Molecular cloning, expression and immunological analysis of the capsid precursor polypeptide (P1) from swine vesicular disease virus.
Swine vesicular disease virus (SVDV) is the aetiological agent of a highly contagious viral disease of pigs, whose symptoms are indistinguishable from those caused by foot-and-mouth disease virus (FMDV). The gene coding for the capsid protein precursor of SVDV (P1) from a recent spanish isolate (SPA/1/'93) was cloned and expressed in bacteria, and the antigenicity and immunogenicity of the recombinant product were evaluated. The recombinant P1 was recognised by antibodies against SVDV induced in pigs infected experimentally with different SVDV strains. Immunisation of swine with recombinant P1-induced SVDV-specific cellular and humoral immune responses. The implications of these results in SVD diagnostic as well as in vaccine development are discussed.


A novel hermit crab optimization algorithm.
High-dimensional optimization has numerous potential applications in both academia and industry. It is a major challenge for optimization algorithms to generate very accurate solutions in high-dimensional search spaces. However, traditional search tools are prone to dimensional catastrophes and local optima, thus failing to provide high-precision results. To solve these problems, a novel hermit crab optimization algorithm (the HCOA) is introduced in this paper. Inspired by the group behaviour of hermit crabs, the HCOA combines the optimal search and historical path search to balance the depth and breadth searches. In the experimental section of the paper, the HCOA competes with 5 well-known metaheuristic algorithms in the CEC2017 benchmark functions, which contain 29 functions, with 23 of these ranking first. The state of work BPSO-CM is also chosen to compare with the HCOA, and the competition shows that the HCOA has a better performance in the 100-dimensional test of the CEC2017 benchmark functions. All the experimental results demonstrate that the HCOA presents highly accurate and robust results for high-dimensional optimization problems.


Gallium 67 citrate scanning in the diagnosis of intraabdominal abscess.
Fifty-one consecutive gallium scans in fifty patients with suspected intraabdominal abscess are reviewed. There were twelve true-positive, seven false-positive, twenty-nine true-negative, and two false-negative scans. Accumulation of gallium in the colon and in areas of healing and repair caused soem interpretive difficulty. Despite a significant number of false-positive results, we believe that gallium scanning is a valuable diagnostic tool. Careful attention to technic and cautious interpretation should significantly reduce false-positive and false-negative scans.


Changes in the breath sound spectrum during methacholine inhalation in children with asthma.
An effort-independent breath sound analysis is expected to be a safe and simple method for clinical assessment of changes in airway function. The effects of bronchoconstriction and bronchodilation on novel breath sound parameters in asthmatic children were investigated. The study population included 49 children with atopic asthma (male = 33; mean age: 10.2 years). We evaluated breath sound parameters of the highest frequency of the power spectrum (HFp), frequency limiting 50% and 99% of the power spectrum (F50 and F99 ) and roll-off from 600 Hz to the HFp (Slope). We also assessed new parameters obtained using the ratios of sound spectrum parameters (spectrum curve indices), such as the ratio of the third and fourth power area to the total power area (P3 /PT and P4 /PT ), the ratio of the third and fourth areas to the total area under the curve (A3 /AT and B4 /AT ) and the ratio of power and frequency at 75% of HFp and 50% of HFp (RPF75 and RPF50 ). This was measured before and after methacholine inhalation challenge and after β2 agonist inhalation. The parameters, F50 and F99 , showed no changes after methacholine inhalation. Conversely, the A3 /AT (12.5-10.0%, P < 0.001), B4 /AT (7.6-5.5%, P < 0.001), RPF75 (6.7-4.0 dBm/Hz, P < 0.001) and RPF50 (5.8-4.3 dBm/Hz, P < 0.001) were significantly decreased. These values returned to the original level after β2 agonist inhalation. Spectrum curve indices indicate bronchoconstriction and bronchodilation. These parameters may play a role in the assessment of airway narrowing in asthmatic children.


Ellagic acid: insight into its protective effects in age-associated disorders.
The disparity in the free radical generation and the production of antioxidants to counteract its effect is known as oxidative stress. Oxidative stress causes damage to the macromolecules such as lipids, carbohydrates, proteins, and DNA and RNA. The oxidative damage to the cellular components leads to a process of aging and various age-associated disorders. The literature survey for this review was done using PubMed, Google Scholar, and Science Direct. The papers showing the studies related to aging and age-associated disorders have been selected for reviewing this paper. Ellagic acid has been used as the keyword, and more emphasis has been put on papers from the last 10 years. However, some papers with significant studies prior to 10 years have also been considered. Almost 250 papers have been studied for reviewing this paper, and about 135 papers have been cited. Ellagic acid (EA) is present in high quantities in pomegranate and various types of berries. It is known to possess the antioxidant potential and protects from the harmful effects of free radicals. Various studies have shown its effect to protect cardiovascular, neurodegenerative, cancer, and diabetes. The present review focuses on the protective effect of ellagic acid in age-associated disorders. The effect of EA has been studied in various chronic disorders but the scope of this review is limited to cancer, diabetes, cardiovascular and neurodegenerative disorders. All the disease aspects have not been addressed in this particular review.


Evaluation of effects of platelet-rich fibrin on treatment outcomes after impacted mandibular third molar surgery: A randomized controlled clinical study.
Impaction of the third molar teeth is a common disorder which often necessitates their removal. After third molar surgery, the common postoperative sequelae are pain, trismus, and buccal swelling. Our study sought to evaluate the effect of platelet-rich fibrin (PRF) on postoperative pain, swelling, trismus after surgical extraction of impacted mandibular 3rd molars. Over a period of 22 months (December 1, 2016-September 30, 2018), 44 patients in the age group of 18-40 years, who required surgical extraction of impacted third molar and met the inclusion criteria were recruited. After surgical extraction of the third molar, only primary closure was performed in the control group (22 Group), whereas PRF was placed in the socket followed by primary closure in the study group (22 patients). The outcome variables were pain, swelling, and maximum mouth opening were measured with a follow-up period of 1 week. The application of PRF in the study group lessens the severity of immediate postoperative sequelae such as pain, swelling, and trismus compared to the control group. The treatment outcomes and postoperative sequel were better in the PRF group as compared to other control group on days 1, 3, and 7 postoperatively.


Synthesis and biological evaluation of conjugates of deoxypodophyllotoxin and 5-FU as inducer of caspase-3 and -7.
In order to generate compounds with superior antitumor activity and reduced toxicity, a series of conjugates of deoxypodophyllotoxin and 5-FU were synthesized by coupling 4'-demethyl-4-dexoypodophyllotoxin with N-(5-fluorouracil-N(1)-ly acetic)- amino acids (or 5-fluorouracil-N(1)-ly acetic acid). The cytotoxic activity of these compounds against four human cancer cell lines (HL-60, A-549, HeLa and SiHa) were evaluated, and results indicated that these compounds were more potent in terms of cytotoxicity than either parent compound DPT or anticancer drug VP-16 and 5-FU. In addition, we found that 14d induced cell cycle arrest in the G2/M phase accompanied by apoptosis in A-549 cells, and 14d activated caspase-3 and -7. These results suggested that caspase-mediated pathways are involved in 14d induced apoptosis.


Rat NTE-related esterase is a membrane-associated protein, hydrolyzes phenyl valerate, and interacts with diisopropylfluorophosphate through a serine catalytic machinery.
The serine hydrolases constitute multi-families of proteins that include lipases, esterases, and proteases. These enzymes contain a signature motif GXSXG, in which the serine residue acts as the nucleophile and initiates catalysis. This report describes the characterization of a novel serine hydrolase from rat. This enzyme exhibits a moderate sequence identity with the neuropathy target esterase (NTE), thus is designated NTE-related esterase (NRE). Transfection with the NRE cDNA resulted in marked increases in the hydrolysis of phenyl valerate and reactivity with diisopropylfluorophosphate. Such increases, however, were markedly or completely abolished in mutants that had a substitution (Ala, Cys, Asp, or His) on the serine residue in the GXSXG motif, providing direct evidence that NRE is a serine hydrolase. By Northern blot analyses, three NRE transcripts were detected and they differed markedly in length (approximately 2.6, 4.2, and 5.0 kb). The 4.2-kb transcript was present in all organs analyzed except the testis, in which both 2.6- and 5.0-kb transcripts were detected. The testicular transcripts were completely depleted in rats treated with clofibrate, whereas the levels of NRE mRNA in the liver were markedly increased in rats treated with perfluorodecanoic acid. Both clofibrate and perfluorodecanoic acid are efficacious activators of the peroxisome proliferator activated receptor-alpha (PPAR-alpha). The differential effects on the levels of NRE mRNA suggest that these chemicals regulate the expression of NRE through mechanism(s) rather than the activation of PPAR-alpha.


The impact of intravenous isotonic and hypotonic maintenance fluid on the risk of delirium in adult postoperative patients: retrospective before-after observational study.
To assess the impact of intravenous isotonic and hypotonic maintenance fluid on the risk of delirium in adult postoperative patients, we conducted retrospective before-after study in a tertiary teaching hospital. We examined all adult patients admitted ICU after an elective operation for head and neck cancer, or esophageal cancer from February 2014 to January 2017. From February 2014 to July 2015, patients were administered hypotonic fluid (sodium; 35 mmol/L) as the National Institute for Health and Care Excellence (NICE) have recommended. From August 2015 to January 2017, patients were administered isotonic fluid (sodium; 140 mmol/L). We defined the incidence of delirium as the primary outcome. The delirium was defined as the Intensive Care Delirium Screening Checklist during the ICU stay ≥ 4. A propensity score-matched model was used to adjust confounders. As postoperative intravenous maintenance fluid, hypotonic fluid was administered to 119 patients and isotonic fluid was administered to 92 patients. Among those total cohorts, the incidence of postoperative delirium in the hypotonic group was 21.8%, which was significantly higher than that (9.8%) in the isotonic group (p = 0.019). After propensity score matching, we selected 77 patients in each group. The incidence of delirium during the ICU stay in the hypotonic group was 26.0%, which was significantly higher than the incidence of 11.7% in the isotonic group (p = 0.023). In this study, the use of postoperative hypotonic maintenance fluid was associated with a higher risk of postoperative delirium than that when isotonic maintenance fluid was used.


