Determination of divalent carboxylic acids in traditional Chinese herbal and patent medicines using HPLC with double cell quartz crystal detector.
A rapid, simple and sensitive high performance liquid chromatography (HPLC) method combined with a novel double cell quartz crystal (DCQC) detector is described for the determination of divalent carboxylic acids in traditional Chinese herbal and patent medicines. The chromatographic system involves the use of a muBondapak-NH2 column with 20 mM KH2PO4 (pH 3.4, adjusted by H3PO4)/acetonitrile (95:5%) as a mobile phase. The DCQC detector has a low temperature coefficient and high conductance sensitivity independent of the background from 7.2 to 2500 microS. Analysis of sample is completed without the use of an ion suppression device.


Ultrastructure of photoreceptors in the eye of Hermissenda labelled with intracellular injections of horseradish peroxidase.
The terminal processes of single and of pairs of identified photoreceptors in the eyes of the nudibranch mollusc Hermissenda crassicornis were studied by light and transmission electron microscopy after their somata were labelled by intracellular iontophoresis of horseradish peroxidase (HRP). The HRP spread from the somata into the axons and fine terminal processes within the neuropil of the cerebropleural ganglia. The photoreceptors ended in extensive secondary branches in the neuropil where previous electrophysiological studies had indicated the probable site of synaptic interactions between photoreceptors. Clear round vesicles (54-126 nm diameter) within labelled processes were similar to the vesicles found in the somata and axon hillocks. The terminal processes of pairs of type B photoreceptors contained different intensities of the HRP label. Uniform intensities of the HRP label were found in the terminal processes of single type B photoreceptors. These differences in intensity suggested that the terminal processes were from different type B photoreceptors. This finding suggests that the connections between type B photoreceptors are probably monosynaptic.


Distribution of perfluoroalkyl acids in fish species from the Baltic Sea and freshwaters in Finland.
Occurrence and distribution of perfluoroalkyl acids (PFAAs), a sub-category of per- and polyfluoroalkyl substances (PFASs), is widespread in the environment. Food, especially fish meat, is a major pathway via which humans are exposed to PFAAs. As fish is an integral part of Nordic diet, therefore, in this study, several fish species, caught in selected Baltic Sea basins and freshwater bodies of Finland, were analysed for PFAAs. Perfluorooctane sulfonate (PFOS) was detected in all Baltic Sea fish samples and in >80% fish samples from freshwaters. PFOS contributed between 46 and 100% to the total PFAA concentration in Baltic Sea fish samples and between 19 and 28% in fish samples from freshwaters. Geographically, concentration ratios of PFOS to other PFAAs differed between fish from the Baltic Sea and Finnish lakes suggesting that distribution of PFAAs differ in these environments. Results were compared with current safety thresholds - environmental quality standard for biota (EQSbiota) set by the European Commission and a group tolerable weekly intake (TWI) for the sum of four PFASs (∑PFAS-4) i.e. perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorohexane sulfonate (PFHxS) and PFOS, recommended by the European Food Authority (EFSA). EQSbiota compliance was observed for PFOS in all species except smelt caught in the Baltic Sea and also in the River Aurajoki, where smelt had migrated from the Baltic Sea for spawning. Moderate consumption of most Baltic fishes (200 g week-1) results in an exceedance of the new TWI (4.4 ng kg-1 body weight week-1) for ∑PFAS-4.


Systematic unenhanced CT for acute abdominal symptoms in the elderly patients improves both emergency department diagnosis and prompt clinical management.
To assess the added-value of systematic unenhanced abdominal computed tomography (CT) on emergency department (ED) diagnosis and management accuracy compared to current practice, in elderly patients with non-traumatic acute abdominal symptoms. Institutional review board approval and informed consent were obtained. This prospective study included 401 consecutive patients 75 years of age or older, admitted to the ED with acute abdominal symptoms, and investigated by early systematic unenhanced abdominal CT scan. ED diagnosis and intended management before CT, after unenhanced CT, and after contrast CT if requested, were recorded. Diagnosis and management accuracies were evaluated and compared before CT (clinical strategy) and for two conditional strategies (current practice and systematic unenhanced CT). An expert clinical panel assigned a final diagnosis and management after a 3-month follow-up. Systematic unenhanced CT significantly improved the accurate diagnosis (76.8% to 85%, p=1.1x10-6) and management (88.5% to 95.8%, p=2.6x10-6) rates compared to current practice. It allowed diagnosing 30.3% of acute unsuspected pathologies, 3.4% of which were unexpected surgical procedure requirement. Systematic unenhanced abdominal CT improves ED diagnosis accuracy and appropriate management in elderly patients presenting with acute abdominal symptoms compared to current practice. • Systematic unenhanced CT improves significantly diagnosis accuracy compared to current practice. • Systematic unenhanced CT optimizes appropriate hospitalization by increasing the number of discharged patients. • Systematic unenhanced CT allows detection of about one-third of acute unsuspected abdominal conditions. • It should allow boosting emergency department management decision-making confidence in old patients.


