Microvascular Alterations in Alzheimer's Disease.
Alzheimer's disease (AD) is a neurodegenerative disorder associated with continual decline in cognition and ability to perform routine functions such as remembering familiar places or understanding speech. For decades, amyloid beta (Aβ) was viewed as the driver of AD, triggering neurodegenerative processes such as inflammation and formation of neurofibrillary tangles (NFTs). This approach has not yielded therapeutics that cure the disease or significant improvements in long-term cognition through removal of plaques and Aβ oligomers. Some researchers propose alternate mechanisms that drive AD or act in conjunction with amyloid to promote neurodegeneration. This review summarizes the status of AD research and examines research directions including and beyond Aβ, such as tau, inflammation, and protein clearance mechanisms. The effect of aging on microvasculature is highlighted, including its contribution to reduced blood flow that impairs cognition. Microvascular alterations observed in AD are outlined, emphasizing imaging studies of capillary malfunction. The review concludes with a discussion of two therapies to protect tissue without directly targeting Aβ for removal: (1) administration of growth factors to promote vascular recovery in AD; (2) inhibiting activity of a calcium-permeable ion channels to reduce microglial activation and restore cerebral vascular function.


[The Wolf-Parkinson-White syndrome and peroperative arrhythmias].
The influence of anaesthetic drugs or techniques on the development of arrhythmias in patients with the Wolff-Parkinson-White syndrome still remains controversial. Most of the literature is based on single case reports from which no clear-cut attitude can be defined. In this retrospective study we tried to evaluate if a particular drug or technique could be recommended. We also discuss on the basis of electrophysiology of the Wolff-Parkinson-White syndrome situations in which the potential for arrhythmias is enhanced.


Nontraumatic osteonecrosis of the humeral head.
The humeral head is the second most common site for nontraumatic osteonecrosis after the femoral head, yet it has attracted relatively little attention. Osteonecrosis is associated with many conditions, such as corticosteroid use, sickle-cell disease, alcoholism, dysbarism (or caisson disease), Gaucher's disease, and other systemic conditions. The diagnosis is a clinical and radiographic one, the latter forming the basis for its staging. Treatment depends on the chronicity and severity of symptoms, as well as the degree of clinical and radiographic progression. Surgical treatment includes arthroscopic debridement and core decompression for early osteonecrosis and hemiarthroplasty or total shoulder arthroplasty for more advanced disease. This report reviews osteonecrosis of the humeral head, with an emphasis on current treatment options.


A new species of Proctoeces and reinstatement of Proctoeces humboldti George-Nascimento and Quiroga 1983 (Digenea: Fellodistomidae) based on molecular and morphological evidence.
The most studied digenean of marine organisms in Chile is by far Proctoeces humboldti, a parasite of the intestine of the clingfish Sicyases sanguineus and gonad of the keyhole limpet Fissurella spp. (progenetic metacercariae). The mussel Perumytilus purpuratus has been suggested as the first intermediate host for this digenean. In a study examining the parasites of S. sanguineus from central Chile, we found specimens of Proctoeces showing significant morphological differences with P. humboldti. To assist in the resolution of the taxonomic identification of these specimens, as well sporocysts obtained from the mussel P. purpuratus from central and northern Chile, phylogenetic studies using DNA sequences from the SSU rRNA, as well the LSU rRNA and Cox 1 gene were performed. Results showed that the clingfish S. sanguineus is a host for two species of Proctoeces (P. humboldti and P. syciases n. sp.) along the northern and central Chilean coast, without geographic separation; the mussel P. purpuratus is the first intermediate host for P. syciases n. sp. but not for P. humboldti in central and northern Chile. Fissurellids (Archaeogastropoda) along the Chilean coast harbor only progenetic stages of P. humboldti, but there is no evidence of progenesis for P. syciases. The reinstatement of Proctoeces humboldti is strongly suggested.


Risk factors of adolescent and young adult trauma victims.
Repeated injury, or recidivism, because of intentional or unintentional injury is a growing chronic health problem among urban adolescents and young adults in the United States. To describe demographic, social, environmental, psychological, and developmental antecedents and risk-taking behaviors, and to examine their relationships to type of trauma and rate of trauma recidivism in adolescent and young adults in an urban trauma center. One hundred adolescent and young adult trauma victims in an urban trauma center were interviewed, using the Adolescent Risk-Taking Instrument, the Brief Anger/Aggression Questionnaire, and the Trauma Risk Factor Interview Schedule. Bivariate correlation, multiple regression, and discriminant function analysis were used to examine the data. Of the sample, 89% experienced trauma related to interpersonal violence, including firearm injuries, stab wounds, and blunt trauma. Male gender, unemployment, past arrest, lower levels of spirituality, and higher levels of anger/aggression and thrill-seeking accounted for 25% of the variance in the number of risk-taking behaviors. Factors such as male gender, past arrest, unemployment, having been a crime victim in the past, lower autonomy, use of weapons, fighting, and no psychological counseling distinguished subjects with firearm-related injuries from subjects with other injury sources. Use of alcohol on weekdays, past arrest, and higher education levels were associated with trauma recidivism, explaining 14% of the variance. Social/environmental and psychological/developmental variables, as well as risk-taking behaviors, are important correlates of trauma and recidivism. These findings suggest the importance of advocacy for social policies conductive to reducing the risks of violence and trauma and risk-reduction interventions as components of posttrauma care.


Social predictors of sunscreen and self-tanning product use.
This study investigated social predictors of sunscreen and self-tanning product use among 164 undergraduates. Immediate family members' sunscreen use predicted participants' facial sunscreen use while sunbathing but not their sunscreen use on other areas of the body. In addition, familial support of a tanned appearance was inversely associated with self-tanning product use, whereas romantic partners' support of a tanned appearance was positively associated with this behavior. The results of this study suggest that it may be important to include socially significant others in interventions for reducing the risk of skin cancer in college students.


Point-of-care Ultrasound to Distinguish Retinal Detachment and Ruptured Arterial Microaneurysm.
We present the case of an older male with point-of-care-ultrasound (POCUS) imaging consistent with retinal detachment who was instead found by ophthalmology to have a ruptured arterial microaneurysm with vitreous and preretinal hemorrhage. The patient later had complete resolution of his symptoms. We discuss this retinal detachment "mimic." Preretinal hemorrhage is an uncommon condition that can be mistaken for ophthalmologic emergencies such as retinal detachment. The images and videos shown here add to the body of evidence that POCUS is useful in diagnosing pre-retinal hemorrhage but must be differ-entiated from retinal detachment. These images also emphasize the need for further research and application of POCUS for the identification of preretinal hemorrhage.


The Combination of High Levels of Adiponectin and Insulin Resistance Are Affected by Aging in Non-Obese Old Peoples.
Adipokine dysregulation is a key feature of insulin resistance and a metabolic syndrome associated with obesity. Low adiponectin levels are associated with higher risks of cardiovascular diseases (CVD). However, high adiponectin levels have also been associated with increased all-cause and cardiovascular mortality in the elderly. This adiponectin paradox has yet to be clarified, which has hindered our understanding of the biological role of adiponectin. Adipokine dysregulation and insulin resistance are also associated with energy-deprivation conditions, such as frailty in old age. The objective of this study was to investigate the association between plasma adiponectin and insulin resistance using the homeostasis model assessment for insulin resistance (HOMA-IR) classified by age. In particular, we sought to determine the factors of the subjects associated with both high adiponectin levels and HOMA-IR (H-adiponectin/H-HOMA) and high adiponectin levels and low HOMA-IR (H-adiponectin/L-HOMA). The eligible subjects in this cross-sectional study were 33,216 individuals who had undergone health checkups at the Physical Checkup Center of Sumitomo Hospital between April 2008 and December 2018. After excluding 26,371 individuals who were under 60 years old, 529 who had been taking medications for diabetes mellitus, and 690 with missing data, the present study included 5,673 (3,467 males, 2,206 females) subjects with no missing data. The relationship between serum adiponectin levels and HOMA-IR was assessed using logistic regression models adjusted by clinically relevant factors. In the multivariable logistic regression analysis, age and low BMI were shown to positively correlate with the characteristics of H-adiponectin/H-HOMA. In females, systolic blood pressure was also shown to be an associated factor. In conclusion, this study showed that aging or a low BMI may contribute to high adiponectin levels and insulin resistance.


[The epidemiological study on human cytomegalovirus infection of pregnant women and the maternal-fetal transmission in three Chinese metropolis].
To analyze the state of human cytomegalovirus (HCMV) infection of pregnant women and the maternal-fetal transmission in three chinese metropolis, and to study the methods of early prenatal diagnosis for intrauterine infection. Enzyme linked immunosorbent assay (ELISA) technique was employed to screen HCMV specific antibodies in 5,015 pregnant women of different trimesters. From this cohort study, 301 cases of active infection were selected to detect HCMV DNA by polymerase chain reaction (PCR) technique in their appendages of fetus, blood and urine of neonates, as well as breast milk. The overall HCMV infection rate was 88.93% in the three metropolis and they were 96.74% and 91.42% in Shenyang and Shanghai respectively, which were significantly higher than that (79.53%) in Wuhan. The active infection rate was 5.42% generally while they were 11.23% and 10.89% in Wuhan and Shenyang respectively, which were significantly higher than that in Shanghai. In addition, the active infection rate of women with history of abnormal pregnancy was significantly higher than that was of the control group (14.59% vs 3.70%). By PCR technique, the detective rate of HCMV DNA were 16.00% in chroionic villi of early pregnancy and 35.33% in amniotic fluid of mid-trimester, which were not significantly different from these in umbilical blood, placentea at delivery and neonatal blood. In China, the HCMV infection rates during pregnancy varied in different regions. A majority of women at children bearing age had HCMV infection before pregnancies; the yertical transmission frequently occurs from the actively infected mother. ELISA combined with PCR techniques is a valuable method for early prenatal diagnosis of HCMV congenital infection.


Anticancer activity of bergenin against cervical cancer cells involves apoptosis, cell cycle arrest, inhibition of cell migration and the STAT3 signalling pathway.
Bergenin is a secondary metabolite that may be primarily isolated from Bergenia species. Although it has been found to exhibit significant biological activities, the anticancer activity of bergenin against cervical cancer cells has not been explored. The present study was designed to evaluate the anticancer effects of bergenin on HeLa cervical cancer cells. The results showed that bergenin reduced the cell viability of the HeLa cervical cancer cells in a dose-dependent pattern. However, the anticancer effects of bergenin were found to be comparatively lower on the normal cervical cells. Furthermore, the anticancer effects of bergenin were primarily found to be due to induction of apoptosis in the HeLa cervical cancer cells. Notably, bergenin also enhanced the expression of Bax and decreased the expression of Bcl-2. WThe effect of bergenin on cell cycle phase distribution of HeLa cells was also investigated and it was found that bergenin could induce G0/G1 cell cycle arrest. Furthermore, bergenin could also inhibit the migration of HeLa cancer cells as well as the phosphorylation of STAT3. Taken together, bergenin may be a promising candidate for the management of cervical cancer.