Evidence for transcriptional interference in a dual-luciferase reporter system.
The dual-luciferase reporter assay is widely used for microRNA target identification and the functional validation of predicted targets. To determine whether curcumin regulates expression of the histone methyltransferase enhancer of zeste homolog 2 (EZH2) by targeting its 3'untranslated region (3'UTR), two luciferase reporter systems containing exactly the same sequence of the EZH2 3'UTR were used to perform dual-luciferase reporter assays. Surprisingly, there were certain discrepancies between the luciferase activities derived from these two reporter constructs. We normalized luciferase activity to an internal control to determine the amount of the reporter construct successfully transfected into cells, induced a transcriptional block with flavopiridol, quantified renilla luciferase mRNA levels, and compared the absolute luciferase activity among the different groups. The results suggested that curcumin promoted the transcription of the luciferase genes located downstream of the simian vacuolating virus 40 (SV40) early enhancer/promoter, but not those located downstream of the human cytomegalovirus (CMV) immediate-early or the herpes simplex virus thymidine kinase (HSV-TK) promoters. These results explain the discrepancies between the two luciferase reporter systems. The current study underscores the importance of taking caution when interpreting the results of dual-luciferase reporter assays and provides strategies to overcome the potential pitfall accompanying dual-luciferase reporter systems.


Motoric Cognitive Risk Syndrome: Prevalence and Risk of Cognitive Impairment in a Population Studied in the Mexican Health and Aging Study 2012-2015.
The aim of this study was to determine the prevalence of Motoric Cognitive Risk (MCR) syndrome, describe associated risk factors and to determine the risk of progression to cognitive impairment after three years of follow-up, in a sample of Mexican older adults. A prospective panel study of health and aging in Mexico. Baseline and follow-up information was obtained from the Mexican Health and Aging Study's 2012 and 2015 waves. A total of 726 subjects aged 60 years or older with normal cognition at baseline were classified into 4 groups: 1) with MCR, 2) with memory complaint only, 3) with slow gait speed only and, 4) without MCR. Cox regression analysis controlling for confounder factors was performed to determine the risk of progression to cognitive impairment in the MCR group. Data such as gait speed, functional status and cognitive performance (standardized by age and sex in Mexican population) was collected. MCR prevalence was 14.3%. When compared with non-MCR subjects, the presence of MCR was associated with older age (p<0.01), lower educational status (p=0.05), having two or more comorbidities (p<0.05) and diabetes mellitus diagnosis (p<0.05). At follow-up and after adjusting for confounders, MCR was associated with a 2.4-fold increased risk (95% CI: 1.28-4.26, p=.000) of cognitive impairment. MCR syndrome increases the risk of cognitive impairment in Mexican older adults. Simple measurements such as gait evaluation in subjects with memory complaints could allow early identification of those at risk of developing cognitive impairment.


Contralateral conditioning to the soleus H-reflex as a function of age and physical activity.
Coordination between ipsilateral and contralateral muscles of the lower limbs has a critical role in movement control. However, the roles that aging and physical activity have in maintaining bilateral coordination are understudied. The aim of this study was to examine the roles of physical activity and age on pathways between the soleus and tibialis anterior muscles. Fourteen young and 14 older subjects (7 active, 7 sedentary) participated. A Hoffmann (H)-reflex was elicited in the ipsilateral soleus following a conditioning stimulus to the contralateral common peroneal nerve at differing intervals (25-300 ms). Significant H-reflex facilitation from the control value was observed for the sedentary group at the 50-ms (28.7 %), 75-ms (24.5 %), and 150-ms (34.0 %) intervals when compared with the physically active group. There were also significant differences between the young and older groups. Results demonstrated differences in soleus H-reflex excitability as a result of contralateral conditioning and highlighted the influence of age and physical activity in maintaining these neural pathways.


Pathologic breast conditions in childhood and adolescence: evaluation by sonographic diagnosis.
The growing awareness of female breast cancer has led to increased sensitivity toward pathologic breast conditions in children and adolescents. Thus, approximately 15% of patients in child and adolescent gynecology are referred for the first time because of conspicuous features of the breast such as pain, palpable masses, and other findings on visual inspection. The aim of this study was to analyze the underlying diagnoses and diseases and determine the status of breast sonography in the diagnostic process. The study population consisted of 62 female patients between 8 weeks and 20 years of age (1997-2002) who were examined clinically, followed by standardized sonography (7.5-13 MHz, conventional B-mode panoramic sonography). Presumed diagnoses were confirmed by biopsy in some patients (n = 16) and by follow-up with clinical examination and sonography in most cases (n = 46). The clinical and sonographic evaluation confirmed 4 main groups of diagnoses: benign tumors (15), developmental disturbances (14), cystic changes (11), and inherent defects (7). In the remaining cases, the findings were no abnormality (9), nipple discharge without evidence of pathologic or morphologic correlates (3), abscesses (2), and epidermoid cyst (1). Knowledge of regular breast development and its variants is essential for the physician. Given knowledge of the sonographic appearance of physiologic breast development and specific lesions, breast sonography is most helpful in identifying and characterizing abnormalities and guiding further investigation.


Quantitative detection of metallo-beta-lactamase of blaIMP-cluster-producing Pseudomonas aeruginosa by real-time polymerase chain reaction with melting curve analysis for rapid diagnosis and treatment of nosocomial infection.
In this study, we established the rapid quantitative detection of metallo-beta-lactamase-producing Pseudomonas aeruginosa in clinical isolates and samples using real-time polymerase chain reaction (PCR) targeting gyrB (identification of P. aeruginosa) and blaIMP. The relative sensitivities and specificities of this real-time PCR assay were as follows: 100.0% and 100.0% for clinical isolates, and 100.0% and 98.4% for clinical specimens, respectively. The relative sensitivities and specificities of blaIMP-PCR were 100.0% in both clinical isolates and clinical specimens. The present PCR assay was easily and quickly performed, and it accurately detected P. aeruginosa and metallo-beta-lactamase.


Mechanisms of the defect in glomerular ultrafiltration associated with gentamicin administration.
Micropuncture studies were performed in three groups of Munich-Wistar rats: eight normal hydropenic controls (group I) and two groups (eight rats each) which were treated with gentamicin in doses of either 4 or 40 mg/kg/day for ten days (groups II and III, respectively). Following gentamicin administration, values for single nephron (SN) GFR were reduced markedly, from the control mean of 31 +/- 0.7 (SEM) nl/min to 22.4 +/- 1.5 and 20.5 +/- 0.9 for groups II and III, respectively. Declines in whole kidney GFR paralleled these falls in SNGFR. The primary cause of the reduction in SNGFR was a marked decline in glomerular capillary ultrafiltration coefficient, Kf, in both gentamicin treatment groups. None of the other determinants of glomerular ultrafiltration were significantly affected in the low dose group (group II). In the high dose group (group III), however, mean values for initial glomerular plasma flow rate and mean transglomerular hydraulic pressure difference were significantly lower than in the control group, accounting for the somewhat greater decline in SNGFR observed in group III. Electron microscopic examination of kidney tissue from rats treated with both doses of gentamicin revealed no obvious abnormalities of the glomerular capillary wall, whereas the previously described morphologic aberrations of proximal convoluted tubule cells were readily demonstrable.


Management of cervical premalignant lesions.
Management of cervical preneoplasia starts with an abnormal smear result. The use of the Bethesda system is recommended. The management of patients with low-grade abnormal smear results varies around the world. Patients with atypical squamous cells on cytology are recommended to be subclassified into atypical squamous cells of undetermined significance (ASCUS) and atypical squamous cells where high-grade squamous intra-epithelial lesions (HSIL) cannot be excluded (ASCH) groups. While patients with ASCUS can be followed with cytology or colposcopy, the risk of having cervical intra-epithelial neoplasia (CIN) is higher in patients with ASCH. Such patients, as well as those with low-grade squamous intra-epithelial lesions on cytology, should be referred for colposcopy to ensure that diagnosis and treatment in CIN is detected. Patients with HSIL should be referred promptly for colposcopic assessment. This should, usually at the same clinic visit, be followed by large loop excision of the transformation zone (LLETZ). Although this is effective treatment, around 15% of patients will have persistent/recurrent disease on cytological follow-up. Patients with positive human papillomavirus DNA tests at follow-up seem to have a considerably higher risk of recurrent preneoplasia than those who have negative tests. Patients over 50 years of age have much higher recurrence risks than younger patients. These factors impact on second-line treatment and follow-up schedules. An important benefit of conservative treatment for CIN with LLETZ is retention of fertility. LLETZ is associated with an increased risk of preterm prelabour rupture of membranes and preterm birth, but not with other adverse pregnancy outcome measures. Conservative excisional management of adenocarcinoma in situ by LLETZ or cold knife cone biopsy is not reported to be as effective as that of CIN, with high risk of residual and recurrent disease at follow-up. Conversely, LLETZ may be acceptable treatment for micro-invasive squamous carcinoma if the excision margins are free of disease and there is no evidence of lymphovascular involvement. The ability to detect and treat premalignant lesions on the cervix reversed the natural history of cervical cancer. Methods of conservative treatment that evolved over decades have been proven safe and effective, allowing retention of fertility. Good clinical guidelines have been developed for most clinical scenarios while some uncertainties persist for other scenarios.


A trade-off in replication in mosquito versus mammalian systems conferred by a point mutation in the NS4B protein of dengue virus type 4.
An acceptable live-attenuated dengue virus vaccine candidate should have low potential for transmission by mosquitoes. We have identified and characterized a mutation in dengue virus type 4 (DEN4) that decreases the ability of the virus to infect mosquitoes. A panel of 1248 mutagenized virus clones generated previously by chemical mutagenesis was screened for decreased replication in mosquito C6/36 cells but efficient replication in simian Vero cells. One virus met these criteria and contained a single coding mutation: a C-to-U mutation at nucleotide 7129 resulting in a Pro-to-Leu change in amino acid 101 of the nonstructural 4B gene (NS4B P101L). This mutation results in decreased replication in C6/36 cells relative to wild-type DEN4, decreased infectivity for mosquitoes, enhanced replication in Vero and human HuH-7 cells, and enhanced replication in SCID mice implanted with HuH-7 cells (SCID-HuH-7 mice). A recombinant DEN4 virus (rDEN4) bearing this mutation exhibited the same set of phenotypes. Addition of the NS4B P101L mutation to rDEN4 bearing a 30 nucleotide deletion (Delta30) decreased the ability of the double-mutant virus to infect mosquitoes but increased its ability to replicate in SCID-HuH-7 mice. Although the NS4B P101L mutation decreases infectivity of DEN4 for mosquitoes, its ability to enhance replication in SCID-HuH-7 mice suggests that it might not be advantageous to include this specific mutation in an rDEN4 vaccine. The opposing effects of the NS4B P101L mutation in mosquito and vertebrate systems suggest that the NS4B protein is involved in maintaining the balance between efficient replication in the mosquito vector and the human host.


