Regulation of ClC-2 gating by intracellular ATP

ClC-2 is a voltage-dependent chloride channel that activates slowly at voltages negative to the chloride reversal potential. Adenosine triphosphate (ATP) and other nucleotides have been shown to bind to carboxy-terminal cystathionine-ß-synthase (CBS) domains of ClC-2, but the functional consequences of binding are not sufficiently understood. We here studied the effect of nucleotides on channel gating using single-channel and whole-cell patch clamp recordings on transfected mammalian cells. ATP slowed down macroscopic activation and deactivation time courses in a dose-dependent manner. Removal of the complete carboxy-terminus abolishes the effect of ATP, suggesting that CBS domains are necessary for ATP regulation of ClC-2 gating. Single-channel recordings identified long-lasting closed states of ATP-bound channels as basis of this gating deceleration. ClC-2 channel dimers exhibit two largely independent protopores that are opened and closed individually as well as by a common gating process. A seven-state model of common gating with altered voltage dependencies of opening and closing transitions for ATP-bound states correctly describes the effects of ATP on macroscopic and microscopic ClC-2 currents. To test for a potential pathophysiological impact of ClC-2 regulation by ATP, we studied ClC-2 channels carrying naturally occurring sequence variants found in patients with idiopathic generalized epilepsy, G715E, R577Q, and R653T. All naturally occurring sequence variants accelerate common gating in the presence but not in the absence of ATP. We propose that ClC-2 uses ATP as a co-factor to slow down common gating for sufficient electrical stability of neurons under physiological conditions.     

Phosphate Cements Based on Calcined Dolomite: Influence of Calcination Temperature and Silica Addition

The aim of this study is to assess the possibility of obtaining phosphate cements based on dolomite calcined at various temperatures with/without quartz sand addition. A lower calcination temperature of dolomite (1200 °C) determines a high increase in the system temperature when calcined dolomite is mixed with KH₂PO₄ (MKP) solution and also a rapid expansion of the paste. The increase in calcination temperature up to 1400 °C reduces the oxides reactivity; however, for lower dosages of MKP, the expansion phenomenon is still recorded. The increase in MKP dosage increases the compressive strength due to the formation of K-struvite. The mixing of dolomite with sand, followed by thermal treatment at 1200 °C, modifies its composition and reactivity; the compressive strength of phosphate cements obtained by mixing this solid precursor with MKP increases up to 28 days of curing. We assessed the nature of hydrates formed in the phosphate systems studied by X-ray diffraction in order to explain the hardening processes and the mechanical properties of these systems. The microstructure and elemental composition of hardened cement pastes were assessed by scanning electronic microscopy with energy-dispersive spectroscopy. The phosphate cements based on calcined magnesite or dolomite were used to immobilize an industrial hazardous waste with high chromium content. The partial substitution of calcined magnesite/dolomite with this waste determines an important decrease in compressive strengths. Nevertheless, the leaching tests confirm an adequate immobilization of chromium in some of the matrices studied (for a waste dosage corresponding to 0.5 wt % Cr).     

New Zn3Mg-xY Alloys: Characteristics,Microstructural Evolution and Corrosion Behavior

Zinc biodegradable alloys attracted an increased interest in the last few years in the medical field among Mg and Fe-based materials. Knowing that the Mg element has a strengthening influence on Zn alloys, we analyze the effect of the third element, namely, Y with expected results in mechanical properties improvement. Ternary ZnMgY samples were obtained through induction melting in Argon atmosphere from high purity (Zn, Mg, and Y) materials and MgY (70/30 wt%) master alloys with different percentages of Y and keeping the same percentage of Mg (3 wt%). The corrosion resistance and microhardness of ZnMgY alloys were compared with those of pure Zn and ZnMg binary alloy. Materials were characterized using scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), X-ray diffraction (XRD), linear and cyclic potentiometry, and immersion tests. All samples present generalized corrosion after immersion and electro-corrosion experiments in Dulbecco solution. The experimental results show an increase in microhardness and indentation Young Modulus following the addition of Y. The formation of YZn12 intermetallic phase elements with a more noble potential than pure Zinc is established. A correlation is obtained between the appearance of new Y phases and aggressive galvanic corrosion.     

