Communication requested: Boar semen transport through the uterus and possible consequences for insemination.
Recent insemination techniques bypass the interactions between sperm and the uterine wall because the semen is deposited deep into the tip of uterine horn or directly into the oviduct. Such techniques allow high dilution of the ejaculates. After normal mating, semen entering the uterus communicates with the uterine milieu. Intact sperm of high mitochondrial membrane potential bind to uterine epithelial cells, whereas most of the unbound sperm in the uterine lumen have damaged membranes. Lectins are the most likely factors to mediate these sperm-uterine interactions. The lectin wheat germ agglutinin is known to induce the strongest binding of sperm, whereas binding is impaired when sialic acid receptors are blocked by wheat germ agglutinin. This suggests that sialic acid is involved in porcine sperm-endometrium interactions, and it is hypothesized that the use of a semen extender supplemented with sialidase would allow insemination with reduced sperm numbers. A lack of contact of sperm and seminal plasma with the uterine wall, as a result of deep insemination, may adversely affect (1) events during ovulation, (2) induction of immunologic tolerance against paternal antigens, (3) preparation of the endometrium for implantation and placentation, and (4) immunologic support required for the fetus during pregnancy. Seminal plasma is known to signal post-insemination changes in the uterine endometrium involving the redistribution of leukocytes. This may involve migration of leukocytes from the uterine wall to the ovary, as seminal plasma particularly increases the appearance of the major histocompatibility complex class II-positive cells. Uterine epithelial cells respond to sperm binding by the production of pro- or anti-inflammatory cytokines. These cytokines may include synchronizing substances, transferred through a counter-current pathway to the ipsilateral ovary, thereby accelerating the final maturation of preovulatory follicles and advancing time of ovulation. In several species, an ovulation-inducing factor exists in seminal plasma, first identified as ß-nerve growth factor in camelid semen, indicating another pathway that influences the hypothalamic-pituitary-gonadal axis. In summary, low-dose inseminations may not necessarily require semen deposition deep into the uterine horn, as binding inhibitors can circumvent the binding of sperm to the uterine wall. However, subsequent immune-relevant events that control ovulation and prepare the uterine milieu for the developing embryo should be taken into account.


Low-dose lenalidomide plus cytarabine in very elderly, unfit acute myeloid leukemia patients: Final result of a phase II study.
Outcome for elderly patients with acute myeloid leukemia (AML) is extremely poor. Intensive induction chemotherapy is often unsuitable. Sixty-six newly diagnosed AML patients (median age: 76years), ineligible for standard therapy, were consecutively treated with low-dose lenalidomide (10mg/day orally, days 1-21) plus 10mg/m2 low-dose cytarabine, subcutaneously, twice a day (days 1-15) every six weeks, up to 6 cycles. Complete remission (CR) rate was 36.3% according to intention-to-treat. Responding patients had a longer median overall survival than non-responders (517 vs. 70days, P<0.001). The achievement of CR was not predicted by bone marrow blast count, cytogenetics, molecular markers, prior MDS, white blood cell count. Conversely, by studying the global gene expression profile, we identified a molecular signature, including 309 genes associated with clinical response (CR versus no CR). Based on the expression of a minimal set of 16 genes, we developed an algorithm to predict treatment response, that was successfully validated by showing an overall accuracy of 88%. We met the primary endpoint of the study, by beating the estimated successful CR rate (P1) fixed at 30%. Moreover, CR induced by this 2-drug combo was efficiently predicted by genetic profiling, identifying a biomarker that warrants validation in independent series.


'Dementia praecocissima': the Sante De Sanctis model of mental disorder in child psychiatry in the 20th century.
The aim of this article is to describe the nosographical contribution of the Italian psychiatrist Sante De Sanctis (1862-1935) to early twentieth-century child psychiatry. De Sanctis first proposed the category of 'dementia praecocissima' in 1906, and it was recognized by Kraepelin. Dementia praecocissima has its roots in a theoretical and methodological conception of mental disorder based on 'psycho-physical proportionalism' and the 'law of circle'. This article deals with De Sanctis's model, which has so far been neglected by historiographers; it shows the pioneering role that this Italian psychiatrist played in child psychiatry in Italy.


One- versus two-stage single-incision laparoscopic cyst excision and hepaticojejunostomy in patients with completely perforated choledochal cysts and good medical conditions.
The aim of the current study was to evaluate the efficacy of one- and two-stage single-incision laparoscopic hepaticojejunostomy (SILH) for perforated CDCs with good medical conditions. Between June 2015 and December 2020, 57 patients were reviewed: Group 1: patients who underwent one-stage SILH (n = 16); Group 2: patients who underwent two-stage SILH (n = 41). The demographic characteristics, operational details, postoperative outcomes and postoperative complications were evaluated. The mean follow-up durations of group 1 and 2 were 39.3 and 38.6 months, respectively. One patient (6.3%) in group 1, and 4 patients (9.8%) in group 2 were converted to laparotomy (p = 0.67). No statistical significance was found in operative time, blood transfusion, time to resume full diet, duration of drainage after definitive surgery and postoperative hospital stays between the two groups. Four patients in group 2 developed bile leakage, which was higher than that in group 1 (9.8% vs 0, p = 0.20). None suffered incidental injury, bleeding, anastomotic stenosis, cholangitis, cholelithiasis, pancreatic leakage, pancreatitis, Roux-loop obstruction, adhesive intestinal obstruction or wound infection. Liver function normalized within 1 year postoperatively in both groups. In experienced hands, one-stage single-incision laparoscopic hepaticojejunostomy is safe and effective for patients with complete perforations and good medical conditions.


Quantification of pore size distribution in reservoir rocks using MRI logging: A case study of South Pars Gas Field.
Pore size distribution (PSD) is an important factor for controlling fluid transport through porous media. The study of PSD can be applicable in areas such as hydrocarbon storage, contaminant transport, prediction of multiphase flow, and analysis of the formation damage by mud infiltration. Nitrogen adsorption, centrifugation method, mercury injection, and X-ray computed tomography are commonly used to measure the distribution of pores. A core sample is occasionally not available because of the unconsolidated nature of reservoirs, high cost of coring operation, and program limitations. Magnetic resonance imaging logging (MRIL) is a proper logging technique that allows the direct measurement of the relaxation time of protons in pore fluids and correlating T2 distribution to PSD using proper mathematical equations. It is nondestructive and fast and does not require core samples. In this paper, 8 core samples collected from the Dalan reservoir in South Pars Gas Field were studied by processing MRIL data and comparing them by PSD determined in the laboratory. By using the MRIL method, variation in PSD corresponding to the depth for the entire logged interval was determined. Moreover, a detailed mineralogical composition of the reservoir samples related to T2 distribution was obtained. A good correlation between MRIL and mercury injection data was observed. High degree of similarity was also observed between T2 distribution and PSD (R2 = 0.85 to 0.91). Based on the findings from the MRIL method, the obtained values for clay bond water varied between 1E-6 and 1E-3µm, a range that is comprehended from an extra peak on the PSD curve. The frequent pore radius was determined to be 1µm.


Regulation of Ig gene expression in normal lymphocytes. I. The half-life of secreted mu chain mRNA differs from that of membrane mu chain mRNA in resting and activated B cells.
Resting and activated B lymphocytes were used to study the stability of mu-specific precursor and mature mRNA. Resting cells which predominantly process the mu precursor towards micron do so rather slowly as reflected in a precursor half-life (T1/2) of 1-2 h. The small amount of secreted mu chain mRNA is fairly stable (T1/2 approximately 8 h) compared to membrane mu chain (T1/2 approximately 4 h). After activation the precursor processing is very fast (T1/2 approximately 10 min) and the stability of mu2, which now predominates, increases (T1/2 approximately 16 h) while the half-life of micron remains at about 4 h. The data indicate that normal B cells regulate mu-specific mRNA stability differently from tumor cells of the B cell lineage.


Turning Cancer Cells into Cancer Killers.
Researchers have changed leukemia cells into natural killer cells by adding a specific antibody to bone marrow cells from patients with acute myeloblastic leukemia. The induced natural killer cells killed leukemia cells in culture. The antibody does not trigger the same conversion in bone marrow from healthy patients.


Principles of ophthalmic anesthesia.
Ophthalmic surgery presents the anesthesiologist with many unique challenges. The exigencies of this subspecialty include a comprehensive knowledge of ocular physiology and pharmacology and an understanding of the anesthetic implications intrinsic to a wide variety of ophthalmic procedures.


Does enhanced CT influence the biological GTV measurement on FDG-PET images?
To test the influence of media injection in PET/CT on the functional or gross tumour volume measurement. Thirty-three patients (56 ± 19 years) with non-Hodgkin's lymphoma (n=22) or Hodgkin's disease (n=11) were prospectively studied at staging. PET/CTs were performed 60 min after injection of FDG. Iopamiron 300 (Iopamidol, 1.5cc/kg) was injected immediately after, followed 50s later by a second craniocaudal CT (CT+). PET images were successively reconstructed using the unenhanced CT (PET-) and the CT+ (PET+) for attenuation correction using iterative reconstruction (4 iterations, 8 subsets, 5mm post-filtering). The SUVmax, SUVmean, SUVpeak and functional tumoural volume were measured in tumoural lymphadenopathies or malignant tissues (n=56 VOIs) using 5 3D-thresholding methods on PET- and PET+ images: absolute SUV value of 2.5; 40% of SUVmax, and 3 adaptative thresholding methods (Vauclin, Black and Schaefer methods). The SUVmean and the volume measurement were significantly different (p<0.001) for the five segmentation methods for PET- (p<0.001) and PET+ (p<0.001). The SUVmax, SUVmean and SUVpeak increased significantly in PET+ compared to PET- (2-5%). The SUVpeak was not significantly different for the five segmentation methods. The functional volume measurements were significantly different between PET- and PET+ only for the 2.5 segmentation method (+3%; p=0.001), but not for the 40%, Vauclin, Black and Schaefer methods. The functional volume could be measured in PET/CT when CT was performed with enhanced media. Caution should be taken when using the volume delineation method. Volume delineation methods using absolute threshold may artefactually increase the functional volume when enhanced CT is used for attenuation correction. The delineation volume using the relative or adaptative method should be preferred when contrast media are used for PET/CT.


The histologic similarity between craniopharyngioma and odontogenic lesions: a reappraisal.
The histologic similarities between the craniopharyngioma and the ameloblastoma are well recognized and supported by their common embryologic origin from oral ectoderm. Differences in these lesions include a greater tendency for craniopharyngiomas to be cystic and form ghost cells and calcifications. The keratinizing and calcifying odontogenic cyst (KCOC), a lesion that features proliferating ameloblastic epithelium, ghost keratin, calcification, and cyst formation, may more precisely mimic the craniopharyngioma. The histologic features of twenty-seven craniopharyngiomas were studied. Twenty cases resembled KCOC microscopically. Two examples duplicated the histologic features of infiltrative ameloblastoma, while five showed characteristics of both lesions. This study shows that the range of histologic features in craniopharyngioma includes and spans both odontogenic lesions but more often simulates KCOC. The results suggest that the KCOC and the ameloblastoma may be closely related developmentally.