Comparing 5G mobile stroke unit and emergency medical service in patients acute ischemic stroke eligible for t-PA treatment: A prospective, single-center clinical trial in Ya'an, China.
This study aims to assess and compare the functional outcomes of patients with acute ischemic stroke (AIS) eligible for tissue plasminogen activator (t-PA) treatment who received care from either a fifth-generation(5G) mobile stroke unit (MSU) or traditional emergency medical service (EMS). The study recruited patients between February 2020 and January 2022, with the final 90-day follow-up concluded in April 2022. Prior to enrollment, patients were assigned to either EMS or MSU care based on predetermined rules. The primary outcome measure was the Modified Rankin Scale (mRS) score at 90 days, with secondary outcome measures including time metrics, mRS and National Institutes of Health Stroke Scale scores at 7-day follow-up, and hospitalization costs. Of the 2281 enrolled patients, 207 were eligible for t-PA treatment, with 101 allocated to MSU care and 106 to EMS care. The percentage of patients achieving a favorable mRS score (0-2) at 90 days was 82.2% in the MSU group compared to 72.6% in the EMS group (p < .05). Median times from symptom onset to thrombolysis were 146 min in the MSU group and 204 min in the EMS group, while median times from ambulance alert to computed tomography (CT) completion were 53 and 128 min, respectively. Hospitalization charges averaged approximately $3592 in the MSU group and $4800 in the EMS group. Our findings indicate that 5G MSU care significantly reduces the time from symptom onset to stroke diagnosis and intravenous thrombolysis in patients with AIS, resulting in improved functional outcomes compared to EMS care. As China continues its deployment of 5G technology and other digital infrastructures, the adoption of 5G MSU care on a broader scale may eventually supplant traditional stroke treatment approaches.


Transcriptomic classes of BCR-ABL1 lymphoblastic leukemia.
In BCR-ABL1 lymphoblastic leukemia, treatment heterogeneity to tyrosine kinase inhibitors (TKIs), especially in the absence of kinase domain mutations in BCR-ABL1, is poorly understood. Through deep molecular profiling, we uncovered three transcriptomic subtypes of BCR-ABL1 lymphoblastic leukemia, each representing a maturation arrest at a stage of B-cell progenitor differentiation. An earlier arrest was associated with lineage promiscuity, treatment refractoriness and poor patient outcomes. A later arrest was associated with lineage fidelity, durable leukemia remissions and improved patient outcomes. Each maturation arrest was marked by specific genomic events that control different transition points in B-cell development. Interestingly, these events were absent in BCR-ABL1+ preleukemic stem cells isolated from patients regardless of subtype, which supports that transcriptomic phenotypes are determined downstream of the leukemia-initialing event. Overall, our data indicate that treatment response and TKI efficacy are unexpected outcomes of the differentiation stage at which this leukemia transforms.


Home-made rapid urease test compared with commercial kit for diagnosis of Helicobacter pylori infection.
To evaluate the sensitivity and specificity of home-made rapid urease test compared with commercial kit for diagnosis of Helicobacter pylori infection. A cross-sectional study of patients who underwent esophagogastro-duodenoscopy from June 2009 to May 2010 was carried out. Gastric biopsy specimens were taken from antrum and body of the stomach for home-made rapid urease testing, commercial kit (hpfast) urease testing, and histological study. One hundred and ninety nine patients were included in the present study. The sensitivity of home-made rapid urease test and hpfast were 40% and 48.5% at 1 hour and 91.4% and 91.4% at 24 hours. The specificity, positive and negative predictive value and accuracy of home-made rapid urease test vs. hpfast were 100% vs. 100%, 100% vs. 100%, 95.5% vs. 95.5% and 96.9% vs. 96.9% respectively. Furthermore 45.3% of home-made rapid urease test and 54. 7% of hpfast showed positive results within 1 hour Home-made rapid urease test has good sensitivity and specificity comparable to commercial kit for the diagnosis of H. pylori infection.


Five degradates of imidacloprid in source water, treated water, and tap water in Wuhan, central China.
Imidacloprid (IMI) is one of the most applied neonicotinoid insecticides worldwide. The occurrence of its degradates such as desnitro-imidacloprid (DN-IMI), imidacloprid-urea (IMI-urea), and desnitro-imidacloprid-olefin (DN-IMI-olefin) in environment water and their fate during drinking water treatment were seldom documented. In this study, IMI and its degradates were determined in source water (the Yangtze River and its largest tributary, the Hanshui River), treated water, and tap water (n = 20, 20, and 169, respectively) in different seasons of 2019 in Wuhan, central China. Their occurrence, removal efficiency, and seasonal variations were evaluated. Advanced water treatment with ozone combined with activated carbon might remove target analytes efficiently but conventional water treatment cannot. IMI and its degradates were 100% detectable in the conventionally treated water samples in July. IMI and DN-IMI decreased while IMI-urea, DN-IMI-olefin, imidacloprid-olefin (IMI-olefin), and 5-hydroxy-imidacloprid (5-OH-IMI) increased during conventional drinking water treatment. IMI and its degradates were found in the tap water samples treated conventionally (range: 1.17-32.0 ng/L for IMI; 0.57-7.00 ng/L for DN-IMI; 0.58-4.50 ng/L for IMI-urea; 0.04-0.65 ng/L for DN-IMI-olefin; < method detection limit [MDL]-0.80 ng/L for IMI-olefin; < MDL-0.35 ng/L for 5-OH-IMI). The concentrations of DN-IMI and IMI-urea observed in this study were higher than those observed in North America. Sodium sulfite did not increase the levels of DN-IMI and IMI-urea in tap water samples in the present study. This is the first study to demonstrate the occurrence of DN-IMI and IMI-urea in water in China and the occurrence of DN-IMI-olefin, IMI-olefin, and 5-OH-IMI in water.


Burden of Growth Hormone Deficiency and Excess in Children.
Longitudinal growth results from multifactorial and complex processes that take place in the context of different genetic traits and environmental influences. Thus, in view of the difficulties in comprehension of the physiological mechanisms involved in the achievement of normal height, our ability to make a definitive diagnosis of GH impairment still remains limited. There is a myriad of controversial aspects in relation to GH deficiency, mainly related to diagnostic controversies and advances in molecular biology. This might explain the diversity in therapeutic responses and may also serve as a rationale for new "nonclassical" treatment indications for GH. It is necessary to acquire more effective tools to reach an adequate evaluation, particularly while considering the long-term implications of a correct diagnosis, the cost, and safety of treatments. On the other hand, overgrowth constitutes a heterogeneous group of different pathophysiological situations including excessive somatic and visceral growth. There are overlaps in clinical and molecular features among overgrowth syndromes, which constitute the real burden for an accurate diagnosis. In conclusion, both GH deficiency and overgrowth are a great dilemma, still not completely solved. In this chapter, we review the most burdensome aspects related to short stature, GH deficiency, and excess in children, avoiding any details about well-known issues that have been extensively discussed in the literature.


Reduced expression of CXCL16/CXCR6 is involved in the pathogenesis of hidradenitis suppurativa.
Mutations in the γ-secretase complex have been well-described in familial hidradenitis suppurativa (HS). No gene mutations have been identified in sporadic HS, which comprises 60%-70% of all HS cases. Obesity and smoking are risk factors for HS and are closely related to DNA methylation, an essential epigenetic phenomenon. Hence, we hypothesized that epigenetic modifications might be involved in sporadic HS. To investigate genes with aberrant methylation in sporadic HS cases and assess their expression in skin lesions and blood from patients with HS. Skin lesion samples and corresponding normal skin were obtained from three patients with HS and subjected to whole-genome DNA methylation sequencing. Blood samples were collected from 20 patients with HS and 20 healthy controls (HCs). The HS mouse model was established by applying tamoxifen to NcstnΔKC mice. Target gene expression was analysed by immunohistochemistry, immunofluorescence, western blotting, enzyme-linked immunosorbent assay (ELISA) and semiquantitative real-time polymerase chain reaction (RT-qPCR). Among 10 807 differentially methylated genes, we filtered 2101 genes with hypermethylated promoter regions, and following bioinformatics analyses, we focused on CXC chemokine ligand 16 (CXCL16). Subsequent functional experiments confirmed the downregulation of CXCL16 and its receptor, CXC chemokine receptor (CXCR) 6, in skin tissue from HS patients and NcstnΔKC mice. Serum CXCL16 concentrations were also significantly decreased in patients with HS. Our data revealed the downregulation of CXCL16 and CXCR6 in HS.


Phenotypic shift in human differentiated gastric cancers from gastric to intestinal epithelial cell type during disease progression.
BACKGROUND: The phenotypic expression of tumor cells is widely thought to resemble that of the tissue of origin. In the present study, to assess phenotypic changes that occur with disease progression, we investigated human differentiated gastric cancers at different depths of invasion for component cancer cell types.METHODS: Using a combined mucin histochemical and immunohistochemical approach, we classified surgical specimens of 301 differentiated gastric cancers into three types: gastric epithelial cell (G) type, intestinal epithelial cell (I) type and mixed gastric and intestinal (GI) type, according to the phenotypic differentiation of the component cancer cells. The relation between the phenotypic type of cancer and their depth of invasion was evaluated.RESULTS: The proportion of G type cancers was 41.4% in early (tumor invasion of mucosa or submucosa) cases, decreasing to 22.2% in advanced (tumor invasion of muscularis propia or deeper) cases, whereas the proportion of I type cancers increased with progressive disease from 23.5% to 31.1% ( P < 0.01). Cancers invading the subserosa or deeper included more I type cases and fewer G type than cancers limited to the mucosa ( P < 0.01). In most cases of each phenotypic type, intestinal metaplasia was recognized in the surrounding background mucosa, but no clear relation was shown between the phenotype of cancers and the degree of intestinal metaplasia in the background mucosa, suggesting that intestinal metaplasia is not always a preneoplastic lesion.CONCLUSIONS: A phenotypic shift from G to I type expression was observed with the progression of human differentiated gastric cancers. Intestinalization may occur independently in cancerous and noncancerous gastric mucosa.


