Hormonal stimulation of Mg2+ uptake was further confirmed by injection of vasopressin + glucagon into the jugular vein (to avoid any stimulation of the liver by the anterior mesenteric vein injection itself); mitochondrial Mg2+ increased from 43 (+/-0.9) (10-min sham) to 57 (+/-1.3) mmol/kg dry weight, with 10-min vasopressin + glucagon injection (p less than 0.01). These results demonstrate that hormones can release Ca2+ from the endoplasmic reticulum and modulate mitochondrial Mg2+ content in vivo without causing detectable changes in mitochondrial Ca2+.


Association of left ventricular mass with the AGTR1 A1166C polymorphism.
The A1166C polymorphism is located within the microRNA-155 binding site of the human angiotensin II (Ang II) type-1 receptor (AGTR1) gene. The C allele interferes with the base-pairing complementariness between AGTR1 mRNA and microRNA-155 and thereby increases AGTR1 protein expression in vitro. We hypothesized that left ventricular (LV) mass is associated with the AGTR1 A1166C polymorphism. Among 708 individuals (mean age, 49.4 years; 51.8% women) randomly recruited in a white European population, we measured LV structure by two-dimensional guided M-mode echocardiography, the AGTR1 A1166C polymorphism and the 24-h urinary aldosterone. We applied a mixed model to assess phenotype-genotype associations while adjusting for covariables and accounting for relatedness. The AA (49.1%), AC (42.8%), and CC (8.1%) genotypes were in Hardy-Weinberg equilibrium. Using a recessive model, CC homozygotes compared to A-allele carriers showed significant increases (P < 0.021) in LV mass index (+5.78 ± 2.25 g/m(2)), mean wall thickness (MWT) (+0.48 ± 0.15 mm), interventricular septum (IVS) (+0.60 ± 0.18 mm) and posterior wall thickness (PWT) (+0.34 ± 0.15 mm), but lower 24-h urinary aldosterone excretion (geometric mean, 22.4 vs. 19.0 nmol; P = 0.050). Sensitivity analyses in 552 participants untreated for hypertension were confirmatory. LV mass index is associated with the AGTR1 A1166C polymorphism. Further research should clarify to what extent this association might be mediated via different expression of AGTR1 as modulated by microRNA-155.


Middle east tuberculosis in an immunocompromised patient: Case report and review of the literature.
Tuberculosis is an airborne disease caused by Mycobacterium tuberculosis. In 15-20% cases of active disease extrapulmonary tuberculosis may occur, most commonly in the head and neck region. Tuberculous otitis media accounts for 0,1% of the total number of tuberculosis patients. This paper provides insight into current state of literature of tuberculous otitis media. It also includes the case of a 53-year-old patient with tuberculous otitis media. The patient had a liver transplantation and she showed an atypical manifestation of the disease including acute otitis media and coinfection with Achromobacter xylosoxidans. The paper describes in detail the methods of diagnosis and the infection treatment. Considering the polymorphic clinical presentation of tuberculous otitis media in cases with long lasting otorrhoea differential diagnosis should include an infection with Mycobacerium tuberculosis.


Conversion of angiotensin I to angiotensin II and inactivation of bradykinin in canine peripheral vascular beds.
We studied the effects of angiotensin I (AI), angiotensin II (AII), and bradykinin (BK) on systemic blood pressure and blood flow in the renal, mesenteric, coeliac, external iliac, and internal iliac vascular beds in the presence and absence of the converting enzyme inhibitor captopril in pentobarbital-anesthetized dogs. AI and AII caused dose-dependent pressor responses and blood flow reductions, and BK caused dose-related depressor responses and an increase in blood flow. The pressor response to AI was decreased and the depressor response to BK was potentiated by captopril. However, the effectiveness of captopril was greater when the peptides were injected intravenously than when they were injected intraaortically. The average conversion of AI to AII in the mesenteric, coeliac, external iliac, internal iliac, and renal vascular beds was 45.7, 31.6, 30.6, 28.0, and 8.9%, respectively. The dose ratio of equipotent BK-induced responses before and after captopril in the mesenteric, coeliac, external iliac, internal iliac, and renal vascular beds was 4.6, 3.5, 2.8, 2.5 and 1.4, respectively. This order was similar to that of the percentage conversion of AI to AII. These results suggest that the greatest proportion of angiotensin conversion and BK inactivation occurs in the pulmonary circulation and that the least proportion occurs in the kidney.


Assay of urinary vanilmandelic, homovanillic, and 5-hydroxyindole acetic acids by liquid chromatography with electrochemical detection.
A reversed-phase liquid chromatographic method with amperometric detection has been developed for the simultaneous determination of the noradrenaline metabolite, vanilmandelic acid, the dopamine metabolite, homovanillic acid, and the serotonin metabolite, 5-hydroxyindole acetic acid, in human urine. After purification by an extraction procedure, the metabolites were rapidly separated under isocratic conditions. Detection and quantification were performed with an electrochemical detector using a carbon paste electrode. The present method is sensitive, selective and, achieves a high degree of precision by the use of isovanilmandelic acid as an internal standard. This provides a suitable tool for clinical and research applications.


Cognitive conflict in a syllable identification task causes transient activation of speech perception area.
It has previously been shown that task performance and frontal cortical activation increase after cognitive conflict. This has been argued to support a model of attention where the level of conflict automatically adjusts the amount of cognitive control applied. Conceivably, conflict could also modulate lower-level processing pathways, which would be evident as trial-to-trial changes in domain specific activation. The present fMRI experiment used a syllable identification task where conflict is manipulated by presenting recently ignored syllables. Results showed that on trials following a high conflict trial, activation increased primarily in the planum temporale region of the left temporal cortex, an area believed to be involved in syllable discrimination. The experiment thus showed a transient, domain specific attention effect that was modulated on a trial-to-trial basis. We argue that this indicates a self-regulating system where increased levels of conflict directs resources in order to improve performance.