Clinical Management for Survivors of Sudden Cardiac Death.
Sudden cardiac death is believed to affect as many as 400,000 people each year in the United States and is therefore an important public health problem. A common cause of sudden cardiac death is ventricular fibrillation. This article reviews the clinical and electrophysiologic aspects of sudden arrhythmic death and discusses current clinical management for survivors of sudden death. Particular emphasis is placed on the implantable cardioverter-defibrillator (ICD).


Contribution of membrane-associated prostaglandin E2 synthase to bone resorption.
This study initially confirmed that, among prostaglandins (PGs) produced in bone, only PGE(2) has the potency to stimulate osteoclastogenesis and bone resorption in the mouse coculture system of osteoblasts and bone marrow cells. For the PGE(2) biosynthesis two isoforms of the terminal and specific enzymes, membrane-associated PGE(2) synthase (mPGES) and cytosolic PGES (cPGES) have recently been identified. In cultured mouse primary osteoblasts, both mPGES and cyclooxygenase-2 were induced by the bone resorptive cytokines interleukin-1, tumor necrosis factor-alpha, and fibroblast growth factor-2. Induction of mPGES was also seen in the mouse long bone and bone marrow in vivo by intraperitoneal injection of lipopolysaccharide. In contrast, cPGES was expressed constitutively both in vitro and in vivo without being affected by these stimuli. An antisense oligonucleotide blocking mPGES expression inhibited not only PGE(2) production, but also osteoclastogenesis and bone resorption stimulated by the cytokines, which was reversed by addition of exogenous PGE(2). We therefore conclude that mPGES, which is induced by and mediates the effects of bone resorptive stimuli, may make a target molecule for the treatment of bone resorptive disorders.


A copper complex bearing a TEMPO moiety as catalyst for the aerobic oxidation of primary alcohols.
A new bifunctional, triazine-based ligand has been designed with the aim to generate a copper(II) complex holding a TEMPO (2,2,6,6-tetramethylpiperidinyloxy) moiety. The coordination compound obtained from the ligand 4-(2-(3-(pyridin-2-yl)-1H-pyrazol-1-yl)ethoxy)-6-(4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl)-N,N-diphenyl-1,3,5-triazin-2-amine (pypzt-1) and copper(II) bromide (i.e. complex 8) is capable of catalysing the selective, aerobic oxidation of benzyl alcohol to 84% of benzaldehyde in 24 h. This "galactose oxidase activity" of the copper/TEMPO complex is observed as well for the conversion of the non-activated alkyl alcohol octan-1-ol to octanal with a yield of 29% after the same reaction time. The single-crystal X-ray structure of 8 shows that its crystal lattice contains [Cu(I)Br(2)](-) anions which appear to be stabilised by means of both anion-pi and hydrogen bonding interactions. In addition, the solid state structure of 8 exhibits (lone-pair)-pi interactions between the nitrogen atom of an acetonitrile molecule and a triazine ring. The magnetic properties of 8 have been investigated by EPR and magnetic susceptibility measurements.


[Familial Degos' atrophic papulosis (mother-daughter)].
Degos' disease (malignant atrophic papulosis) occurring in mother and daughter is described. Mother's eruption is composed of multiple characteristic lesions (up to 600). She does not have any gastrointestinal, neurological nor other visceral manifestations after a 9-year course. One year after the onset of the disease, she had a daughter. The pregnancy was normal and the newborn did not have any cutaneous manifestation. The daughter's first skin lesion appeared when she was 3-months old. She has now been under observation for nearly nine years and developed only four skin lesions without any visceral manifestation. Laboratory investigations show an increase in fibrinogen in both mother and child, without any sign of disseminated intravascular coagulation. The research for "slow virus" by a primate's intravascular inoculation of mother's skin lesion in negative.


Effect Of Non- Surgical Periodontal Treatment On Glycemic Control Among Type 2 Diabetes Mellitus Patients With Periodontitis.
Periodontitis and Diabetes Mellitus are two closely, bidirectional linked disease where periodontitis is a well-known complication of diabetes it is also considered to be a cause for poor glycaemic control. The present study objective was to evaluate the glycaemic control in patients suffering from both Diabetes Mellitus and Periodontitis after non-surgical periodontal treatment. A comparative cross-sectional study was conducted with two groups of patients attending Diabetic Clinic, Jinnah Hospital, Lahore, during six months from September 2013 to February 2014. Forty-six diabetes mellitus subjects who were undergoing non-surgical treatment of periodontal disease that includes mechanical removal of supra- and sub gingival bacterial plaque with scalers, antibiotics and or root canal if required while 46 subjects with diabetic mellitus having periodontal disease did not had treatment for periodontal disease. HbA1c was compared at base line and at three months. Data was compiled and analysed through SPSS version 16. Quantitative variables like HbA1c was presented as mean±SD. Qualitative variables like gender, education status, economic status, treatment for diabetes mellitus and periodontal disease were described by using frequency percentages. The t-test was applied to assess statistical significance in mean difference HbA1c between two groups. p-value <0.05 was considered significant. Forty-six subjects who received non-surgical treatment for periodontitis 43 (93.5%) received scaling only while 3 (6.5%) received scaling plus antibiotics. Fall in the level of HbA1c was observed among subjects with treatment of periodontal disease indicating a good control of diabetes while in group without treatment there was either no change or increase in HbA1c. Mean HbA1c at baseline in group with treatment of periodontitis at baseline was 7.672±.6414 and without treatment was 6.957±.3494. (t= -1.008, p<.279). Mean HbA1c after 3 months in group with treatment of periodontitis was 6.867±.6168, and in group without treatment was 6.983±.3678. (t=6.641, p<.000). Non-surgical periodontal treatment is associated with improved glycaemic control (reduced HbA1c level) in type 2 diabetic patients.


A proposal of new ocular items in Sjögren's syndrome classification criteria.
To verify whether ocular surface tests other than those included in primary Sjögren's syndrome (SS-I) classification criteria (Schirmer I, Break up Time, vital dye staining) may contribute to SS I diagnosis. Two hundred and sixty-two patients (78 SS-1, 91 non-SS autoimmune diseases, 93 Sicca syndrome) filled a validated questionnaire on symptoms and were evaluated by Schirmer test without (Schirmer I) and with (Jones test) topical anaesthesia, Break Up Time (BUT), corneal aesthesiometry, tear clearance rate, vital dye (lissamine green) staining, impression conjunctival cytology, concentration of tear lysozyme and lactoferrin. Thresholds were selected from Receiver Operating Curves; sensitivity, specificity, likelihood ratio (LR+), predictive values were calculated for each test. A logistic regression model was constructed representing the best diagnostic index for SS. Data showed a poor diagnostic performance of Schirmer test I (LR+ 1.38) and BUT (LR+ 1.05); results from lissamine green staining may be unreliable due to incorporation bias. Tear lactoferrin (LR+ 4.52), Jones test (LR+ 6.24), tear lysozyme (LR+ 8.0), symptom questionnaire (LR+ 8.62), tear clearance rate (LR+ 18.73) and corneal aesthesiometry (LR+ 20.96) exhibited high diagnostic performance also taken together in the regression model. Because many of the tests we have screened in this study can be carried out by a trained ophthalmologist in any clinical setting, we recommend that ocular surface impairment is studied with the combination of tests proved to be helpful for the SS I diagnosis.


Functional inactivity and mutations of p53 differentially affect sensitivity to 5-fluorouracil and antifolate inhibitors of thymidylate synthase (TS) by altering TS levels in colorectal cancer cells.
The role of p53 in altering TS expression and chemosensitivity was studied in colorectal cancer cells with wildtype, mutated, or functionally inactive p53. Cytotoxicity of TS inhibitors was studied by MTT, while PCR, Western blot, and activity assays assessed whether p53 status influenced TS expression. Lovo-175X2 cells showed increased resistance to TS inhibitors and significantly greater than wildtype expression and activity of TS. In contrast, Lovo-273X17 and Lovo-li were more sensitive to TS inhibitors and had reduced TS expression, due either to reduced TS mRNA or altered regulation of TS activity. Thus, functional inactivity and mutations of p53 differentially affect TS, potentially influencing response to TS inhibitor-based treatment.


Metabolic/bariatric surgery worldwide 2011.
Metabolic/bariatric procedures for the treatment of morbid obesity, as well as for type 2 diabetes, are among the most commonly performed gastrointestinal operations today, justifying periodic assessment of the numerical status of metabolic/bariatric surgery and its relative distribution of procedures. An email questionnaire was sent to the leadership of the 50 nations or national groupings in the International Federation for the Surgery of Obesity and Metabolic Disorders (IFSO). Outcome measurements were numbers of metabolic/bariatric operations and surgeons, types of procedures performed, and trends from 2003 to 2008 to 2011 worldwide and in the regional groupings of Europe, USA/Canada, Latin/South America, and Asia/Pacific. Response rate was 84%. The global total number of procedures in 2011 was 340,768; the global total number of metabolic/bariatric surgeons was 6,705. The most commonly performed procedures were Roux-en-Y gastric bypass (RYGB) 46.6%; sleeve gastrectomy (SG) 27.8%; adjustable gastric banding (AGB) 17.8%; and biliopancreatic diversion/duodenal switch (BPD/DS) 2.2%. The global trends from 2003 to 2008 to 2011 showed a decrease in RYGB: 65.1 to 49.0 to 46.6%; an increase, followed by a steep decline, in AGB: 24.4 to 42.3 to 17.8%; and a marked increase in SG: 0.0 to 5.3 to 27.89%. BPD/DS declined: 6.1 to 4.9 to 2.1%. The trends from the four IFSO regions differed, except for the universal increase in SG. Periodic metabolic/bariatric surgery surveys add to the knowledge and understanding of all physicians caring for morbidly obese patients. The salient message of the 2011 assessment is that SG (0.0% in 2008) has markedly increased in prevalence.


PKMζ Is Not Required for Development of Postsurgical Pain.
Previous studies have shown that protein kinase M zeta (PKMζ), a brain-specific isoform of protein kinase C, is involved in the central processing of nociception in several pain models by using a synthetic zeta inhibitory peptide. In the present study, we investigated whether PKMζ contributes to the pathogenesis of postsurgical pain using both conditional and conventional PKMζ knockout mice. Our results showed that the expression of PKMζ in anterior cingulate cortex, but not spinal cord, of the conditional PKMζ knockout mice was inhibited following tamoxifen injection. And the conditional PKMζ knockout mice displayed similar plantar incision-produced postsurgical pain responses as those in wild-type mice. Moreover, the expression of PKMζ was inhibited in both anterior cingulate cortex and spinal cord of the conventional PKMζ knockout mice. And there were no significant differences in the development of postsurgical pain among wild-type, heterozygous, and homozygous conventional PKMζ knockout mice. These data suggest that PKMζ is not required for the development of postsurgical pain after plantar incision.