[False aneurysm in Behçet's syndrome].
A 32-year-old man developed acute right-sided sore throat, a thick voice and epistaxis. 13 years previously he had erythema nodosum, 12 and 10 year ago deep vein thrombosis. On admission he had Horner's syndrome, bulging of the gums and swelling of the paratracheal space. He had been on anticoagulation therapy with phenprocoumon since the leg vein thrombosis. Computed tomography demonstrated a false aneurysm of the right internal carotid artery. 9 months later a right radial artery aneurysm occurred, which was treated surgically. An arterial cannula had previously been placed at this site for pressure monitoring. 2 months later a false aneurysm of the right femoral artery was diagnosed: it had previously been used for an intravascular intervention. As embolization to the popliteal artery occurred after sonographically controlled compression had failed and reduction of anticoagulation treatment, this aneurysm, too, was treated surgically. Because of the tendency to aneurysm formation after arterial puncture and the history of venous thromboses the diagnosis of Behçet's syndrome was considered, confirmed by subsequently elucidated history of recurrent oral aphthous ulcers and folliculitis. There were no other manifestations of the syndrome. Immunosuppressive treatment was instituted after another two aneurysm recurrences were noted in the right common femoral artery. This case illustrates that the diagnosis of Behçet's syndrome may be made more difficult if its manifestation is primarily vascular with minimal mucocutaneous involvement. It should be considered in the differential diagnosis of recurrent arterial aneurysms in a young person.


Risk of type 2 diabetes is increased in nonobese women with polycystic ovary syndrome: the National Health Insurance Service-National Sample Cohort Study.
To investigate the relationship between polycystic ovary syndrome (PCOS) and type 2 diabetes mellitus (T2DM) in Korean women. Longitudinal case-control study. Not applicable. PCOS patients aged 15 to 44 years (n = 1,136) and control individuals (n = 5,675), matched 1:5 by age group, income, and region of residence. Not applicable. The occurrence of T2DM. In the PCOS and control groups, 15.7% and 14.4%, respectively, were obese (body mass index ≥25 kg/m2). The incidence rate of T2DM was 15.84/1,000 and 5.80/1,000 person-years in the PCOS and control groups, respectively. The unadjusted hazard ratio (HR) of T2DM in women with PCOS was 2.6-fold higher than that in control individuals. Women with PCOS still had a higher HR of T2DM than did control individuals after adjustment for body mass index, family history of T2DM, physical exercise level, and total cholesterol. PCOS was significantly associated with T2DM in women both with and without obesity. PCOS is independently associated with an increased incidence of T2DM in both obese and nonobese women. Screening for T2DM should be considered for both obese and nonobese women with PCOS in Korea.


[Effects of obstructive sleep apnea hypopnea syndrome on cardiac function in patients with chronic obstructive pulmonary disease].
Objective: To analyze the clinical characteristics of patients with chronic obstructive pulmonary disease (COPD) and COPD overlapping obstructive sleep apnea hypopnea syndrome (overlap syndrome), and to study the relationship between overlap syndrome and cardiovascular diseases. Methods: A total of 126 stable COPD patients admitted to the Respiratory Department of Peking University Third Hospital from September 2016 to October 2018 were included in this study, including 112 males and 14 females, ranging in age from 48 to 89 years, with a median of 67 years. With apnea hypopnea index (AHI) 5 times/h for the cutoff value, we classified the patients into a simple COPD group (31 cases) and an overlap syndrome group (95 cases), and compared the patients' demographic characteristics, respiratory symptoms, lung function, the incidence of cardiovascular events and the cardiac function with echocardiography (E/e'), left atrium diameter (LAD) and left ventricular ejection fraction (LVEF), by using independent-samples T test and chi-square test. Results: There were no statistically significant differences in demographic characteristics, respiratory symptoms, pulmonary function, cardiac function between COPD patients and overlap syndrome patients, but significant differences in blood oxygen level at night and left ventricular mass index(LVMI) between these groups (P=0.014,P<0.001,P<0.001,P<0.001, P=0.047, respectively) were observed. By comparing the severe sleep apnea hypopnea syndrome (AHI≥30) with sleep apnea hypopnea syndrome patients(AHI<30), there were statistically significant differences in echocardiographic indicators, among which there were statistically significant differences in E/e'(P=0.013), LAD(P=0.006), LVMI (P=0.051) and LVEF (P=0.030).There were also significant differences in the history of coronary heart disease and congestive heart failure between the two groups (P=0.025, P<0.001). After dividing the patients with overlap syndrome by mild, moderate and severe severity, E/e' and LAD were significantly correlated with severity (P=0.045, P=0.011). In terms of blood oxygen level at night, there was a significant correlation between average blood oxygen saturation at night and E/e', LAD, and LVMI (r=-0.195, P=0.033; r=-0.197, P=0.030; r=-0.195, P=0.044); moreover, there was also a significant correlation between the ratio of blood oxygen≤90% and LAD (r=0.209, P=0.021). In the multiple linear regression model, E/e' increased by 0.070 on average for each unit increase in AHI, and 0.084 on average for each unit increase in oxygen desaturation index (ODI). Conclusions: Patients with COPD overlapping severe sleep apnea hypopnea syndrome showed worse left diastolic function and higher risk of congestive heart failure and coronary heart disease compared with the patients with COPD alone. In addition, the degree of impairment of left heart diastolic function was associated with the severity of COPD overlapping sleep apnea hypopnea syndrome. The higher the AHI and the ODI became, the more severe the left heart diastolic restriction and structures changed.


Cardiovascular and Bleeding Risks in Acute Myocardial Infarction Newly Treated With Ticagrelor vs. Clopidogrel in Taiwan.
There are few data on ticagrelor in Asian patients. This study evaluated clinical outcomes with ticagrelor and clopidogrel in Taiwanese patients with acute myocardial infarction (AMI).Methods and Results:We used the Taiwan National Health Insurance Research Database to identify 27,339 AMI patients aged ≥18 years between January 2012 and December 2014, and only patients who survived greater than or equal to 30 days after AMI and took dual antiplatelet therapy were included. Cohorts of ticagrelor and clopidogrel were matched 1:8, based on propensity score matching, to balance baseline covariates. The primary efficacy endpoints were death from any cause, AMI, or stroke. The safety endpoints consisted of major gastrointestinal bleeding or intracerebral hemorrhage. Following propensity matching, the primary efficacy endpoint rate was 22% lower in the ticagrelor group than in the clopidogrel group (10.6% and 16.2%, respectively; adjusted HR, 0.779; 95% CI: 0.684-0.887). The safety endpoint rate was similar between the ticagrelor and clopidogrel groups (3.2% and 4.1% respectively; adjusted HR, 0.731; 95% CI: 0.522-1.026). In real-world AMI Taiwanese patients, ticagrelor seemed to offer better anti-ischemic protection than clopidogrel, without an increase in the rate of major bleeding. A large-scale randomized trial is needed to assess the efficacy and safety of ticagrelor in East Asian AMI patients.


Synthesis and pharmacological evaluation of new progesterone esters as 5alpha-reductase inhibitors.
In this study we report the synthesis and pharmacological evaluation of four new progesterone derivatives; 17alpha-hydroxy-16beta-methylpregna-4,6-diene-3,20-dione 12, 17alpha-cyclopropylcarbonyloxy-16beta-methylpregna-4,6-diene-3,20-dione 13, 17alpha-cyclobutylcarbonyloxy-16beta-methylpregna-4,6-diene-3,20-dione 14, 17alpha-acetoxy-16beta-methylpregna-4,6-diene-3,20-dione 15 and the pregnatriene compound 17alpha-cyclobutylcarbonyloxy-16beta-methylpregna-1,4,6-triene-3,20-dione 16. The pharmacological effect of these compounds was determined in vivo as well as in vitro. The evaluation in vivo was carried out on gonadectomized male hamsters that were injected subcutaneously daily with testosterone (T) and/or finasteride, or with the novel compounds. At the end of the treatments the animals were sacrificed and the prostates were weighed. It was observed that when testosterone (T) and finasteride or compounds 12-16 were injected together, the weight of the prostate decreased significantly as compared to that of the testosterone-treated animals. The 5alpha-reductase inhibitory activity was evaluated in vitro using human prostate homogenates. These experiments showed the following IC50 values: compound 12 (alcohol at C-17) 1.2 x 10(-6) M, 13 (cyclopropyl substituent at C-17) 7.9 x 10(-10) M, 14 (cyclobutyl substituent) 3.2 x 10(-8) M, 15 (acetoxy substituent) 6.3 x 10(-11) M and 16 (cyclobutyl substituent) 3.9 x 10(-6) M. It is evident from these data that when the size of the substituent at C-17 is decreased, the 5alpha-reductase inhibitory activity increases. Apparently, in this biological model, the 5alpha-reductase inhibitory activity depends upon the steric effect of the substituent at C-17. However, the free alcohol 12 showed much lower 5alpha-reductase inhibitory activity.


Respiratory Properties of Mitochondria from Rice Seedlings Germinated under Water and Their Changes during Air Adaptation.
Respiratory activities were compared among rice seedlings germinated in air for 6 days (aerobic seedlings), those germinated under water for 5 days (submerged seedlings), and those grown in air for 1 day after 5 days' submerged germination (air-adapted seedlings). The respiratory activity of the submerged seedlings increased rapidly on transfer to air and reached a plateau at 16 hours in air. Respiration of the submerged seedlings was as sensitive to cyanide as those of aerobic and air-adapted seedlings. 2,4-Dinitrophenol had no effect on the respiration of the submerged seedlings, but stimulated those of the other two types of seedlings. Mitochondria from three types of seedlings did not differ in the ADP/O ratio and the respiratory control ratio (RCR) when succinate was oxidized. However, mitochondria from submerged seedlings (submerged mitochondria) showed poor RCR of about unity when malate was oxidized. Both the rate of succinate oxidation and succinate dehydrogenase activity were low in submerged mitochondria, but increased during air adaptation. Although submerged mitochondria oxidized malate very slowly, this activity increased after exposure to air without any increase in malate dehydrogenase activity. When NAD(+) was added to submerged mitochondria, oxidation of malate was restored to the level of the aerobic controls. Addition of NAD(+) enhanced the state 3 rate in submerged mitochondria, and RCR recovered to nearly the same value as that of the aerobic controls. Similar effects of NAD(+) on 2-oxoglutarate oxidation were observed. All these defects in submerged mitochondria were repaired during air adaptation. These results suggest that NAD(+)-linked substrate oxidation was low in submerged mitochondria because of NAD(+) deficiency, and that the oxidation increased with an increasing level of NAD(+) during air adaptation.