Population modelling to compare chronic external radiotoxicity between individual and population endpoints in four taxonomic groups.
In this study, we modelled population responses to chronic external gamma radiation in 12 laboratory species (including aquatic and soil invertebrates, fish and terrestrial mammals). Our aim was to compare radiosensitivity between individual and population endpoints and to examine how internationally proposed benchmarks for environmental radioprotection protected species against various risks at the population level. To do so, we used population matrix models, combining life history and chronic radiotoxicity data (derived from laboratory experiments and described in the literature and the FREDERICA database) to simulate changes in population endpoints (net reproductive rate R0, asymptotic population growth rate λ, equilibrium population size Neq) for a range of dose rates. Elasticity analyses of models showed that population responses differed depending on the affected individual endpoint (juvenile or adult survival, delay in maturity or reduction in fecundity), the considered population endpoint (R0, λ or Neq) and the life history of the studied species. Among population endpoints, net reproductive rate R0 showed the lowest EDR10 (effective dose rate inducing 10% effect) in all species, with values ranging from 26 μGy h(-1) in the mouse Mus musculus to 38,000 μGy h(-1) in the fish Oryzias latipes. For several species, EDR10 for population endpoints were lower than the lowest EDR10 for individual endpoints. Various population level risks, differing in severity for the population, were investigated. Population extinction (predicted when radiation effects caused population growth rate λ to decrease below 1, indicating that no population growth in the long term) was predicted for dose rates ranging from 2700 μGy h(-1) in fish to 12,000 μGy h(-1) in soil invertebrates. A milder risk, that population growth rate λ will be reduced by 10% of the reduction causing extinction, was predicted for dose rates ranging from 24 μGy h(-1) in mammals to 1800 μGy h(-1) in soil invertebrates. These predictions suggested that proposed reference benchmarks from the literature for different taxonomic groups protected all simulated species against population extinction. A generic reference benchmark of 10 μGy h(-1) protected all simulated species against 10% of the effect causing population extinction. Finally, a risk of pseudo-extinction was predicted from 2.0 μGy h(-1) in mammals to 970 μGy h(-1) in soil invertebrates, representing a slight but statistically significant population decline, the importance of which remains to be evaluated in natural settings.


Effect of lead toxicity on the organ concentration of glutathione and glutathione-related free amino acids in the chick.
Total non-protein sulfhydryl (NPSH) and glutathione (GSH) concentrations in liver and kidney and GSH-related free amino acid concentrations in liver, kidney and plasma were examined in the chick following intoxication with 2000 ppm dietary lead (Pb). After 3 weeks, NPSH content was significantly (P less than 0.05) increased by Pb in both liver and kidney while only liver GSH was increased by Pb treatment. The concentrations of glutamate, glycine and methionine were elevated in liver by Pb while glycine, cysteine and cystathionine concentrations were increased in the kidney. In plasma, Pb significantly decreased cysteine, taurine and cystathionine concentrations.


Statistical methods for measuring interactions between protectors and sensitizers for freeze-thaw survival data.
A statistical model is developed to generate the survival probabilities of cells subjected to freeze-thaw treatments using various sensitizing and/or protective agents. The purpose is to determine whether different freeze-thaw protective agents act independently or whether there is an interaction between the agents. The model permits a statistical analysis of the data to yield an objective quantitative assessment of the size and nature of the interaction.


Fluorescence as an analytical tool for assessing the conversion of oil into biodiesel.
In this work fluorescence-based method to assess the biodiesel production from different refined vegetable oils is presented. Four different refined oils (soybean, sunflower, canola, and corn) and their respective biodiesel were used and the fluorescence of the compounds contained in their compositions was taken as a probe. The results show that the fluorescence intensity of the biodiesel is lower than one verified in the vegetable oil. The data achieved point out that the ratio between the fluorescence intensity of biodiesel and oil is about 0.6 regardless of the vegetable oil feedstock investigated. Reduced content of fluorophores as well as low viscosity of the biodiesel regarding the oil have been raised as hypotheses to explain the low fluorescence intensity of the biodiesel. The results obtained may provide the basis for the development of an alternative method able to give fast and accurate information about the conversion of oil into biodiesel without the requirement of dilution or pre-treatment of the biodiesel.


Interest of routine MR spectroscopic techniques for differential diagnosis between radionecrosis and progression of brain tumor lesions.
The main objective of the study is to assess the feasibility and reproducibility of routine MRS to assist in the differential diagnosis between post-radiation necrosis and tumor progression. The secondary objective is to evaluate the accuracy of the method. An additional sequence of MRS was added to the standard protocol routinely used for patient follow-up. To assess discomfort a control group was formed. The time required to perform MRS and analysis of results, and data about artefacts and technical limitations were collected. MRS results analyzed independently by two neuroradiologists were compared. The diagnostic accuracy of MRS was calculated using a composite reference standard. The experimental group included 38 patients, the control group 41. The discomfort felt during the examination, is not significantly different between the groups. The average quality of SRM is rated as low. The frequency of cerebral radionecrosis is 13 % based on the reference standard used, 54 % and 46 % based on MRS results for the two observers. The additional time is 19,5 min. There is strong inter-observer agreement. The sensitivity and specificity of MRS are respectively for the diagnosis of radionecrosis of 60 % and 45 % (PPV = 16 %NPV = 87 %), for the diagnosis of tumor tissue of 25 % and 94 % (PPV = 80 %NPV = 57%). MRS is probably not applicable in routine clinical practice; however, in view of our results and the literature, in selected cases, it could be a support in the diagnosis of radionecrosis or brain tumor progression. Radionecrosis is probably underestimated.


The 5-HT7 receptors in the VLO contribute to the development of morphine-induced behavioral sensitization in rats.
The 5-hydroxytryptamine 7 receptor (5-HT7R) is one of the most recently cloned serotonin receptors which have been implicated in many physiological and pathological processes including drug addiction. Behavioral sensitization is the progressive process during which re-exposure to drugs intensified the behavioral and neurochemical responses to drugs. Our previous study has demonstrated that the ventrolateral orbital cortex (VLO) is critical for morphine-induced reinforcing effect. The aim of the present study was to investigate the effect of 5-HT7Rs in the VLO on morphine-induced behavioral sensitization and their underlying molecular mechanisms. Our results showed that a single injection of morphine, followed by a low challenge dose could induce behavioral sensitization. Microinjection of the selective 5-HT7R agonist AS-19 into the VLO during the development phase significantly increased morphine-induced hyperactivity. Microinjection of the 5-HT7R antagonist SB-269970 suppressed acute morphine-induced hyperactivity and the induction of behavioral sensitization, but had no effect on the expression of behavioral sensitization. In addition, the phosphorylation of AKT (Ser 473) was increased during the expression phase of morphine-induced behavioral sensitization. Suppression of the induction phase could also block the increase of p-AKT (Ser 473). In conclusion, we demonstrated that 5-HT7Rs and p-AKT in the VLO at least partially contribute to morphine-induced behavioral sensitization.


Density effects of flowering phenology and mating potential in Nicotiana alata.
We investigated effects of plant density on floral phenology and potential mating in artificial populations of the outcrossing ornamental Nicotiana alata planted at three densities. Path analysis revealed that increasing plant density yielded significantly earlier peak flowering dates, significantly earlier last flowering dates, and significantly lower plant biomass. Direct effects of density on final flower number were not significant. Variation among replicate plots for first date of flowering was larger than variation among densities, indicating that factors other than density influence floral initiation.We did not record actual mating, but determined from phenological data the number and identity of potential mates. Increased density had several effects on potential mating patterns and on potential Ne, effective population number. At high density, fewer focal plants flowered for shorter durations. This led to less overlap in flowering time among plants, decreasing the number of potential parental combinations possible among the progeny. Two outcomes of high density, the lower total number of plants flowering and the lower number of plants flowering at most census dates, tended to reduce potential Ne. In contrast, it was low density, where variance in flower number was greatest, that was most likely to yield the greatest reduction in Ne due to variance in progeny number.At high density the potential for assortative mating among tall plants was much greater and occurred later than among large plants at low density. Much of the potential high density assortative mating occurred late in the phenology of individual plants, when there was likely to be lower fruit set.We discuss how ecological agents that alter flowering phenology can potentially alter the genetics of populations, the level and timing of assortative mating and, if genetic variation for response to such ecological agents exists, the potential selection regime.


The incidence of multiple meningiomas--do solitary meningiomas exist?
Since the advent of computed tomography (CT) the recognition of the occurrence of multiple intracranial meningiomas (MIM) in the same individual has been on the increase. In our material the incidence of MIM at first assessment of CT films was 20%, with distant multiplicity prevailing over the regional one. This incidence will probably change in the course of time as MIM develop not only concurrently but also consecutively. On the other hand our surgical macroscopic incidence of regional multiplicity alone was 49%. The discrepancy between the CT and surgical findings prompted us to reevaluate the CT studies of 100 consecutive patients. This reevaluation demonstrated: 1. in two cases, small meningiomas were overlooked at first assessment; 2. nineteen cases of solitary globoid meningiomas seemed to be the consequence of the coalescence of adjacent smaller masses. Thus, the CT incidence of MIM increased to 40%, with regional multiplicity prevailing over the distant one. The authors think that the aforesaid findings question the very existence of solitary meningiomas as a pathological entity. They would be the end product of a coalescence of multiple adjacent smaller growths. Accordingly, a more aggressive surgical approach is suggested to include the resection of a generous fringe of dura mater around the main tumour. As this is not always possible, or too risky, a comprehensive complement to surgery like radiotherapy could be given a reasonable randomized trial.


Ammonia inhibition on thermophilic anaerobic digestion.
This study evaluated both chronic and acute toxicity of ammonia in thermophilic anaerobic digestion of synthetic wastewater over a range of acclimation concentrations. The inhibition effects of ammonia, in terms of total ammonia nitrogen (TAN), under various pH values and acclimation conditions on thermophilic aceticlastic methanogens were investigated. Completely mixed thermophilic anaerobic reactors operated at a chemical oxygen demand (COD) loading rate of 4 g/lday and a solid retention time (SRT) of 7 days were subjected to TAN concentrations of 0.40, 1.20, 3.05, 4.92, and 5.77 g/l. The reactor operations presented a case of chronic inhibition and it was observed that TAN concentrations of 4.92 and 5.77 g/l caused a drop in methane production by as much as 39% and 64%, respectively with respect to control. Batch anaerobic toxicity assays (ATA) were also performed to evaluate the acute toxicity effects of TAN and pH on methanogenesis at thermophilic condition. Modeling based on the results of ATA indicated that aceticlastic methanogens acclimated to high concentrations of TAN were less sensitive to increase in TAN and could tolerate wider pH ranges. TAN concentration causing 100% inhibition occurred in the range of 8-13 g/l, depending on acclimation condition and system pH.