Impact of expression system on the function of the C6.5 diabody PET radiotracer.
The ability of engineered antibodies to rapidly and selectively target tumors that express their target antigen makes them well suited for use as radioimaging tracers. The combination of molecular size and bivalent nature makes diabody molecules a particularly promising structure for use as radiotracers for diagnostic imaging. Previous data have demonstrated that the anti-HER2 C6.5 diabody (C6.5db) is an effective radiotracer in preclinical models of HER2-positive cancer. The aim of this study was to evaluate the impact on radiotracer performance, associated with expressing the C6.5db in the Pichia pastoris (P-C6.5db) system as compared to Escherichia coli (E. C6.5db). Glycosylation of P-C6.5db led to faster blood clearance and lower overall tumor uptake than seen with E. coli-produced C6.5db. However, P-C6.5db achieved high tumor/background ratios that are critical for effective imaging. Dosimetry measurements determined in this study for both (124)I-P-C6.5db and (124)I-E-C6.5db suggest that they are equivalent to other radiotracers currently being administered to patients.


Does cardiology hold pharmacogenetics to an inconsistent standard? A comparison of evidence among recommendations.
Current guideline recommendations for pharmacogenetic testing for clopidogrel by the American Heart Association/American College of Cardiology (AHA/ACC) contradict the Clinical Pharmacogenetics Implementation Consortium and the US FDA. The AHA/ACC recommends against routine pharmacogenetic testing for clopidogrel because no randomized controlled trials have demonstrated that testing improves patients' outcomes. However the AHA/ACC and the National Comprehensive Cancer Network (NCCN) recommend other pharmacogenetic tests in the absence of randomized controlled trials evidence. Using clopidogrel as a case example, we compared the evidence for other pharmacogenetic tests recommended by the AHA/ACC and NCCN. In patients that received percutaneous coronary intervention, the evidence supporting pharmacogenetic testing for clopidogrel is stronger than other pharmacogenetic tests recommended by the AHA/ACC and NCCN.


Dynamism and regulation of the stator, the energy conversion complex of the bacterial flagellar motor.
Many motile bacteria swim by rotating their motility organ, the flagellum. Rotation of the flagellum is driven by a motor at its base, and torque is generated by the rotor-stator interaction coupled with the specific ion flow through the channel in the stator. Because the stator works as an energy-conversion complex in the motor, understanding the functional mechanism of the stator is critically important. But its characterization has been hampered due to the difficulty in isolating the functional stator complex from the membrane. Recently, successful new approaches for studying the stator have been reported that reveal its novel properties. Two of those, visualization of the in vivo behavior of stator units using fluorescently tagged proteins and structure-guided functional analyses of the soluble region in the stator, are summarized in this short review.


Cystic fibrosis and survival to 40 years: a study of cystic fibrosis transmembrane conductance regulator function.
Significant survival heterogeneity exists in cystic fibrosis. Our aim was to determine whether residual function of the cystic fibrosis transmembrane conductance regulator (CFTR) is present in long-term survivors with severe mutations. Nasal potential difference (PD) and sweat chloride were measured in 34 long-term survivors (aged ≥ 40 yrs) and compared with young patients (18-23 yrs) with severe (n = 30) and mild (n = 31) lung disease. Baseline PD was not significantly different across the three groups (long-term survivors, -42.8 (range -71.0- -20.5) mV; young/mild, -40.5 (-58.8- -19.5) mV; young/severe,-46.3 (-74.0- -20.0) mV). Response to amiloride (ΔAmil) was significantly different across the three groups (p = 0.01); long-term survivors had values (27.8 (range 8.5-46) mV) which were not different to either young group, but the young/severe group had significantly higher values (29.5 (11-47) mV) than those in the young/mild group (22.0 (7-39) mV; p<0.01). Baseline PD and ΔAmil were associated with forced expiratory volume in 1 s (FEV₁) (co-efficient (95% CI) -0.13 (-0.23- -0.03); p = 0.009 and -0.12 (-0.20- -0.04); p = 0.003, respectively). Sweat chloride was lowest (p <0.05) in the young/severe group (93.5 (74-111) mmol·L⁻¹ versus 98.8 (76.5-116.0) mmol·L⁻¹; long-term survivors; and 99.5 (80.0-113.5) mmol·L⁻¹; young/mild). Δ Amil is associated with FEV₁ but our findings indicate that long-term survival cannot be explained by residual CFTR function when measurements are taken in later life.


Methylation Pattern and Expression Dynamics of Methylase and Photosystem Genes Under varying light Intensities in Fugacium kawagutii (Symbiodiniaceae).
Previous studies have documented extensive methylation of CpG islands and abundant methyltransferase gene (DNMT) in Fugacium kawagutii (formerly Symbiodinium kawagutii) genome. However, whether DNA methylation plays a role in regulating gene expression in this and other dinoflagellates remains unclear. Here, we characterized gene body methylation levels using methylation-specific PCR (MS-PCR) and bisulfite sequencing PCR (BSP) and measured transcriptional levels for three photosystem genes in F. kawagutii under different light conditions (20, 100, and 600 µE · m-2 · s-1 ). To explore the association of methylation with DNA methylase, the expression of DNA methyltransferase (Symbio-DIRS-Dnmt3) was also measured. Our results showed that peridinin-chlorophyll a-binding protein (PCP), light-harvesting complex (LHC), and chlorophyll a-c-binding protein complex (acpPC) gene expression was all significantly up-regulated under low light in which their methylation level was down-regulated, constant, and elevated, respectively. Symbio-DIRS-Dnmt3 exhibited elevated transcriptional level under increased light intensity. The results led us to hypothesize that DNA methylation level can be modulated by environmental conditions such as irradiance, probably through the regulation of Symbio-DIRS-Dnmt3 transcription level, and in turn may regulate the expression of genes in F. kawagutii. Further study is needed to determine whether the same gene methylation and expression characteristics reported here occur in other dinoflagellates and to explore their ecological implications.


An animal analogue of forced unilateral nostril breathing: relevance for physiology and pharmacology.
Since forced unilateral nostril breathing activates the contralateral brain hemisphere, an animal analogue of this technique could be provided by methylmethacrylate gluing large plastic pellets in either the right or left nostrils in a group of rats. A large number of physiological, pharmacological, and immunological parameters may be differentially affected.


Rapid development of tissue bank achieved by International Atomic Energy Agency (IAEA) Tissue Banking Programme in China.
Before 1986, the development of tissue banking in China has been slow and relatively uncoordinated. Under the support of International Atomic Energy Agency (IAEA), Tissue Banking in China experienced rapid development. In this period, China Institute for Radiation Protection tissue bank mastered systematic and modern tissue banking technique by IAEA training course and gradually developed the first regional tissue bank (Shanxi Provincial Tissue Bank, SPTB) to provide tissue allograft. Benefit from training course, SPTB promoted the development of tissue transplantation by ways of training, brochure, advertisement and meeting. Tissue allograft transplantation acquired recognition from clinic and supervision and administration from government. Quality system gradually is developing and perfecting. Tissue allograft transplantation and tissue bank are developing rapidly and healthy.


Is it Time for Competency-Based Education to Move Forward in Pharmacy Education?
Competency-based education is rapidly emerging as a paradigmatic shift in health professions education, as we grapple with the realities of ever-changing and increasing demands of society and health systems. While pharmacy educators are becoming more familiar with this paradigm, colleagues in medical education have been exploring models and methods of competency-based education for many years, and their experiences can be illuminating for us. The persistent question that drives continuous quality improvement in pharmacy education and the development of initiatives within American Association of Colleges of Pharmacy might be stated as "Is there a better (more effective, more efficient) way to prepare pharmacists (future and current) to meet the medication-related needs of the public?"


Overexpression, purification and characterization of a new salicylate hydroxylase from naphthalene-degrading Pseudomonas sp. strain ND6.
A new salicylate hydroxylase from naphthalene-degrading Pseudomonas sp. strain ND6, NahU, has been identified. The nahU is an isofunctional gene of the classic salicylate hydroxylase gene, nahG, and situated outside the transcriptional unit forming the naphthalene degradation lower pathway. Both genes, nahU and nahG of Pseudomonas sp. ND6, have been cloned and overexpressed in Escherichia coli BL21 (DE3). NahU contains 429 amino acid residues and NahG contains 434 amino acid residues. SDS-PAGE analysis showed that both NahG and NahU are about 47 kDa. Both enzymes exhibit broad substrate specificities and metabolize salicylate, sulfosalicylate, aspirin, methylsalicylate, chlorosalicylate and 3,5-dinitrosalicylate. The comparison of the Km and Vmax values for NahG and NahU demonstrated that NahU possesses a higher binding ability to salicylate and cofactors and catalytic efficiency.


Evidence for the participation of endogenous opioids in the sympathoadrenal response to hypoglycaemia in man.
The effects of the long acting met-enkephalin analogue D-Ala2-MePhe4-met-enkephalin-O-ol (DAMME) and the opiate antagonist naloxone on the plasma catecholamine responses to insulin-induced hypoglycaemia have been investigated in two separate studies. DAMME depressed basal noradrenaline and adrenaline at 15 min, and blunted both the noradrenaline and adrenaline responses to hypoglycaemia. Naloxone did not alter basal plasma catecholamines, but caused a significant enhancement of the adrenaline response to hypoglycaemia. Neither DAMME nor naloxone altered the blood glucose response to insulin-induced hypoglycaemia. These data are consistent with an inhibitory modulation of endogenous opioids in the sympathoadrenal response to insulin-induced hypoglycaemia in man.


N-1 and C-3 substituted indole Schiff bases as selective COX-2 inhibitors: synthesis and biological evaluation.
A group of N-1 and C-3 disubstituted-indole Schiff bases bearing an indole N-1 (R'=H, CH(2)Ph, COPh) substituent in conjunction with a C-3 -C=HN-C(6)H(4)-4-X (X=F, Me, CF(3), Cl) substituent were synthesized and evaluated as inhibitors of cyclooxygenase (COX) isozymes (COX-1/COX-2). Within this group of Schiff bases, compounds 15 (R(1)=CH(2)Ph, X=F), 17 (R(1)=CH(2)Ph, X=CF(3)), 18 (R(1)=COPh, X=F) and 20 (R(1)=COPh, X=CF(3)) were identified as effective and selective COX-2 inhibitors (COX-2 IC(50)'s=0.32-0.84 μM range; COX-2 selectivity index (SI)=113 to >312 range). 1-Benzoyl-3-[(4-trifluoromethylphenylimino)methyl]indole (20) emerged as the most potent (COX-1 IC(50) >100 μM; COX-2 IC(50)=0.32 μM) and selective (SI >312) COX-2 inhibitor. Furthermore, compound 20 is a selective COX-2 inhibitor in contrast to the reference drug indomethacin that is a potent and selective COX-1 inhibitor (COX-1 IC(50)=0.13 μM; COX-2 IC(50)=6.9 μM, COX-2 SI=0.02). Molecular modeling studies employing compound 20 showed that the phenyl CF(3) substituent attached to the CN spacer is positioned near the secondary pocket of the COX-2 active site, the CN nitrogen atom is hydrogen bonded (N···NH=2.85 Å) to the H90 residue, and the indole N-1 benzoyl is positioned in a hydrophobic pocket of the COX-2 active site near W387.