Adenylate kinase motions during catalysis: an energetic counterweight balancing substrate binding.
Adenylate kinases undergo large conformational changes during their catalytic cycle. Because these changes have been studied by comparison of structures from different species, which share approximately one-third of their residues, only rough descriptions have been possible to date. We have solved the structure of unligated adenylate kinase from Escherichia coli at 2.2 degree resolution and compared it with the high-resolution structure of the same enzyme ligated with an inhibitor mimicking both substrates, ATP and AMP. This comparison shows that, upon substrate binding, the enzyme increases its chain mobility in a region remote from the active center. As this region 'solidifies' again on substrate release, we propose that it serves as a 'counterweight' balancing the substrate binding energy. The comparison of two very different conformations of the same polypeptide chain revealed kinematic details of the catalytic cycle. Moreover, it indicated that there exists an energetic counterweight compensating the substrate binding energy required for specificity. This counterweight prevents the enzyme from dropping into a rate-reducing energy well along the reaction coordinate.


Scan-Chain-Fault Diagnosis Using Regressions in Cryptographic Chips for Wireless Sensor Networks.
Scan structures, which are widely used in cryptographic circuits for wireless sensor networks applications, are essential for testing very-large-scale integration (VLSI) circuits. Faults in cryptographic circuits can be effectively screened out by improving testability and test coverage using a scan structure. Additionally, scan testing contributes to yield improvement by identifying fault locations. However, faults in circuits cannot be tested when a fault occurs in the scan structure. Moreover, various defects occurring early in the manufacturing process are expressed as faults of scan chains. Therefore, scan-chain diagnosis is crucial. However, it is difficult to obtain a sufficiently high diagnosis resolution and accuracy through the conventional scan-chain diagnosis. Therefore, this article proposes a novel scan-chain diagnosis method using regression and fan-in and fan-out filters that require shorter training and diagnosis times than existing scan-chain diagnoses do. The fan-in and fan-out filters, generated using a circuit logic structure, can highlight important features and remove unnecessary features from raw failure vectors, thereby converting the raw failure vectors to fan-in and fan-out vectors without compromising the diagnosis accuracy. Experimental results confirm that the proposed scan-chain-diagnosis method can efficiently provide higher resolutions and accuracies with shorter training and diagnosis times.


[Mutation of p53 gene in the transformed fibroblasts detected by nonradioisotopic single strand conformation polymorphism analysis].
The human embryonic lung fibroblasts transformation was induced by chemical mutant Glycidyl Methacrylate (GMA) in vitro. Transformed clonies were isolated and then exon 5 and exon 8 of p53 gene were specifically amplified by polymerase chain reaction. Amplified fragments were detected by using silver stained single strand conformation polymorphism analysis. The results showed that exon 8 altered in the transformed cells, indicating that p53 gene played an important role in the human embryonic lung fibroblasts transformation induced by GMA.


[Analysis of diagnosis and treatment of Alport syndrome].
To investigate the clinical characteristics and the status of diagnosis and treatment of patients with Alport syndrome in China. Patients with affirmative diagnosis of Alport syndrome from Department of Pedatrics, Peking University First Hospital in the past 20 years (1995-2015) were analyzed retrospectively. The clinical data including initial symptoms, visit reasons, age at onset of disease, family history, hereditary mode, methods of diagnosis, misdiagnosis and mistreatment were collected. A total of 398 patients with Alport syndrome were included in this study, 48.2% of patients had the onset of symptoms before age of 3 years. The rate of onset of symptoms and diagnosis before age of 17 years were 95.7%. The initial symptoms included gross hematuria (37.2%), microscopic hematuria and proteinuria (25.1%), microscopic hematuria (14.8%), edema of eyelid and lower limbs (10.3%), increased foam in urine (4.3%), etc.; 39.5% of patients had no symptoms of urinary tract. Only 14.0% of the patients were diagnosed as Alport syndrome for the first time, and 86.0% of the patients were misdiagnosed. Hormones and immunosuppressive agents were used in 19.0% of patients diagnosed as Alport syndrome, and in 43.0% of patients there was misdiagnosis. Skin biopsy and immunofluorescence of type Ⅳ collagen ɑ5 chain in epithelial basement membrane had a detection rate of 77.8%. Electron microscopy of glomerular basement membrane had a detection rate of 92.6%, and genetic testing 96.6%. The time interval of diagnosis was 18.2 months and was gradually shortened in recent years. Alport syndrome developed at a very young age. Hematuria was the most frequent initial symptom. There was a high rate of misdiagnosis and mistreatment for Alport syndrome. Genetic testing for Alport syndrome had advantages of high detection rate, genetic consultation and prenatal diagnosis.


Effects of Individual and Coexisting Diabetes and Cardiomyopathy on Diastolic Function in Rats (Rattus norvegicus domestica).
The goal of this study was to evaluate diastolic intraventricular pressure gradients (IVPG) and 2-dimensional tissue tracking (2DTT) patterns during diabetes and cardiomyopathy. Rats (n = 60) were induced to become diabetic (DM group, n = 15) by using streptozotocin, to become cardiomyopathic (CM group, n = 15) by using isoproterenol, and to become both diabetic and cardiomyopathic (DMCM group, n = 15); control rats (CT group, n = 15) were injected with saline. Two months after induction, all rats underwent conventional echocardiography, IVPG, and 2DTT and then were euthanized for microscopic examination of cardiac fibrosis. Compared with the controls, all 3 treated groups showed diastolic dysfunction and delayed cardiac relaxation. DMCM rats showed the most pronounced cardiac abnormalities. In addition, CM and DMCM groups had showed decreased middle IVPG, whereas DMCM rats had decreased midapical IVPG. Although the overall IVPG of the CM group was normal, the middle segment was significantly decreased. 2DTT results showed that the DMCM group had a delay in relaxation compared with other groups. IVPG and 2DTT can be used to overcome the limitation of conventional echocardiographic methods and reveal diastolic dysfunction. DM worsened diastolic function during cardiac disease.


The molecular genetic background of familial hypercholesterolemia: data from the Slovak nation-wide survey.
Familial hypercholesterolemia (FH) is most frequently caused by LDLR or APOB mutations. Therefore, the aim of our study was to examine the genetic background of Slovak patients suspected of FH. Patients with clinical suspicion of FH (235 unrelated probands and 124 family relatives) were recruited throughout Slovakia during the years 2011-2015. The order of DNA analyses in probands was as follows: 1. APOB mutation p.Arg3527Gln by real-time PCR method, 2. direct sequencing of the LDLR gene 3. MLPA analysis of the LDLR gene. We have identified 14 probands and 2 relatives with an APOB mutation p.Arg3527Gln, and 89 probands and 75 relatives with 54 different LDLR mutations. Nine of LDLR mutations were novel (i.e. p.Asp90Glu, c.314-2A>G, p.Asp136Tyr, p.Ser177Pro, p.Lys225_Glu228delinsCysLys, p.Gly478Glu, p.Gly675Trpfs*42, p.Leu680Pro, p.Thr832Argfs*3). This is the first study on molecular genetics of FH in Slovakia encompassing the analysis of whole LDLR gene. Genetic etiology of FH was confirmed in 103 probands (43.8 %). Out of them, 86.4 % of probands carried the LDLR gene mutation and remaining 13.6 % probands carried the p.Arg3527Gln APOB mutation.


[Role of percutaneous endoscopic gastrostomy in amyotrophic lateral sclerosis].
Percutaneous endoscopic gastrostomy (PEG) is an enteral nutritional assistance technique using a simple device compatible with conventional feeding and thus enabling the patient to be integrated into his or her social and familial surroundings. This inexpensive device is quickly and easily inserted under local anaesthesia. It causes little morbidity and virtually no mortality and has many advantages for patients with amyotrophic lateral sclerosis (ALS). We report the results of PEG in 28 ALS patients with bulbar involvement. Three of these patients developed minor complications during 6 consecutive months of PEG-assisted nutrition (2 had periostomial infection, 1 had mild haematemesis). There were no major complications, and mortality directly ascribable to PEG was nil. All patients put on weight or had their weight stabilized, and GEP was well accepted in all cases.


Post-transcriptional regulation in lymphocytes: the case of CD154.
The control of mRNA decay is emerging as an important control point and a major contributor to gene expression in both immune and non-immune cells. The identification of protein factors and cis-acting elements responsible for transcript degradation has illuminated a comprehensive picture of precisely orchestrated events required to both regulate and establish the decay process. One gene that is highly regulated at the post-transcriptional level is CD40 ligand (CD154 or CD40L). CD154 on CD4(+) T cells is tightly controlled by an interacting network of transcriptional and post-transcriptional processes that result in precise surface levels of protein throughout an extended time course of antigen stimulation. The activation-induced stabilization of the CD154 transcript by a polypyrimidine tract-binding protein (PTB)-complex is a key event that corresponds to the temporal expression of CD154. In this review, we discuss known and potential roles of major mRNA decay pathways in lymphocytes and focus on the unique post-transcriptional mechanisms leading to CD154 expression by activated CD4(+) T cells.


Ultrafast Aggregation-Induced Tunable Emission Enhancement in a Benzothiadiazole-Based Fluorescent Metal-Organic Framework Linker.
Aggregation-induced emission enhancement (AIEE) is a process recently exploited in solid-state materials and organic luminophores, and it is explained by tight-molecular packaging. However, solution-phase AIEE and its formation mechanism have not been widely explored. This work investigated AIEE phenomena in two donor-acceptor-donor-type benzodiazole-based molecules (the organic building block in metal-organic frameworks) with an acetylene and phenyl π-conjugated backbone tapered with a carboxylic acid group at either end. This was done using time-resolved electronic and vibrational spectroscopy in conjunction with time-dependent density functional theory (TD-DFT) calculations. Fluorescence up-conversion spectroscopy and time-correlated single-photon counting conclusively showed an intramolecular charge transfer-driven aggregate emission enhancement. This is shown by a red spectral shift of the emission spectra as well as an increase in the fluorescence lifetime from 746 ps at 1.0 × 10-11 to 2.48 ns at 2.0 × 10-3 M. The TD-DFT calculations showed that a restricted intramolecular rotation mechanism is responsible for the enhanced emission. The femtosecond infrared (IR) transient absorption results directly revealed the structural dynamics of aggregate formation, as evident from the evolution of the C≡C vibrational marker mode of the acetylene unit upon photoexcitation. Moreover, the IR data clearly indicated that the aggregation process occurred over a time scale of 10 ps, which is consistent with the fluorescence up-conversion results. Interestingly, time-resolved results and DFT calculations clearly demonstrated that both acetylene bonds and the sulfur atom are the key requirements to achieve such a controllable aggregation-induced fluorescence enhancement. The finding of the work not only shows how slight changes in the chemical structure of fluorescent chromophores could make a tremendous change in their optical behavior but also prompts a surge of research into a profound understanding of the mechanistic origins of this phenomenon. This may lead to the discovery of new chemical strategies that aim to synthesize novel chromophores with excellent optical properties for light-harvesting applications.