Skip Laminectomy Compared with Laminoplasty for Cervical Compressive Myelopathy: A Systematic Review and Meta-Analysis.
This meta-analysis evaluated the clinical outcomes of skip laminectomy relative to laminoplasty for the treatment of cervical compressive myelopathy. The Cochrane library, PubMed MEDLINE, EMBASE, and Web of Science databases were comprehensively searched to identify relevant articles published up to March 18, 2018. All values of weighted mean difference (WMD) or odds ratio are expressed as skip laminectomy relative to laminoplasty. Four studies comprising 241 patients were included. Skip laminectomy and laminoplasty were comparable in terms of cervical lordotic curvature (weighted mean difference [WMD] -2.37°; 95% confidence interval [CI] -6.18 to 1.43; P = 0.22) and range of motion (WMD -2.65°; 95% CI -6.02 to 0.72; P = 0.12). The pooled data revealed that the mean visual analogue scale score for pain of the skip laminectomy group was significantly lower than that of the laminoplasty group (WMD -0.97; 95% CI -1.90 to -0.05; P = 0.04), and the rate of axial pain was also significantly lower (WMD 0.26; 95% CI 0.07-0.93; P = 0.04). The atrophy rates of the deep extensor muscles in the skip laminectomy group (14%) were significantly lower than that of the laminoplasty group (60%). This meta-analysis determined that skip laminectomy was superior to laminoplasty in terms of visual analogue scale score and rates of axial pain and muscle atrophy. These results warrant further confirmation in future research.


Lead recovery from waste CRT funnel glass by high-temperature melting process.
In this research, a novel and effective process for waste CRT funnel glass treatment was developed. The key to this process is removal of lead from the CRT funnel glass by high-temperature melting process. Sodium carbonate powder was used as a fusion agent, sodium sulfide serves as a catalytic agent and carbon powder acts as reducing agent. Experimental results showed that lead recovery rate increased with an increase in the amount of added sodium carbonate, sodium sulfide, carbonate, temperature and holding time initially, and then reached a stable value. The maximum lead recovery rate was approximately 94%, when the optimum adding amount of sodium carbonate, sodium sulfide, carbonate, temperature and holding time were 25%, 8%, 3.6%, 1200°C and 120min, respectively. In the high-temperature melting process, lead silicate in the funnel glass was firstly reduced, and then removed. The glass slag can be made into sodium and potassium silicate by hydrolysis process. This study proposed a practical and economical process for recovery of lead and utilization of waste glass slag.


A protocol and guide for the in vitro rat hepatocyte DNA-repair assay.
The in vitro rat-hepatocyte DNA-repair assay is a valuable tool in assessing the genotoxic activity of chemical agents. An advantage of the assay is that the target cells themselves are metabolically competent, so that the patterns of metabolic activation and detoxification closely reflect those in the whole animal. This article provides a typical procedure and guidelines for conducting the rat in vitro hepatocyte DNA-repair assay.


Thermal ecosystem engineering by songbirds promotes a symbiotic relationship with ants.
Nesting birds can act as thermal ecosystem engineers by providing warm habitats that may attract arthropods to colonise the nest structure. This cohabitation of birds and nest-dwelling invertebrates may foster symbiotic relationships between them, but evidence is lacking. We investigated whether ants are attracted to bird nests by the heat generated by the hosts, and/or the nests' structural insulation properties, to raise their broods (larvae and/or pupae) in advantageous thermal conditions. We found that the endothermic activity of birds within their nests created 'heat islands', with thermal conditions potentially promoting the survival and development of ant larvae in cool environments. We experimentally confirmed that the presence of heat within bird nests, and not the structure itself, attracted the ants to colonise the nests. As ants might benefit from exploiting warm bird nests, this may be a previously overlooked commensal, mutualistic or parasitic relationship which may be ecologically significant and globally widespread among various nesting birds and reproducing ants. Similar interspecific interactions may exist with other arthropods that reproduce in avian and mammalian nests. Further research is needed to reveal the nature of these relationships between such taxa, and to understand the role of warm-blooded animals as thermal ecosystem engineers.