Capsaicin-induced substance P release and sensory control of vascular permeability in the guinea-pig ureter.
Substance P-immunoreactivity (SP-IR) in the guinea-pig ureter was found to be totally depleted after systemic capsaicin pretreatment. Removal of the inferior mesenteric ganglion (IMG) led to a total depletion of SP-IR from the rostral third of the ureter and to a partial depletion from the caudal third. Electrical stimulation of the IMG caused Evans blue extravasation mainly in the rostral third of both ureters, whereas stimulation of the right pelvic nerve caused Evans blue extravasation in the caudal third of the ureters on both sides. The responses to nerve stimulation were absent in capsaicin-pretreated animals. Furthermore, capsaicin caused release of SP-IR from ureter slices in vitro, this release was not inhibited by tetrodotoxin. Potassium (60 and 120 mM) also released SP-IR. It is concluded that SP-IR in the ureter is contained in capsaicin-sensitive sensory neurons reaching the ureter via both parasympathetic (caudal part) and sympathetic nerves (rostral part). Activation of these neurons by capsaicin leads to a peripheral release of SP-IR which most likely increases vascular permeability.


Predictors of choosing life-long screening or prophylactic surgery in women at high and moderate risk for breast and ovarian cancer.
The aim of this study is to summarize published empirical data describing the predictors of adhering to screening practices and choosing to have prophylactic surgery in women at increased risk for breast and ovarian cancer. Pubmed, Psychinfo and Cinahl databases were searched to identify studies on the predictors of adherence to breast and ovarian cancer screening and predictors of having a prophylactic mastectomy or salpingo-oophorectomy. We found 37 empirical studies that met our inclusion criteria. The main predictors of the use of preventive measures are related to DNA test results, socio-demographic characteristics, and psychological outcome measures. It is concluded that there is no unequivocal relationship between age, education, risk perception, or anxiety and adherence to breast and ovarian cancer screening practices. Worrying about cancer is associated with a higher adherence to screening practices.


A dynamic actin cytoskeleton is required to prevent constitutive VDAC-dependent MAPK signalling and aberrant lipid homeostasis.
The dynamic nature of the actin cytoskeleton is required to coordinate many cellular processes, and a loss of its plasticity has been linked to accelerated cell aging and attenuation of adaptive response mechanisms. Cofilin is an actin-binding protein that controls actin dynamics and has been linked to mitochondrial signaling pathways that control drug resistance and cell death. Here we show that cofilin-driven chronic depolarization of the actin cytoskeleton activates cell wall integrity mitogen-activated protein kinase (MAPK) signalling and disrupts lipid homeostasis in a voltage-dependent anion channel (VDAC)-dependent manner. Expression of the cof1-5 mutation, which reduces the dynamic nature of actin, triggers loss of cell wall integrity, vacuole fragmentation, disruption of lipid homeostasis, lipid droplet (LD) accumulation, and the promotion of cell death. The integrity of the actin cytoskeleton is therefore essential to maintain the fidelity of MAPK signaling, lipid homeostasis, and cell health in S. cerevisiae.


Neuropsychological assessment in preoperative and postoperative evaluation.
Neuropsychological assessment in the surgical management of the epilepsies includes comprehensive neuropsychological examination for baseline, diagnostic, and follow up purposes, and specialized diagnostic procedures. The developmental competence of the individual provides an organizing principle for psychological work and is reflected in the neurosurgical strategy. Adaptive functioning and psychosocial adjustment are as important in determining outcome as performance on neuropsychological tasks. The techniques and tools of neuropsychological assessment are discussed in this article; presurgical functioning and post-surgical status and management affect outcome.


Nutritional support in lung cancer: Time to combine immunonutrition with immunotherapy?
Although there is substantial evidence on the impact of nutritional-status deterioration on quality of life, treatment tolerance, morbidity, and mortality in people with cancer, clinical nutrition intervention trials in oncology are still limited. The rationale for deepening this topic is also justified by the availability of innovative treatment options, such as immunotherapy, which take into consideration potential modulation of the immune system by several factors. In this article, we aimed to focus on the unexplored issue of immunonutrition and its potential modulatory activity on treatment response in people receiving immunotherapy. With this perspective, we propose a clinical-trial model to explore the potential impact of immunonutrition on nutritional, functional, immunologic, safety, and efficacy parameters in people with advanced non-small cell lung cancer undergoing first-line immunotherapy-based anticancer treatment.


On four epibiotic peritrichous ciliates (Protozoa, Ciliophora) found in Lake Weishan Wetland: morphological and molecular data support the establishment of a new genus, Parapiosoma gen. nov., and two new species.
During a study on the diversity of ciliated protists in Lake Weishan Wetland, the largest wetland in northern China, four epibiotic sessilid peritrichs were isolated from aquatic host animals. Two of them, i.e., Epistylis cambari Kellicott, 1885 and Epistylis lwoffi Fauré-Fremiet, 1943, were known species whereas the other two, i.e., Parapiosoma typicum gen. nov., sp. nov. and Orborhabdostyla gracilis sp. nov., are new to science. The new genus Parapiosoma gen. nov. is characterized by its branched non-contractile stalk, everted peristomial lip, obconical macronucleus and transverse silverlines. Two species are assigned to the new genus, namely Parapiosoma typicum sp. nov. and Parapiosoma gasterostei (Fauré-Fremiet, 1905) comb. nov. Morphologically, P. typicum sp. nov. is recognized by its goblet-shaped zooids, single-layered peristomial lip, dichotomously branched stalk, and infundibular polykinety 3 (P3) containing three equal-length rows. Orborhabdostyla gracilis sp. nov. is characterized by its slender zooid, curved macronucleus, and three equal-length rows in infundibular P3. Improved diagnoses and redescriptions of E. cambari and E. lwoffi are provided including, for the first time, data on the ciliature of E. cambari. Phylogenetic analyses based on SSU rDNA, ITS1-5.8S rDNA -ITS2, and LSU rDNA sequence data strongly support the assertion that the family Epistylididae comprises morphospecies with different evolutionary lineages and indicate that Parapiosoma gen. nov. may represent a new taxon at family level.


A hybrid symbolic-numerical method for determining model structure.
In this article, we present a method for determining whether a model is at least locally identifiable and in the case of non-identifiable models whether any of the parameters are individually at least locally identifiable. This method combines symbolic and numeric methods to create an algorithm that is extremely accurate compared to other numeric methods and computationally inexpensive. A series of generic computational steps are developed to create a method that is ideal for practitioners to use. The algorithm is compared to symbolic methods for two capture-recapture models and a compartment model.


Living donor liver transplantation for alveolar echinococcus is a difficult procedure.
Surgical resection is the best treatment for early stage alveolar echinococcosis of the liver. In the stages that are not appropriate for resection and when the case develops complications, a liver transplant can be a lifesaver. The liver transplants of alveolar echinococcosis are technically difficult because of prior operation, interventional radiological procedures, and large mass. Despite such difficulty, living donor liver transplantation can save one's life.


[The effect of proteolytic inhibitors on tolerance to renal ischemia].
Proteolytic inhibitors like Contrykal are able to protect kidney tissue from ischemic injury and therefore recommended for cadaver donor preparation.


Bone marrow aplasia associated with proliferation of large granular lymphocytes and subsequent transformation to acute lymphoblastic leukemia.
Proliferation of large granular lymphocytes may be associated with neutropenia and, less frequently, thrombocytopenia. In this report, we describe a patient with severe aplastic anemia in the setting of a proliferation of cells with natural killer (NK) phenotype. We demonstrated evolution to acute lymphoblastic leukemia by cells of identical phenotype.


Induction of growth hormone release by Pueraria thunbergiana BENTH.
Puerariae Radix (PR), Puerariae Flos (PF), and Puerariae Surculus (PS) as well as their constituents were tested for induction of rat growth hormone (rGH) release by both rat pituitary cell culture and in vivo experimentation in order to develop them to novel drugs. Through a calibration curve of the rGH released by addition of rat growth hormone-releasing hormone (rGHRH) to rat pituitary cells, the 70 % ethanol extracts of PR and PS increased rGH release by about 1.6 and 1.7 times as high, respectively, as the control group (264.6 +/- 13.6 pM). However, each puerarin type as a representative constituent of PR in Korea Pharmacopeia (KP) and tectorigenin and an important ingredient of PF were twice as effective as in the control group. The acid hydrolysate of Puerariae Surculus (HPS) increased rGH release concentration-dependently, and its EC (50) was approximately 10.4 microg/ml. The T (max) value for rGH after injection of 20 microg/kg of rGHRH was 10 - 30 min, while the C (max) value was increased by approximately 12-fold compared to the control group (198.2 +/- 25.0 pM) and the AUC (0 - 45) was increased to 10 times the level of the control group (10,840.9 +/- 845.5 min. pM). On the other hand, T (max) for the HPS was 60 min, while C (max) was increased approximately to 5.8 fold compared to control (244.1 +/- 36.4 pM). C (max) for puerarin was 1,028.6 +/- 502.7 pM, that is, approximately 5.2 times as high as the control level. However, tectorigenin (20 microg/kg) was of no statistical significance. Therefore, we suggest that the HPS and puerarin act either on GH secretagogue receptors or on GHRH receptor of somatotrophin as possible agonists or an inhibitor on somatostatin receptor to release rGH, respectively.