Localization of Nitrogen-Assimilating Enzymes in the Chloroplast of Chlamydomonas reinhardtii.
The specific activities of nitrate reductase, nitrite reductase, glutamine synthetase, glutamate synthase, and glutamate dehydrogenase were determined in intact protoplasts and intact chloroplasts from Chlamydomonas reinhardtii. After correction for contamination, the data were used to calculate the portion of each enzyme in the algal chloroplast. The chloroplast of C. reinhardtii contained all enzyme activities for nitrogen assimilation, except nitrate reductase, which could not be detected in this organelle. Glutamate synthase (NADH- and ferredoxin-dependent) and glutamate dehydrogenase were located exclusively in the chloroplast, while for nitrite reductase and glutamine synthetase an extraplastidic activity of about 20 and 60%, respectively, was measured. Cells grown on ammonium, instead of nitrate as nitrogen source, had a higher total cellular activity of the NADH-dependent glutamate synthase (+95%) and glutamate dehydrogenase (+33%) but less activity of glutamine synthetase (-10%). No activity of nitrate reductase could be detected in ammonium-grown cells. The distribution of nitrogen-assimilating enzymes among the chloroplast and the rest of the cell did not differ significantly between nitrate-grown and ammonium-grown cells. Only the plastidic portion of the glutamine synthetase increased to about 80% in cells grown on ammonium (compared to about 40% in cells grown on nitrate).


Radical-Mediated C-H Functionalization: A Strategy for Access to Modified Cyclodextrins.
A simple and efficient radical C-H functionalization to access modified cyclodextrins (CDs) has been developed. The well-defined conformation of glycosidic and aglyconic bonds in α-, β-, and γ-CDs favors the intramolecular 1,8-hydrogen atom transfer (HAT) promoted by the 6I-O-yl radical, which abstracts regioselectively the hydrogen at C5II of the contiguous pyranose. The C5II-radical evolves by a polar crossover mechanism to a stable 1,3,5-trioxocane ring between two adjacent glucoses or alternatively triggers the inversion of one α-d-glucose into a 5-C-acetoxy-β-l-idose unit possessing a 1C4 conformation. The 6I,IV- and 6I,III-diols of α- and β-CDs behave similarly to the monoalcohols, forming mostly compounds originating from two 1,8-HAT consecutive processes. In the case of 6I,II-diols the proximity of the two 6-O-yl radicals in adjacent sugar units allows the formation of unique lactone rings within the CD framework via a 1,8-HAT-β-scission tandem mechanism. X-ray diffraction carried out on the crystalline 1,4-bis(trioxocane)-α-CD derivative shows a severe distortion toward a narrower elliptical shape for the primary face.


Dynamic changes in ear temperature in relation to separation distress in dogs.
Infrared thermography can visualize changes in body surface temperature that result from stress-induced physiological changes and alterations of blood flow patterns. Here we explored its use for remote stress monitoring (i.e. removing need for human presence) in a sample of six pet dogs. Dogs were tested in a brief separation test involving contact with their owner, a stranger, and social isolation for two one-minute-periods. Tests were filmed using a thermographic camera set up in a corner of the room, around 7m from where the subjects spent most of the time. Temperature was measured from selected regions of both ear pinnae simultaneously. Temperatures of both ear pinnae showed a pattern of decrease during separation and increase when a person (either the owner or a stranger) was present, with no lateralized temperature differences between the two ears. Long distance thermographic measurement is a promising technique for non-invasive remote stress assessment, although there are some limitations related to dogs' hair structure over the ears, making it unsuitable for some subjects.


[Application of metal ions and their complexes in medicine II. Application of platina complexes in the treatment of tumor].
The rapid development of inorganic medical chemistry opens enormous potential for various applications of a range of inorganic substances in the medicine. Thus inorganic chemistry offers real possibilities to pharmaceutical industries, which used to be dominated by organic chemistry alone. The field has particularly been stimulated by the success-story of cisplatin, which is the World's best selling anticancer drug. Nowadays orally administered Pt(IV) complexes with reduced toxicity, and activity against resistant tumors are on various phases of clinical trial.


Red Grape Skin Polyphenols Blunt Matrix Metalloproteinase-2 and -9 Activity and Expression in Cell Models of Vascular Inflammation: Protective Role in Degenerative and Inflammatory Diseases.
Matrix metalloproteinases (MMPs) are endopeptidases responsible for the hydrolysis of various components of extracellular matrix. MMPs, namely gelatinases MMP-2 and MMP-9, contribute to the progression of chronic and degenerative diseases. Since gelatinases' activity and expression are regulated by oxidative stress, we sought to evaluate whether supplementation with polyphenol-rich red grape skin extracts modulated the matrix-degrading capacity in cell models of vascular inflammation. Human endothelial and monocytic cells were incubated with increasing concentrations (0.5-25 μg/mL) of Negroamaro and Primitivo red grape skin polyphenolic extracts (NSPE and PSPE, respectively) or their specific components (0.5-25 μmol/L), before stimulation with inflammatory challenge. NSPE and PSPE inhibited, in a concentration-dependent manner, endothelial invasion as well as the MMP-9 and MMP-2 release in stimulated endothelial cells, and MMP-9 production in inflamed monocytes, without affecting tissue inhibitor of metalloproteinases (TIMP)-1 and TIMP-2. The matrix degrading inhibitory capacity was the same for both NSPE and PSPE, despite their different polyphenolic profiles. Among the main polyphenols of grape skin extracts, trans-resveratrol, trans-piceid, kaempferol and quercetin exhibited the most significant inhibitory effects on matrix-degrading enzyme activities. Our findings appreciate the grape skins as rich source of polyphenols able to prevent the dysregulation of vascular remodelling affecting degenerative and inflammatory diseases.


Cellular expansion at low temperature as a cause of membrane lesions.
Rates of solute leakage from excised discs of cucumber (Cucumis sativus L. cv Straight Eight) cotyledons were altered by temperature during plasmolysis in the manner of a simple diffusion phenomenon; the log of the leakage rate increased in proportion to the temperature. During deplasmolysis, however, leakage rates responded to temperature with a very different pattern: chilling conditions (below about 20 degrees C) caused large increases in leakage rates, indicating disruption of membrane integrity in the tissues. The time course of restoration of normal leakage rates after deplasmolysis/chilling damage indicated a rapid repair of the lesions. A similar sensitivity to low temperatures was found during rehydration after leaf desiccation, with low temperatures again causing high leakage rates. It is suggested that low temperatures interfere with membrane expansion, possibly by lowering elasticity and hindering the incorporation of lipid material into the expanding membrane. The expansion of tissues at low temperatures may cause lesions in cellular membranes, contributing to chilling injury.


A different approach to leakage of esophageal atresia in children.
In this study, we aimed to present the results of patients treated for esophageal leakage with a different conservative approach. Ninety-eight patients with esophageal atresia and tracheoesophageal fistula (EA) who underwent surgery in our clinic between February 2013 and January 2018 were retrospectively reviewed in this study. Patients' anastomosis leakage, gestational week, gender, body weight, referral date, recovery time and stenosis were recorded. After leakage detection, the nasogastric catheter was fluoroscopically converted into a nasojejunal catheter using a guidewire and feeding continued. Anastomotic leakage developed in 18 (18.3%) patients. The average gestational age at birth was 35.4 weeks; the patients included ten girls and eight boys of average weight 2.41 kg; the average referral period was 2.1 days after birth and the average time of surgery was 2.4 days after birth. The average recovery time was 21.1 days (range: 8-60 days). Eight patients developed stenosis that recovered with dilatation. Our findings suggest that our conservative treatment approach, which uses a nasojejunal catheter, is an effective method that would reduce complications, enable earlier feeding, and reduce the cost compared to other treatment approaches.


[Effects of bariatric surgery on mental and social well-being].
Morbid obesity is associated with severely invalidizing symptoms and a strong stigma, which restrict the management of daily life. The handicaps of morbid obesity are so severe that patients are ready to accept even inconvenient adverse effects or high risks from the treatment. Seeking antiobesity surgery is mainly done for health reasons, but is perceived to have a broad effect on functional capacity, self-image as well as on mental and social well-being. By the help of anti-obesity surgery, many patients not only gain control over eating, but also over other fields of life.


Bayesian analysis and inference from QSAR predictive model results.
QSAR models have been under development for decades but acceptance and utilization of model results have been slow, in part, because there is no widely accepted metric for assessing their reliability. We reapply a method commonly used in quantitative epidemiology and medical decision-making for evaluating the results of screening tests to assess reliability of a QSAR model. It quantifies the accuracy (expressed as sensitivity and specificity) of QSAR models as conditional probabilities of correct and incorrect classification of chemical characteristic, given a true characteristic. Using Bayes formula, these conditional probabilities are combined with prior information to generate a posterior distribution to determine the probability a specific chemical has a particular characteristic, given a model prediction. As an example, we apply this approach to evaluate the predictive reliability of a CATABOL model and base on it a "ready" and "not ready" biodegradability classification. Finally, we show how predictive capability of the model can be improved by sequential use of two models, the first one with high sensitivity and the second with high specificity.