Automatic and Quantitative Measurement of Spectrometer Aberrations.
The performance of electron energy loss spectrometers can often be limited by their electron optical aberrations. Due to recent developments in high energy resolution and momentum-resolved electron energy loss spectroscopy (EELS), there is renewed interest in optimizing the performance of such spectrometers. For example, the "ω - q" mode of momentum-resolved EELS, which uses a small convergence angle and requires aligning diffraction spots with the slot aperture, presents a challenge in the realignments of the spectrometer required by the adjustment of the projection lenses. Automated and robust alignment can greatly benefit such a process. The first step toward this goal is automatic and quantitative measurement of spectrometer aberrations. We demonstrate the measurement of geometric aberrations and distortions in EELS within a monochromated scanning transmission electron microscope (STEM). To better understand the results, we present a wave mechanical simulation of the experiment. Using the measured aberration and distortion coefficients as inputs to the simulation, we find a good match between the simulation and experiment, verifying formulae used in the simulation. From verified simulations with known aberration coefficients, we can assess the accuracy of measurements. Understanding the errors and inaccuracies in the procedure can guide further progress in aberration measurement and correction for new spectrometer developments.


Highly Breathable, Stretchable, and Tailorable TPU Foam for Flexible Gas Sensors.
Continuous real-time monitoring of air quality is of great significance in the realms of environmental monitoring, personal safety, and healthcare. Recently, flexible gas sensors have gained great popularity for their potential to be integrated into various smart wearable electronics and display devices. However, the development of gas sensors with superior sensitivity, breathability, and stretchability remains a challenge. Here, a new high porosity thermoplastic polyurethane (HP-TPU) foam was reported for gas sensors, which exhibited large three-dimensional network structures and excellent mechanical properties. The HP-TPU foam was achieved by using a simple steam-induced method, which was suitable for mass production. The unique structure endowed this foam with 77.5% porosity, 260% strain ability, and 0.45 MPa Young's modulus, which improved 35, 31, and 80%, respectively, compared to previously reported traditional TPU foam (T-TPU) prepared by the drying method. In addition, the foam presented high gas permeability (312 g/m-2, 24 h) and excellent stability, and it remained undamaged even after 2000 cycles at 70% strain. The sensing material was coated on a PET flexible interdigital electrode and sandwiched between two HP-TPU foam layers for a gas sensitivity test. Due to the easy diffusion of gas between the pores and contact with the sensing materials, the HP-TPU foam exhibited a significant reduction of 85% in average response time and 46% in average recovery time, compared to the T-TPU foam. A wearable sensing device, comprising sensing, data processing, and wireless transmission modules, was successfully developed to enable outdoor testing and achieved a detection range at the ppb level. Finally, the cytotoxicity test results confirmed that this flexible gas sensor did not harm human health. These results proved that this HP-TPU foam was an ideal matrix for the flexible gas sensor, exhibiting great application potential in the fields of seamless human-machine integration.


Hepatic arterial blood flow in large hepatocellular carcinoma with or without portal vein thrombosis: assessment by transcutaneous duplex Doppler sonography.
As liver cirrhosis progresses, the portal venous blood (PVBF) flow decreases, accompanied by an increase in hepatic arterial blood flow. Large hepatocellular carcinoma is a hypervascular tumour with a rapid growth, which seems to require an increase of the tumoral arterial blood flow. Furthermore, hepatocellular carcinoma is frequently associated with portal vein thrombosis, which subsequently impedes portal blood supply. The purpose of our study was to estimate alterations in the hepatic arterial blood flow in large hepatocellular carcinomas occurring in liver cirrhosis, in comparison with liver cirrhosis and controls. Liver blood flow measurements were determined by duplex Doppler sonography in 47 patients with large hepatocellular carcinomas (13 with portal vein thrombosis and 34 without this thrombosis), 42 liver cirrhosis patients and 30 controls. The Doppler perfusion index was calculated as the ratio of hepatic arterial blood flow to total hepatic blood flow. The patients with liver cirrhosis had a significant increase of hepatic arterial blood flow as compared to controls (P < 0.001), accompanied by a significant reduction in PVBF (P < 0.005). As a result, the Doppler perfusion index was increased in patients with liver cirrhosis as compared to controls (P < 0.001). The hepatic arterial blood flow was increased in patients with hepatocellular carcinoma but without portal vein thrombosis as compared to the cirrhotic patients (P < 0.001), with a significant reduction of PVBF (P < 0.001). Hepatic arterial blood flow was also increased in patients with both hepatocellular carcinoma and portal vein thrombosis as compared to the patients without this thrombosis (P < 0.001). These results suggest that in large hepatocellular carcinomas there is a decreased PVBF, accompanied by an increased hepatic arterial blood flow. The hepatic arterial buffer response seems to be active in hepatocellular carcinomas and maintains liver perfusion to adequate levels.


The case against the DNP: history, timing, substance, and marginalization.
Doctor of Nursing Practice (DNP) or not? The answer is not! Within the historical context of our discipline, a doctorate degree should stand for advancing and translating knowledge. Clinical practice is the core of this knowledge. Separating the practice and research missions could undermine our ability to be equal partners in universities, as well as diminish our effectiveness in establishing the evidence for quality and safe health care.


Fetal echocardiography: new insight into fetal cardiology--a review.
Recent advance in echocardiography has permitted detailed imaging of the fetal heart, facilitating the prenatal diagnosis of congenital heart disease and the diagnosis and treatment of fetal arrhythmias. New advance in Doppler echocardiography has provided important information about the physiology of normal and abnormal fetal circulation. From 1980 to 1986, we performed echocardiography on 564 fetuses, including 254 normal and 310 high risk pregnants. Results are discussed in terms of the method and accuracy of the prenatal diagnosis of congenital heart disease, the recognition of and intrauterine treatment of fetal arrhythmias, the diagnosis of fetal heart failure, the assessment of fetal circulation by Doppler echocardiography, the management of the fetus with cardiac problems, and the ethical aspects of fetal cardiology.


Effect of postweaning feed intake on performance, intestinal morphology, and the probability of diarrhoea in piglets.
Changes in gastrointestinal architecture, high incidence of diarrhoea, and low feed intake (FI) are commonly observed around weaning of pigs, but the relationship between postweaning FI and diarrhoea is unclear. This study aimed to determine the effect of low or high FI during the first days after weaning on growth performance, diarrhoea probability, intestinal permeability, and morphology in pigs until postweaning day (PWD) 28. A total of 120 pigs (7.20 ± 0.26 kg) weaned at 28 days of age (PWD 0) were randomly allocated to five diets and housed individually until PWD 28. Two diets differed in CP and three diets differed in threonine and tryptophan levels. At PWD 4, pigs with the 25% lowest accumulated FI (LOW; n = 30) and 25% highest accumulated FI (HIGH; n = 30) were selected for the study. Faecal consistency was evaluated daily using a 4-scale visual scoring system. Blood was collected at PWD 4, 14, 21 and 28, and small intestinal and colonic tissue was obtained at slaughter on PWD 28. Until PWD 4, LOW pigs consumed approximately 20% (35.7 ± 5.9 g/day) of the FI of HIGH pigs (181 ± 5.75 g/day; P < 0.05) and their average daily gain (ADG) was -103 ± 15.1 g/day. At PWD 28, average daily feed intake, ADG, and feed conversion ratio were still negatively affected by the FI level (P < 0.05) and pigs in the LOW group were on average 4.4 kg lighter than HIGH pigs. Pigs in the HIGH group showed a 55% higher probability of diarrhoea compared with LOW pigs during PWD 0-28. The number of antibiotic treatment days against diarrhoea was 2.38 days higher for HIGH compared with LOW pigs (P = 0.04). The intestinal permeability markers diamine oxidase and D-lactate in plasma were unaffected by the level of FI (P > 0.10). The systemic inflammatory markers haptoglobin and C-reactive protein were higher for HIGH pigs at PWD 4 (P = 0.005), but not affected in the following periods (P > 0.10). Pigs in the HIGH group had an increased area of acidic mucin-producing cells in the small intestine compared with LOW pigs (P < 0.05), but other intestinal morphology measurements at PWD 28 were unaffected by the level of FI. In conclusion, high FI just after weaning was associated with higher growth performance but also higher probability of diarrhoea and more frequent use of antibiotics until PWD 28.


[Effect of the hypothalamo-hypophyseal-adrenocortical system on the functional state of Hageman-dependent systems of blood after immobilization stress].
The reaction of haemostatic system under the condition of sympathetic receptions blocking and the suppression of the hypothalamic-hypophyseal-adrenocortical system reactivity as the result of immobilisation stress have been studied in the experiments on rabbits. It was found that the sympathetic nervous system and HHAS took part in the regulation of the blood coagulation, fibrinolysis and kininogenesis under stress-syndrome development by the activation of lysosomal apparatus of neutrophilic leukocytes of peripheral blood.


Chicory extracts from Cichorium intybus L. as potential antifungals.
In this work extracts from roots of the common vegetable Cichorium intybus L., highly appreciated for its bitter taste, were studied to investigate their possible biological activity on fungi from a variety of ecological environments: some are parasites on plants (phytopathogens) or of animals and humans (zoophilic and anthropophilic dermatophytes), others live on the soil and only seldom parasitize animals (geophilic dermatophytes). The extracts were ineffective on geophilic species and on tested phytopathogens, with the exception of Pythium ultimum, whereas they inhibited the growth of zoophilic and anthropophilic dermatophytes, in particular Trichophyton tonsurans var. sulfureum, whose treatment caused morphological anomalies, here observed by scanning electron microscopy. This behaviour is discussed on the basis of the presence in the chicory extract of the two main sesquiterpene lactones, 8-deoxylactucin and 11 beta,13-dihydrolactucin.


In vitro immunoglobulin synthesis by human intestinal lamina propria lymphocytes.
The concentration of IgG and IgA was measured in the supernatants of peripheral blood mononuclear cells and of cells harvested from the intestinal lamina propria, which were cultured in vitro in the presence or absence of mitogens. The lamina propria mononuclear cells were harvested by collagenase digestion of macroscopically normal mucosa from 10 fresh surgical resections for carcinoma. Secretion of IgA in cultures of unstimulated lamina propria mononuclear cells greatly exceeded that of IgG. The addition of pokeweed mitogen increased Ig secretion by cultures of peripheral blood mononuclear cells but decreased Ig secretion by lamina propria mononuclear cells. The addition of concanavalin A suppressed Ig synthesis by pokeweed mitogen stimulated cells more in cultures of peripheral blood mononuclear cells than in lamina propria mononuclear cells. Cycloheximide inhibited Ig secretion by more than 90% in cultures of peripheral blood mononuclear cells, but there was less inhibition in cultures of lamina propria mononuclear cells. In the four unstimulated cultures of lamina propria mononuclear cells examined, over 75% of the Ig was secreted in the first three to four days of culture. The results indicate that lamina propria mononuclear cells are refractory to the inductive and suppressive signals of mitogens, and represent an activated cell population which is committed to Ig secretion before being cultured.