Radiationless mechanism of UV deactivation by cuticle phenolics in plants.
Hydroxycinnamic acids present in plant cuticles, the interphase and the main protective barrier between the plant and the environment, exhibit singular photochemical properties that could allow them to act as a UV shield. Here, we employ transient absorption spectroscopy on isolated cuticles and leaf epidermises to study in situ the photodynamics of these molecules in the excited state. Based on quantum chemical calculations on p-coumaric acid, the main phenolic acid present in the cuticle, we propose a model in which cuticle phenolics display a photoprotective mechanism based in an ultrafast and non-radiative excited state deactivation combined with fluorescence emission. As such, the cuticle can be regarded as the first and foremost protective barrier against UV radiation. This photostable and photodynamic mechanism seems to be universal in land plants giving a special role and function to the presence of different aromatic domains in plant cuticles and epidermises.


Intramuscular changes of soft and hard areas after low-level static contraction of the masseter muscle and the correlations with muscle hardness and increase in water content: evaluations with sonographic elastography and magnetic resonance imaging.
To investigate the intramuscular changes on sonographic elastography (SE) after low-level static contraction of the masseter muscle, and to clarify the relationship with the total hardness and edematous change. Ten healthy volunteers performed sustained bilateral biting at 20% of maximal voluntary contraction for 10 min. The SE and magnetic resonance (MR) scans of the masseter muscles were performed before, immediately after, and 10 min after exercise. The masseter muscle elasticity index (MEI) ratio, muscle thickness, and intramuscular soft and hard areas distribution were evaluated on SE images. The signal to noise ratio (SNR), indicating the water content, was measured on MR images. The soft area ratio showed significant correlations with the water content expressed as SNR. The hard area ratio showed significant correlations with the total muscle hardness expressed as the MEI ratio. Intramuscular soft and hard areas could be used both clinically and experimentally.


Cross communication of diet-microbiome-immune interactions in cancer immunotherapy.
Simpson et al. have highlighted a diet-driven microbiome community, which paves the way for landmark therapeutic avenues for facilitating efficacy and minimizing immune-related adverse events during neoadjuvant immune checkpoint inhibitor treatment in melanoma patients. This innovative attempt inspires application of the diet-microbiome-immune interaction axis to maximize clinical benefits.


Therapeutic plasma exchange in children with acute autoimmune central nervous system disorders.
There is a growing evidence for autoimmunity in acute central nervous system (CNS) disorders and treatment with therapeutic plasma exchange (TPE) may be considered. The aim was to share our experience on the clinical application of TPE in these disorders and to present a reproducible protocol which can be used even in small children. We present a series of 8 children aged 2-12 years with transverse myelitis, Bickerstaff's brainstem encephalitis, neuromyelitis optica, and acute paraneoplastic or unspecified encephalitis in whom TPE was used as a second-line or rescue treatment. A total of 104 TPE sessions were performed where 80-110 ml/kg of plasma was exchanged using 4% albumin solution and fresh frozen plasma. Six episodes of TPE-related adverse events were documented. Fibrinogen concentrations decreased after the first TPE, whereas platelets decreased gradually. One patient died in the course of the acute illness. Three children achieved a complete resolution of symptoms, 2 children have mild sequelae; whereas 2 children remain paraplegic after a follow-up of 3 to 17 months. We report 8 children with presumably autoimmune-mediated, acute CNS disorders treated with TPE as a rescue therapy. Although the effect of TPE can only be inferred, 5 children had a good clinical outcome. TPE is feasible even in small children with acute autoimmune CNS disorders.


Is running good or bad for your knees? A systematic review and meta-analysis of cartilage morphology and composition changes in the tibiofemoral and patellofemoral joints.
The general health benefits of running are well-established, yet concern exists regarding the development and progression of osteoarthritis. To systematically review the immediate (within 20 min) and delayed (20 min-48 h) effect of running on hip and knee cartilage, as assessed using magnetic resonance imaging (MRI). Studies using MRI to measure change in hip or knee cartilage within 48 h pre- and post-running were identified. Risk of bias was assessed using a modified Newcastle-Ottawa Scale. Percentage change in cartilage outcomes were estimated using random-effects meta-analysis. Certainty of evidence was evaluated with the Grading of Recommendations Assessment, Development and Evaluation tool. Twenty-four studies were included, evaluating 446 knees only. One third of studies were low risk of bias. Knee cartilage thickness and volume decreased immediately after running, with declines ranging from 3.3% (95% confidence interval [CI]: 2.6%, 4.1%) for weight-bearing femoral cartilage volume to 4.9% (95% CI: 4.43.6%, 6.2%) for patellar cartilage volume. T1ρ and T2 relaxation times were also reduced immediately after running, with the largest decline being 13.1% (95% CI: -14.4%, -11.7%) in femoral trochlear cartilage. Tibiofemoral cartilage T2 relaxation times recovered to baseline levels within 91 min. Existing cartilage defects were unchanged within 48 h post-run. There is very low certainty evidence that running immediately decreases the thickness, volume, and relaxation times of patellofemoral and tibiofemoral cartilage. Hip cartilage changes are unknown, but knee changes are small and appear transient suggesting that a single bout of running is not detrimental to knee cartilage.


Effect of GABA (gamma-aminobutyric acid) on neurotransmission in inferior colliculus slices from the guinea pig.
Inferior colliculus (IC) slices from guinea pigs were prepared by cutting the IC parasagittally and incubating the obtained slices in the standard medium. Postsynaptic field potentials (PSFP) were recorded in the superficial layer of the pericentral nucleus (PN) by stimulating the deep layer of the PN. GABA (gamma-aminobutyric acid) and its agonists (muscimol and baclofen) and antagonist (bicuculline) were applied in the perfusion medium. GABA (1-12.5 mM), muscimol (1-200 microM) and (-)-baclofen (0.1-20 microM) reduced the amplitude of the PSFP in a dose-dependent manner. Bicuculline (1-10 microM) enhanced the amplitude of the PSFP and evoked the epileptiform burst discharge (EBD). The incubation of IC slices with methoxypyridoxin (100 microM) and 3-mercaptopropionic acid (100 microM) for 2 h reduced the GABA level of the slice to about 50% of the initial value, at which point a distinct EBD appeared. The application of GABA (5 mM) to the medium in this condition blocked the EBD completely. The removal of chloride from the medium as well as the application of furosemide (100 microM) enhanced the amplitude of the PSFP and also elicited the EBD; GABA application in this case did not block the EBD. These results indicate that GABA plays an inhibitory role in the IC, and that the reduction of GABA and the blockade of GABA function cause the appearance of EBD in the IC.


Biological Nitrogen Removal through Nitritation Coupled with Thiosulfate-Driven Denitritation.
A novel biological nitrogen removal system based on nitritation coupled with thiosulfate-driven denitritation (Nitritation-TDD) was developed to achieve a high nitrogen removal rate and low sludge production. A nitritation sequential batch reactor (nitritation SBR) and an anoxic up-flow sludge bed (AnUSB) reactor were applied for effective nitritation and denitritation, respectively. Above 75% nitrite was accumulated in the nitritation SBR with an influent ammonia loading rate of 0.43 kg N/d/m(3). During Nitritation-TDD operation, particle sizes (d50) of the sludge decreased from 406 to 225 um in nitritation SBR and from 327-183 um in AnUSB reactor. Pyrosequencing tests revealed that ammonium-oxidizing bacteria (AOB) population was stabilized at approximately 7.0% (calculated as population of AOB-related genus divided by the total microbial population) in the nitritation SBR. In contrast, nitrite-oxidizing bacteria (NOB) population decreased from 6.5-0.6% over the same time, indicating the effective nitrite accumulation in the nitritation SBR. Thiobacillus, accounting for 34.2% in the AnUSB reactor, was mainly responsible for nitrogen removal via autotrophic denitritation, using an external source of thiosulfate as electron donor. Also, it was found that free nitrous acid could directly affect the denitritation activity.


Mammographic and Ultrasonographic Findings of Oxidized Regenerated Cellulose in Breast Cancer Surgery: A 5-Year Experience.
The purpose of this study was to describe the ultrasonographic (US) and mammographic (MX) findings in patients who underwent breast-conserving surgery followed by oxidized regenerated cellulose (ORC) implantation in the surgical cavity and their size variations in follow-up. We retrospectively reviewed 417 MX and 743 US images performed between January 2009 and January 2014 for 262 women who underwent breast-conserving surgery. All patients underwent US, only 203 women underwent MX examination. In 170 of 262 patients, US examinations showed abnormal findings. Three main US patterns were identified: (1) complex masses: well-encapsulated ipoisoechoic lesions with circumscribed margins with internal hyperechoic nodules (56%); (2) hypoanechoic lesions without internal hyperechoic nodules (24%); and (3) completely anechoic collections (20%). Moreover, Doppler ultrasound examination was performed on all of the patients. In 95 of 203 patients, MX examinations showed abnormalities. Four main MX patterns were identified: (1) round or oval opacity with circumscribed margins (58%); (2) round or oval opacity with indistinct or ill-defined margins (17%); (3) irregular opacity with indistinct or spiculated margins (9%); and (4) architectural distortion or focal asymmetry (15%). Most of the lesions showed a decrease in size at US and MX follow-up examination and the decrease was statistically significant (P < .01). When applied to the surgical residual cavity, ORC aids to control local hemorrhage and reduce the risk of postoperative infections, but can lead to alterations in surgical scar. Thus, knowledge of the radiological findings might allow avoidance of misdiagnosis of tumor recurrence or unnecessary diagnostic examinations.


Acylation of a Plasmodium falciparum merozoite surface antigen via sn-1,2-diacyl glycerol.
The 195-kDa merozoite protein synthesized in schizonts of Plasmodium falciparum (Holder, A. A., and Freeman, R. R. (1982) J. Exp. Med. 156, 1528-1538) contains ester-linked fatty acid. Enzymatic treatment of the purified acylated protein established that the lipid is present as sn-1,2-diacyl glycerol, most probably linked to a phosphodiester at the 3-position of glycerol. The phosphodiglyceride is not directly esterified to an amino acid residue on the polypeptide backbone. The 195-kDa protein is processed to three fragments (83, 42, and 19 kDa) on the surface of free merozoites (Holder, A. A., and Freeman, R. R. (1984) J. Exp. Med. 160, 624-629), of which only the 42-kDa polypeptide is acylated.


A model of the temperature rise in the head due to magnetic resonance imaging procedures.
A simple model of power deposition in the head is presented in which the temperature increase in the head in general and, in particular, in a small spherical region of unperfused tissue contained within the head is calculated. The result of the calculation provides a limit on the SAR needed to ensure that a 1 degree C temperature rise is not exceeded for unperfused spheres of different sizes, imaging sessions of different lengths of time, and different blood flow rates to the head. The model assumes that the rest of the body during a head imaging session can act as a perfect heat sink at 37 degrees C. The model suggests that current practices in MRI imaging will not cause a temperature rise in the center of small unperfused regions such as the eye of more than 1 degree C.