Analyses of chondrogenic induction of adipose mesenchymal stem cells by combined co-stimulation mediated by adenoviral gene transfer.
Adipose-derived stem cells (ASCs) have the potential to differentiate into cartilage under stimulation with some reported growth and transcriptional factors, which may constitute an alternative for cartilage replacement approaches. In this study, we analyzed the in vitro chondrogenesis of ASCs transduced with adenoviral vectors encoding insulin-like growth factor-1 (IGF-1), transforming growth factor beta-1 (TGF-β1), fibroblast growth factor-2 (FGF-2), and sex-determining region Y-box 9 (SOX9) either alone or in combinations. Aggregate cultures of characterized ovine ASCs were transduced with 100 multiplicity of infections of Ad.IGF-1, Ad.TGF-β1, Ad.FGF-2, and Ad.SOX9 alone or in combination. These were harvested at various time points for detection of cartilage-specific genes expression by quantitative real-time PCR or after 14 and 28 days for histologic and biochemical analyses detecting proteoglycans, collagens (II, I and X), and total sulfated glycosaminoglycan and collagen content, respectively. Expression analyses showed that co-expression of IGF-1 and FGF-2 resulted in higher significant expression levels of aggrecan, biglycan, cartilage matrix, proteoglycan, and collagen II (all P ≤0.001 at 28 days). Aggregates co-transduced with Ad.IGF-1/Ad.FGF-2 showed a selective expression of proteoglycans and collagen II, with limited expression of collagens I and × demonstrated by histological analyses, and had significantly greater glycosaminoglycan and collagen production than the positive control (P ≤0.001). Western blot analyses for this combination also demonstrated increased expression of collagen II, while expression of collagens I and × was undetectable and limited, respectively. Combined overexpression of IGF-1/FGF-2 within ASCs enhances their chondrogenic differentiation inducing the expression of chondrogenic markers, suggesting that this combination is more beneficial than the other factors tested for the development of cell-based therapies for cartilage repair.


Antiproliferative effects of the serotonin type 2 receptor antagonist, ketanserin, on smooth muscle cell growth in rats.
We defined the role of a serotonin type 2 receptor antagonist, ketanserin, in the growth of aortic vascular smooth muscle cells (VSMCs) from Wistar rats, using cell culture and cell synchrony methods. Deoxyribonucleic acid (DNA) replication in the G0/G1- or G1/S-synchronized VSMCs was assessed by [3H]thymidine uptake into DNA. Ketanserin at 2 x 10(-5) M significantly decreased the thymidine uptake by 48% in the proliferating VSMCs, whereas methysergide, a nonspecific serotonin inhibitor, unaffected the thymidine uptake. Ketanserin at 10(-5) M did not influence the duration of the G1 resting period. However, this dose of ketanserin significantly lowered DNA replication in the DNA synthetic (S) period in a dose-dependent manner. Neither methysergide nor the alpha 1-adrenoceptor antagonist, prazosin, affected DNA synthesis in the S period. Ketanserin exhibits antiproliferative effects on rat VSMC growth probably through the suppression of DNA replication in the S phase. This property would also contribute to the vascular protective effects of ketanserin with its well-documented antihypertensive action.


Dyslexia and dyscalculia: two learning disorders with different cognitive profiles.
This study tests the hypothesis that dyslexia and dyscalculia are associated with two largely independent cognitive deficits, namely a phonological deficit in the case of dyslexia and a deficit in the number module in the case of dyscalculia. In four groups of 8- to 10-year-olds (42 control, 21 dyslexic, 20 dyscalculic, and 26 dyslexic/dyscalculic), phonological awareness, phonological and visual-spatial short-term and working memory, naming speed, and basic number processing skills were assessed. A phonological deficit was found for both dyslexic groups, irrespective of additional arithmetic deficits, but not for the dyscalculia-only group. In contrast, deficits in processing of symbolic and nonsymbolic magnitudes were observed in both groups of dyscalculic children, irrespective of additional reading difficulties, but not in the dyslexia-only group. Cognitive deficits in the comorbid dyslexia/dyscalculia group were additive; that is, they resulted from the combination of two learning disorders. These findings suggest that dyslexia and dyscalculia have separable cognitive profiles, namely a phonological deficit in the case of dyslexia and a deficient number module in the case of dyscalculia.


Caribbean immigrants in Britain and Canada: socio-economic adjustment.
This paper compares the socioeconomic experiences of Caribbean immigration in Britain and Canada and shows how differing immigration trends together with changing economic circumstances influenced the process of integration. Caribbean immigrants in Canada are more recent arrivals than those in Britain and, in 1981, were still experiencing initial adjustment problems aggravated by an economy in which unemployment is still high. Unlike Britain, which has a large population born in that country of West Indian parentage, the "2nd generation" in Canada is small and mostly still in school. Despite higher levels of education and qualifications than their counterparts in Britain, Caribbean immigrants in Canada faced similar problems. Males were relatively more concentrated in manufacturing industries in Canada and in transportation in Britain, sectors which were undergoing significant structural change and experiencing high levels of unemployment. Earned income was below average in both countries but there were interesting gender differences. Caribbean women experienced the same "earnings gap", relative to men, that characterized most women in the labor force. However, Caribbean women were relatively more successful than men, as measured by unemployment rates and earned incomes. This appears to be due to their qualifications in nursing and other service occupations that continued to expand, and to be in demand in the 1970s and 1980s, when other occupations were declining in response to technological change and "post-industrial" developments. In both countries there were residual disadvantages, faced by Caribbean men and women, which cannot be statistically explained by factors such as age, education, period of immigration, or structural changes in the economy. These can be attributed, at least in part, to the institutionalized prejudice and discrimination against racial minorities which is prevalent in both societies. In absolute terms Caribbean immigrants in Canada are clearly better off than their counterparts in Britain. However, relative to other immigrants, and the native-born population with similar demographic characteristics and educational qualifications, those in Canada experience similar disadvantages.


Lipid emulsion-mediated reversal of toxic-dose aminoamide local anesthetic-induced vasodilation in isolated rat aorta.
Intravenous lipid emulsion has been used to treat systemic toxicity of local anesthetics. The goals of this in vitro study were to determine the ability of two lipid emulsions (Intralipid® and Lipofundin® MCT/LCT) to reverse toxic dose local anesthetic-induced vasodilation in isolated rat aortas. Isolated endothelium-denuded aortas were suspended for isometric tension recording. Vasodilation was induced by bupivacaine (3 × 10(-4) M), ropivacaine (10(-3) M), lidocaine (3 × 10(-3) M), or mepivacaine (7 × 10(-3) M) after precontraction with 60 mM KCl. Intralipid® and Lipofundin® MCT/LCT were then added to generate concentration-response curves. We also assessed vasoconstriction induced by 60 mM KCl, 60 mM KCl with 3 × 10(-4) M bupivacaine, and 60 mM KCl with 3 × 10(-4) M bupivacaine plus 1.39% lipid emulsion (Intralipid® or Lipofundin® MCT/LCT). The two lipid emulsions reversed vasodilation induced by bupivacaine, ropivacaine, and lidocaine but had no effect on vasodilation induced by mepivacaine. Lipofundin® MCT/LCT was more effective than Intralipid® in reversing bupivacaine-induced vasodilation. The magnitude of lipid emulsion-mediated reversal of vasodilation induced by high-dose local anesthetics was as follows (from highest to lowest): 3 × 10(-4) M bupivacaine-induced vasodilation, 10(-3) M ropivacaine-induced vasodilation, and 3 × 10(-3) M lidocaine-induced vasodilation. Lipofundin® MCT/LCT-mediated reversal of bupivacaine-induced vasodilation was greater than that of Intralipid®; however, the two lipid emulsions equally reversed vasodilation induced by ropivacaine and lidocaine. The magnitude of lipid emulsion-mediated reversal of vasodilation appears to be correlated with the lipid solubility of the local anesthetic.


Comparison of C-reactive protein levels with delivered dose of Kt/V in patients with end-stage renal disease on maintenance hemodialysis.
The objective of our study is to compare the C-reactive protein (CRP) levels with the delivered dose of dialysis in terms of Kt/V in patients undergoing maintenance hemodialysis (HD). This is a comparative, cross-sectional survey. The study was conducted at the HD unit of the Shaikh Zayed Hospital, Lahore, Pakistan. Patients who fulfilled the inclusion and exclusion criteria were enrolled in this study. The delivered dose of HD (Kt/V) was assessed by an online clearance module (OCM) in Fresenius machines at the end of every dialysis session and the weekly Kt/V was determined by adding all three Kt/V values. The serum CRP sample was taken after each session of HD and the mean CRP was calculated and considered elevated if it was >6 mg/dL. Both weekly Kt/V and CRP values were entered in a pre-designed proforma. Data were analyzed by using statistical software SPSS and P-value £0.05 was considered significant. Of 100 patients on maintenance HD, high serum CRP level (>6 mg/dL) was found in 38 patients. When the Kt/V was compared with the CRP level, there was a negative correlation between the two parameters (r = 0.212, P = 0.032). Low Kt/V means dialysis inadequacy, which is associated with chronic inflammatory state, resulting in high CRP levels. We suggest that the quality of life of dialysis patients can be improved by offering an adequate dose of HD reflected by Kt/V ≥3.6/week.


Comparative Genome Analysis Reveals Natural Variations in the Genomes of Erwinia pyrifoliae, a Black Shoot Blight Pathogen in Apple and Pear.
Erwinia pyrifoliae is a Gram-negative bacterial plant pathogen that causes black shoot blight in apple and pear. Although earlier studies reported the genome comparison of Erwinia species, E. pyrifoliae strains for such analysis were isolated in 1996. In 2014, the strain E. pyrifoliae EpK1/15 was newly isolated in the apple tree showing black shoot blight in South Korea. This study aimed to better understand the similarities and differences caused by natural variations at the genomic level between newly isolated E. pyrifoliae EpK1/15 and the strain Ep1/96, which were isolated almost 20 years apart. Several comparative genomic analyses were conducted, and Clusters of Orthologous Groups of proteins (COG) database was used to classify functional annotation for each strain. E. pyrifoliae EpK1/15 had similarities with the Ep1/96 strain in stress-related genes, Tn3 transposase of insertion sequences, type III secretion systems, and small RNAs. The most remarkable difference to emerge from this comparison was that although the draft genome of E. pyrifoliae EpK1/15 was almost conserved, Epk1/15 strain had at least three sorts of structural variations in functional annotation according to COG database; chromosome inversion, translocation, and duplication. These results indicate that E. pyrifoliae species has gone natural variations within almost 20 years at the genomic level, and we can trace their similarities and differences with comparative genomic analysis.


Rapid early growth is associated with increased risk of childhood type 1 diabetes in various European populations.
To confirm that early growth is associated with type 1 diabetes risk in European children and elucidate any role of infant feeding. Five centers participated, each with a population-based register of type 1 diabetes diagnosed at <15 years of age. Control subjects were randomly chosen from population registers, schools, or polyclinics. Growth data were obtained from routine records and infant feeding information from parental questionnaire or interview. Patient/control subject differences in mean standard deviation score (SDS) were obtained for each center and pooled. Odds ratios (ORs) were pooled by the Mantel-Haenszel method, and logistic regression was used to adjust for confounders. Growth data were available for 499 patients and 1,337 control subjects. Height and weight SDS were significantly increased among patients from 1 month after birth, the maximum differences of 0.32 (95% CI 0.14-0.50) and 0.41 (0.26-0.55), respectively, occurring between 1 and 2 years of age. Significant excesses in BMI SDS were observed from 6 months of age, with the largest difference of 0.27 (0.10, 0.44) evident between 1 and 2 years. Breast-feeding was associated with reduced disease risk, OR 0.75 (0.58-0.96). Introduction of cow's milk, formula, or solid foods before 3 months was not associated with significant risk elevation. Increased early growth is associated with disease risk in various European populations. Any role of infant feeding in this association remains unclear.