Development of shellfish allergy after exposure to dual immune checkpoint blockade.
Hepatocellular carcinoma (HCC) is a major health problem worldwide with limited systemic therapies available. Immunotherapy is a fast-moving field that is quickly evolving as a treatment for HCC with three recent clinical trials published treating HCC with immune checkpoint inhibitors with promising results. Checkpoint inhibition may lead to a unique adverse event profile with the potential to cause immune-related adverse events by unbalancing the immune system. Here, we report a case of a 61-year-old male with advanced HCC who developed a shellfish allergy after completing three cycles of combination of tremelimumab and durvalumab therapy.


Apatinib Inhibits Angiogenesis in Intrahepatic Cholangiocarcinoma by Regulating the Vascular Endothelial Growth Factor Receptor-2/Signal Transducer and Activator of Transcription Factor 3/Hypoxia Inducible Factor 1 Subunit Alpha Signaling Axis.
Intrahepatic cholangiocarcinoma (ICC), which is difficult to diagnose and is usually fatal due to its late clinical presentation and a lack of effective treatment, has risen over the past decades but without much improvement in prognosis. The study aimed to investigate the role of apatinib that targets vascular endothelial growth factor receptor-2 (VEGFR2) in ICC. MTT assays, cell scratch assays, and tube formation assays were used to assess the effect of apatinib on human ICC cell line (HuCCT-1) and RBE cells proliferation, migration, and angiogenic capacity, respectively. Expression of vascular endothelial growth factor (VEGF), VEGFR2, signal transducer and activator of transcription factor 3 (STAT3), pSTAT3, and hypoxia inducible factor 1 subunit alpha (HIF-1α) pathway proteins was assessed using Western blotting and mRNA expression analysis in HuCCT-1 was performed using RT-qPCR assays. The pcDNA 3.1(-)-VEGFR2 and pcDNA 3.1(-)-HIF-1α were transfected into HuCCT-1 and RBE cells using Lipofectamine 2,000 to obtain overexpressed HuCCT-1 and RBE cells. We found that apatinib-inhibited proliferation, migration, and angiogenesis of HuCCT-1 and RBE cells in vitro in a dose-dependent manner. We also proved that apatinib effectively inhibits angiogenesis in tumor cells by blocking the expression of VEGF and VEGFR2 in these cells. In addition, we demonstrated that apatinib regulates the expression of STAT3 phosphorylation by inhibiting VEGFR2. Finally, we showed that apatinib regulates ICC angiogenesis and HIF-1α/VEGF expression via STAT3. Based on the above findings, we conclude that apatinib inhibits HuCCT-1 and RBE cell proliferation, migration, and tumor angiogenesis by inhibiting the VEGFR2/STAT3/HIF-1α axis signaling pathway. Apatinib can be a promising drug for ICC-targeted molecular therapy.


Supramolecular Nanofibers of Drug-Peptide Amphiphile and Affibody Suppress HER2+ Tumor Growth.
Antibody-based medicines and nanomedicines are very promising for cancer therapy due to the high specificity and efficacy of antibodies. However, antibody-drug conjugates and antibody-modified nanomaterials frequently suffer from low drug loading and loss of functions due to the covalent modification of the antibody. A novel and versatile strategy to prepare supramolecular nanomaterials by the coassembly of an affibody (antiHER2) and drug-peptide amphiphiles is reported here. During the enzyme-instructed self-assembly process, the drug-peptide amphiphile can coassemble with the affibody, resulting in supramolecular nanofibers in hydrogels. The drug loading in the supramolecular nanofibers is high (>30 wt%), and the stability of antiHER2 is significantly improved in the nanofibers at 37 °C (>15 d in vitro). The supramolecular nanofibers exhibit high affinity for HER2+ cancer cells and can be efficiently taken up by these cells. In a mouse tumor model, the supramolecular nanofibers abolish HER2+ NCI-N87 tumor growth due to the good accumulation and retention of nanofibers in tumor. This study provides a novel strategy to prepare nanomedicines with high drug loading and high specificity.


Dosimetry study on radioactive particle brachytherapy in oral carcinoma.
To investigate the therapeutic effects of different doses of 125I radioactive particle brachytherapy on oral cancer. Between September 2012 and September 2015, 78 patients with oral cancer who received 125I radioactive particle brachytherapy for the first time in our hospital were enrolled in this study. Patients were divided into high dose (≥3) and low dose (<3) groups. The treatment outcome, serum tumor marker levels and the expression levels of autophagy and apoptotic genes in tumor cells were compared between groups. Complete remission (CR)+partial remission (PR) ratio in the high dose group was significantly higher than that of the low dose group. Stable disease (SD)+ progressive disease (PD) ratio was significantly lower in the high dose group. The serum levels of TSGF, SCCA, CEA, CA125, CA15.3, CA19.9 and PSA oral cancer markers were significantly lower than those of the low dose group. In the high dose group, the expression levels of Beclin-1 and MAP1LC3 (autophagic genes) mRNAs were significantly higher than those of the low dose group, while the expression levels of EMMPRIN and MMP-14 (invasive genes) mRNAs were significantly lower in the high dose group. Also survival rates in the responsive patients were significantly better in comparison to non-responsive patients. High dose particle brachytherapy with radioactive 125I is a safe and effective treatment and its clinical results were more beneficial than the low dose therapy.


Hyperperfusion after Clipping of Aneurysm: A Rare Entity.
Cerebral vasospasm is an uncontrollable and sometimes fatal complication occurring after subarachnoid hemorrhage. However, cerebral hyperperfusion syndrome is a rare complication after subarachnoid hemorrhage. Although plain computed tomography of cerebral hyperperfusion syndrome looks similar to cerebral infarction induced by cerebral vasospasm, they should be distinguished from each other because they require completely different treatments. A 65-year-old man complained of severe headache and vomiting. A computed tomography scan of his head showed subarachnoid hemorrhage with acute hydrocephalus caused by intraventricular hematoma and aneurysm of the left middle cerebral artery. After endoscopic irrigation of the ventricular hematoma to decrease the intracranial pressure, we performed neck clipping for the ruptured aneurysm. We used a temporary clip to the proximal M1 segment twice for a total of 15 minutes. Five days after the clipping, a computed tomography scan of the patient's head showed a large low-density area in the left cerebral hemisphere. Although cerebral infarction caused by cerebral vasospasm was suspected, his perfusion computed tomography demonstrated a state of hyperperfusion corresponding to the low-density area. We started treatment to prevent vasodilation and excessive cerebral blood flow instead of treatment for cerebral vasospasm. After changing the treatment, the patient's symptoms gradually improved, and his perfusion computed tomography (8 days after surgery) showed no excessive increased blood flow. We present a case of cerebral hyperperfusion syndrome and its successful treatment, distinct from that of cerebral vasospasm, after ruptured aneurysm clipping. In addition, we discuss the mechanism of this rare syndrome based on previous reports.


Coupled reference interaction site model/simulation approach for thermochemistry of solvation: theory and prospects.
We present a new methodology for computing solvation free energy, which is based upon the reference interaction site model (RISM)/hypernetted chain (HNC) solvation free energy expression, but which substitutes radial distribution functions taken from simulations for those calculated by simultaneous solution of the RISM and HNC equations. Consequently, solvation free energy can be obtained from a single molecular dynamics or Monte Carlo simulation. Here we describe in detail the coupled RISM/simulation approach, and offer some error analysis. Finally we give the results of its application to a set of small test molecules in aqueous solution. The success shown in some of our results demonstrates that the coupled RISM/simulation approach is worth considering further as a potentially useful tool in studies of solvated systems, such as aqueous molecular biosystems.


Comparison of slow and forced vital capacities on ability to predict survival in ALS.
Slow (SVC) and forced (FVC) vital capacities are the most used pulmonary function tests in amyotrophic lateral sclerosis (ALS). It is unknown if they equally predict survival in ALS. The aim of the present study was to compare both measures in predicting survival in this disease. Consecutive definite/probable ALS patients (2000-2014) in whom respiratory tests were performed at baseline and four months later were included. All patients were evaluated with the revised ALS functional rating scale (ALSFRS-R), respiratory (RofALSFRS-R), bulbar (ALSFRSb), upper and lower limb subscores, SVC, FVC, maximal inspiratory (MIP) and expiratory (MEP) pressures. King's functional staging system was applied retrospectively. Survival analysis was carried out by univariate Kaplan-Meier log-rank test. Multivariate Cox proportional hazards model determined significant independent variables. We included 469 patients (270 males; mean onset age 61.0 ± 11.5 years; mean disease duration from first symptoms to first visit: 15.8 ± 16.1months; 329 spinal and 140 bulbar onset). FVC and SVC were strongly correlated (r2 = 0.981, p < 0.001). Significant survival prognostic variables (Kaplan-Meier analyses) were onset region, age, disease duration, ALSFRS-R, ALSFRSb, RofALSFRS-R, ALSFRS-R decay, SVC, FVC, MIP, MEP and King's staging (p ≤ 0.01). Final Cox model including the significant variables showed similar results for FVC and SVC (p < 0.001). Moreover, 1% decrease in either predicted values increased death probability by 1.02. FVC and SVC are inter-changeable in predicting survival in ALS.


Increased Goodpasture antigen-binding protein expression induces type IV collagen disorganization and deposit of immunoglobulin A in glomerular basement membrane.
Increased expression of Goodpasture antigen-binding protein (GPBP), a protein that binds and phosphorylates basement membrane collagen, has been associated with immune complex-mediated pathogenesis. However, recent reports have questioned this biological function and proposed that GPBP serves as a cytosolic ceramide transporter (CERT(L)). Thus, the role of GPBP in vivo remains unknown. New Zealand White (NZW) mice are considered healthy animals although they convey a genetic predisposition for immune complex-mediated glomerulonephritis. Here we show that NZW mice developed age-dependent lupus-prone autoimmune response and immune complex-mediated glomerulonephritis characterized by elevated GPBP, glomerular basement membrane (GBM) collagen disorganization and expansion, and deposits of IgA on disrupted GBM. Transgenic overexpression of human GPBP (hGPBP) in non-lupus-prone mice triggered similar glomerular abnormalities including deposits of IgA on a capillary GBM that underwent dissociation, in the absence of an evident autoimmune response. We provide in vivo evidence that GPBP regulates GBM collagen organization and its elevated expression causes dissociation and subsequent accumulation of IgA on the GBM. Finally, we describe a previously unrecognized pathogenic mechanism that may be relevant in human primary immune complex-mediated glomerulonephritis.