Hepatic mTORC2 compensates for loss of adipose mTORC2 in mediating energy storage and glucose homeostasis.
Mammalian target of rapamycin complex 2 (mTORC2) is a protein kinase complex that plays an important role in energy homeostasis. Loss of adipose mTORC2 reduces lipogenic enzyme expression and de novo lipogenesis in adipose tissue. Adipose-specific mTORC2 knockout mice also display triglyceride accumulation in the liver. However, the mechanism and physiological role of hepatic triglyceride accumulation upon loss of adipose mTORC2 are unknown. Here, we show that loss of adipose mTORC2 increases the expression of de novo lipogenic enzymes in the liver, thereby causing accumulation of hepatic triglyceride and hypertriglyceridemia. Simultaneous inhibition of lipogenic enzymes in adipose tissue and liver by ablating mTORC2 in both tissues prevented accumulation of hepatic triglycerides and hypertriglyceridemia. However, loss of adipose and hepatic mTORC2 caused severe insulin resistance and glucose intolerance. Thus our findings suggest that increased hepatic lipogenesis is a compensatory mechanism to cope with loss of lipogenesis in adipose tissue, and further suggest that mTORC2 in adipose tissue and liver plays a crucial role in maintaining whole body energy homeostasis.NEW & NOTEWORTHY Loss of adipose and hepatic mTORC2 causes diabetes.


Mononuclear and dinuclear complexes of 99mTc.
In the labeling of penicillamine (Pen) with 99mTc, various complexes were detected. Studies of the conditions for differentiating the product formed in order to understand the chemical and biological behavior were carried out. Marked roles of pH and SnCl2 concentration were observed. Controlled delivery of Sn2+ ion was obtained with the tin-adsorbed resin (Sn-resin) developed. Radiopharmaceutical and biological characterization of mononuclear and dinuclear complexes of Tc-Pen, under given sets of labeling condition, were established. Those studies provided a good basis in technetium chemistry which facilitated the development of new Tc-radiopharmaceuticals. Selection of the appropriate ligand offered a stable mononuclear complex of Tc-bleomycin for tumor detection, Tc-Pen-ethyl-ester for blood-element labeling and, above all, development of a bis-thiosemicarbazone derivative as a new bifunctional chelating agent to be coupled to proteins, fatty acids, glucose etc. On the other hand, various cholescintigraphic agents were better conceived of as dinuclear complexes and this created the possibility of generating a new agent, a phthalein derivative, Tc-PC, containing the required coordination environment for the technetium to be bridged in a dinuclear state.


[Notes about other epidemics in Colonial Chile].
In chronicles or in the historiography of the Colony in Chile there are few references about epidemics different to smallpox; like typhus, typhoid fever, dysentery, etc. Almost all, fast spreading in the country and some with high lethality, which led to overflowing the capacity of hospitals in the Chilean colonial period.


Structure and genetics of biosynthesis of the glycosyl phosphate-containing O-polysaccharide of Escherichia coli O160.
On mild acid degradation of the lipopolysaccharide of Escherichia coli O160, the O-polysaccharide was cleaved by acid-labile glycosyl phosphate linkages in the main chain. The resultant oligosaccharide and the alkali-treated lipopolysaccharide were studied by sugar analysis along with (1)H and (13)C NMR spectroscopies, and the following structure of the branched pentasaccharide repeating unit of the O-polysaccharide was established: The O-antigen gene cluster of E. coli O160 was found to be consistent with the O-polysaccharide structure established.


Contrast-enhanced power Doppler sonography of the intestinal wall in the differentiation of hypervascularized and hypovascularized intestinal obstructions in patients with Crohn's disease.
To use power Doppler sonography to quantify the vascularization in the area of stenosed bowel segments in patients with Crohn's disease and to draw conclusions from these findings with regard to the development of these stenoses. The study collective included 11 patients with confirmed Crohn's disease and sonographically visualized stenoses of the small bowel together with intermittent abdominal cramping as a clinical correlate. Power mode examination was repeated after application of a sonographic signal-enhancing agent. Semiquantitative evaluation based on the sonographically indicated degree of vascularization led to the presumptive diagnosis of either inflammatory or cicatricial intestinal obstruction. Sonographic diagnoses were compared with the findings of surgery and subsequent histologic examination or with patients' clinical responses to conservative therapy. Nine of 11 patients underwent surgery within 1 year of examination. All 3 cases in which sonography had facilitated the diagnosis of cicatricial stenosis were confirmed at postoperative histologic examination; similarly, the surgical and histologic findings in the other 6 patients confirmed the sonographic diagnosis of inflammatory stenosis. Power Doppler sonography in combination with the use of a signal-enhancing agent appears to be effective in the recognition of predominantly cicatricial stenoses in patients with Crohn's disease.


Seasonal and taxonomic aspects of the size of arthropods in the tropics and its possible influence on size-selectivity in the prey of a tropical spider community.
During one year in Panama the size (=body length) of arthropods (representing the potential prey of a spider community) was determined by sampling with pitfall traps, bowl traps and sweep-netting. Most arthropods found were small and the distribution of their size is considerably skewed to the left (Figs. 1, 2). Pitfall traps and bowl traps yielded similar results but sweep-netting collected larger arthropods and may be size-selective. Although the variation of arthropod size is high, no seasonal influence on body size could be detected in the main prey groups of spiders (Figs. 3, 4). Differences in the size spectra of the actual prey of a tropical spider community are therefore not caused by seasonal variations in the availability of particular prey size classes. Species-specific prey size spectra, however, may be dependent on properties of the webs concerned, microhabitat selection or other, e.g. physiological or ethological differences between the spider species.


Urinary diversion in high-risk elderly patients: modified cutaneous ureterostomy or ileal conduit?
To evaluate the efficacy and safety of the type of urinary diversion during radical cystectomy in high-risk elderly patients by comparing a modified cutaneous ureterostomy with the ileal conduit urinary diversion. Of 481 patients who underwent radical cystectomy between 1993 and 2002, 54 individuals older than 75 years with an American Society of Anesthesiologists score of 3e, 4, or 4e were characterized as high risk. These patients were grouped according to those who underwent a modified cutaneous ureterostomy (group 1, 29 patients) and those who underwent ileal conduit urinary diversion (group 2, 25 patients). Student's t and Fisher's exact tests were used for statistical analysis. The patients in group 2 had a longer operative time (P < 0.001), an increased need for blood transfusion (P = 0.025), an increased need for intensive care monitoring (P = 0.032), and a longer mean hospitalization time (P < 0.001) than the patients in group 1. In group 2, we recorded statistically greater rates of intraoperative complications (P = 0.035), early medical and surgical complications (P = 0.031 and P = 0.012, respectively), and late surgical complications (P = 0.004). The intraoperative, early, and late surgical complication rate was 13.7%, 24.1%, and 17.2% in group 1 and 40%, 60%, and 56% in group 2, respectively. One patient in group 2 died in the early postoperative period. Cutaneous ureterostomy represents a simplified alternative for urinary diversion in high-risk elderly patients. It can be performed quickly, with few early and late postoperative complications compared with the ileal conduit operation.


How To Assess a Claudication and When To Intervene.
Peripheral artery disease (PAD) affects close to 200 million people worldwide. Claudication is the most common presenting symptom for patients with PAD. This review summarizes the current diagnostic and treatment options for patients with claudication. Comprehensive history and physical examination in order to differentiate between claudication secondary to vascular disease vs. neurogenic causes is paramount for initial diagnosis. Ankle-brachial index is the most commonly used test for screening and diagnostic purposes. Treatment consists of four different approaches, which are best utilized in combination: non-pharmacological treatment for claudication improvement, pharmacological treatment for claudication improvement, pharmacological treatment for secondary risk reduction, and interventional treatment for claudication improvement. Cilostazol is the only Food and Drug Administration (FDA)-approved agent for symptomatic treatment of claudication. Supervised exercise programs provide the maximum benefit for claudication improvement, but home-based exercise programs are an alternative. High-intensity statins and an antiplatelet agent should be prescribed to all patients with PAD. Angiotensin-converting-enzyme inhibitors can provide additional risk reduction, especially in patients with diabetes or hypertension. Rivaroxaban of low dosage (2.5 mg twice daily) in combination with aspirin further decreases cardiovascular risk, but this reduction comes at the cost of higher bleeding risk. Peripheral artery disease (PAD) is a form of atherosclerotic disease that affects hundreds of millions of people worldwide-one of its most common manifestations is intermittent claudication (IC), which results from insufficient blood flow to meet the metabolic demands of an affected extremity. This paper reviews the current literature regarding the workup, diagnosis, diagnostic modalities, treatment options, and management of intermittent claudication.


Stability of stevioside in food processing conditions: unexpected recombination of stevioside hydrolysis products in ESI source.
Stevioside is the main and the sweetest glycoside of stevia plant. It is attractive as a natural sweetener to diabetics and others on carbohydrate-controlled diets. This paper discusses the stability of stevioside under food processing conditions. It was found that stevioside was transformed not only to rubusoside, steviolbioside, steviol monoside and steviol but also to previously unknown stevioside α-anomer and rubusoside α-anomer. Those two identified stevioside transformation products are formed not only during the heating of acidic, neutral and alkaline stevioside standard solutions and stevia leaves suspensions in water and ethanol/water solvents but also during the processing of foods containing stevia. Apart from presenting the new compounds, the paper additionally shows that the recombination of sugar moiety with steviolbioside molecule in MS/ESI source can occur. The effect of molecule recombination in the MS source is known from the literature; however, it has not been reported previously in relation to stevioside derivatives.


Combination human umbilical cord perivascular and endothelial colony forming cell therapy for ischemic cardiac injury.
Cell-based therapeutics are promising interventions to repair ischemic cardiac tissue. However, no single cell type has yet been found to be both specialized and versatile enough to heal the heart. The synergistic effects of two regenerative cell types including endothelial colony forming cells (ECFC) and first-trimester human umbilical cord perivascular cells (FTM HUCPVC) with endothelial cell and pericyte properties respectively, on angiogenic and regenerative properties were tested in a rat model of myocardial infarction (MI), in vitro tube formation and Matrigel plug assay. The combination of FTM HUCPVCs and ECFCs synergistically reduced fibrosis and cardiomyocyte apoptosis, while promoting favorable cardiac remodeling and contractility. These effects were in part mediated by ANGPT2, PDGF-β, and VEGF-C. PDGF-β signaling-dependent synergistic effects on angiogenesis were also observed in vitro and in vivo. FTM HUCPVCs and ECFCs represent a cell combination therapy for promoting and sustaining vascularization following ischemic cardiac injury.