Non-Dupuytren's disease of the palmar fascia.
The typical Dupuytren's disease patient is of Northern European descent with bilateral progressive multiple digital contractures and is genetically predisposed, with a family history. Palmar fascial proliferations sometimes present as a different entity without the typical Dupuytren's disease characteristics. We identified 39 patients (20 women and 19 men) over a 4-year period with "Non-Dupuytren's palmar fascial disease", with unilateral involvement, without family history or ectopic manifestations. Twenty-three patients presented with unrelated complaints and were discovered, incidentally, to have the condition. In 28 patients, prior ipsilateral hand surgery or trauma precipitated the condition. Other related factors were diabetes mellitus and cardiovascular disease. Ten patients had skin tethering and subcutaneous thickening akin to Dupuytren's nodules and 29 had palmar fascial thickening into ill-defined pretendinous cords. The diseased tissue was in the line of the ring finger in 30 patients. The time from insult to onset of contracture averaged 3.6 months and from onset to follow-up averaged 5.3 years. The condition was non-progressive, or partially regressive, in 33 patients. Seven patients had operations for unrelated conditions and underwent simultaneous fasciectomy without recurrence. Environmental factors, especially trauma, surgery and diabetes, are important in the pathogenesis of Non-Dupuytren's palmar fascial disease, but these patients do not appear to be genetically predisposed for Dupuytren's disease. Typical Dupuytren's disease and Non-Dupuytren's palmar fascial disease are two clinical entities that run different courses and do not share a similar prognosis. This should be taken into account in future epidemiological and outcome studies.


Effects of single nucleotide polymorphisms in the 5'-flanking region of heat shock protein 70.2 gene on semen quality in boars.
This study aims to elucidate the effects of single nucleotide polymorphisms (SNPs) in the 5'-flanking region of porcine heat shock protein 70.2 gene (HSP70.2) on semen quality in boars. Genomic DNA isolated from 55 boars (41 Duroc, nine Landrace, and five Yorkshire) was subjected to PCR amplification of the 5'-flanking region of HSP70.2. The nucleotide sequences were determined by automated sequencing. Five SNPs (sites 44, 232, 250, 345, and 393) were detected in this region. Semen quality was evaluated in terms of sperm motility, percentage of normal sperm, percentage of sperm with proximal plasma droplet, percentage of abnormal sperm, sperm concentration, semen volume per ejaculate and total sperm number per ejaculate. The effect of the SNPs on semen quality was evaluated based on breed-corrected data within a season. During the cool season, the sperm motility of boars with AA genotype at the 232 site was significantly higher than that of boars with CC genotype (P<0.05). Meanwhile, boars with AC genotype at the 232 site had higher total sperm number per ejaculate than did those with CC genotype. In the hot season, heterozygotes at both the 232 and 250 sites had significantly higher total sperm number of per ejaculate than AA homozygotes (P<0.05). Semen volume of boars with TT and TC genotypes at the 345 site was significantly larger than that of those with CC genotype (P<0.05). Meanwhile, semen quality for boars with TT genotype at the 345 site was significantly higher than that of boars with TC or CC genotype (P<0.05), that is the semen contained higher percentages of normal sperm and lower percentages of abnormal sperm or sperm with proximal plasma droplets. Results herein suggest that the SNPs in the 5'-flanking region of porcine HSP70.2 are associated with semen quality traits in the hot season.


Longitudinal association of sedentary time and physical activity with pain and quality of life in fibromyalgia.
To analyze changes over time and the predictive value of baseline and changes of sedentary time (ST) and physical activity (PA) on pain, disease impact, and health-related quality of life (HRQoL) at 2- and 5-year follow-up in women with fibromyalgia. This is a longitudinal and exploratory study with three time points. A total of 427 women with fibromyalgia (51.4 ± 7.6 years) were followed after 2 (n = 172) and 5 years (n = 185). ST and PA (light and moderate-to-vigorous [MVPA]) were assessed using triaxial accelerometers. Pain, disease impact, and HRQoL were measured using: pressure pain threshold, the pain subscale of the revised fibromyalgia impact questionnaire (FIQR), the bodily pain subscale of the 36-item short-form health survey (SF-36), a visual analog scale (VAS), the FIQR, and the SF-36 physical and mental components. Over 5 years, pressure pain threshold, ST, light PA, and MVPA variables were worsened, while FIQR and SF-36 variables were improved (Cohen's d < 0.1-0.3). Baseline ST or light PA were not associated with future outcomes, whereas greater MVPA at baseline was associated with better SF-36 bodily pain at 5-year follow-up (β = 0.13). Reducing ST and increasing light PA were associated with better bodily pain (β = -0.16 and 0.17, respectively) and SF-36 physical component (β = -0.20 and 0.17, respectively) at 5-year follow-up. Increasing MVPA was associated with less pain (pressure pain threshold, VAS, and FIQR-pain) and better SF-36 physical component at 2- and 5-year follow-up (β's from -0.20 to 0.21). Objectively measured variables slightly worsened over years, while for self-reported outcomes there was a trend for improvement. Reductions in ST and increases in light PA and MVPA were associated with better HRQoL at 5-year follow-up, and increases in MVPA were additionally associated with better pain and HRQoL at 2-year follow-up.


A non-LTR retrotransposon from the Hawaiian Drosophila: the LOA element.
An interspersed sequence has been isolated from the genome of D. silvestris, a species endemic to the Hawaiian Islands. The LOA element is 7.7 kb long and its 3' end consists of (TAA)n tandem repeats. Five different LOA elements were isolated, of which three were truncated at their 5' ends. Large deletions within the elements were frequent. A consensus sequence of the LOA element has been constructed using the nucleotide sequence of three elements. Two overlapping open reading frames (ORF) are present in the LOA element. In ORF1 two 'cys' motifs characteristic for gag proteins are found. The protein translated from ORF2 has similarities with retroviral pol genes. A protein databank search revealed 22% to 25% identity with the reverse transcriptase domains of retrotransposons. This region also shows the pattern of invariant amino acid residues which are most conserved in retroviral reverse transcriptases. In ORF2 an integrase specific 'cys' motif and a conserved sequence of retroviral proteases were identified. Structural similarities with LINE-like elements suggest that the LOA element represents a new non-LTR retrotransposon.


Annual nonmethane hydrocarbon trends in Beijing from 2000 to 2019.
High loads of ground-level ozone have occurred with the implementation of the Air Pollution Prevention and Control Action Plan. However, the long temporal variation in precursor nonmethane hydrocarbons (NMHCs) has rarely been studied. In this study, we examined the evolution of NMHCs in Beijing based on ambient measurements from 2000 to 2019. The results indicated that the annual variation of ambient NMHCs during 2000 and 2019 could be divided into two stages. The mixing ratios of NMHCs rapidly rose during 2000 and 2009 (1.76 ppbv/year) but exhibited a downward trend from 2009 to 2019 at rate of 0.80 ppbv/yr. Moreover, the notable decrease in alkenes and aromatics after 2009 led to a sharp decrease in the propylene-equivalent concentration (PEC) (-0.80 ppbv/year). Implementation of emission reduction measures in Beijing have effectively reduced the contribution of vehicle-related sources, but the contribution of solvent usage and fuel consumption increased, which will become the focus of VOC control in Beijing in the future.


Effects of interventions on trajectories of health-related quality of life among older patients with hip fracture: a prospective randomized controlled trial.
Health-related quality of life (HRQoL) has been used to assess subjects' prognosis and recovery following hip fracture. However, evidence is mixed regarding the effectiveness of interventions to improve HRQoL of elders with hip fracture. The purposes of this study were to identify distinct HRQoL trajectories and to evaluate the effects of two care models on these trajectories over 12 months following hip-fracture surgery. For this secondary analysis, data came from a randomized controlled trial of subjects with hip fracture receiving three treatment care models: interdisciplinary care (n = 97), comprehensive care (n = 91), and usual care (n = 93). Interdisciplinary care consisted of geriatric consultation, discharge planning, and 4 months of in-home rehabilitation. Comprehensive care consisted of interdisciplinary care plus management of malnutrition and depressive symptoms, fall prevention, and 12 months of in-home rehabilitation. Usual care included only in-hospital rehabilitation and occasional discharge planning, without geriatric consultation and in-home rehabilitation. Mental and physical HRQoL were measured at 1, 3, 6, and 12 months after discharge by the physical component summary scale (PCS) and mental component summary scale (MCS), respectively, of the Medical Outcomes Study Short Form 36, Taiwan version. Latent class growth modeling was used to identify PCS and MCS trajectories and to evaluate how they were affected by the interdisciplinary and comprehensive care models. We identified three quadratic PCS trajectories: poor PCS (n = 103, 36.6 %), moderate PCS (n = 96, 34.2 %), and good PCS (n = 82, 29.2 %). In contrast, we found three linear MCS trajectories: poor MCS (n = 39, 13.9 %), moderate MCS (n = 84, 29.9 %), and good MCS (n = 158, 56.2 %). Subjects in the comprehensive care and interdisciplinary care groups were more likely to experience a good PCS trajectory (b = 0.99, odds ratio [OR] = 2.69, confidence interval [CI] = 7.24-1.00, p = 0.049, and b = 1.32, OR = 3.75, CI = 10.53-1.33, p = 0.012, respectively) than those who received usual care. However, neither care model improved MCS. The interdisciplinary and comprehensive care models improved recovery from hip fracture by increasing subjects' odds for following a trajectory of good physical functioning after hospitalization. ClinicalTrials.gov ( NCT01350557 ).


Adventures in peptides and science with students! The joys of research.
Working with students at the undergraduate, graduate and postdoctoral levels has brought me great joy and satisfaction. Each student is a unique human being, so each provides an important opportunity for learning, creativity and accomplishment in research and scholarship. In this reflection, several examples of this scientific process are discussed in the context of solving scientific problems which led to novel and critical scientific insights.


Shifts in the seasonal distribution of deaths in Australia, 1968-2007.
Studies in temperate countries have shown that both hot weather in summer and cold weather in winter increase short-term (daily) mortality. The gradual warming, decade on decade, that Australia has experienced since the 1960s, might therefore be expected to have differentially affected mortality in the two seasons, and thus indicate an early impact of climate change on human health. Failure to detect such a signal would challenge the widespread assumption that the effect of weather on mortality implies a similar effect of a change from the present to projected future climate. We examine the ratio of summer to winter deaths against a background of rising average annual temperatures over four decades: the ratio has increased from 0.71 to 0.86 since 1968. The same trend, albeit of varying strength, is evident in all states of Australia, in four age groups (aged 55 years and above) and in both sexes. Analysis of cause-specific mortality suggests that the change has so far been driven more by reduced winter mortality than by increased summer mortality. Furthermore, comparisons of this seasonal mortality ratio calculated in the warmest subsets of seasons in each decade, with that calculated in the coldest seasons, show that particularly warm annual conditions, which mimic the expected temperatures of future climate change, increase the likelihood of higher ratios (approaching 1:1). Overall, our results indicate that gradual climate change, as well as short-term weather variations, affect patterns of mortality.