Nonablative laser resurfacing: a systematic review of the literature.
'Nonablative laser resurfacing' is a new treatment for photoaged skin, the aim of which is to wound the upper dermis in order to induce dermal fibrosis and improve the clinical appearance. Unlike conventional laser resurfacing or dermabrasion, the epidermis is protected and retained to avoid the problems associated with open wounds and reepithelialization. A number of lasers and light sources have been developed or adapted for this purpose.


Electrophysiology and arrhythmogenic activity of single cardiomyocytes from canine superior vena cava.
The superior vena cava (SVC) has been proved to be a focal point in the initiation of paroxysmal atrial fibrillation. The autonomic nervous system plays an important role in the genesis of atrial fibrillation. However, the arrhythmogenic potentials of SVC and its responses to autonomic agents are not clear. The purpose of this study was to isolate single SVC cardiomyocytes and to investigate their electrophysiological characteristics, as well as the direct effects of autonomic agents. Canine SVC cardiomyocytes were isolated by perfusion with digestive enzymes. The action potentials and ionic currents were investigated in single SVC cardiomyocytes using the whole-cell clamp technique. Dissociation of the SVC yielded rod-shaped single cardiomyocytes with (n=74, 51%) or without (n=71, 49%) pacemaker activities. There were similar densities of inward Ca2+, delayed rectifier K+, transient inward, inward rectifier K+, and pacemaker currents between SVC cardiomyocytes with and without pacemaker activity. SVC cardiomyocytes with pacemaker activity have, however, greater transient outward currents than those without pacemaker activity. In SVC cardiomyocytes, acetylcholine (5.5 micromol/L) abolished the spontaneous activities, but isoproterenol (10 nmol/L), atropine (10 micromol/L), and phenylephrine (10 micromol/L) accelerated the spontaneous activity and induced the occurrences of early or delayed afterdepolarizations. These findings suggest that SVC cardiomyocytes have distinct action potentials and ionic current profiles that may be responsible for the arrhythmogenic activity of the SVC.


Longer Withdrawal Time Is Associated With a Reduced Incidence of Interval Cancer After Screening Colonoscopy.
Withdrawal times and adenoma detection rates are widely used quality indicators for screening colonoscopy. More rapid withdrawal times have been associated with undetected adenomas, which can increase risk for interval colorectal cancer. We analyzed records of 76,810 screening colonoscopies performed between 2004 and 2009, by 51 gastroenterologists practicing in Minneapolis and St Paul, MN. Colonoscopy records were linked electronically to the state cancer registry (Minnesota Cancer Surveillance System) to identify incident interval cancers that were diagnosed within 5.5 years after the screening examination. The physicians' mean ± SD withdrawal time was 8.6 ± 1.7 minutes and adenoma detection rates were 25% ± 9%. Longer mean withdrawal times were associated with higher adenoma detection rates (3.6% per minute; 95% confidence interval: 2.4% to 4.8%; P < .0001). We identified 78 cancers during 410,687 person-years of follow-up, for an annual rate of 0.19/1000 person-years. Physicians' mean annual withdrawal times were inversely associated with cancer incidence (P < .0001). Compared with withdrawal times ≥6 minutes, the adjusted incidence rate ratio for withdrawal times of <6 minutes was 2.3 (95% confidence interval: 1.5-3.4; P < .0001). Shorter mean annual withdrawal times during screening colonoscopies were independently associated with lower adenoma detection rates and increased risk of interval colorectal cancer.


Decreased bioavailability of rifampin and other antituberculosis drugs in patients with advanced human immunodeficiency virus disease.
We evaluated the effects of human immunodeficiency virus (HIV) disease on pharmacokinetics of antituberculosis medications by measuring concentrations of isoniazid and rifampin in blood and of pyrazinamide and ethambutol in urine. Peak concentration and exposure were reduced for rifampin, and rapid acetylators of isoniazid had lower drug levels. HIV and HIV-tuberculosis patients who have diarrhea and cryptosporidial infection exhibit decreased bioavailability of antituberculosis drugs.


Evaluation of the role of facet joints in persistent low back pain in obesity: a controlled, prospective, comparative evaluation.
Chronic low back pain and obesity are two common medical conditions. Obesity has been associated with symptoms such as adverse fat distribution and multiple secondary disorders, including low back pain. Obesity is defined as being 30% over ideal weight, which influences normal body mechanics as well as recovery from an injury. Facet joints have been described as contributing to a significant proportion of patients suffering with persistent or chronic low back pain, variably from 15% to 45%. Since an obese patient is at a higher risk of disability compared to a patient with normal weight, obesity has been described as a confounding factor in persistent low back pain. This study included 100 patients, with 50 patients in Group I who were of normal weight and 50 patients in group II who were obese, by random allocation. Facet joints were investigated with diagnostic blocks using lidocaine 1% initially, followed by bupivacaine 0.25%. The results showed that the prevalence rate of facet joint pain in chronic low back pain in Group I or nonobese patients was 36%, in contrast to 40% in Group II, or the obese patient group, with no significant differences among the two groups. The study also showed a false-positive rate of 39% in the total sample, or 44% in Group I nonobese patients and 33% in Group II, or obese patients. It is concluded that the prevalence of lumbar facet joint mediated pain of 40% in obese patients and 36% in patients of normal weight with a false-positive rate of 33% in obese patients and 44% in nonobese patients is similar to the results of multiple previous studies concluding that facet joint mediated pain is a common occurrence in obese patients; however, the incidence of facet joint mediated pain is similar in obese patients and nonobese patients.


Operative versus non-operative management of rib fractures in flail chest after cardiopulmonary resuscitation manoeuvres.
Blunt chest trauma after mechanical resuscitation manoeuvres appears to have a significant impact on the often complicated course. Due to a lack of data in the literature, the purpose of this study was to investigate the feasibility and immediate outcome of chest wall stabilization for flail chest in this vulnerable patient population. We retrospectively reviewed the medical records of patients after cardiopulmonary resuscitation between January 2014 and December 2018 who were diagnosed with flail chest. We attempted to compare patients after surgery with those after conservative treatment. Of a total of 56 patients with blunt chest trauma after mechanical resuscitation and after coronary angiography, 25 were diagnosed with flail chest. After the exclusion of 2 patients because of an initial decision to palliate, 13 patients after surgical stabilization could be compared with 10 patients after conservative therapy. Although there was no significant difference in the total duration of ventilatory support, there was a significant advantage when the time after stabilization to extubation was compared with the duration of ventilation in the conservative group. The presence of pulmonary contusion, poor Glasgow Coma Scale score or the development of pneumonia negatively affected the outcome, but additional sternal fracture did not. Surgical stabilization for chest wall instability is well tolerated even by this vulnerable patient population. Our results should be used for further randomized controlled approaches. It is necessary to evaluate the situation with all parameters in an interdisciplinary manner and to decide on a possible surgical therapy at an early stage if possible.


Treatment of long-term stored DNA--comparison between different methods to obtain high-quality material.
Long-term stored DNA can be sometimes the only source of genetic material of an organism that does not exist anymore, but a research interest still persists. However, there is a lack of information about useful methods to improve quality from such type of material. In this study, we compared four different protocols using DNA samples collected in 1998. Fresh DNA was also tested aiming to check the differences between these two material types. Sixteen samples of each DNA type treated with phenol-chloroform with PEG 5.0%, silica-gel membrane spin column, PEG 7.5%, and glass-fiber matrix spin column were submitted to spectrophotometer measurements, electrophoresis, PCR, and RFLP-PCR to assess the best method concerning yield, quality, and purity. Based on the results, purification with PEG 7.5% was considered the best method to treat aged DNA samples. In addition to the efficiency, this protocol has low cost. Analyzing the data, we also conclude that long-term stored DNA may be considered a reliable and potential resource for future molecular studies.


Triterpene Biosynthesis in the Latex of Euphorbia lathyris: Effect of Calmodulin Antagonists and Chlorinated Phenoxy Compounds.
Recognized calmodulin antagonists and chlorinated phenoxyalkylamines were tested as inhibitors of mevalonate incorporation into triterpenols and their fatty acid esters in a centrifuged pellet from the latex of Euphorbia lathyris. The calmodulin antagonists, chlorpromazine (II), fluphenzine, and trifluoperazine were good inhibitors; I(50) values for II and trifluoperazine were 150 and 55 micromolar, respectively. Inhibition by the phenoxyalkylamines increased with increasing chlorine substitution, and I(50) for 2-(pentachlorophenoxy)ethyl N,N-diethylamine (IX) was 35 micromolar. The calmodulin-stimulated phosphodiesterase catalyzed hydrolysis of cAMP was used as an assay to quantitate the calmodulin antagonism of the tested compounds. Compounds II and IX were calmodulin antagonists over a concentration range similar to their effective range in the biosynthesis of triterpenes. The antagonism of the chlorinated phenoxy compounds increased in parallel to their inhibitory effect upon triterpene biosynthesis.


Dose-ranging antiemetic evaluation of the serotonin antagonist RG 12915 in patients receiving anticancer chemotherapy.
RG 12915 is a potent, selective 5-HT3 receptor antagonist with a biologic half-life of 11-20 hours. RG 12915 prevents cisplatin-induced emesis in ferrets at doses of 0.03 mg/kg. Animal toxicology studies permitted safe testing in humans at doses of up to 2.0 mg/kg. This dose-ranging trial of intravenous RG 12915 was performed to determine the optimal dosage and adverse effects and to observe for antiemetic effects in patients receiving anticancer chemotherapy. Twenty-six patients receiving chemotherapy likely to cause vomiting received a single intravenous dose of RG 12915 at a rate of 3 ml/minute beginning 60 minutes before chemotherapy. Four dose levels were explored: 0.25, 0.50, 1.0, and 2.0 mg/kg. No dose-limiting toxicities were observed. All adverse effects were mild and transient and included discomfort at the infusion site, hyperglycemia, headache, serum aspartate transaminase (AST) and alanine transaminase (ALT) elevations, and sedation. Antiemetic efficacy was seen in patients receiving cisplatin at doses of greater than or equal to 100 mg/m2. RG 12915 can be administered safely at the dose levels explored. Single intravenous doses of RG 12915 prevented or lessened emesis caused by chemotherapy, including cisplatin given at doses of greater than or equal to 100 mg/m2. RG 12915 warrants further testing. Of the doses tested, the 2.0 mg/kg dose is the most appropriate for further exploration.