How to successfully implement population health management: a scoping review.
Despite international examples, it is unclear for multisector initiatives which want to sustainably improve the health of a population how to implement Population Health Management (PHM) and where to start. Hence, the main purpose of this research is to explore current literature about the implementation of PHM and organising existing knowledge to better understand what needs to happen on which level to achieve which outcome. A scoping review was performed within scientific literature. The data was structured using Context-Mechanism-Outcome, the Rainbow model of integrated care and six elements of PHM as theoretical concepts. The literature search generated 531 articles, of which 11 were included. Structuring the data according to these three concepts provided a framework that shows the skewed distribution of items that influence the implementation of PHM. It highlights that there is a clear focus on normative integration on the organisational level in 'accountable regional organisation'. There is less focus on the normative integration of 'cross domain business model', 'integrated data infrastructure', and 'population health data analytics', and overall the perspective of citizen and professionals, indicating possible gaps of consideration. A first step is taken towards a practical guide to implement PHM by illustrating the depth of the complexity and showing the partial interrelatedness of the items. Comparing the results with existing literature, the analysis showed certain gaps that are not addressed in practice, but should be according to other frameworks. If initiators follow the current path in literature, they may be missing out on some important components to achieve proper implementation of PHM.


HIV-1 subtypes and circulating recombinant forms (CRFs) in Northern Greece.
In order to understand the genetic diversity of virus isolates associated with the human immunodeficiency virus type one (HIV-1) epidemic in Northern Greece, 51 specimens from HIV-1 infected individuals were classified into subtypes by sequence-based phylogenetic analysis of the polymerase (pol) region of the viral genome. Forty two (82.3%) specimens were identified as pol subtype B, three (5.9%) as A, and one (2%) as CRF01_AE, while the remaining five (9.8%) specimens appeared to be complex recombinants, belonging to the Cypriot/Greek form CRF04_cpx. The proportion of CRF04_cpx strains is larger than previously reported, suggesting that the CRF04_cpx is significantly contributing to the Greek HIV-1 epidemic.


Clinical and epidemiological aspects of the infection by Babesia, Theileria and Trypanosoma species in horses from northeastern Colombia.
Piroplasmosis and trypanosomiasis are debilitating diseases of great economic impact on the equine industry of Latin America. Considering the lack of studies in the northeastern part of Colombia, this study aimed to determine the epidemiological, clinical and genetic features associated with infection of the Babesia, Theileria, and Trypanosoma species in horses from this geographical area. Two hundred and eighty horses from the Arauca, Meta, and Santander departments were molecularly analyzed for infection with Babesia caballi, Theileria equi, Trypanosoma evansi, and Trypanosoma vivax. Furthermore, clinical, epidemiological and entomological analyses were performed on the data sets. Molecular analysis showed 25.7% and 3.9% prevalence for T. equi and T. evansi, respectively, without positive animals for B. caballi and T. vivax. There were no differences in the prevalence of T. equi between departments, whereas T. evansi was detected exclusively in Santander. A total of 633 ticks were collected from 72 horses across the three departments, with 84.7% corresponding to Dermacentor nitens, 10.9% to Amblyomma cajennense (sensu lato) (s.l). and 4.4% to Rhipicephalus microplus. For T. equi, genetic analyses showed that Colombian isolates belong to genotype C of species, along with sequences of Brazil and Mexico. Epidemiological analysis revealed a significant association between tick infestation and lack of vector control with molecular infection of T. equi, whereas clinical analysis revealed a significant reduction in packed cell volume, red blood cells, and mean corpuscular volume in positive animals to this pathogen. Furthermore, molecular infection by T. evansi was associated with epidemiological characteristics in the Santander department. In conclusion, our analysis revealed a moderate infection rate by T. equi of genotype C in horses from northeastern Colombia, which affects their clinical conditions. Control of ticks and treatment of symptomatic animals should be considered to reduce the economic impact associated with these infections in the equine industry.


Effects of beta-adrenergic catecholamines on potassium transport in turkey erythrocytes.
Isoproterenol stimulates cellular accumulation of cyclic adenosine 3':5'-monophosphate (cyclic AMP) and produces a 2- to 4-fold increase in bidirectional potassium fluxes in turkey erythrocytes. Ouabain, which does not alter catecholamine-stimulated cellular cyclic AMP, inhibits potassium influx by 50 to 70%, does not alter potassium outflux or isoproterenol-stimulated potassium influx, but increases isoproterenol-stimulated potassium outflux. Stimulation of potassium transport by isoproterenol can be reproduced by adding cyclic AMP to the medium and is inhibited by propranolol or dichloroisoproterenol but not by phentolamine. Theophylline at concentrations which inhibit cyclic nucleotide phosphodiesterase in isolated turkey erythrocyte plasma membranes by greater than 90%, does not augment isoproterenol stimulation of cellular cyclic AMP or of potassium transport but does potentiate stimulation of potassium influx produced by adding cyclic AMP to the medium. Isoproterenol-stimulated cellular cyclic AMP increases steadily for at least 2 hours. Potassium transport, however, increases rapidly, becomes maximal after 20 to 30 min of incubation, and thereafter decreases progressively so that after 2 hours of incubation potassium fluxes are only slightly greater than for the control. Ouabain prolongs the duration of catecholamine-stimulated potassium influx and potassium outflux, reflecting its ability to relieve the refractoriness developed by turkey erythroyctes to endogenous cyclic AMP.


A crystal molecular conformation of leucine-enkephalin related to the morphine molecule.
Leucine-enkephalin (Try1-Gly2-Gly3-Phe4-Leu5) has been crystallized as a trihydrate from water solution. X-ray diffraction reveals a tightly folded molecular conformation with two fused beta III- (Gly2-Gly3) and beta I- (Gly3-Phe4) turns. The Tyr1 and Phe4 aromatic rings have a close orthogonal arrangement analogous to the tyramine and cyclohexenyl rings in morphine. This suggests that the conformation found in the trihydrate crystal structure could be required for recognition by mu-receptor sites.


Developmental anatomy of the fifth shoot-borne root in young sporophytes of Ceratopteris richardii.
Young sporophytes of the homosporous fern Ceratopteris richardii produce a single shoot-borne root below each leaf. The developmental anatomy of the fifth sporophyte root is described using scanning electron microscopy and histological techniques. Three merophyte orthostichies in the body of the root originate from three proximal division faces of a tetrahedral root apical cell. Eight or nine divisions occur in a relatively regular sequence within each merophyte and produce a characteristic radial anatomical pattern in the root. The exact number of early divisions within a merophyte depends on the merophyte's position within the root as a whole. Predictable inter-merophyte differences arise because a 2-fold (diarch) anatomical symmetry that is characteristic of mature roots is superimposed on a 3-fold radial symmetry that originates behind the apical cell. Before early formative divisions within a merophyte are completed, additional proliferative divisions begin to increase the number of cells within previously established tissue zones. The cellular parameters of early fifth root development in C. richardii are relatively invariant, and are reminiscent of patterns previously described for the heterosporous fern Azolla. Young sporophytes of C. richardii provide a useful model to further investigate the genetic regulation of root development in a non-seed plant, where the anatomy of meristem organization differs from that seen in flowering plant species.


Appropriate indication of fronto-orbital advancement by distraction osteogenesis in syndromic craniosynostosis: Beyond the conventional technique.
Currently the distraction technique could be very useful for posterior expansion in syndromic craniosynostosis. Even for fronto-orbital advancement (FOA), it is thought that distraction has the definitive advantage over the conventional technique. The authors describe the appropriate indication of distraction for FOA in our series of craniosynostosis patients. Since 1998, FOA by distraction has been used for 61 cases of simple and syndromic craniosynostosis. Among these, seven severe cases were extracted with a conspicuous craniofacial deformity with a multiple honeycomb appearance in 3DCT views. Early surgery for FOA by distraction to the extent possible was performed and a retrospective study was conducted. Seven children were identified. All of them exhibited a severe craniofacial deformity. Pfeiffer syndrome in 5 children and clover-leaf skull in two unidentified children were diagnosed. Mean age at surgery for FOA by distraction ranged 10-18 months. Mean operative time: 3-3.5 h. Blood loss: 230-320 mL. The mean advancement by distraction: 20-27 mm. We conclude FOA by distraction when a large amount of advancement is required for early severe cases as our series can be definitely one of the most appropriate candidates beyond the conventional technique, despite disadvantages.


The association between diabetes mellitus and HRQoL of older people in Shanghai.
This study aimed to explore the association between diabetes mellitus and health-related quality of life (HRQoL) of older people in Shanghai, China, especially regarding the differences in each aspect of the EQ-5D and how large the score gaps are between older people with and without diabetes. A total of 11,103 people of either sex older than 60 years were enrolled from 17 districts of Shanghai. The EQ-5D-3L was used to assess the HRQoL of older people. The Wilcoxon rank sum test and t-test were used to compare the difference in HRQoL between people with or without diabetes. After univariate regression, multiple linear regression and ordinal logistic regression were conducted to evaluate the influence of diabetes mellitus and other confounding variables on the EQ VAS scores and on the five dimensions of the EQ-5D. Twelve percent of all participants had diabetes mellitus, and the proportion was almost the same between men and women. The EQ VAS scores of people with diabetes mellitus were approximately 3.70 points lower than those of people without diabetes (95% CI = -4.40, -2.99, p < 0.001) after adjusting for confounding variables. People with diabetes mellitus had increased problems with mobility (OR = 1.57, 95% CI = 1.33, 1.85), self-care (OR = 1.65, 95% CI = 1.35, 2.01), usual activities (OR = 1.78, 95% CI = 1.51, 2.11), pain/discomfort (OR = 1.42, 95% CI = 1.24, 1.64), and anxiety/depression (OR = 1.33, 95% CI = 1.07, 1.64). This study showed that diabetes mellitus was associated with the HRQoL of older people and that older people with diabetes had poorer performance in every aspect of EQ-5D measurements.


Iron (III) hydroxocomplex-methyl viologen dication system as a prospective tool for determination of hydroxyl radical reaction rate constants with environmental pollutants.
Reactivity of oxidative species with target pollutants is one of the crucial parameters for application of any system based on advanced oxidation processes (AOPs). This work presents new useful approach how to determine the hydroxyl radical reaction rate constants (kOH) using UVA laser flash photolysis technique. Fe (III) hydroxocomplex at pH 3 was applied as a standard source of hydroxyl radicals and methyl viologen dication (MV2+) was used as selective probe for •OH radical. Application of MV2+ allows to determine kOH values even for compounds which do not generate themselves optically detectable transient species in reaction with hydroxyl radicals. Validity of this approach was tested on a wide range of different persistent pesticides and its main advantages and drawbacks in comparison with existing steady-state and time-resolved techniques were discussed.