Relationship of serum bilirubin levels and hearing impairment in newborn infants.
A comparison has been made between 39 infants with a birthweight of 1500 g or less and a bilirubinlevel of 240 mumol/l or above, born between January 1980 and December 1983 and 19 infants with the same criteria, born between January 1984 and December 1985. Eight of the 22 high risk and two of the 17 low risk infants were diagnosed to have sensorineural deafness (SND) during the first period and this was strongly associated with the duration of the hyperbilirubinaemia. During the second period, more active intervention for hyperbilirubinaemia led to an increased number of exchange transfusions and a marked drop in the mean duration of hyperbilirubinaemia (less than 240 mumol/l). None of the very low birth weight (VLBW) infants born in the second period have developed SND. To investigate the independent effect of hyperbilirubinaemia on hearing, six low risk infants with bilirubin levels less than 320 mumol/l were studied by serial auditory brainstem responses (ABR). Impairment of the ABRs was found in four infants, with further deterioration with the persistence of high bilirubin levels in two. Although recovery of hearing thresholds was noted in all infants with impaired ABRs, an absence of wave I was noted in three infants at 6 months of age, which could indicate damage to the auditory nerve-cochlear complex. These findings suggest that hyperbilirubinaemia in itself can have an adverse effect on hearing and that careful management of hyperbilirubinaemia may reduce the incidence of sensorineural deafness.


Isolation, characterization and thin-layer chromatography method development of clerosterol palmityl ester: a chemical marker for standardization of leaves of Clerodendrum phlomidis.
Clerosterol palmityl ester (CPE) is a unique clerosterol derivative isolated and characterized from the leaves of Clerodendrum phlomidis. Considering the uniqueness of this compound, the present study was planned to use CPE as a specific chemical marker and develop a new validated thin-layer chromatography (TLC) method for standardisation of C. phlomidis. Separation and quantification of CPE were achieved by TLC using a mobile phase of petroleum ether (60 to 80 degrees centigrade) and ethyl acetate (95:5, volume ratio) (Rf 0.64) on precoated silica gel 60F(254) aluminium plates. Densitometric determination was carried out after derivatization with anisaldehyde sulphuric acid reagent in absorption mode at 527 nm. The calibration curve was linear in the concentration range of 100 to 500 ng/spot. The method was validated for precision, repeatability and accuracy. The proposed method was found to be simple, specific, precise, accurate, rapid and cost-effective. This TLC procedure may be used effectively for quantitative determination of CPE, identification of the plant and standardization of this plant or its derived products.


[Progression of coronary disease: minutes, weeks, decades...].
The slow progression over decades of coronary atheroma is often compensated for by arterial remodeling and collateral circulation. Coronary artery disease is therefore often asymptomatic. Sudden rupture of unstable atheromatous plaque always leads to endocoronary thrombus formation. The magnitude and the time frame of this endovascular thrombotic process determine the severity of its clinical consequences: no symptoms, exercise angina, unstable angina, acute transmural myocardial infarction, or sudden death. Two amply validated treatments have the potential to decrease both the probability and the severity of plaque rupture: statins and platelet inhibitors, which are both indicated in all cases of coronary disease. The other therapeutic tools - anti-ischemic drugs, ACE inhibitors, angioplasty, and coronary bypass - are widely used in the management of coronary disease, but their indications should be tailored to each individual clinical situation.


Social cognition, psychopathological symptoms, and family functioning in a sample of inpatient adolescents using variable-centered and person-centered approaches.
The process of diagnosis and treatment planning for adolescents requires clinicians to integrate information about various domains of functioning especially: clinical signs and symptoms, social cognition and family functioning. In the current study we applied an integrative analytic approach to mirror case conceptualization by clinicians. Our analyses were performed on the data gathered from the 328 inpatient adolescents. We used a broad range of measures of social-cognitive constructs, family functioning and parent-and self-reported psychopathology. Using a combination of variable-based (PCA) and person-centered (LCA) analyses we determined class membership of adolescents based on variation in social cognition, psychopathology, and family functioning. We identified five latent classes: two internalizing groups, two externalizing groups and a severe psychopathology group. Patterns of general hyperfunctioning (characterized by hypermentalizing and hypervigilance to emotional stimuli) and hypofunctioning (manifested in undermentalizing and under-reactivity to emotional stimuli), can be observed in these groups.


Intensive pulmonary care after liver surgery: a retrospective survey from a single center.
Prevention from postoperative pulmonary complications (PPCs) has been an important topic. The aims of this study were to determine the risk factors for PPC after liver surgery and to analyze the efficacy of postoperative pulmonary care on PPC prevention. We retrospectively analyzed variables of 81 patients who underwent hepatectomy and 4 transplantations between January 2007 and March 2012. Nineteen patients suffered PPCs (22.4%). Bivariate analysis identified four risk factors: preoperative anemia (odds ratio [OR] = 5.69), the American Society of Anesthesiologists (ASA) score of 3 or 4 (OR = 5.36), blood transfusion (OR = 2.81), and prolonged operative time (OR = 1.01). Upon multivariate analysis, only prolonged operative time was an independent risk factor for PPC (OR = 1.01). Pulmonary function test (PFT) was performed for 22 of 41 patients with an ASA score ≥ 2 (53.7%); there was no significant relationship between abnormal PFTs (n = 13) and the development of PPCs (P = .12). The elimination of risk factors may reduce the incidence of PPCs. Postoperative intensive pulmonary care should be given to all patients after liver surgery but particularly to patients with high ASA scores and those with abnormal PFTs irrespective of age.


Long-acting thyroid stimulator (LATS) and long acting thyroid stimulator protector (LATS-P) in untreated thyrotoxicosis.
The prevalence of serum LATS and LATS-P in untreated Graves' disease has been studied in eighty-three patients with thyroid overactivity; twelve (14%) were found to have significant levels of LATs and LATS-P whilst fifty-nine (72%) had significant levels of LATS-P alone. Twelve (14%) had neither activity. There was a very wide range in both activities. LATS was invariably found in association with a significantly greater concentration of LATS-P. There was no correlation between LATS-P and thyroid mass, as estimated from scintiscanning, thyroidal radioiodine uptake at 4 and 48 h, total serum T4 and total serum T3. Neither LATS nor LATS-P were detected in eleven patients with toxic multinodular goitre nor four with solitary toxic adenoma.


Comparison of percutaneous transforaminal endoscopic lumbar discectomy through unilateral versus bilateral approach for L3/4 or L4/5 lumbar disc herniation with bilateral symptoms: technical notes and a prospective randomized study.
In this study, the authors described the technical notes of percutaneous transforaminal endoscopic lumbar discectomy (PTELD) through unilateral approach and compared PTELD through unilateral versus bilateral approach for L3/4 or L4/5 lumbar disc herniation with bilateral symptoms. A prospective randomized clinical study was performed from June 2014 to October 2016. A total of 71 patients with lumbar disc herniation (L3/4 or L4/5) and bilateral symptoms were divided randomly into Unilateral-Approach group (n = 35) or Bilateral-Approach group (n = 36). Operation time, blood loss, intraoperative fluoroscopy and recurrences were recorded and analyzed statistically. Visual Analogue Scale scores, Oswestry Disability Index and the MacNab standard were used to analyze the clinical outcomes of the two groups. The baseline data of the two groups were statistically similar. There was significant postoperative improvement in VAS and ODI scores in both the groups, and clinical outcomes are comparable according to the MacNab standard. However, VAS score of back pain at 1 day after surgery in Unilateral-Approach group was significantly lower than that in Bilateral-Approach group (P < 0.05). Moreover, operation time and cumulative time of intraoperative fluoroscopy of Unilateral-Approach group were significantly shorter than that of Bilateral-Approach group (P < 0.05). For L3/4 or L4/5 LDH with bilateral symptoms, PTELD through unilateral approach is effective, with advantage of shorter operation time, shorter cumulative time of intraoperative fluoroscopy and milder postoperative short-term back pain compared to bilateral approach. These slides can be retrieved under Electronic Supplementary Material.


Treatment of sporadic acute puerperal mastitis.
The purposes of this study were to compare the efficacy of amoxicillin and cephradine for the treatment of sporadic acute puerperal mastitis (SAPM) and to evaluate the microbiology and clinical parameters of this infection. We conducted a prospective, randomized, single-blinded study comparing amoxicillin, 500 mg orally q 8 h for 7 days, and cephradine, 500 mg orally q 6 h for 7 days. The diagnostic criteria for SAPM included a temperature of > or =37.56 (> or =99.6) and erythema and tenderness of the breast(s). Twenty-seven consecutive outpatients with SAPM were evaluated for admission to the study, and 25 of these were enrolled. The mean temperature at enrollment was 38.17 (100.7), with a mean WBC count of 11,440/microl. The most frequent bacterial isolates from expressed milk were Staphylococcus aureus (7), staphylococcal species (coagulase negative) (8), and alpha-hemolytic streptococci (4). There were no significant differences between the 2 antibiotic regimens in cure rate, mean days to resolution of symptoms, or recurrence within 30 days. Both of the treatment failures and 1 of the 3 recurrences within 30 days were amoxicillin-treated patients whose cultures grew S. aureus. Oral amoxicillin and cephradine appear equally effective in the treatment of SAPM. Staphylococci were the most frequent isolates from the milk of women with mastitis.


A meta-analysis of antibiotic use for the secondary prevention of cardiovascular diseases.
A number of clinical trials have examined whether antibiotics decrease the incidence of adverse events in patients with cardiovascular diseases. However, results have occasionally been conflicting, and a meta-analysis may provide additional clarification. To address whether antibiotic use can reduce the risk of future cardiac events among patients with established cardiovascular diseases. PubMed and the Cochrane Central Register of Controlled Trials were searched using the key words "antibiotic" and "cardiovascular diseases". Only randomized, placebo-controlled trials of patients with established cardiovascular disease and reporting cardiovascular outcomes were included. A random effects model was used and a fixed model was applied for sensitivity analysis. A total of 393 papers published between January 1, 1994, and April 31, 2006, were initially identified. Thirteen trials (12,491 patients in the treatment group and 12,518 patients in the control group) were retained and included in the present meta-analysis. The pooled RR for the composite event end point, including death, myocardial infarction admission and unplanned revascularization procedures, was 0.96 (95% CI 0.90 to 1.04). No associations were seen for the individual outcomes of mortality (RR 1.07, 95% CI 0.96 to 1.19) or myocardial infarction/unstable angina (RR 0.96, 95% CI 0.85 to 1.07). Subgroup analyses based on patient populations (stable or unstable), type of antibiotics, or restricted to those with immunoglobulin G Chlamydia pneumoniae antibodies were also negative for a beneficial treatment effect. Similar results were found using a fixed effects model. The meta-analysis did not provide evidence of an association between antibiotic use and the secondary prevention of cardiac events. Further research in this area does not appear to be promising.