[Trends in antibiotic consumption in Spain, 1985-2000].
The purpose of this study was to analyse the trend in antibiotics consumption to draw on the National Health System (NHS) over the last 16 years in Spain and its different Autonomous Communities (AC). Consumption data for all antibiotics used in Spain, either alone or in fixed-dose combinations, were obtained using the database ECOM. This database includes all the packages sold through retail pharmacies and reimbursed by the NHS. Data are expressed as defined dairy doses per 1,000 inhabitants per day (DHD), in accordance with the methodology recommended by the World Health Organization. Demographic data were provided by the National Institute of Statistics. In 1985 the overall consumption of antibiotics was 21.9 DHD, while in 2000 it was 20.4 DHD. It was possible to distinguish three phases over the study period. The first phase lasts until 1989, where a mild decreasing trend was observed (1.1 DHD; 5.0%), mainly due to the fall of fixed-dose combinations of antibiotics and the association of sulfamethoxazole-trimethoprim. The second phase, lasting until 1996, was characterized by a generalized increase in the consumption in all AC, with an average of 2.3 DHD (+ 11.1%), ranging from 0.4 to 4.6 DHD; this increase was mainly due to the marketing of new macrolides, cephalosporins and quinolones. Finally, there was a third phase beginning in 1996, where the consumption of antibiotics came into a sustained and generalized decline, ranging from 0.5 to 5.1 DHD, and depending on the AC (national average 2.7 DHD, 11.7% lower than that in 1996). This latter trend was mainly due to the fall of wide-spectrum penicillins. Differences between AC regarding the level of consumption were huge over the study period, although the pattern of use was quite similar. There was, for instance, a difference of 10.4 DHD between Región de Murcia and Islas Baleares in 2000, or 9.9 DHD between the former and Madrid in the same year. The consumption of antibiotics in Spain and all its AC has declined since 1996, probably related to the campaigns launched by public administrations to promote the rational use of these agents. The main subgroup involved in this trend is wide-spectrum penicillins. Differences in antibiotics use between AC are too big to be accounted for by different epidemic patterns and, therefore, should be analysed further.


Considering sources and detectors distributions for quantitative photoacoustic tomography.
Photoacoustic tomography (PAT) is a hybrid imaging modality that takes advantage of high optical contrast brought by optical imaging and high spatial resolution brought by ultrasound imaging. However, the quantification in photoacoustic imaging is challenging. Multiple optical illumination approach has proven to achieve uncoupling of diffusion and absorption effects. In this paper, this protocol is adopted and synthetic photoacoustic data, blurred with some noise, were generated. The influence of the distribution of optical sources and transducers on the reconstruction of the absorption and diffusion coefficients maps is studied. Specific situations with limited view angles were examined. The results show multiple illuminations with a wide field improve the reconstructions.


Altered prostanoid metabolism contributes to impaired angiogenesis in persistent pulmonary hypertension in a fetal lamb model.
Persistent pulmonary hypertension of the newborn (PPHN) is associated with decreased lung angiogenesis and impaired pulmonary vasodilatation at birth. Prostanoids are important modulators of vascular tone and angiogenesis. We hypothesized that altered levels of prostacyclin (PGI₂), a potent vasodilator, and thromboxane A₂ (TXA₂), a vasoconstrictor, contribute to impaired angiogenesis of pulmonary artery endothelial cells (PAEC) in PPHN. PAEC were isolated from fetal lambs with PPHN induced by prenatal ductus arteriosus constriction or from sham operated controls. Expression and activity of PGI₂ synthase (PGIS) and TXA₂ synthase (TXAS), expression of cyclooxygenases 1 and 2 (COX-1 and COX-2), and the role of PGIS/TXAS alterations in angiogenesis were investigated in PAEC from PPHN and control lambs. PGIS protein and activity were decreased and PGIS protein tyrosine nitration was increased in PPHN PAEC. In contrast, TXAS protein and its stimulated activity were increased in PPHN PAEC. COX-1 and COX-2 proteins were decreased in PPHN PAEC. Addition of PGI₂ improved in vitro tube formation by PPHN PAEC, whereas indomethacin decreased tube formation by control PAEC. PGIS knockdown decreased the in vitro angiogenesis in control PAEC, whereas TXAS knockdown increased the in vitro angiogenesis in PPHN PAEC. Reciprocal alterations in PGI₂ and TXA₂ may contribute to impaired angiogenesis in PPHN.


[Adult-Onset Neuronal Intranuclear Inclusion Disease in Two Female Siblings].
Neuronal intranuclear inclusion disease (NIID) in two adult siblings (both women, aged 76 and 68 years) is reported on here. The elder sister had a resting tremor and bradykinesia at age 66 years, and treatment with L-DOPA was initiated(L-3, 4-dihydroxyphenylalanine). Three years later, she showed a frozen gait that was associated with the medication wearing off. The clinical manifestations did not improve with the administration of antiparkinson drugs. Six years later, she showed impaired cognitive functions, which had occured gradually, and she began to take donepezil. At age 76, she was diagnosed with NIID based on a skin biopsy. The younger sister exhibited peculiar behaviors at age 62 years, and showed impaired cognitive function 4 years later. At age 68 years, she died because of an accident in the bath tub. In both cases, diffusion-weighted magnetic resonance imaging (DWI) showed high-intensity signals in the U fiber area of the corticomedullary junction. These signals began in the frontal lobe at the initial stages of the disease, and extended to the parietal and temporal lobes at later stages. High-intensity signal areas were detected in the deep white matter in T2-weighted and fluid-attenuated inversion recovery (FLAIR) images in the elder sister. The histological examination via a skin biopsy was useful in diagnosing NIID. (Received August 18, 2016; Accepted December 8, 2016; Published March 1, 2017).


Genomic map of cardiovascular phenotypes of hypertension in female Dahl S rats.
Genetic linkage analyses in human populations have traditionally combined male and female progeny for determination of quantitative trait loci (QTL). In contrast, most rodent studies have focused primarily on males. This study represents an extensive female-specific linkage analysis in which 236 neuroendocrine, renal, and cardiovascular traits related to arterial pressure (BP) were determined in 99 female F2 rats derived from a cross of Dahl salt-sensitive SS/JrHsdMcwi (SS) and Brown Norway normotensive BN/SsNHsdMcwi (BN) rats. We identified 126 QTL for 96 traits on 19 of the 20 autosomal chromosomes of the female progeny. Four chromosomes (3, 6, 7, and 11) were identified as especially important in regulation of arterial pressure and renal function, since aggregates of 8-11 QTL mapped together on these chromosomes. BP QTL in this female population differed considerably from those previously found in male, other female, or mixed sex population linkage analysis studies using SS rats. Kidney weight divided by body weight was identified as an intermediate phenotype that mapped to the same region of the genome as resting diastolic blood pressure and was correlated with that same BP phenotype. Seven other phenotypes were considered as "potential intermediate phenotypes, " which mapped to the same region of the genome as a BP QTL but were not correlated with BP. These included renal vascular responses to ANG II and ACh and indices of baroreceptor responsiveness. Secondary traits were also identified that were likely to be consequences of hypertension (correlated with BP but not mapped to a BP QTL). Seven such traits were found, notably heart rate, plasma cholesterol, and renal glomerular injury. The development of a female rat systems biology map of cardiovascular function represents the first attempt to prioritize those regions of the genome important for development of hypertension and end organ damage in female rats.


Cardiotoxicity of cancer therapy.
Because cancer is a leading cause of mortality in the United States, the number of therapeutic modalities available for the treatment of neoplastic processes has increased. This has resulted in a large number of patients being exposed to a wide variety of cancer therapy. Historically, it has been well recognized that antineoplastic agents may have adverse effects on multiple organs and normal tissues. The most commonly associated toxicities occur in tissues composed of rapidly dividing cells and may spontaneously reverse with minimal long-term toxicity. However, the myocardium consists of cells that have limited regenerative capability, which may render the heart susceptible to permanent or transient adverse effects from chemotherapeutic agents. Such toxicity encompasses a heterogeneous group of disorders, ranging from relatively benign arrhythmias to potentially lethal conditions such as myocardial ischemia/infarction and cardiomyopathy. In some instances, the pathogenesis of these toxic effects has been elucidated, whereas in others the precise etiology remains unknown. We review herein the various syndromes of cardiac toxicity that are reported to be associated with antineoplastic agents and discuss their putative mechanisms and treatment.


Feline visceral leishmaniasis in Kerman, southeast of Iran: Serological and molecular study.
Visceral leishmaniasis (VL) is a fatal zoonotic disease in tropical and sub-tropical countries including Iran. Dogs constitute the main domestic reservoir for VL (kala-azar) in Iran but incidence of the disease in cats from Fars and East Azerbaijan provinces has led to propose them as secondary reservoirs, and possible expansion of the feline role in the transmission of disease. The aim of this study was to evaluate the prevalence of Leishmania infantum infection in stray cats in Kerman City by ELISA and PCR methods. In this cross-sectional descriptive study, 60 stray cats were randomly live trapped from different parts of Kerman City during a six month period between March and September 2014. About 3 ml blood samples were drawn from jugular vein of captured cats and a detailed questionnaire about demographic characteristics and clini- cal status of each cat was recorded by attending veterinarian. The complete blood counts and biochemistry analysis were performed for all cats. Finally collected sera samples were tested by an indirect enzyme-linked immunosorbent assay (ELISA) kit and PCR amplification method. Prevalence of Leishmania infantum infection was 6.7 and 16.7% by ELISA and PCR assays, respectively. Infection rate was significantly higher in leukopenic cats, which were older than 3 yr. The results of the study indicate that stray cats are at risk of L. infantum infection in Kerman City. Further, studies are required to elucidate the role of cats as potential reservoir host in the epidemiol- ogy of VL in endemic regions.


[Anti-HLA antibodies in nephropathic patients].
The presence of anti-human leukocyte antigen (HLA) alloantibodies in nephropathic patients is due to immunogenic stimuli such as transfusions, pregnancies, and transplantations. These stimuli can be highlighted using a classic aspecific serologic technique, such as complement-dependent cytotoxicity (CDC) or using more recent and specific techniques, such as cytofluorimetrics or enzyme linked immunoabsorbant assay (ELISA). Because the presence of anti-HLA preformed antibodies is linked to the largest incidence of both acute and chronic rejection, it seems appropriate to re-evaluate that data obtained using aspecific classic serological analysis techniques by using the more specific cytofluorimetric technique. To aid in the possible prevention of ant-HLA antibody formation, it is also appropriate to analyze the influence of immunogenic stimuli on the development of these antibodies. We studied 116 patients (37 women and 79 men). Anti-HLA antibodies were detected using microlymphotoxic technique after separation of B and T lymphocytes. This separation was obtained using magnetic balls. We used a 30-cell panel. We also used a recent cytofluorimetric test (Flow Pra screening; One Lambda Inc., 21001 Kittridge St., Canoga Park, California, U.S.A.) with a panel of micrograins covered with class I and class II purified antigens. Statistical analysis was performed using chi-square analysis or Fischer s exact test. For each test, sensibility, specificity, and positive and negative value were measured. Among 33 patients testing positive using the classic CDC-PRA technique (17 positive for B-lymphocytes and 16 positive for both B and T lymphocytes), using cytometry, 25 were positive for anti-HLA-specific antibodies (10 among the B lymphocyte-positive patients and 15 among the B + T lymphocyte-positive patients). Two patients were shown positive only using the cytofluorimetric method. Of the 27 patients positive at cytometry, 18 were positive for class I and class II, 4 for class I, and 5 for class II. FLOW-PRA screening results were less sensitive and more specific. The results obtained by the two methods are comparable(p<0.0001). The immunogenic stimuli found responsible for immunization were: transfusion in 10 of 25 patients, pregnancies in 3/9 patients, transplant in 4/8 patients, and different immunogenic stimuli in 10/12 patients. The results were not statistically significant (p>0.05). Data show that positivity for B lymphocytes obtained using CDC-PRA is not always linked to the development of anti-HLA antibodies, whereas positivity for B+T lymphocytes, obtained using CDC -PRA, is often linked to specific antibody development. Immune response is more often directed against class I and II antibodies. The specific detection of HLA antibodies using the cytofluorimetric method allows us to identify patients at risk for rejection, and it suggests that red cells should be filtrated to prevent anti-HLA immunization secondary to transfusion in transplantation candidates.