Prolonged absorption and susceptibility to enterohepatic circulation after oral administration of ergot alkaloids in ewes.
The objective of this study was to evaluate the pharmacokinetics profile of ergot alkaloids when administered to sheep orally. Although ergot alkaloids frequently contaminate animal feed, current understanding of their pharmacokinetics in animals cannot adequately predict toxicity. Blood samples were collected from ewes at 0.5, 1, 3, 5, and 12 h after oral exposure to 4 ergot alkaloids: ergocornine, ergocristine, ergocryptine, and ergosine, followed by serum analysis of these alkaloids using high performance liquid chromatography and tandem mass spectrometry. The alkaloids showed extended absorption time, in addition to clear signs of enterohepatic circulation. This pharmacokinetic profile suggests potential enhanced toxicity in animals with disorders related to secretion of bile acid. It may also explain the high susceptibility of sheep to ergot poisoning compared to other species. An extended sampling protocol (> 12 h) is necessary, however, to identify the pharmacokinetic properties of ergot alkaloids in ewes. In conclusion, ewes exposed to ergot alkaloids showed a prolonged absorption phase and enterohepatic circulation, which is in contrast with human ergot pharmacokinetics.


Double-Blind Placebo-Controlled Treatment Trial of Chlamydia trachomatis Endocervical Infections in Pregnant Women.
The purpose of this study was to determine if treatment of pregnant women with Chlamydia trachomatis infection would lower the incidence of preterm delivery and/or low birth weight. Pregnant women between the 23rd and 29th weeks of gestation were randomized in double-blind fashion to receive either erythromycin 333 mg three times daily or an identical placebo. The trial continued until the end of the 35th week of gestation. When the results were examined without regard to study site, erythromycin had little impact on reducing low birth weight (8% vs. 11%, P = 0.4) or preterm delivery (13% vs. 15%, P = 0.7). At the sites with high persistence of C. trachomatis in the placebo-treated women, low birth weight infants occurred in 9 (8%) of 114 erythromycin-treated and 18 (17%) of 105 placebo-treated women (P = 0.04) and delivery <37 weeks occurred in 15 (13%) of 115 erythromycin-treated and 18 (17%) of 105 placebo-treated women (P = 0.4). The results of this trial suggest that the risk of low birth weight can be decreased by giving erythromycin to some women with C. trachomatis. Due to the high clearance rate of C. trachomatis in the placebo group, these data do not provide unequivocal evidence that erythromycin use in all C. trachomatis-infected women prevents low birth weight.


[Electrophysiologic analysis of interaction between afferent inputs to the rat neostriatum].
The interaction of the efferent inputs of the caudate nucleus in the region of their maximal overlapping was studied by paired stimulation. The stimulation of the n. paracentralis and cortex resulted in an increased amplitude of the tested response. On the contrary, the tested responses to stimulation of substantia nigra (zona compacta) and n. raphe (dorsal region) were inhibited. The paired stimulation showed a particular hierarchy of different afferent inputs as to their mutual influence: frontal cortex--thalamic intralaminar nucleus--midbrain structures. The afferent inputs from higher levels, while molulating the activity of those from lower ones, do not reliably change their own activity under the action of the latter. Possible mechanisms of this modulation are discussed.


Potentially inappropriate medications in the elderly: a comprehensive protocol.
Elderly patients are at increased risk of drug-related morbidity and mortality. Avoiding the use of potentially inappropriate medications (PIMs) is one of the strategies that has been widely adopted to reduce the harmful consequences of drug use. There are several PIM screening tools available. In this review, we provide an overview of existing screening tools to detect PIMs in the elderly, emphasizing the advantages and disadvantages of each. Combining previously published and adopted tools (adjusted Beers list, French consensus panel, McLeod's list, and Lindblad's list of clinically important drug-disease interactions), we develop a new comprehensive tool that also includes the adjusted Hanlon's and Malone's lists of potentially serious drug-drug interactions in the elderly. In addition to listed PIMs and clinically important drug-drug interactions, alternative therapeutic solutions are suggested. The new protocol differentiates: drugs with an unfavorable benefit/risk ratio (to be avoided regardless of the underlying disease/condition), drugs with a questionable efficacy, and drugs to be avoided with certain diseases/conditions, and provides a list of potentially serious drug-drug interactions. A tool consisting of PIMs and potential drug-drug interactions within the same protocol provides more comprehensive quality assessment of drug-prescribing behavior to the elderly, which in turn may lead to better prescribing practices.


Long-term Oncological Outcomes from an Early Phase Randomised Controlled Three-arm Trial of Open, Robotic, and Laparoscopic Radical Cystectomy (CORAL).
The long-term oncological outcomes of laparoscopic (LRC) and robotic-assisted radical cystectomy (RARC) are still maturing compared with open radical cystectomy (ORC). To evaluate the 5-yr oncological outcomes of patients recruited into the randomised trial of Open, Laparoscopic and Robot Assisted Cystectomy (CORAL) and extracorporeal urinary diversion. A review of prospectively maintained database of 60 patients with muscle-invasive bladder cancer (MIBC) or high-risk nonmuscle-invasive bladder cancer (HRNMIBC) who were previously randomised in the CORAL trial to receive ORC, RARC, or LRC. This trial was designed to compare the perioperative and early oncological outcomes of these techniques. The outcomes of interest included 5-yr recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS). Kaplan-Meier curves were used to plot the recurrence and survival data. The curves between RFS, CSS, and OS were compared using the log-rank test. A two-sided p value <0.05 was considered significant. Results were analysed on the basis of intention to treat. A total of 60 patients with either MIBC (n=38) or HRNMIBC (n=21) were randomised in the CORAL trial to receive ORC, RARC, or LRC. The 5-yr RFS was 60%, 58%, and 71%; 5-yr CSS was 64%, 68%, and 69%; and 5-yr OS was 55%, 65%, and 61% for ORC, RARC, and LRC, respectively. There was no significant difference in RFS, CSS, and OS between the three surgical arms. The principal limitation is the small sample size. There was no difference in 5-yr RFS, CSS, and OS rates of patients who underwent ORC, RARC, and LRC for management of bladder cancer. Minimally invasive techniques achieved equivalent oncological outcomes to the gold standard of ORC. However, the study was based at a single institution with a small sample size. Patients who agreed to participate in the randomised trial of either open, laparoscopic, or robotic-assisted radical cystectomy for bladder cancer did not have different cancer outcomes at 5yr.


Analyzing Signaling Pathways Using Antibody Arrays.
Cell signaling is comprised of complex networks that regulate homeostasis and human diseases. The analyses of such pathways would improve our understanding of disease pathology and direct drug development. However, it remains a great challenge to study pathways using traditional methods. We developed a high-throughput sandwich-based antibody array technology for the simultaneous detection of multiple targets, capable of identifying the relative expression levels or phosphorylation levels of major signaling pathway proteins. This array-based system features a nitrocellulose membrane or glass slide solid support, spotted with antibodies targeting key proteins of major signaling pathways, including RTK, EGFR, MAPK, AKT, apoptosis, TGFb, JAK/STAT, NFkB, and insulin receptor pathways. We employed these antibody arrays to investigate how the anti-cancer drugs, camptothecin and phorbol 12-myristate 13-acetate (PMA), alter protein phosphorylation in Jurkat and HeLa cells, respectively. Our array data suggest that camptothecin treatment induced DNA double-strand breaks in Jurkat cells and activated the DNA damage pathways ATM and Chk2, which then further induced apoptosis through caspase 3 and PARP. PMA induced the MAPK pathway in HeLa cells through the activation of ERK, CREB, and RSK1. These array results are consistent with previous studies using traditional methods and were validated with Western blotting. Our studies demonstrate that pathway antibody arrays provide a rapid, efficient, and multiplexed approach for profiling phosphorylated proteins.


Cellulose fibers modified with nano-sized antimicrobial polymer latex for pathogen deactivation.
Antimicrobial cellulose fibers and paper products are of great importance for various applications. In this work, novel core-shell antimicrobial latexes based on hydrophobic acrylate monomers and antimicrobial macromonomer (GPHGH) were successfully prepared via a seeded semi-continuous emulsion copolymerization in the presence of a cationic surfactant. The surface properties as well as size of latex were tailored by varying the amount of GPHGH incorporated during the copolymerization. The resulting cationic nano-sized latexes showed the strong adsorption and formed monolayer on the surfaces of bleached sulfite fibers, thus rendering the cellulose fibers antimicrobial. An excellent antimicrobial activity (>99.99% inhibition) of modified fiber toward Escherichia coli was achieved at 0.3wt% of latex dosage (on dry fibers). Results of transmission electron microscopy (TEM) observation confirmed that the particles obtained indeed possessed a desired core-shell structure. The latexes themselves exhibited high antimicrobial activities against E. coli with the minimum inhibitory concentration (MIC) as low as 6.25ppm (similar to that of pure guanidine-based polymer). Moreover, the mechanical strength of the hand-sheets made from latex-modified cellulose fibers was also improved due to the filming of the latex on fiber surfaces.


Biomarkers of obesity-mediated insulin resistance: focus on microRNAs.
Obesity and metabolic syndromes are becoming increasingly prevalent worldwide. Insulin resistance (IR) is a common complication of obesity. However, IR occurrence varies across individuals with obesity and may involve epigenetic factors. To rationalize the allocation of healthcare resources, biomarkers for the early risk stratification of individuals with obesity should be identified. MicroRNAs (miRNAs) are closely associated with metabolic diseases and involved in epigenetic regulation. In this review, we have summarized the changes in miRNA expression in the peripheral circulation and tissues of patients and animals with obesity-associated IR over the last 5 years and identified several candidate biomarkers that predict obesity-related IR. There are areas for improvement in existing studies. First, more than the predictive validity of a single biomarker is required, and a biomarker panel needs to be formed. Second, miRNAs are often studied in isolation and do not form a network of signaling pathways. We believe that early biomarkers can help clinicians accurately predict individuals prone to obesity-related IR at an early stage. Epigenetic regulation may be one of the underlying causes of different clinical outcomes in individuals with obesity. Future studies should focus on objectively reflecting the differences in miRNA profile expression in individuals with obesity-related IR, which may help identify more reliable biomarkers. Understanding the metabolic pathways of these miRNAs can help design new metabolic risk prevention and management strategies, and support the development of drugs to treat obesity and metabolic disorders.