Current concepts in the pathogenesis and management of exfoliation syndrome and exfoliative glaucoma.
Exfoliative glaucoma is a common, sight-threatening disease that develops as a consequence of exfoliation syndrome. There are important differences in the clinical appearance, course, and prognosis of exfoliative glaucoma versus primary open-angle glaucoma. At the clinical, biochemical, and cellular levels, exfoliative glaucoma is a distinct entity, with an intriguing mechanism of development and numerous systemic manifestations that require further elucidation. The subtlety of clinical signs results in the diagnosis of exfoliative glaucoma often being overlooked and resulting in less-than-ideal management. We provide an overview of recent studies investigating the medical, laser, and surgical therapy of exfoliative glaucoma, with a focus on innovative approaches that may slow the progression of, or even prevent, the development of exfoliation syndrome and exfoliative glaucoma.


Computer analysis of the performance of the BTE Work Simulator.
The BTE Work Simulator (Baltimore, Therapeutic Equipment Co., Hanover, Md.) recreates the work environment by providing a rotatable shaft to which a variety of tools can be attached. The patient can simulate the coordinated muscle and joint movements involved in the work situation, exercising either isometrically or isotonically, and thereby increase the potential for return to work. The BTE Work Simulator has four major components: the exercise head to provide variable resistance, tools that attach to the exercise head, a control console containing a microprocessor that calculates work and power, and the Quest software package (Baltimore Therapeutic Equipment Co.). Quest provides four static/isometric and seven dynamic/isotonic tests that can be used to document the extent of a patient's impairment. In addition, it has daily treatment options and acts as an extensive data base capable of retrieving any stored test or treatment results. This software system greatly facilitates the use of the BTE Work Simulator by providing instant calculations of power and coefficients of variation, immediate patient feedback, graphic expansion of the data, and printed evaluation reports.


[Detection of Leptospira organisms in Rattus rattus of two islands in the Mozambique Channel: Europa and Juan-de-Nova].
Europa and Juan-de-Nova are two little coral islands in the Mozambique Channel. They are only occupied by a troop detachment of 15 men, who exercise the French sovereignty and maintain the island. During these activities, the men work in dampness and they can encounter rats. The aim of this survey is to show presence of leptospirosis in these islands by testing rat kidney by specific PCR. The results found a positive specimen on each island (2/52) indicating a previously unknown presence of Leptospira organisms in these islands.


Uncovering the Potential of Lipid Drugs: A Focus on Transient Membrane Microdomain-targeted Lipid Therapeutics.
Membrane lipids are generally viewed as inert physical barriers, but many vital cellular processes greatly rely on the interaction with these structures, as expressed by the membrane hypothesis that explain the genesis of schizophrenia, Alzheimer's and autoimmune diseases, chronic fatigue or cancer. The concept that the cell membrane displays transient membrane microdomains with distinct lipid composition providing the basis for the development of selective lipid-targeted therapies, the membrane-lipid therapies (MLTs). In this concern, medicinal chemists may design therapeutically valuable compounds 1) with a higher affinity for the lipids in these microdomains to restore the normal physiological conditions, 2) that can directly or 3) indirectly (via enzyme inhibition/activation) replace damaged lipids or restore the regular lipid levels in the whole membrane or microdomain, 4) that alter the expression of genes related to lipid genesis/metabolism or 5) that modulate the pathways related to the membrane binding affinity of lipid-anchored proteins. In this context, this mini-review aims to explore the structural diversity and clinical applications of some of the main membrane and microdomain-targeted lipid drugs.


Inherited genetic predisposition in breast cancer. A population-based perspective.
Two classes of inherited susceptibility genes may be considered in the etiology of breast and other common cancers. First, genes have been identified that confer a high degree of breast cancer (BC) risk, usually associated with hereditary syndromes, but disease-associated germline variants in these genes are relatively rare in the general population. These include BRCA1, BRCA2, and TP53. The proportion of BC in the general population that can be explained by these genes is relatively small. Second, variant genotypes at other loci may confer a relatively smaller degree of cancer risk, but they are carried by a larger proportion of the general population. As a result, the proportion of BC that could be explained by these genes may be relatively large. To understand the genetic basis for BCs in the general population, both of these classes of genes may need to be considered. This paper presents an overview of genes thought to be involved in BC susceptibility. Genes that confer a high degree of risk are more likely to result in hereditary patterns of cancer that are amenable to identification by genetic epidemiologic methods using pedigree data. More common (e.g., nonhereditary) forms of BC may be optimally analyzed by molecular epidemiologic studies using case-case, case-control, or cohort designs. The use of an appropriate study design is crucial to the identification of genes with relatively small effects on BC risk. To understand the inherited factors that explain BC in the general population, consideration should be given to genes with different allele frequencies and magnitudes of effect, using appropriate analytical approaches. By understanding the complex interactions of these genes with one another and with exposures, improved risk assessment and potential for targeted cancer prevention strategies may be possible.


Breast cancer presenting as a mass in the axilla: a report of two cases.
Breast cancer presenting initially as enlarged axillary lymph node is very unusual. To highlight the less frequent clinical presentation of breast cancer as persistent isolated, unilateral axillary lymphadenopathy. A report of two patients who presented with persistent axillary lymphadenopathy. Case one was a 65-year old woman who presented with an eight-month history of a painless mass in the right axilla. Clinical breast examination was normal. A mammogram was performed. The sub-clinical mass was excised using wire-guided localization providing a specimen for histology. A complete dissection of the right axilla was done and the specimen sent for histological examination. In a second case a 73-year old otherwise healthy woman reported for the assessment of two painful masses in the right axilla. Two hard ovoid masses 2.5 cm x 3.5 cm and 3.0 cm x 3.5 cm were palpated in the right axilla. No other masses were palpable. Both breasts were normal on examination. Mammograms and chest X-rays were done. Fine needle aspiration cytology was done on both masses. A right sided complete axillary lymph node dissection was performed. In case one, mammogram revealed a 5-mm sub mass in the right breast that was shown to be carcinoma. In case two the mammograms and chest X-rays were normal. Histologic examination of the surgical specimen from the axilla showed that four of the seven lymph nodes removed contained metastases. Axillary nodal metastasis as the initial presentation of breast cancer in our women is no different from the presentation in women from other populations.


Is mitochondrial dysfunction a driving mechanism linking COPD to nonsmall cell lung carcinoma?
Chronic obstructive pulmonary disease (COPD) patients are at increased risk of developing nonsmall cell lung carcinoma, irrespective of their smoking history. Although the mechanisms behind this observation are not clear, established drivers of carcinogenesis in COPD include oxidative stress and sustained chronic inflammation. Mitochondria are critical in these two processes and recent evidence links increased oxidative stress in COPD patients to mitochondrial damage. We therefore postulate that mitochondrial damage in COPD patients leads to increased oxidative stress and chronic inflammation, thereby increasing the risk of carcinogenesis.The functional state of the mitochondrion is dependent on the balance between its biogenesis and degradation (mitophagy). Dysfunctional mitochondria are a source of oxidative stress and inflammasome activation. In COPD, there is impaired translocation of the ubiquitin-related degradation molecule Parkin following activation of the Pink1 mitophagy pathway, resulting in excessive dysfunctional mitochondria. We hypothesise that deranged pathways in mitochondrial biogenesis and mitophagy in COPD can account for the increased risk in carcinogenesis. To test this hypothesis, animal models exposed to cigarette smoke and developing emphysema and lung cancer should be developed. In the future, the use of mitochondria-based antioxidants should be studied as an adjunct with the aim of reducing the risk of COPD-associated cancer.


Fabrication of Electrospun Polylactic Acid/Cinnamaldehyde/β-Cyclodextrin Fibers as an Antimicrobial Wound Dressing.
Cinnamaldehyde (CA) was successfully encapsulated in β-cyclodextrin (β-CD), and polylactic acid (PLA)-based composite fibers were prepared by incorporating CA/β-CD via electrospinning. Morphological, structural, spectral, and antibacterial properties of different weight ratios of PLA:β-CD/CA (88:12, 94:6, 97:3, and 98.5:1.5) and PLA/CA/β-CD fibers were investigated. PLA and CA/β-CD were incorporated by mixing of CA/β-CD inclusions to enhance the viscosity of the mixed solution. The mechanical properties and hydrophilicity of nanofibers were improved following the addition of CA/β-CD. Moreover, CA/β-CD improved the antibacterial activities of the mixture against Escherichia coli and Staphylococcus aureus. PLA/CA/β-CD-3 exhibited excellent antibacterial effects and low cytotoxicity. Thus, our study showed that PLA/CA/β-CD fibers may have applications as wound dressing materials and for use in other biomedical applications.


Association of demographic, career, and lifestyle factors with resilience and association of resilience with mental health outcomes in veterinarians in Canada.
To investigate the association of demographic, career, and lifestyle factors with resilience and the association of resilience with mental health outcomes in Canadian veterinarians. 1,130 veterinarians in clinical practice across Canada. An online questionnaire was used to collect participant data and included 5 validated psychometric scales to evaluate resilience (through the Connor-Davidson Resilience Scale [CD-RISC]), perceived stress (through the Perceived Stress Scale), emotional distress (through the Hospital Anxiety and Depression Scale), burnout (through the Maslach Burnout Inventory), and secondary traumatic stress (through the Professional Quality of Life Scale). A multivariable linear regression model was used to investigate associations between CD-RISC scores and demographic, career, and lifestyle characteristics. Univariable linear regression models were used to assess the relationship between resilience scores and other mental health outcomes. The strongest positive association was between CD-RISC score and overall health. The level of satisfaction with support from friends and workplace resources had positive associations with the CD-RISC score. The presence of mental illness had the strongest negative association with the CD-RISC score. Being married, working in a small animal practice, or having an associate role were negatively associated with the CD-RISC score. The CD-RISC score had negative associations with scores for perceived stress, anxiety, depression, burnout, and secondary traumatic stress. Models provided evidence for the role of resilience in protecting against negative mental health outcomes in veterinarians. Both personal and workplace factors were associated with resilience, presenting opportunities for intervention at each of these levels.