Increased anticoagulation reduces proximal deep vein thrombosis in mechanically ventilated COVID-19 patients: Venous thrombosis prevention & COVID-19

We screened stored samples collected before COVID-19 had been reported in Brazil. 989 samples were tested for SAR-CoV-2 antibodies using two different methods; 16 (1.6%) were positive (7 (43.8%) IgM, 3 (18.8%) IgG and 6 (37.5%) IgG/IgM positive), suggesting SARS-CoV-2 had circulated before the first reported COVID-19 case in Brazil.     

T1‐weighted–SPACE dark blood whole body magnetic resonance angiography (DB‐WBMRA): Initial experience

Purpose:

To evaluate the feasibility of the dark blood fast spin echo (FSE) T1‐weighted–Sampling Perfection with Application of optimized Contrasts using different flip angle Evolution (T1w‐SPACE) sequence in assessing whole body arterial wall information from the extracranial carotids to the popliteal artery.

Materials and Methods:

Twenty‐eight subjects were subjected to noncontrast, dark blood whole body magnetic resonance angiography (DB‐WBMRA) using a T1w‐SPACE sequence optimized for each of the individual stations: carotid artery, thoracic aorta, abdominal aorta, and thigh/superficial femoral artery (SFA). Image quality/vessel wall visualization and the time required to image the four stations were evaluated. Two observers checked the reproducibility of vessel wall depiction by performing quantitative measurements in registered initial and repeat studies (six subjects) of vessel wall and lumen area at 17 locations along the arterial tree.

Results:

In 25 of the 28 scanned subjects, dark blood arterial images acquired in approximately 1 hour total imaging time allowed whole body arterial vessel wall visualization. Quantitative measurements showed high correlation between the initial and repeat studies for each of the observers as well as high interobserver reproducibility (r > 0.95; P < 0.01).

Conclusion:

DB‐WBMRA using T1w‐SPACE is feasible and can be performed with a high degree of reliability. J. Magn. Reson. Imaging 2010; 31: 502–509. © 2010 Wiley‐Liss, Inc.     

Neuritic pathology is lacking in the entorhinal cortex,subiculum and hippocampus in middle-aged adults with schizophrenia,bipolar disorder or unipolar depression

Earlier reports have provided conflicting results regarding the association between Alzheimer's disease (AD) and mental disorders. Using a well-characterized postmortem series of 40 middle-aged human brains, we have performed quantitative analysis of neurofibrillary tangles and senile plaques in the entorhinal cortex, subiculum and rostral hippocampus in 9 subjects with schizophrenia, 8 with bipolar disorder, 12 with depression, and 11 age- and sex-matched controls. No significant differences were found among the four groups. Our study indicates that the Alzheimer-type changes, which might be related to the likelihood of AD development later in life, are not increased in middle-aged subjects with mental illness. The result also supports the more recent reports that have demonstrated no increased incidence of AD in mentally ill patients.     

Dietary survey in an obese population

The body mass index (BMI) shows a rate of 17.4% patients suffering from first degree fatness and 56.5% from second degree fatness. The frequency of the illness increases with age, the differences established being statistically important for a p of 0.001. 45.6% persons were diagnosed with HTA, with differences statistically important at a p of 0.01, so the number of cases increases with age. The same situation is to be found in cardiovascular illnesses (angina pectoris, ischaemic cardiopathy). The high level of cholesterol is more frequent at older people, and still the differences established are statistically not significant. In these conditions, the diet must be adapted to the patient's condition. A comparative study was made on groups of age, using the following groups of food: cereal derivatives, vegetables, fruits, dairy product, meat, fish. In most of the cases, the differences established are statistically not significant. So, even if the diagnosis is known, the patient doesn't give up his eating habits.     

Diagnostic traps in porphyria: case report and literature review

Porphyrias are metabolic disorders of heme biosynthesis, which encompass a broad range of symptoms and signs, neurologic, cutaneous or mixed. Because of lack of specificity and polymorphous clinical picture, porphyrias can mimic either neuropsychiatric, dermatologic, or gastrointestinal diseases. We present the case of a 58 years old man to whom clinical presentation suspicious of Addison's disease (melanoderma, fatigue, weight loss, intermittent abdominal pain) was the disguise of porphyria cutanea tarda. A general background of porphyrias and differential diagnosis with other forms of hepatic porphyria, as well as other causes of hyperpigmentation, are given. The clinician should be aware of the protean manifestations of porphyrias and include them in clinical judgment in various situations.