[Effect of gypenosides on DMN-induced liver fibrosis in rats].
To study the effect of gypenosides on DMN-induced liver fibrosis in rats. A rat liver fibrosis model was established by injecting DMN intraperitoneally. Four weeks later, model rats were randomly devided into three groups: the model group, the gypenosides treated group (200 mg x kg(-1)) and the colchicine treated group (0.1 mg x kg(-1)), with 10 specimens for each group. After a 2-week treatment, following parameters were observed: (1) last body weight, weight ratio between liver and spleen; (2) content of liver hydroxyproline (Hyp); (3) activity of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyltransferase (gamma-GT), content of albumin (Alb) and total bilirubin( TBiL) in serum; (4) liver pathology (Sirius red staining and HE staining); (5) activity of liver superoxide dismutase (SOD), glutathione reduced (GSH), glutathione peroxidase (GSH-Px) and content of liver maleic dialdehyde (MDA). There were classic liver cirrhosis pathological changes in model groups. Compared with the normal group, liver Hyp content, activity of serum ATL, AST, gamma-GT and content of serum TBiL, MDA of model groups significantly increased; content of serum Alb and liver GSH, activity of liver SOD and GSH-Px decreased significantly in model groups. In comparison with the model group, liver cirrhosis remarkable improved in the gypenosides group, content of liver Hyp reduced significantly (P < 0.01), which was equal to the colchicine group. Compared with the model group, liver function parameters improved markedly in the gypenosides group; liver SOD and GSH-Px activities significantly increased; MDA content reduced significantly (P < 0.05). Gypenosides shows an effect in treating DMN-induced liver fibrosis in rats.


Reproductive cessation in female mammals.
In female mammals, fertility declines abruptly at an advanced age. The human menopause is one example, but reproductive cessation has also been documented in non-human primates, rodents, whales, dogs, rabbits, elephants and domestic livestock. The human menopause has been considered an evolutionary adaptation, assuming that elderly women avoid the increasing complications of continued childbirth to better nurture their current children and grandchildren. But an abrupt reproductive decline might be only a non-adaptive by-product of life-history patterns. Because so many individuals die from starvation, disease and predation, detrimental genetic traits can persist (or even be favoured) as long as their deleterious effects are delayed until an advanced age is reached, and, for a given pattern of mortality, there should be an age by which selection would be too weak to prevent the onset of reproductive senescence. We provide a systematic test of these alternatives using field data from two species in which grandmothers frequently engage in kin-directed behaviour. Both species show abrupt age-specific changes in reproductive performance that are characteristic of menopause. But elderly females do not suffer increased mortality costs of reproduction, nor do post-reproductive females enhance the fitness of grandchildren or older children. Instead, reproductive cessation appears to result from senescence.


Participant [correction of Patient] observation in nursing home research: who was that masked woman?
Undertaking fieldwork in nursing home environments can present researchers with many challenges, particularly when the researcher also happens to be a registered nurse. This article discusses the issues that one nurse researcher faced during participant observation in three New Zealand nursing homes. These include the complexity of the nurse researcher role, the blurring of role boundaries, and various ethical concerns that arose, including the difficulties of ensuring that all those who were involved in the study were kept informed as to the researcher's role and purpose. Strategies used to maintain ethical and role integrity are outlined, with further debate and discussion around fieldwork issues and experiences for nurse researchers called for.


Tim-3 expression in cervical cancer promotes tumor metastasis.
T cell immunoglobulin mucin-3 (Tim-3) has been identified as a negative regulator of anti-tumor immunity. Recent studies highlight the important role of Tim-3 in the CD8(+) T cell exhaustion that takes place in both human and animal cancer models. However, the nature of Tim-3 expression in the tumor cell and the mechanism by which it inhibits anti-tumor immunity are unclear. This present study aims to determine Tim-3 is expressed in cervical cancer cells and to evaluate the role of Tim-3 in cervical cancer progression. A total of 85 cervical tissue specimens including 43 human cervical cancer, 22 cervical intraepithelial neoplasia (CIN) and 20 chronic cervicitis were involved. Tim-3 expression in tumor cells was detected and was found to correlate with clinicopathological parameters. Meanwhile, expression of Tim-3 was assessed by RT-PCR, Western Blot and confocal microscopy in cervical cancer cell lines, HeLa and SiHa. The migration and invasion potential of Hela cells was evaluated after inhibiting Tim-3 expression by ADV-antisense Tim-3. We found that Tim-3 was expressed at a higher level in the clinical cervical cancer cells compared to the CIN and chronic cervicitis controls. We supported this finding by confirming the presence of Tim-3 mRNA and protein in the cervical cell lines. Tim-3 expression in tumor cells correlated with clinicopathological parameters. Patients with high expression of Tim-3 had a significant metastatic potential, advanced cancer grades and shorter overall survival than those with lower expression. Multivariate analysis showed that Tim-3 expression was an independent factor for predicting the prognosis of cervical cancer. Significantly, down-regulating the expression of Tim-3 protein inhibited migration and invasion of Hela cells. Our study suggests that the expression of Tim-3 in tumor cells may be an independent prognostic factor for patients with cervical cancer. Moreover, Tim-3 expression may promote metastatic potential in cervical cancers.


Serum alkaline phosphatase is elevated and inversely correlated with cognitive functions in subjective cognitive decline: results from the ReGAl 2.0 project.
Alkaline phosphatase has been found on neuronal membranes and plasma alkaline phosphatase (ALP) activity increases during brain injury and cerebrovascular diseases, suggesting that its levels may reflect the neuronal loss. It is known that ALP is higher in subjects affected by Alzheimer's dementia and inversely correlated with cognitive functions. No study has investigated the relationship between ALP and cognitive functions in old-age subject with pre-clinical cognitive impairment. This is a cross-sectional study with data gathered from the ReGAl 2.0 project (Rete Geriatrica Alzheimer-Geriatric Network on Alzheimer's disease), a large Italian multicentric clinical-based study. A cohort of 209 old-age subjects healthy controls (HC), Subjective cognitive decline (SCD), and Mild Cognitive Impairment (MCI) was included in the study. Cognitive performances were assessed with a large neuropsychological battery. The same day, serum alkaline phosphatase activity was measured in all subjects. We found that the SCD group had significantly higher ALP levels as compared with HC (p = 0.001). Among all neuropsychological tests, in all population ALP levels negatively correlated with scores at attentional matrices (r = - 0.243, p = 0.002), Digit Span Forward (r = - 0.241, p = 0.003) and Letter Fluency Test (r = - 0.196, p = 0.044). Attentional Matrices (r = - 0.208, p = 0.014) and Letter Fluency Test (r = - 0.229, p = 0.019) remained significantly correlated with ALP even after controlling for gender. In the SCD group, only the Attentional Matrices significantly and negatively correlated with ALP (r = - 0.344 p = 0.035), while no significant correlations were found in HC or MCI. Results indicate that serum alkaline phosphatase activity is increased in SCD and inversely correlates with cognitive functions. Further studies are needed to investigate the role of ALP in the progression to AD.


Flavanols from Japanese quince (Chaenomeles japonica) fruit inhibit human prostate and breast cancer cell line invasiveness and cause favorable changes in Bax/Bcl-2 mRNA ratio.
Polyphenols are natural compounds of high structural diversity which translates into a very wide spectrum of biological activities, including chemoprevention. Here we report that a Japanese quince fruit flavanol preparation (JQFFP) caused favorable changes in Bax/Bcl-2 mRNA ratio, which rendered normal and cancer cells more resistant and more sensitive, respectively, to apoptosis. DU145 human prostate cancer cells were characterized by the most advantageous Bax/Bcl-2 ratio. The growth and invasiveness of MDA-MB-231 human breast cancer cells were strongly suppressed by JQFFP, which was accompanied with a decrease in MMP-9 activity and stimulation of TIMP-1 expression. Importantly, JQFFP did not decrease normal human prostate PNT1A cell number, whereas Bax/Bcl-2 ratio decreased which implies increased resistance to apoptosis. In conclusion, JQFFP exhibited a potent antiproliferative effect against cancer cells, inhibited their invasiveness, and decreased expression level of several genes involved in apoptosis, angiogenesis, and metastasis.


Dancing My Age: Emotions, Interactions, and Bodily Sensations.
While there is a growing body of research on the social aspects of older people's dance, studies focusing on emotions are rare. In this study, we use an interactionist sociological perspective to examine the role of emotions in older social dancers' experiences in Sweden. Through qualitative interviews with 29 active or previously active dancers, we found that their experiences of emotional energy and experiences of flow override concerns of age and aging. Age, however, did become significant as the age differences at dance events could bring forth feelings of alienation associated with feeling old. In addition, cultural and gendered norms of appropriate age differences between dancing partners produced shame and pride as well as feelings of being either old or young. Moreover, certain bodily experiences were interpreted in terms of age. Overall, the study contributes to the discussions of the complexity of subjective experiences of age by highlighting its emotional aspects through social partner dancing.


Medicinal chemistry of P2X receptors: allosteric modulators.
P2X receptors are trimeric ligand-gated ion channels whose potential as novel drug targets for a number of diseases has been recognized. They are mainly involved in inflammatory processes, including neuroinflammation, and pain sensation. The orthosteric binding site is lined by basic amino acid residues that bind the negatively charged agonist ATP. Therefore it is not easy to develop orthosteric ligands that possess drug-like properties for such a highly polar binding site. However, ligand-gated ion channels offer multiple additional binding sites for allosteric ligands, positive or negative allosteric modulators enhancing or blocking receptor function. So far, the P2X3 (and P2X2/3), as well as the P2X7 receptor subtype have been the main focus of drug development efforts. A number of potent and selective allosteric antagonists have been developed to block these receptors. We start to see the development of novel allosteric ligands also for the other P2X receptor subtypes, P2X1, P2X2 and especially P2X4. The times when only poor, non-selective, non-drug-like tools for studying P2X receptor function were available have been overcome. The first clinical studies with allosteric P2X3 and P2X7 antagonists suggest that P2X therapeutics may soon become a reality.