Assessment of the risk and biomechanical consequences of lateral epicondylalgia by estimating wrist and finger muscle capacities in tennis players.
Previous studies suggested that a pronounced weakness of the extensor muscles relative to the flexor muscles could increase the risk of occurrence of lateral epicondylalgia. This study investigates this hypothesis by estimating the ratio of extensor to flexor muscle capacities among healthy non-players (n = 10), healthy tennis players (n = 20), symptomatic players (n = 6), and players who have recovered from lateral epicondylalgia (n = 6). Maximum net joint moments in flexion or extension were measured during seven tasks involving the voluntary contraction of wrist and fingers. Using these data, the muscle capacities of the main muscle groups of the hand (wrist flexors, wrist extensors, finger flexors, finger extensors, and intrinsic muscles) were estimated using a musculoskeletal model. These capacities were then used to compute the extensor/flexor capacity ratios about the wrist and the finger joints. Compared to healthy non-players, healthy players presented higher extensor muscle capacities and greater capacity ratios showing that playing tennis generates specific adaptations of muscle capacities. Interestingly, symptomatic players, similar to those of non-players, showed more imbalanced ratios than healthy players. These results confirm that the ratio of extensor/flexor muscle capacities seems to be associated with lateral epicondylalgia and can be further used to understand its incidence and consequences.


Frailty and physical function in older HIV-infected adults.
HIV patients have seen accelerated ageing. Our objective was to determine the prevalence of frailty, to evaluate factors associated with frailty and to evaluate physical function in older HIV-infected adults. this was a cross-sectional study. outpatient clinics of two public university hospitals in Madrid (Spain). frailty was defined according to the criteria of Fried: shrinking, weakness, poor endurance and energy, slowness and low physical activity level, being frail those who met at least three criteria, prefrail one or two criteria and robust when they met no criteria. Physical function was assessed using standardised methods. we evaluated 117 HIV-infected patients. Mean age was 61.3 ([standard deviation] 6.87) years. All patients were on antiretroviral therapy. Median current CD4+ T-cell count was 638 (144-1871) cells/μl, and median CD4/CD8 ratio was 0.79 (0.00-3.62). The prevalence of frailty was 15.4%, and that of prefrailty was 52.1%. In the multivariate analyses depressive symptoms (OR [95% CI], 9.20 [2.17-39.05]) and CD4/CD8 ratio (OR 0.11 [0.02-0.61]) were associated with frailty. Even though 100% of the patients were able to walk and perform basic activities of daily life independently, functional impairment was high (20% slow gait and 55% Short Physical Performance Battery ≤9). HIV-infected patients aged ≥55 years have a high prevalence of frailty and a high burden of functional impairment. Optimal management of this population requires close collaboration between infectious diseases specialists and geriatricians.


American Gastroenterological Association medical position statement: diagnosis and treatment of gastroparesis.
This document presents the official recommendations of the American Gastroenterological Association (AGA) on Diagnosis and Treatment of Gastroparesis. It was approved by the Clinical Practice Committee on May 16, 2004, and by the AGA Governing Board on September 23, 2004.


Rheological properties of erythrocytes in patients suffering from morbid obesity. Examination with LORCA device.
Obesity is associated with many comorbid pathologies that lead to increased morbidity and increased mortality. Hemorheological changes in obesity are currently investigated as one of the risk factors for many comorbid pathologies. It has been found that erythrocyte hyperaggregation and a decrease in erythrocyte filterability have also been well documented in obesity patients. The aim of this study is to present preliminary results of the influence of weight reduction after vertical banded gastroplasty (VBG) on aggregation of red cells and red blood cells deformability. We studied seven patients who underwent VBG, median age 46 years (range 35-52), median BMI 52.1 kg/m(2) (range 36.6-66). Blood rheology changes and selected biochemical parameters were examinated before and 6 months after VBG. Erythrocyte elongation and red blood cells (RBC) aggregation were measured using the Laser-assisted Optical Rotational Cell Analyser (LORCA). The RBC aggregation index was significantly decreased, while the aggregation half-time (t(1/2)) significantly elongated after surgery. The syllectogram amplitude did not change. No differences in RBC deformability were observed in the postoperative period. We could conclude that among morbidly obese patients six months after VBG some beneficial changes of erythrocyte rheological parameters are observed. Further studies are necessary to confirm our preliminary results.


Na(+)-coupled transport of L-carnitine via high-affinity carnitine transporter OCTN2 and its subcellular localization in kidney.
The mechanism of Na(+)-dependent transport of L-carnitine via the carnitine/organic cation transporter OCTN2 and the subcellular localization of OCTN2 in kidney were studied. Using plasma membrane vesicles prepared from HEK293 cells that were stably transfected with human OCTN2, transport of L-carnitine via human OCTN2 was characterized. Uptake of L-[(3)H]carnitine by the OCTN2-expressing membrane vesicles was significantly increased in the presence of an inwardly directed Na(+) gradient, with an overshoot, while such transient uphill transport was not observed in membrane vesicles from cells that were mock transfected with expression vector pcDNA3 alone. The uptake of L-[(3)H]carnitine was specifically dependent on Na(+) and the osmolarity effect showed that Na(+) significantly influenced the transport rather than the binding. Changes of inorganic anions in the extravesicular medium and of membrane potential by valinomycin altered the initial uptake activity of L-carnitine by OCTN2. In addition, the fluxes of L-carnitine and Na(+) were coupled with 1:1 stoichiometry. Accordingly, it was clarified that Na(+) is coupled with flux of L-carnitine and the flux is an electrogenic process. Furthermore, OCTN2 was localized on the apical membrane of renal tubular epithelial cells. These results clarified that OCTN2 is important for the concentrative reabsorption of L-carnitine after glomerular filtration in the kidney.


Paediatric sleep resources in Canada: The scope of the problem.
Sleep-disordered breathing (SDB) is prevalent in children and is associated with significant comorbidity. To describe paediatric sleep physician and diagnostic testing resources for SDB in Canadian children. A 38-item, Internet-based survey was sent to the 32 members of the Canadian Pediatric Sleep Network (CPSN). A shorter telephone survey was administered to all 182 non-CPSN sleep laboratories across Canada. Responses were obtained from 29 of 31 (91%) CPSN members and 121 of 182 (66%) non-CPSN sleep facilities. Sixty-seven of 121 (55%) of the responding non-CPSN facilities reported that they see children <18 years of age. Thirty-six of 121 (30%) and 23 of 121 (19%), respectively, see children ≤12 years of age or ≤8 years of age. Marked disparities across provinces/territories were observed, with no practitioners or polysomnography in the Yukon, Northwest Territories, Nunavut, Saskatchewan, New Brunswick, Prince Edward Island, and Newfoundland and Labrador. Alberta has the smallest ratio of children to practitioners (approximately 167,000 to 1) and Ontario has the smallest ratio of children to polysomnograms performed per year (approximately 487,000 to 1). Reported wait times for polysomnography ranged from <1 month, to 1.5 to 2 years. In paediatric tertiary care centres, the number of polysomnograms performed per year ranged from 55 to 700 (median 480) and in other laboratories the range was 400 to 4000 (median 1100). The present study demonstrates a significant lack of resources and services for paediatric SDB care across Canada, with pronounced geographical disparities. Even if only affected children were tested with polysomnography, the authors estimate there are 7.5 times more children with SDB than current testing capacity.


Determination of multiple mycotoxins in dietary supplements containing green coffee bean extracts using ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS).
An ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method for the determination of 34 mycotoxins in dietary supplements containing green coffee bean (GCB) extracts was developed, evaluated, and used in the analysis of 50 commercial products. A QuEChERS-like procedure was used for isolation of target analytes from the examined matrices. Average recoveries of the analytes were in the range of 75-110%. The precision of the method expressed as relative standard deviation was below 12%. Limits of detection (LODs) and limits of quantitation (LOQs) ranged from 1.0 to 50.0 μg/kg and from 2.5 to 100 μg/kg, respectively. Due to matrix effects, the method of standard additions was used to ensure accurate quantitation. Ochratoxin A, ochratoxin B, fumonisin B1 and mycophenolic acid were found in 36%, 32%, 10%, and 16% of tested products, respectively. Mycotoxins occurred in the following concentration ranges: ochratoxin A, <1.0-136.9 μg/kg; ochratoxin B, <1.0-20.2 μg/kg; fumonisin B1, <50.0-415.0 μg/kg; mycophenolic acid, <5.0-395.0 μg/kg. High-resolution mass spectrometry operated in full MS and MS/MS mode was used to confirm the identities of the reported compounds.


Uptake of technetium-99m-teboroxime in cultured myocardial cells: comparison with thallium-201 and technetium-99m-sestamibi.
The effects of metabolic inhibition on the uptake of 99mTc-teboroxime were assessed in cultured myocardial cells and compared with 201Tl and 99mTc-sestamibi. Metabolic impairment was induced by cyanide (CN), a blocker of the mitochondrial respiratory chain, iodoacetate (IAA), an inhibitor of the glycolytic pathway, and ouabain, an inhibitor of Na(+)-K+ sarcolemmal ATPase. Cellular viability was appreciated by the trypan blue exclusion method. The effects of low temperature and of cellular death resulting from osmotic lysis were also assessed. Net cellular uptake of the radiotracers and the amount of proteins in the culture dishes were measured. All experiments were performed in parallel with control conditions and the results were expressed relatively to the control values. Teboroxime uptake was clearly decreased at low temperature (29.6% +/- 2.2% at 0 degree C, p < 0.001), while metabolic inhibition or osmotic lysis had no definite effect. The uptake of 201Tl and sestamibi was severely diminished in the presence of a mixture of 5 mM CN and 0.1 mM IAA, but 201Tl was less resistant than sestamibi (13.7% +/- 0.3% and 73.5% +/- 3.3%, respectively, after 1 hr of preincubation, p < 0.001 for both). Uptake of both tracers was very low in the presence of dead cells (12.1% +/- 1.3% for 201Tl and 4.1% +/- 0.2% for sestamibi, p < 0.001 for both). Ouabain had a detrimental effect only on 201Tl uptake at doses higher than 100 microM. Of these three currently available coronary blood flow imaging agents, teboroxime shows the lowest sensitivity to metabolic impairment.


[Advantages of two- or polyvalent binding of a receptor to the corresponding ligand in comparison to univalent binding].
The features of monovalent and bivalent binding of receptors (or antibodies) with a polyvalent ligand (or with an antigen) are considered. It is shown that the rigid connection of the binding sites of the receptor brings to high increase of binding affinity for the corresponding ligand, but only in case if its epitopes are fully complementary to both sites of the receptor binding. If not, then there is no advantage of the binding of bivalent receptor before univalent binding. If the binding sites of the receptor are connected by a flexible linker, then regardless of location of epitopes of the corresponding ligand there is the successful fastening of receptor and ligand. Exactly the connection by a flexible linker is used by Nature in most cases at constructing of polyvalent receptors.