The role of the polymer matrix in solvent-free hot melt extrusion continuous process for mechanochemical synthesis of pharmaceutical cocrystal.
Solid-state synthesis of pharmaceutical cocrystals is of contemporary interest as it offers an efficient way to modify the physicochemical properties of Active Pharmaceutical Ingredient (API) including its melting point, solubility, compressibility or physical stability, without compromising its structural integrity and bioactivity. Therefore, research of novel and emerging techniques for solvent-free, continuous and scalable methods for cocrystal formation is of paramount importance for further industrial development. In this work we form a basis for knowledge-based synthesis and formulation of model pharmaceutical cocrystal (flufenamic acid, FFA: nicotinamide, NA; 1:1) via matrix-assisted cocrystallisation (MAC) using Hot Melt Extrusion (HME). Five different polymers frequently used in pharmaceutical drug delivery: Poloxamer P407 (PXM), PEG-PVA copolymer, Soluplus® (SOL), PVPVA64 and HPMCAS with different structural features and physicochemical properties were investigated as functional matrices for FFA:NA cocrystal synthesis via HME. Significant decrease of the torque value during MAC process was observed for all investigated polymers as compared to extrusion of neat FFA:NA cocrystal. The FFA:NA cocrystal encapsulated in the polymer matrix was successfully formed using semicrystalline PXM and PEG-PVA polymers at all investigated FFA:NA/polymer ratios. The use of amorphous polymers (SOL, PVPVA64, HPMCAS) as a cocrystallisation matrix resulted in formation of FFA:NA cocrystal embedded in an amorphous FFA:NA/polymer matrix (at polymer contents of 10 and 20 wt.%) or FFA:NA/polymer amorphous composites at SOL and PVPVA64 content of 30 wt.%. Furthermore, the significant increase of FFA dissolution was observed for FFA:NA cocrystal encapsulated in PXM and PEG-PVA matrices as compared to neat FFA form I. FFA form III and FFA:NA cocrystal. The presented work enables for the first time knowledge-based approach for simultaneous synthesis and formulation of pharmaceutical cocrystals via Hot Melt Extrusion a solvent-free, scalable and continuous process.


Combination of radiotherapy and immunotherapy for brain metastases: A systematic review and meta-analysis.
Radiotherapy (RT) represents a mainstay in the treatment of brain metastases (BMs) from solid tumors. Immunotherapy (IT) has improved survival of metastatic cancer patients across many tumor types. The combination of RT and IT for the treatment of BMs has a strong rationale, but data on efficacy and safety of this combination is still limited. A systematic search of PubMed, the Cochrane Central Register of Controlled Trials, and EMBASE was conducted. 33 studies were included for a total of 1520 patients, most of them with melanoma (87%). Median pooled OS was 15.9 months (95%CI 13.9-18.1). One- and 2-year OS rates were 55.2% (95% CI 49.3-60.9) and 35.7% (95% CI 30.4-41.3), respectively. Addition of IT to RT was associated with improved OS (HR = 0.54, 95%CI 0.44-0.67; P < 0.001). For patients with BMs from solid tumors, addition of concurrent IT to brain RT is able to increase survival and provide long term control.


Miniaturized INtrinsic DISsolution Screening (MINDISS) assay for preformulation.
This study describes a novel Miniaturized INtrinsic DISsolution Screening (MINDISS) assay for measuring disk intrinsic dissolution rates (DIDR). In MINDISS, compacted mini disks of drugs (2-5mg/disk) are prepared in custom made holders with a surface area of 3mm(2). Disks are immersed, pellet side down, into 0.35ml of appropriate dissolution media per well in 96-well microtiter plates, media are stirred and disk-holders are transferred to new wells after defined periods of time. After filtration, drug concentration in dissolution media is quantified by Ultra Performance Liquid Chromatography (UPLC) and solid state property of the disk is characterized by Raman spectroscopy. MINDISS was identified as an easy-to-use tool for rapid, parallel determination of DIDR of compounds that requires only small amounts of compound and of dissolution medium. Results obtained with marketed drugs in MINDISS correlate well with large scale DIDR methods and indicate that MINDISS can be used for (1) rank-ordering of compounds by intrinsic dissolution in late phase discovery and early development, (2) comparison of polymorphic forms and salts, (3) screening and selection of appropriate dissolution media, and (4) characterization of the intestinal release behavior of compounds along the gastro intestinal tract by changing biorelevant media during experiments.


Self-assembled nanostructured aqueous dispersions as dermal delivery systems.
Due to their high interfacial area and capability of loading hydrophobic, hydrophilic and amphiphilic drugs, self-assembled nanoparticles are the subject of much attention in view of an application of these dispersions as carrier systems for a variety of different active ingredients. Therefore, the effect of the internal nanostructure of oil-loaded monoglyceride-based nanoparticles on the dermal delivery of diclofenac sodium was investigated. The different self-assembled phases of the nanostructured aqueous dispersions were characterized by small angle X-ray scattering (SAXS). The influence of the different phases ranging from cubic-bicontinuous, over hexagonal and cubic-micellar phases to emulsified microemulsions on the dermal delivery of the incorporated active was examined by Franz-type diffusion cell and in vitro tape stripping experiments on porcine skin. These studies revealed a dependency of the skin permeation of diclofenac sodium on the formulation's internal structure, which could be modified by varying the amount of R-(+)-limonene in the oil phase. A superiority of the emulsified microemulsion, possessing the highest amount of R-(+)-limonene, over cubic or hexagonal phases was evidenced in terms of dermal drug delivery.


Expanding the indications for calcaneal plates beyond foot fractures: a technical trick and case series.
Although non-locking calcaneal plates are designed to treat calcaneal fractures, they present some interesting characteristics that justify using them beyond their current application in fractures of the foot. Calcaneal plates are malleable, have an increased footprint area for fracture containment or buttressing, and present several hole options for screw placement in different trajectories, thereby providing proper fixation even in comminuted fracture patterns. The aim of this study is to describe the unconventional use of calcaneal plates in the orthopaedic trauma scenario.


The Arf tumor suppressor regulates platelet-derived growth factor receptor beta signaling: a new view through the eyes of Arf(-/-) mice.
Arf is a key mammalian tumor suppressor gene known to be activated in response to aberrant mitogenic signals leading to both p53-dependent and -independent effects. We recently uncovered a new and somewhat unexpected function for mouse Arf as a regulator of mural cell accumulation within an ocular vascular bed destined to regress in the postnatal period. We found that the Arf gene product, p19(Arf), blocks mural cell proliferation driven by Platelet-derived growth factor receptor beta (Pdgfrbeta) in the developing vitreous. In vivo studies and analyses of cultured cells indicate that p19(Arf) dampens the expression of Pdgfrbeta. In cultured mouse embryo fibroblasts, p19(Arf) accomplishes this independently of two established effectors - Mdm2 and p53. Our findings indicating that p19(Arf) responds to specific developmental cues to disrupt Pdgfrbeta signaling in the developing eye extend existing paradigms for Arf tumor suppressor gene biology.


Cross-sectional and longitudinal assessments of function in prodromal-to-mild Alzheimer's disease: A comparison of the ADCS-ADL and A-IADL-Q scales.
Prior observational work in a heterogeneous cohort of participants with mild cognitive impairment suggests the Amsterdam Instrumental Activities of Daily Living Questionnaire (A-IADL-Q) may have greater sensitivity for functional decline than the more established Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) scale. However, the relative utility of the A-IADL-Q versus the ADCS-ADL for clinical trials in early Alzheimer's disease (AD) remains uncertain. We compared baseline and longitudinal performance of the A-IADL-Q and ADCS-ADL in participants with biomarker-confirmed prodromal (pAD; n = 158) or mild (mAD; n = 283) AD enrolled in the 18-month Tauriel study of semorinemab (NCT03289143). The A-IADL-Q exhibited numerically stronger discrimination between pAD and mAD participants at baseline per Cohen's d analyses and similar sensitivity to longitudinal decline across cohorts over 18 months relative to the ADCS-ADL. The comparable performance of the ADCS-ADL and A-IADL-Q supports the utility of the A-IADL-Q in early AD clinical trials. The Amsterdam Instrumental Activities of Daily Living Questionnaire (A-IADL-Q) may be more sensitive than the Alzheimer's Disease Cooperative Study-Activities of Daily Living Scale (ADCS-ADL) for distinguishing prodromal and mild Alzheimer's disease (AD).A-IADL-Q and ADCS-ADL are similarly sensitive to decline in early AD over 18 months.Comparable performance of these indices supports A-IADL-Q use in future AD trials.Additional AD clinical trial data could extend findings across more diverse cohorts.


Introduction to, and evaluation of, immunoassays in a malaria research institute in Tanzania.
Various immunoassays have been introduced into, and evaluated at, the Amani Medical Centre in north-east Tanzania. These include immunoblotting to identify mosquito bloodmeals, immunoradiometric and immunoenzymatic assays to assess the presence of circumsporozoite protein in mosquitoes, and enzyme-linked immunosorbent assays to measure antibodies to circumsporozoite antibody in people. The assays were shown to be reliable and practicable for use in the study of malaria epidemiology.


Evidence runs contrary to digestive stability predicting protein allergenicity.
A dogma has persisted for over two decades that food allergens are more stable to digestion compared with non-allergenic proteins. This belief has become enshrined in regulations designed to assess the allergenic risk of novel food proteins. While the empirical evidence accumulated over the last 20+ years has largely failed to confirm a correlation between digestive stability and the allergenic status of proteins, even those who accept this finding often assert that this shortfall is the result of faulty assay design rather than lack of causality. Here, we outline why digestive stability may not in fact correlate with allergenic potential.


On lupus, vitamin D and leukopenia.
Immune regulation is among the noncalcemic effects of vitamin D. So, this vitamin may play a role in autoimmune diseases such as systemic lupus erythematosus (SLE). To study the prevalence of vitamin D deficiency in SLE and its association with clinical, serological and treatment profile as well as with disease activity. Serum OH vitamin D3 levels were measured in 153 SLE patients and 85 controls. Data on clinical, serological and treatment profile of lupus patients were obtained through chart review. Blood cell count and SLEDAI (SLE disease activity index) were measured simultaneously with vitamin D determination. SLE patients have lower levels of vitamin D than controls (p=0.03). In univariate analysis serum vitamin D was associated with leukopenia (p=0.02), use of cyclophosphamide (p=0.007) and methotrexate (p=0.03). A negative correlation was verified with prednisone dose (p=0.003). No association was found with disease activity measured by SLEDAI (p=0.88). In a multiple regression study only leukopenia remained as an independent association (B=4.04; p=0.02). A negative correlation of serum vitamin level with granulocyte (p=0.01) was also found, but not with lymphocyte count (p=0.33). SLE patients have more deficiency of vitamin D than controls. This deficiency is not associated with disease activity but with leucopenia (granulocytopenia).