Hereditary striatonigral and cerebello-olivary degeneration of the Kerry Blue Terrier. II. Ultrastructural lesions in the caudate nucleus and cerebellar cortex.
The character and progression of ultrastructural lesions in the caudate nucleus and cerebellar cortex were studied in four Kerry Blue Terriers afflicted with a hereditary neurodegenerative disease. In the caudate nucleus, the initial lesion was mitochondrial hypertrophy in dendrites of intrinsic neurons. Degeneration of these neurons became widespread while axons of passage and terminal boutons were spared. During the final stages, there was severe disruption of the neuropil with loss of both neurons and glia. A narrow zone bordering the lateral ventricles, however, remained unaffected. In the cerebellar cortex, the lesions involved principally Purkinje cells and progressed through a pattern of degeneration comparable to that involving intrinsic neurons of the caudate nucleus. In the later stages, there was astroglial scarring of the molecular layer. In contrast to the caudate nucleus, there was no disruption of the neuropil with loss of structure in the cerebellum. The fact that progression of lesions during the early stages of the disease in both the caudate nucleus and cerebellar cortex was similar suggested a common mechanism for the neurodegeneration .


Purification, crystallization and halide phasing of a Streptococcus agalactiae backbone pilin GBS80 fragment.
The Gram-positive pathogen Streptococcus agalactiae or group B streptococcus (GBS) is the leading cause of bacterial septicemia, pneumonia and meningitis among neonates around the world. The pathogen assembles two types of pili on its surface, named PI-1 and PI-2, that mediate bacterial adherence to host cells. The GBS PI-1 pilus is formed by the major pilin GBS80, which forms the pilus shaft, and two minor pilins GBS104 and GBS52, which are incorporated into the pilus structure. While considerable structural information exists on Gram-negative pili, the structural study of Gram-positive pili is an emerging area of research. Here, the purification, crystallization and initial phasing of the 35 kDa major fragment of the backbone pilin GBS80 are reported. Crystals were obtained in two different space groups: P2(1) and C2. SAD data collected from an iodide-derivative crystal at the home source were used to obtain initial phases and interpretable electron-density maps.


Dissociation equilibrium constant of beta nerve growth factor.
The beta nerve growth factor (NGF) isolated from the high molecular weight 7 S NGF complex from mouse submaxillary gland is a protein of molecular weight 26,500 which contains two noncovalently associated peptide chains. A variety of techniques were employed to determine whether the NGF dimer dissociates at the low concentrations at which it is biologically active. No dissociation was detected in 48 h at low NGF concentrations using the techniques and minimum concentrations which follow: sedimentation equilibrium of NGF at 200 nM and of 125I-NGF at 2.5 nM; gel filtration chromatography of NGF at 5 nM, of 125I-NGF at 5 pM, and of 125I-NGF from which COOH-terminal arginyl residues, or NH2-terminal octapeptide had been cleaved, at 10 pM; and sucrose gradient centrifugation of 125I-NGF at 10 pM. Dissociation of heavily succinylated 125I-NGF was detected by gel filtration chromatography, and the equilibrium dissociation constant for this material is estimated to be 10 pM.


[Analysis of the Cochrane Review: Use of systemic corticosteroids for acute exacerbations of chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2014, 9:CD001288].
Acute exacerbations of chronic obstructive pulmonary disease are a major cause of hospital admissions and mortality, contributing to the decline in lung function, exercise capacity and quality of life. Infections are the major cause of exacerbations and treatment includes antibiotics, bronchodilators and systemic corticosteroids as anti- inflammatory agents. This Cochrane review compared: 1. use of oral and parenteral corticosteroids with placebo use; 2. routes of administration among themselves. The results indicate that there is evidence for the use of corticosteroids in the treatment of chronic obstructive pulmonary disease exacerbations since early improvement in lung function [assessed by forced expiratory volume in one second (FEV1)] has been noted, the likelihood of treatment failure and relapse in the first month has been reduced and it shortens the hospital stay in patients who do not require intensive care regimen. However, corticosteroid therapy causes an increase in adverse effects associated with drug, namely hyperglycaemia, especially if the route of administration is parenteral. Parenteral route has not shown to be superior to oral route in treatment failure, relapse, or death. Mortality up to 30 days does not seem to be affected by the use of corticosteroids.


To help and not to harm: ethical issues in the treatment of chronic pain in patients with substance use disorders.
Patients with both chronic pain and substance use disorders are increasingly encountered in a variety of treatment settings. The treatment of these patients raises a number of ethical and patient care issues. Consultation-liaison psychiatrists possess the knowledge and skills to constructively address these issues. This chapter provides clinicians with a review of clinical and ethical dilemmas related to opioid treatment of chronic pain in patients with substance use disorders. The core conflict of beneficence and nonmaleficence will be explored in relation to the concepts of autonomy, justice, respect for persons, confidentiality, and informed consent. The thesis of this discussion focuses on the clinician's desire to provide compassionate care and relieve suffering, which sometimes conflicts with the clinician's desire to improve functioning, extend longevity, and enrich quality of life. A harm reduction model for clinical decision making is summarized.


Trichinella spiralis infection in congenitally athymic (nude) mice. Parasitological, serological and haematological studies with observations on intestinal pathology.
In six experiments the course of a Trichinella spiralis infection in congenitally athymic (nu/nu) mice and their heterozygous thymus-bearing littermates (+/nu) was followed. In the +/nu mice worms were expelled at day 10 post infection. In nu/nu mice worms remained in the intestine until the end of the observation period (83 days post infection). In testing the yield of muscle larvae in +/nu and nu/nu mice 4--5 times more muscle larvae were isolated from nu/nu mice than from infected +/nu mice. The following phenomena were observed in +/nu mice only: anti-T. spiralis antibodies detected by immunofluorescence, intestinal plasma-cell production and intestinal eosinophilia. In nu/nu mice no blood eosinophilia was observed in contrast to the induction of eosinophilia both in infected +/nu and infected nu/nu mice reconstituted with thymuses from heterozygous littermates. Intra-epithelial lymphocytes, more numerous in +/nu than in nu/nu mice, were not attracted by Trichinella antigen. The data supported the hypothesis that worm expulsion is a T cell-dependent phenomenon. Plasma cell and antibody production as well as tissue and blood eosinophilia were shown to be thymus-dependent in a T. spiralis infection.


Teaching touch at medical school.
The association between touch and healing is ancient and worldwide. Skilled hands are among the physician's most important diagnostic and therapeutic tools. Yet a survey of medical schools in the English-speaking world revealed that most offer no touch training in their curricula. Of 169 medical schools, only 12 give any formal instruction in the uses and meaning of therapeutic touch in medicine. The teaching modes of these 12 schools are discussed, and the program of the most touch-conscious school, the University of Otago, is described.


Association between LAPTM4B gene polymorphism and susceptibility to and prognosis of diffuse large B-cell lymphoma.
Lysosomal protein transmembrane 4β (LAPTM4B) is an oncogene that is overexpressed in a number of various types of human cancer. There are two known alleles of LAPTM4B: LAPTM4B*1 and LAPTM4B*2. The present study assessed the association between LAPTM4B polymorphisms and the susceptibility to diffuse large B-cell lymphoma (DLBCL) and its prognosis. LAPTM4B genotypes were determined using polymerase chain reaction analysis in 164 DLBCL and 350 healthy control cases. The association between LAPTM4B polymorphisms and the risk of DLBCL was analyzed using unconditional logistic regression. Differences in patient survival were calculated using Kaplan-Meier analysis. The present study indicated no significant differences (P>0.05) in the frequency of LAPTM4B*2 alleles between DLBCL cases (26.5%) and controls (24.1%). The risk of DLBCL was slightly increased in cases with the LAPTM4B*1/2 genotype [odds ratio (OR)=1.160; 95% confidence interval (CI)=0.781-1.724] or the LAPTM4B*2/2 genotype (OR=1.446; 95% CI=0.648-3.227) compared with those with the LAPTM4B*1/1 genotype. There was no significant association between the presence of the LAPTM4B*2 allele and overall survival (OS) and disease-free survival (DFS) in patients with DLBCL (P=0.399 and 0.520, respectively). However, there was a tendency for patients with LAPTM4B*2 and International Prognostic Index (IPI) score 3-5 to have longer OS and DFS (P=0.126 and 0.109, respectively). These findings suggest that genetic polymorphisms of LAPTM4B is not a risk factor for the development of DLBCL, but the LAPTM4B*2 allele may a better prognostic indicator in patients with IPI score 3-5 in DLBCL.


Remission in schizophrenia: the relationship to baseline symptoms and changes in symptom domains during a one-year study.
The concepts of partial recovery and remission have become increasingly important for the evaluation of the effectiveness of schizophrenia therapeutics. The relationship of baseline symptoms and changes in symptoms to remission of psychosis was evaluated. Fifty-six outpatients with residual schizophrenia completed a double-blind trial of olanzapine versus haloperidol and were then enrolled into a one-year open-label trial of olanzapine. Out of these 56 subjects, 13 (23%) met remission criteria at the beginning of the open-label treatment and were excluded. During the one-year study, 7/43 (16%) subjects met remission criteria. These subjects had significantly lower baseline ratings for tardive dyskinesia (TD) than subjects who did not achieve remission (1.8 +/- 1.5 vs. 4.2 +/- 4.6, P = 0.03). As expected, remitted subjects had significantly greater improvements in Brief Psychiatric Rating Scale total scores, positive subscale scores and scale for the Assessment of Negative Symptoms total scores. Remitted subjects also experienced a significantly greater improvement in depressive symptoms (P = 0.001), activation (P = 0.005), and Clinical Global Impressions scores (P < 0.001), as well as greater improvements in extrapyramidal symptoms (P = 0.007) and TD (P < 0.001). These results suggest that the relationship of depressive symptoms and improved side effects to the construct of remission in schizophrenia may deserve special attention. Future studies should aim to relate remission criteria to functional outcomes, cognition, and other important symptom domains.


Decreased TAX1BP1 participates in systemic lupus erythematosus by regulating monocyte/macrophage function.
Systemic lupus erythematosus (SLE) involves disorders of innate and adaptive immune pathways. Tax1-binding protein 1 (TAX1BP1) modulates the production of antibodies in B cells and the T-cell cycle by regulating the NF-κB signaling pathway. However, the potential association of TAX1BP1 with SLE and its role in monocytes/macrophages have not been fully elucidated. In this study, we utilized whole-exome sequencing (WES) in combination with Sanger sequencing and identified 16 gene mutations, including in TAX1BP1, in an SLE family. TAX1BP1 protein expression with western blotting detection was reduced in SLE patients and correlated with disease activity negatively. Furthermore, RNA sequencing and 4D Label-Free Phosphoproteomic analysis were employed to characterize the transcriptome and phosphoproteome profiles in THP-1 and THP-1-differentiated M1 macrophages with TAX1BP1 knockdown. Silencing of TAX1BP1 in THP-1 and THP-1-differentiated M1 macrophages led to an increase in cluster of differentiation 80 (CD80) expression and differential changes in CD14 and CD16 expression, as assessed by flow cytometry. Additionally, western blot analysis showed that knockdown of TAX1BP1 led to a reduction in TRAF6 and p-p65 in THP-1-differentiated macrophages, with or without lipopolysaccharide (LPS) or tumor necrosis factor (TNF)-α stimulation. Taken together, our findings suggest that TAX1BP1 participates in SLE activity by regulating antigen presentation in monocytes and inflammatory responses in M1 macrophages.


5-(1H-Tetra-zol-5-yl)-1H-indole monohydrate.
In the title compound, C(9)H(7)N(5)·H(2)O, the inter-planar angles between the benzene and tetra-zole rings and between the benzene and imidazole rings are 8.71 (3) and 1.32 (2)°, respectively. In the crystal, strong N-H⋯N hydrogen bonds link the organic 5-(1H-tetra-zol-5-yl)-1H-indole mol-ecules into chains extended along the b axis. The chains are further inter-connected into layers parallel to (100) via strong O-H⋯N and N-H⋯O hydrogen bonds. Furthermore, the layers are inter-connected via strong O-H⋯N hydrogen bonds. Moreover, cohesion between the layers is provided by the π-π inter-actions between the imidazole, tetra-zole and benzene rings with centroid-centroid distances of 3.766 (2), 3.832 (2) and 3.733 (2) Å.


Co7Fe3 and Co7Fe3@SiO2 Nanospheres with Tunable Diameters for High-Performance Electromagnetic Wave Absorption.
Ferromagnetic metal/alloy nanoparticles have attracted extensive interest for electromagnetic wave-absorbing applications. However, ferromagnetic nanoparticles are prone to oxidization and producing eddy currents, leading to the deterioration of electromagnetic properties. In this work, a simple and scalable liquid-phase reduction method was employed to synthesize uniform Co7Fe3 nanospheres with diameters ranging from 350 to 650 nm for high-performance microwave absorption application. Co7Fe3@SiO2 core-shell nanospheres with SiO2 shell thicknesses of 30 nm were then fabricated via a modified Stöber method. When tested as microwave absorbers, bare Co7Fe3 nanospheres with a diameter of 350 nm have a maximum reflection loss (RL) of 78.4 dB and an effective absorption with RL > 10 dB from 10 to 16.7 GHz at a small thickness of 1.59 mm. Co7Fe3@SiO2 nanospheres showed a significantly enhanced microwave absorption capability for an effective absorption bandwidth and a shift toward a lower frequency, which is ascribed to the protection of the SiO2 shell from direct contact among Co7Fe3 nanospheres, as well as improved crystallinity and decreased defects upon annealing. This work illustrates a simple and effective method to fabricate Co7Fe3 and Co7Fe3@SiO2 nanospheres as promising microwave absorbers, and the design concept can also be extended to other ferromagnetic alloy particles.


The predicted target gene validation, function, and prognosis studies of miRNA-22 in colorectal cancer tissue.
MicroRNAs are known as small, non-coding, and single-stranded RNAs which can regulate cell proliferation, differentiation, and apoptosis and involve in the development of tumors. In this study, colorectal cancer tissue morphological change in different prognosis in patients was observed by hematoxylin and eosin staining. Thereafter, differentially expressed miR-22 and TIAM1 gene were detected using quantitative polymerase chain reaction and western blot in different colorectal cancer tissues. Meanwhile, luciferase reporter gene system was used to verify the relationship between miR-22 and TIAM1. Eventually, the survival curve was plotted according to follow-up records of patients with colorectal cancer and the expression levels of miR-22 and TIAM1 in different tumor tissues. The hematoxylin and eosin results showed the poor pathological features in the 1-year survival group. The expression level of miR-22 was upregulated and TIAM1 was inhibited, correlating with the extension of patients' survival time. Our results indicated that miR-22 and TIAM1 might play a regulatory role in the occurrence and development of colorectal cancer which were consistent with the survival curve analysis results. Furthermore, the luciferase in miR-22 co-transfected with pmiR-RB-REPORT- TIAM1 group was significantly lower than pmiR-RB-REPORT- TIAM1-mut and Si groups. Collectively, these data suggest that miR-22 may suppress the expression of its target gene TIAM1. The low miR-22 level or the high TIAM1 level will indicate the poor prognosis in colorectal cancer patients.


Effect of Bioinductive Cavity Liners on Shear Bond Strength of Dental Composite to Dentin.
The aim of the current study was to evaluate and compare the influence of Dycal, Lime-Lite, TheraCal LC, Biodentine, resin-modified glass ionomer cement (RMGIC), and Activa BioActive as the pulp capping material on the shear bond strength of resin composite to dentin. A total of 70 extracted caries-free molars were randomly assigned to seven groups. Six test groups were covered with various protective liners: Dycal, TheraCal LC, Lime-Lite, Activa BioActive, Biodentine, and RMGIC. The control group received no liner pretreatment. Each sample was bonded to resin composite using the total-etch Tetric N bond adhesive. The samples were then tested for shear bond strength using the universal testing machine at a cross-head speed of 1 mm/min until bond failure occurred. The data were analyzed using the one-way ANOVA test followed by the Tamhane post hoc test for pairwise comparisons of the groups. Independent of the type of the applied liner, all groups exhibited inferior SBS to dentin compared to the control group. TheraCal and RMGIC showed significantly higher shear bond strength than Biodentine and Dycal, which showed the lowest shear bond strength. Lime-Lite and Activa also had significantly lower SBS results than TheraCal. The mode of fracture was predominantly cohesive in Dycal, Biodentine, and TheraCal and adhesive in Activa. This present study concludes that the bond strength of resin composite to dentin can be affected differently using various types of liners.


AIFNet: Automatic vascular function estimation for perfusion analysis using deep learning.
Perfusion imaging is crucial in acute ischemic stroke for quantifying the salvageable penumbra and irreversibly damaged core lesions. As such, it helps clinicians to decide on the optimal reperfusion treatment. In perfusion CT imaging, deconvolution methods are used to obtain clinically interpretable perfusion parameters that allow identifying brain tissue abnormalities. Deconvolution methods require the selection of two reference vascular functions as inputs to the model: the arterial input function (AIF) and the venous output function, with the AIF as the most critical model input. When manually performed, the vascular function selection is time demanding, suffers from poor reproducibility and is subject to the professionals' experience. This leads to potentially unreliable quantification of the penumbra and core lesions and, hence, might harm the treatment decision process. In this work we automatize the perfusion analysis with AIFNet, a fully automatic and end-to-end trainable deep learning approach for estimating the vascular functions. Unlike previous methods using clustering or segmentation techniques to select vascular voxels, AIFNet is directly optimized at the vascular function estimation, which allows to better recognise the time-curve profiles. Validation on the public ISLES18 stroke database shows that AIFNet almost reaches inter-rater performance for the vascular function estimation and, subsequently, for the parameter maps and core lesion quantification obtained through deconvolution. We conclude that AIFNet has potential for clinical transfer and could be incorporated in perfusion deconvolution software.


Transmission of SARS-CoV-2 from Human to Domestic Ferret.
We report a case of natural infection with severe acute respiratory syndrome coronavirus 2 transmitted from an owner to a pet ferret in the same household in Slovenia. The ferret had onset of gastroenteritis with severe dehydration. Whole-genome sequencing of the viruses isolated from the owner and ferret revealed a 2-nt difference.


Maternal prenatal social experiences and offspring epigenetic aging from birth to mid-childhood.
Investigate associations of maternal social experiences with offspring epigenetic age acceleration (EAA) from birth through mid-childhood among 205 mother-offspring dyads of minoritized racial and ethnic groups. We used linear regression to examine associations of maternal experiences of racial bias or discrimination (0=none, 1-2=intermediate, or 3+=high), social support (tertile 1=low, 2=intermediate, 3=high), and socioeconomic status index (tertile 1=low, 2=intermediate, 3=high) during the prenatal period with offspring EAA according to Horvath's Pan-Tissue, Horvath's Skin & Blood, and Intrinsic EAA clocks at birth, 3 years, and 7 years. In comparison to children of women who did not experience any racial bias or discrimination, those whose mothers reported highest levels of racial bias or discrimination had lower Pan-Tissue clock EAA in early (-0.50 years; 90% CI: -0.91, -0.09) and mid-childhood (-0.75 years; -1.41, -0.08). We observed similar associations for the Skin & Blood clock and Intrinsic EAA. Maternal experiences of discrimination were not associated with Pan-Tissue EAA at birth. Neither maternal social support nor socioeconomic status predicted offspring EAA. Children whose mothers experienced racial bias or discrimination exhibited slower EAA. Future studies are warranted to confirm these findings and establish associations of early-life EAA with long-term health outcomes.


COVID-19 epidemic in The World Health Organization African Region (WHOAR): Situation and forecast.
To describe the dynamics and forecast the main parameters of the COVID-19 pandemic, the time series of daily cases in the World Health Organization African Region (WHOAR) from February 26th to December 29th, 2020 was analyzed. Estimates for expected values of parameters characterizing an epidemic (size of the epidemic, turning point, maximum value of daily cases, and basic reproductive number) were provided for both the first and the second wave, and for the entire ongoing pandemic in WHOAR. To this aim, the classical SIR (Susceptible-Infected-Removed) model and its approximations were applied to each identified wave. Our results suggest that the turning point of the COVID-19 first wave took place around July 20th, 2020. The first wave was expected to disappear by mid-December 2020, with a total of 1,200,000 expected cases. The second wave apparently started around August 19th, with an expected turning point by January 12th, 2021. The second wave is expected to end by August 9th, 2021, with 1,800,000 cumulative cases, and mounting up to 3,000,000 total cases between February 2020 and August 2021. Estimated basic reproduction numbers (R0) were 1.27 (first wave) and 1.15 (second wave); the expected total number of deaths is around 66,000 victims.