Robust ultrasensitive tunneling-FET biosensor for point-of-care diagnostics.
For point-of-care (POC) applications, robust, ultrasensitive, small, rapid, low-power, and low-cost sensors are highly desirable. Here, we present a novel biosensor based on a complementary metal oxide semiconductor (CMOS)-compatible silicon nanowire tunneling field-effect transistor (SiNW-TFET). They were fabricated "top-down" with a low-cost anisotropic self-stop etching technique. Notably, the SiNW-TFET device provided strong anti-interference capacity by applying the inherent ambipolarity via both pH and CYFRA21-1 sensing. This offered a more robust and portable general protocol. The specific label-free detection of CYFRA21-1 down to 0.5 fgml(-1) or ~12.5 aM was achieved using a highly responsive SiNW-TFET device with a minimum sub-threshold slope (SS) of 37 mVdec(-1). Furthermore, real-time measurements highlighted the ability to use clinically relevant samples such as serum. The developed high performance diagnostic system is expected to provide a generic platform for numerous POC applications.


Electric birefringence study of the solution structure of chymotrypsin-cleaved Acanthamoeba myosin II.
After removal of the 66 COOH-terminal amino acids from each of its two heavy chains by chymotrypsin digestion, Acanthamoeba myosin II forms only parallel dimers under conditions in which native myosin II forms bipolar filaments (Kuznicki, J., Cote, G. P., Bowers, B., and Korn, E. D. (1985) J. Biol. Chem. 260, 1967-1972). We have studied the solution structure of the chymotrypsin-cleaved myosin II by electric birefringence. Only two species, known to be monomer and parallel dimer from previous studies, were detected. The contribution to the birefringence decay from dimer increased from about 10 to 70% as the KCl concentration was lowered from 100 mM to 0 in 50% glycerol. At all ionic strengths, the monomer had a relaxation time corrected to water at 20 degrees C of 8.2 microseconds, whereas a relaxation time of 10.3 microseconds was expected for monomers with straight rigid rods. This strongly indicates that the myosin rod in solution is bent. On the assumption that there is a single bend 26 nm from the tip of the tail, as suggested by electron microscopy, it was calculated that the average bend angle would be 110 degrees, in solution, if as seems most likely, the average angle between the two globular heads were 180 degrees. The observed relaxation time of the dimer corrected to water at 20 degrees C was 25 microseconds, independent of ionic strength, which, if the motion of the heads were unrestricted, is consistent with a structure for a parallel dimer in which either the two monomer subunits have straight rigid rods and are staggered by about 28 nm or only one is bent and the stagger is 30 nm. As described in the accompanying Appendix, either of these dimers can be assembled into a bipolar filament compatible with the apparent structure of filaments of native myosin II (Pollard, T.D. (1982) J. Cell Biol. 95, 816-825).


Reliability and validity of the Advanced Basal Cell Carcinoma Index (aBCCdex).
Patient-reported outcome (PRO) questionnaires were recently developed specifically for use with patients with advanced basal cell carcinoma (aBCC) and basal cell carcinoma naevus syndrome (BCCNS). To evaluate the measurement properties of PRO questionnaires for use in patients with aBCC or BCCNS. In total 129 patients from 10 clinical sites in the U.S.A. and the BCCNS Support Network completed the two newly developed questionnaires multiple times over 3 months. Patients also completed the Skindex-16 and the 12-Item Short-Form Health Survey as collateral measures. Psychometric properties of the questionnaires were evaluated, including internal consistency and test-retest reliability, construct and known-groups validity, and responsiveness. Based on the results of exploratory factor analysis and clinical input, the two newly developed questionnaires were combined into a single questionnaire, called the aBCCdex, which is relevant for patients with both aBCC and BCCNS. The internal consistency reliability was acceptable, and all aBCCdex scale scores correlated significantly with conceptually similar scales. When divided into groups that differed based on scores from collateral measures, aBCCdex scale scores differentiated between groups (known-groups validity) and were responsive to change. The aBCCdex is a brief and comprehensive questionnaire appropriate for use with patients with aBCC and BCCNS. Its reliability and validity have been confirmed. Further research is necessary to estimate the minimally important difference in a larger patient population.


Assessing the probability of infection by Salmonella due to sewage sludge use in agriculture under several exposure scenarios for crops and soil ingestion.
A deeper understanding about the risks involved in sewage sludge practice in agriculture is required. The aims of the present study were to determine the annual risk of infection of consuming lettuce, carrots and tomatoes cultivated in soil amended with sewage sludge. The risk to agricultural workers of accidental ingestion of sludge or amended soil was also investigated. A Quantitative Microbial Risk Assessment was conducted based on Salmonella concentrations from five WWTPs were used to estimate the probability of annual infection associated with crops and soil ingestion. The risk of infection was estimated for nine exposure scenarios considering concentration of the pathogen, sewage sludge dilution in soil, variation of Salmonella concentration in soil, soil attachment to crops, seasonal average temperatures, hours of post-harvesting exposure, Salmonella regrowth in lettuce and tomatoes, Salmonella inhibition factor in carrots, crop ingestion and frequency of exposure, sludge/soil ingestion by agricultural workers and frequency of exposure. Annual risks values varied across the scenarios evaluated. Highest values of annual risk were found for scenarios in which the variation in the concentration of Salmonella spp. in both soil and crops (scenario 1) and without variation in the concentration of Salmonella spp. in soil and variation in crops (scenario 3) ranging from 10(-3) to 10(-2) for all groups considered. For agricultural workers, the highest annual risks of infection were found when workers applied sewage sludge to agricultural soils (2.26×10(-2)). Sensitivity analysis suggests that the main drivers for the estimated risks are Salmonella concentration and ingestion rate. These risk values resulted from conservative scenarios since some assumptions were derived from local or general studies. Although these scenarios can be considered conservative, the sensitivity analysis yielded the drivers of the risks, which can be useful for managing risks from the fresh products chain with stakeholders' involvement.


Construction and expression of a mouse-human chimeric antibody against human tumor necrosis factor-alpha.
A mouse anti-human tumor necrosis factor-alpha (TNF-alpha) monoclonal antibody (MoAb), designated as 3B10, has previously been produced and characterized by our laboratory. We report here the construction and the expression of mouse-human chimeric antibody derived from the MoAb. cDNAs encoding variable regions of heavy and light chains were prepared from 3B10 cells by polymerase chain reaction, and introduced to mammalian expression vectors containing cDNA for human gamma1 and kappa constant regions, respectively. Cotransfection of the vectors into CHO cells resulted in production of antibody reacting with human TNF-alpha. In SDS-PAGE analysis, the chimeric antibody, c3B10, migrated at 170 kDa under a nonreducing condition, whereas two bands with 58 and 28 kDa appeared following treatment with 2-mercaptoethanol. Both c3B10 and mouse 3B10 neutralized the cytotoxic activity of human TNF-alpha to the same level, indicating that c3B10 holds the binding activity of its original MoAb. These findings suggest that the introduced genes for chimeric heavy and light chains are transcribed and translated to produce the chimeric heavy and light chain peptides, and that the peptides are assembled to form native IgG molecule. The chimeric anti-TNF-alpha antibody described in this study is expected to be less immunogenic and thus more suitable for possible clinical use.


[Health policy guidelines for ambulatory and brief inpatient surgery. Backgrounds, facts and possible future solutions].
Ambulatory and short-stay surgery in Germany are regulated by two different political committees with different members. Currently, hospitals are permitted to practice ambulatory surgery on the basis of a mere notification sent to the health insurance companies. The details for access, reimbursement, and quality assurance are negotiated between the hospitals' association, the health insurance companies, and the association of the physicians. Compared to other fields of ambulatory care, the legislation for ambulatory surgery is rather loose concerning hospitals' access to this field of health care provision. Short-stay surgery is designated under inpatient care. With the introduction of so-called diagnosis-related groups (DRG) in 2003, a steep decline in length of stay is expected. Further efforts of the government and health insurance companies to extend ambulatory surgery to further indications are expected, too. However, the hurdle of transferring services from the inpatient sector to the ambulatory sector is a major challenge in Germany. We recommend lowering the legislative hurdle hindering hospitals and physicians from entering the area of ambulatory surgery for specific diagnoses. Same-day treatment should also be encouraged.


[Prospective study on surface-enhanced laser desorption/ionization protein fingerprinting for diagnosing gene polymorphism leading to drug resistance drift: sequential therapy with a platinum-based regimen and gefitinib for non-small cell lung cancer].
This study aims to observe the long-term effects of sequential therapy with a platinum-based regimen and gefitinib for non-small cell lung carcinoma (NSCLC) with failed chemotherapy under the guidance of surface-enhanced laser desorption/ionization (SELDI). Nine NSCLC patients with failed chemotherapy and ≤15% abundance of M/Z: 8,693±50H+ were selected. The patients were administered with 250 mg of gefitinib (p.o., once a day). During the therapy, SELDI was applied every 2 months. If the M/Z: 8,693±50H+ abundance was >25%, chemotherapy was applied; if the abundance was ≤15%, gefitinib (p.o.) was applied. In between, we chose gefitinib according to the mass and tumor markers. On the base, we sequentially applied the drug and observed the total survival time. Follow-ups until December 2010 revealed that the median overall survival time of the nine patients was 27 months (10 months-66 months). The treatment benefit ratio and benefit time of anti-NSCLC drugs can be improved by SELDI fingerprinting.


Radio frequency ablation of renal tumors in patients with metastatic renal cell carcinoma.
We retrospectively evaluated the feasibility, safety and outcomes of radio frequency ablation of primary renal tumors to control local disease while preserving renal parenchyma in a series of patients with metastatic renal cell carcinoma in a single institutional, multidisciplinary setting. We evaluated the records of patients with metastatic renal cell carcinoma who underwent percutaneous radio frequency ablation of a primary renal tumor. Patient demographic and disease characteristics, adjunctive medical and surgical therapies, recurrence and clinical outcomes were studied. A total of 15 patients treated between 2002 and 2008 met study inclusion criteria. There was no incomplete ablation or local recurrence. Ten patients had biopsy proven renal cell carcinoma in the ablated renal mass. Eight patients had a solitary metastasis, 3 had metastasis at 2 sites and 4 had 3 or more metastatic sites. Four patients experienced major complications. Median radiographic and clinical followup in patients at risk for an event was 25.5 and 33.0 months, respectively. The overall survival rate 1, 3 and 5 years after radio frequency ablation was 73.3%, 57.1% and 38.1%, respectively. At last evaluation 4 patients were in complete remission, 4 had no evidence of local recurrence but had evidence of distant disease and 7 had died of the disease. Radio frequency ablation is feasible and safe in highly selected patients with metastatic renal cell carcinoma, resulting in durable local control as part of multimodality management and achieving renal preservation. Further investigation is required to define the role of radio frequency ablation in this patient population.


Depressive symptoms-an intercentre comparison.
45 Psychotic Depressives from PGI, Chandigarh have been compared with 90 Psychotic Depressives from Madurai Centre on 40 symptoms using SADD schedule. Differences in the symptomatology have been highlightened.