Neuroprotective effect of ginsenoside Rg1 prevents cognitive impairment induced by isoflurane anesthesia in aged rats via antioxidant, anti-inflammatory and anti-apoptotic effects mediated by the PI3K/AKT/GSK-3β pathway.
Ginsenoside Rg1 is the primary active substance in ginseng, and it has multiple pharmacological actions. Investigations on the pharmacologic action of ginsenoside Rg1 have developed, with a particular focus on the regulation of metabolism. The present study hypothesized that the neuroprotective effects of ginsenoside Rg1 prevent cognitive impairment induced by isoflurane anesthesia via antioxidant, anti‑inflammatory and anti‑apoptotic effects, mediated by the phosphoinositide 3‑kinase (PI3K)/AKT/glycogen synthase kinase‑3β (GSK‑3β) pathway in aged rats. Sprague‑Dawley rats were divided into isoflurane and ginsenoside Rg1 groups and were treated with 20 mg/kg ginsenoside Rg1 for 7 days. Morris water maze was performed to analyze the cognitive function of the rats. Enzyme‑linked immunosorbent assays were used to analyze the levels of malondialdehyde, glutathione, interleukin (IL)‑1β, IL‑6 and caspase 3. The protein expression levels of AKT, GSK 3β, p21WAF1/CIP1 and p53 were measured using western blot analysis. Ginsenoside Rg1 significantly improved cognitive function, and exhibited antioxidant and anti‑inflammatory effects, demonstrating the neuroprotective effects of ginsenoside Rg1 against the effect of isoflurane anesthesia in the rats. In addition, ginsenoside Rg1 significantly reduced caspase‑3 activity, upregulated the expression of PI3K/AKT/GSK‑3β and downregulated the mRNA expression levels of p21WAF1/CIP1 and p53 in the aged rats exposed to isoflurane anesthesia. The data obtained in the present study provided evidence that the neuroprotective effects of ginsenoside Rg1 prevented the cognitive impairment induced by isoflurane anesthesia via antioxidant, anti‑inflammatory and anti‑apoptotic effects, mediated by the PI3K/AKT/GSK‑3β pathway.


Synthesis of functional cubes from octavinylsilsesquioxane (OVS).
Octavinylsilsesquioxane, (CH(2)CH)(8)Si(8)O(12), a cubic molecule with vinyl groups at each vertex, has been elaborated to give a series of potential starting materials for nanohybrid synthesis. Terminal bromophenyl groups were introduced onto the surface of octavinylsilsesquioxane either by cross-metathesis or hydrosilylation to give fully bromide substituted POSS A, POSS B and POSS C; the last two were further capped with trimethylsilylacetylene by Sonogashira coupling to produce POSS D and POSS E, showing interesting potential for more useful end group functionalisation. Heck coupling with iodobenzene was used to make the simple phenyl terminated dendrimer POSS F. Cross-metathesis of 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)styrene with octavinylsilsesquioxane afforded POSS G with eight aryl borate groups on its periphery, suitable for use as a starting material in Suzuki coupling. Finally, POSS H has been functionalized with 8 benzyl chloride groups via Grubbs coupling, allowing further substitutions by nucleophiles.


Complementary and alternative medicine as represented in the HIV/AIDS body of knowledge: a bibliometric analysis.
Although the HIV/AIDS epidemic began more than twenty years ago, there still is no cure for the disease and no vaccine to prevent infection. As with the general population, individuals with HIV/AIDS have sought care using a variety of traditional and nontraditional approaches. The popularity of complementary and alternative interventions among the HIV/AIDS community continues. To understand better the distribution of the HIV/AIDS body of knowledge concerning complementary and alternative medicine (CAM), this study sought to (1) examine the literature specific to the use of complementary and alternative medicine where HIV/AIDS is concerned to determine publication patterns; (2) determine the degree of overlap among bibliographic citation databases that index the literature concerning the use of CAM practices in treating HIV/AIDS; and (3) facilitate access to this body of literature.


Corrigendum to: Application of Two New Feature Fusion Networks to Improve Realtime Prostate Capsula Detection.
We apologize for the error that occurred in the online version of the article. Table 3 was missing in the article entitled "Application of Two New Feature Fusion Networks to Improve Real-time Prostate Capsula Detection" in "Current Medical Imaging", 2021; 17(9): 1128-36 [1]. The original article can be found online at https://www.eurekaselect.com/article/113786 Original: Table 3 was missing. Corrected: Table 3 has been added.


Modeling truncated pixel values of faint reflections in MicroED images.
The weak pixel counts surrounding the Bragg spots in a diffraction image are important for establishing a model of the background underneath the peak and estimating the reliability of the integrated intensities. Under certain circumstances, particularly with equipment not optimized for low-intensity measurements, these pixel values may be corrupted by corrections applied to the raw image. This can lead to truncation of low pixel counts, resulting in anomalies in the integrated Bragg intensities, such as systematically higher signal-to-noise ratios. A correction for this effect can be approximated by a three-parameter lognormal distribution fitted to the weakly positive-valued pixels at similar scattering angles. The procedure is validated by the improved refinement of an atomic model against structure factor amplitudes derived from corrected micro-electron diffraction (MicroED) images.


Proteolytic cleavage of the hyperthermophilic topoisomerase I from Thermotoga maritima does not impair its enzymatic properties.
Using limited proteolysis, we show that the hyperthermophilic topoisomerase I from Thermotoga maritima exhibits a unique hot spot susceptible to proteolytic attack with a variety of proteases. The remaining of the protein is resistant to further proteolysis, which suggests a compact folding of the thermophilic topoisomerase, when compared to its mesophilic Escherichia coli homologue. We further show that a truncated version of the T. maritima enzyme, lacking the last C-terminal 93 amino acids is more susceptible to proteolysis, which suggests that the C-terminal region of the topoisomerase may be important to maintain the compact folding of the enzyme. The hot spot of cleavage is located around amino acids 326-330 and probably corresponds to an exposed loop of the protein, near the active site tyrosine in charge of DNA cleavage and religation. Location of this protease sensitive region in the vicinity of bound DNA is consistent with the partial protection observed in the presence of different DNA substrates. Unexpectedly, although proteolysis splits the enzyme in two halves, each containing part of the motifs involved in catalysis, trypsin-digested topoisomerase I retains full DNA binding, cleavage, and relaxation activities, full thermostability and also the same hydrodynamic and spectral properties as undigested samples. This supports the idea that the two fragments which are generated by proteolysis remain correctly folded and tightly associated after proteolytic cleavage.


Epidemiological Characteristics and Clinical Treatment Outcome of Typhoid Fever in Ningbo, China, 2005-2014: Pulsed-Field Gel Electorophoresis Results Revealing Great Proportion of Common Transmission Sources.
We aimed to describe the molecular epidemiological characteristics and clinical treatment outcome of typhoid fever in Ningbo, China during 2005-2014. Eighty-eight Salmonella Typhi isolates were obtained from 307 hospitalized patients. Three prevalent pulsed-field gel electrophoresis (PFGE) patterns of 54 isolates from 3 outbreaks were identified. Overall, there were 64 (72.7%) isolates from clustered cases and 24 (27.3%) isolates from sporadic cases. Resistance to nalidixic acid (NAL) (n = 47; 53.4%) and ampicillin (AMP) (n = 40; 45.4%) and rare resistance to tetracycline (TET) (n = 2; 2.3%) and gentamicin (GEN) (n = 2; 2.3%) were observed. No isolates resistant to cefotaxime (CTX), chloramphenicol (CL), ciprofloxacin (CIP), and trimethoprim-sulfamethoxazole (SXT) were found. The occurrence of reduced sensitivity to CIP was 52.3% (n = 46). The medians of fever clearance time in cases with and without complications were 7 (interquartile range (IQR): 4-10) and 5 (IQR: 3-7) days (P = 0.001), respectively, when patients were treated with CIP or levofloxacin (LEV) and/or third-generation cephalosporins (CEP). Rates of serious complications were at low levels: peritonitis (2.3%), intestinal hemorrhage (6.8%), and intestinal perforation (1.1%). The present study revealed a long-term clustering trend with respect to PFGE patterns, occasional outbreaks, and the rapid spread of AMP resistance and decreased CIP susceptibility among S. Typhi isolates in recent years.


Sjögren's syndrome and other rare and complex connective tissue diseases: an intriguing liaison.
Sjögren's syndrome (SS) is a systemic autoimmune disease that frequently occurs concomitantly with other systemic connective tissue disorders, including rare and complex diseases such as systemic lupus erythematosus (SLE) and systemic sclerosis (SSc). The presence of SS influences the clinical expression of the other autoimmune diseases, thus offering the unique opportunity to explore the similarities in genetic signatures, as well as common environmental and biologic factors modulating the expression of disease phenotypes. In this review, we will specifically discuss the possibility of defining "SS/SLE" and "SS/SSc" as distinct subsets within the context of connective tissue diseases with different clinical expression and outcomes, thus deserving an individualised assessment and personalised medical interventions.


Neuron-glia networks: integral gear of brain function.
Astrocytes, the most abundant glial cell in the brain, play critical roles in metabolic and homeostatic functions of the Nervous System; however, their participation in coding information and cognitive processes has been largely ignored. The strategic position of astrocyte processes facing synapses and the astrocyte ability to uptake neurotransmitters and release neuroactive substances, so-called "gliotransmitters", provide the scenario for prolific neuron-astrocyte signaling. From studies at single-cell level to animal behavior, recent advances in technology and genetics have revealed the impact of astrocyte activity in brain function from cellular and synaptic physiology, neuronal circuits to behavior. The present review critically discusses the consequences of astrocyte signaling on synapses and networks, as well as its impact on neuronal information processing, showing that some crucial brain functions arise from the coordinated activity of neuron-glia networks.


Current reporting of responsiveness in acute cerebral disorders. A survey of the neurosurgical literature.
One hundred sixty-six papers published in seven neurosurgical journals from 1983 through 1985 have been surveyed to determine the methods used for assessment of overall patient responsiveness in acute cerebral disorders (coma grading). Fifty-one different coma scales or modifications were found. The Glasgow Coma Scale (GCS) sum score (that is, the sum of the scores of the individual eye, verbal, and motor scales) dominated (54%), and was used in 73 (76%) of 96 of the head-injury studies; in 56 (77%) of these 73 studies it was the single method of grading neurological status. The GCS sum score was used in 16 (23%) of 70 studies in patients with other etiologies. The Hunt and Hess scale was used in 26 (57%) of 46 reports of patients with subarachnoid hemorrhage. In 31 (55%) of the 56 studies of head injuries using the GCS alone, it was not obvious if the 12- or 13-grade scale was used. In 13 studies (23%) no reference to methodological investigations was made. In 44 papers (79%) the handling of untestable features, such as intubation or swollen eyes, was not reported. In the 56 studies using the GCS alone, coma was defined in many different ways and in 22 studies the definition of coma was not specified. In 63% of reports, the GCS sum score scale was combined in one to five groups of scores and this was done in 32 different ways. No information was available to describe the procedure of data aggregation or the reliability of the 13-grade GCS sum score. The lack of standardization makes it unnecessarily difficult to perform valid comparisons between different series of patients. Since the GCS sum score is the most widely used scale, it is suggested that the reporting of the GCS sum score should be standardized regarding pseudoscoring, coma definition, and use of combined scores. Further studies on the reliability of the GCS sum score are needed.