A practical strategy for diagnosis of urinary tract infections.
Because urine specimens are not all identical, clinical microbiology laboratories should tailor specimen handling and processing to the specific clinical setting. To quantify uropathogens requires specific ranges that depend on the clinical presentation of a patient and the collection method. A single quantitative breakpoint, for example, the classic "100,000 CFU/mL" cannot be applied to patients with AUS or with indwelling catheters. This article has attempted to review rational adjustments in the traditional urine culture protocol to fit both the clinical setting and the mode of collection.


Arteriolar proliferation in the rat cremaster muscle as a long-term autoregulatory response to reduced perfusion.
Long-term autoregulation of arterial blood flow to sustained increases or decreases in arterial pressure has been previously reported. It is not clear whether the adaptive process at the microscopic level is a modification of vessel caliber or density. The present study was undertaken to assess morphological and hemodynamic changes resulting from a sustained decrease in perfusion to the cremaster muscle in normal rats. The main feeding arteriole to the cremaster muscle was ligated at age 3 weeks in 11 male Wistar rats. At 6 weeks, the cremaster muscles on the ligated and control sides were evaluated microscopically for hemodynamic status and vascular architecture differences. Pressure was reduced 30% on the ligated side without a decrease in volume flow. This was possible because the number of second-order arterioles increased by 48% and the number of third-order arterioles increased by 98% on the ligated side. Although twice as many third-order arterioles were present in the ligated muscle, the same percentage was closed to flow in the resting state as in the control muscle (31 vs 29%). These findings are consistent with a long-term autoregulatory process which modulates arteriolar density in response to altered perfusion or distending pressure. The same process may be responsible for arteriolar rarefaction in response to sustained elevation in arterial pressure in the cremaster muscle of the spontaneously hypertensive rat (SHR).


[Construction and identification of plasmid vector encoding two survivin shRNA].
To construct and identify the eukaryotic expression plasmids encoding two short hairpin RNA (shRNA) of survivin for the purpose of paving the way for the studies of targeted gene therapy for prostatic carcinoma (PCa). Two shRNA of survivin were designed and synthesized respectively, and then both were cloned into plasmids. Finally, the recombinant plasmids were confirmed by sequencing and agarose gel electrophoresis after restriction digestion. The recombinant plasmids encoding two survivin shRNA were constructed and the aim sequence obtained. Successful construction of the recombinant provides a sound basis for the research of targeted gene therapy for PCa.


Intracameral administration of neurotensin induces miosis in the rabbit.
The present investigation was designed to evaluate the effect of selected peptides on pupillary diameter and intraocular pressure (IOP) in rabbits. Intracameral (IC) administration of neurotensin (NT) in doses of 5-100 micrograms produced a significant, long lasting and dose-dependent decrease in pupillary diameter without affecting IOP. NT-induced miosis appears to be relatively specific because a variety of peptides including Gn-RH, somatostatin, met-enkephalin, bombesin, leu-enkephalin or NT1-6, (a biologically inactive N-terminal fragment of NT), produced no effect on pupillary diameter; only substance P produced miosis similar to NT when tested in a dose equimolar to 30 micrograms of NT. In addition, peripheral (intravenous) administration of NT (100 micrograms/kg) was equally ineffective. Inhibition of prostaglandin synthesis with indomethacin, did not prevent subsequent NT-induced miosis. Finally, IC administration of an effective dose of NT (30 micrograms) did not alter the protein concentration in the aqueous humor. These results indicate that NT-induced miosis is not mediated by endogenous prostaglandins and that this effect of NT does not appear to involve disruption of the blood-aqueous barrier, suggesting that NT may play a role in regulation of pupillary diameter.


Detection and quantification of CSF malignant cells by the CellSearch technology in patients with melanoma leptomeningeal metastasis.
Melanoma is the most frequent solid tumor associated with leptomeningeal metastasis (LM). The usual diagnostic tools, that is, cytomorphological assessment of cerebro-spinal fluid (CSF) and gadolinium-enhanced MRI of the entire neuraxis both lack effectiveness. The CellSearch Veridex technology for the detection of circulating tumor cells (CTC) in blood was designed for the follow-up and prognosis of breast, prostate, colorectal, and lung cancer, which express EpCAM markers. We have previously adapted this technology to detect malignant cells in the CSF of breast cancer LM. Our objective here was to check if this technology would also allow the detection and the enumeration of CTC in the CSF of melanoma patients presenting with LM although melanoma does not express EpCAM markers. On the occasion of the intrathecal treatment of LM in 2 melanoma patients, 5 mL of CSF and 7.5 mL of blood were collected on CellSave Preservative Tubes and analyzed within 3 days after CSF sampling using a melanoma-dedicated kit. The CellSearch Veridex technology was then adapted to direct enrichment, enumeration, and visualization of melanoma cells in the CSF. CD146+, HMW-MAA+, CD34-, and CD45- cells with typical morphology could be observed and enumerated sequentially with reproducible results, corresponding to CSF melanoma cells (CSFMC). In contrast to the current gold standard cytomorphological analysis, this new approach allowed a precise quantification of CSFMC in all samples concomitantly analyzed. This methodology, established on a limited volume of sample and allowing delayed processing, could prove of great interest in the diagnosis and follow-up of melanoma patients with LM.


Two-photon laser-scanning microscopy: tests of objective lenses and Ca2+ probes.
The characteristics of objective lenses and Ca2+-sensitive probes were examined for imaging with a two-photon laser-scanning microscope (TP-LSM). The brightness of the images of beads taken by different objectives greatly varied and depended predominantly on their numerical aperture (NA) and less on transmittance and chirping effects. Lateral and axial resolutions, dx and dz, defined as the half decay length of fluorescence intensity of the image of a spherical bead (0.3 m) were 0.12 and 0.42 microm (objective; 40x/0.75). They are far better than those of confocal microscopes (0.3 and 1.5 microm, respectively) measured similarly (Kuba et al., 1994). dx linearly increased with an increase in 1/NA, while dz linearly increased with an increase in n/(NA)2 (n, refractive index) except for an objective of large NA (1.3). The coverslip compensation of objective lenses greatly affected the shape of the X-Z scanned images of 5.0 microm beads as well as resolutions, indicating a large effect of spherical aberration. Two-photon excitation spectra of Ca2+-sensitive fluorescent probes, indo-1, fura-2 and Oregon Green BAPTA-1, lied in a wavelength range shorter than twice that activated by one-photon absorption, while emission spectra were unchanged. Three-dimensional images of a cultured hippocampal neurone loaded with Oregon Green BAPTA-1 showed fine structures of spines, dendrites and axons, while imaging with FM1-43 localized presynaptic boutons and demonstrated synaptic vesicle turnover. Dyes bleached little during the recording of 100 sectioned images. These characteristics of TP-LSM as well as its ability to image deeper tissues provide excellent means to study dynamic, spatial changes in intracellular substances and structures. To achieve the good performance of a TP-LSM, however, the relevant usage of appropriate objectives and fluorescent probes are required.


zVLL-CHO at low concentrations acts as a calpain inhibitor to protect neurons against okadaic acid-induced neurodegeneration.
There is evidence that β-secretase and amyloid precursor protein β-C-terminal fragments (APP-CTF) are involved in the pathogenesis of Alzheimer's disease (AD). Previously, we have reported that N-benzyloxycarbonyl-Val-Leu-leucinal (zVLL-CHO) reduced APP β-CTF accumulation in axonal swellings of degenerating neurons. Here, in an effort to discover more effective neuroprotective agents, we examined the effects of the β-secretase inhibitors, H-KTEEISEVN-stat-VAEF-OH (VAEF) and H-EVNstatineVAEF-NH2 (GL-189) as well as zVLL-CHO on OA (okadaic acid)-induced neurodegeneration. Unexpectedly, we found that pretreatment with zVLL-CHO (1 μM) protected neurons after OA treatment, whereas both VAEF and GL-189 lacked neuroprotective effects. Interestingly, 1 μM zVLL-CHO did not inhibit β-secretase. We previously reported that calpain is activated by OA treatment and calpain inhibitors protect against OA-induced neurodegeneration. The data presented here show that pretreatment with 1 μM zVLL-CHO decreased the levels of calpain-cleaved α-spectrin with a concomitant decrease in LDH release and an increase in average dendritic branch length compared to neurons treated with OA alone. These findings suggest that zVLL-CHO protects against OA-induced neurodegeneration via calpain inactivation.


HIV-1 ancestry primordial expansions of RRE and RRE related sequences.
The human T-lymphotropic retroviruses HTLV-I and HIV-1/-2 share a complementary patchwork homology in which the RRE regions of HIV-1 and -2 cover 78.1% of a 169 nucleotide (nt) region (PX1,2) positioned precisely between open reading frames PX I and PX II of ATLV (HTLV-I). The sequence character of the PX1,2 region is shown to be influenced by a primordial expansion, CTC2T, originating several hundred nucleotides upstream. A second primordial expansion, AGCU(U/C), is identified and shown to represent 52.1% of the HIV-1 RRE region. It is argued that prior to the present AIDS pandemic the efficiency of the rev receptor was enhanced by an ancestral recombination event.


[Observational survey on variations of prostate cancer incidence by stage in the Nord-Pas-de-Calais region between 1998 and 2004].
The aim of this work is to study variations of prostate cancer incidence by stage as a function of time and place in a region of France. Retrospective observational survey conducted in five private and public urology centres representative of the various demographic features of the Nord-Pas-de-Calais region. In each centre, the medical records of the first 25 cases of prostate cancer diagnosed in 1998, 2002 and 2004, identified from histology laboratory data, were studied by means of a case report form evaluating the circumstances of diagnosis, PSA level, grade, stage (TNM 97, classification) and initial management. This analysis was based on 123, 124 and 125 patients in five centres in 1998, 2002 and 2004, respectively. The age at diagnosis ranged from 71.14 to 68.9 years between 1998 and 2004 (p=0.054). Median PSA decreased over this six-year period from 18 to 10.8 ng/ml. Between 1998 and 2004, the percentage of patients with localized cancer (PSA<20 ng/ml) increased from 44.8 to 66.4% (p<0.05), the percentage of patients with locally advanced cancer (PSA between 20 and 50 ng/ml) decreased from 17 to 9.6% (p<0.05), the percentage of patients with regional or distant metastatic disease (N1 and/or M1 and/or PSA>50 ng/ml) decreased from 29.4 to 22.4% (p<0.05) and the percentage of patients receiving curative treatment increased from 30 to 54.4% (p<0.005). The prostate cancer incidence by stage varied between 1998 and 2004, with a significantly higher proportion of localized stages, which can be explained by the increased use of screening and diagnostic tests. Routine surveys can measure trends and the amplitude of incidence variations in the population of a region. A representative survey conducted in centres throughout France would allow evaluation of national trends between two publications of incidence by stage results in French registries.