The immunomodulatory effects of probiotics and azithromycin in dextran sodium sulfate-induced ulcerative colitis in rats via TLR4-NF-κB and p38-MAPK pathway.
Ulcerative colitis (UC), a chronic autoimmune disease of the gut with a relapsing and remitting nature, considers a major health-care problem. DSS is a well-studied pharmacologically-induced model for UC. Toll-Like Receptor 4 (TLR4) and its close association with p-38-Mitogen-Activated Protein Kinase (p-38 MAPK) and nuclear factor kappa B (NF-κB) has important regulatory roles in inflammation and developing UC. Probiotics are gaining popularity for their potential in UC therapy. The immunomodulatory and anti-inflammatory role of azithromycin in UC remains a knowledge need. In the present rats-established UC, the therapeutic roles of oral probiotics (60 billion probiotic bacteria per kg per day) and azithromycin (40 mg per kg per day) regimens were evaluated by measuring changes in disease activity index, macroscopic damage index, oxidative stress markers, TLR4, p-38 MAPK, NF-κB signaling pathway in addition to their molecular downstream; tumor necrosis factor alpha (TNFα), interleukin (IL)1β, IL6, IL10 and inducible nitric oxide synthase (iNOS). After individual and combination therapy with probiotics and azithromycin regimens, the histological architecture of the UC improved with restoration of intestinal tissue normal architecture. These findings were consistent with the histopathological score of colon tissues. Each separate regimen lowered the remarkable TLR4, p-38 MAPK, iNOS, NF-κB as well as TNFα, IL1β, IL6 and MDA expressions and elevated the low IL10, glutathione and superoxide dismutase expressions in UC tissues. The combination regimen possesses the most synergistic beneficial effects in UC that, following thorough research, should be incorporated into the therapeutic approach in UC to boost the patients' quality of life.


Reduction of uranium(VI) phosphate during growth of the thermophilic bacterium Thermoterrabacterium ferrireducens.
The thermophilic, gram-positive bacterium Thermoterrabacterium ferrireducens coupled organotrophic growth to the reduction of sparingly soluble U(VI) phosphate. X-ray powder diffraction and X-ray absorption spectroscopy analysis identified the electron acceptor in a defined medium as U(VI) phosphate [uramphite; (NH4)(UO2)(PO4) . 3H2O], while the U(IV)-containing precipitate formed during bacterial growth was identified as ningyoite [CaU(PO4)2 . H2O]. This is the first report of microbial reduction of a largely insoluble U(VI) compound.


The knockout of cytoglobin 1 in zebrafish (Danio rerio) alters lipid metabolism, iron homeostasis and oxidative stress response.
Cytoglobin (Cygb) is an evolutionary ancient heme protein with yet unclear physiological function(s). Mammalian Cygb is ubiquitously expressed in all tissues and is proposed to be involved in reactive oxygen species (ROS) detoxification, nitric oxide (NO) metabolism and lipid-based signaling processes. Loss-of-function studies in mouse associate Cygb with apoptosis, inflammation, fibrosis, cardiovascular dysfunction or oncogenesis. In zebrafish (Danio rerio), two cygb genes exist, cytoglobin 1 (cygb1) and cytoglobin 2 (cygb2). Both have different coordination states and distinct expression sites within zebrafish tissues. The biological roles of the cygb paralogs are largely uncharacterized. We used a CRISPR/Cas9 genome editing approach and generated a knockout of the penta-coordinated cygb1 for in vivo analysis. Adult male cygb1 knockouts develop phenotypic abnormalities, including weight loss. To identify the molecular mechanisms underlying the occurrence of these phenotypes and differentiate between function and effect of the knockout we compared the transcriptomes of cygb1 knockout at different ages to age-matched wild-type zebrafish. We found that immune regulatory and cell cycle regulatory transcripts (e.g. tp53) were up-regulated in the cygb1 knockout liver. Additionally, the expression of transcripts involved in lipid metabolism and transport, the antioxidative defense and iron homeostasis was affected in the cygb1 knockout. Cygb1 may function as an anti-inflammatory and cytoprotective factor in zebrafish liver, and may be involved in lipid-, iron-, and ROS-dependent signaling.


Neuroprotective interaction effects of NMDA and AMPA receptor antagonists in an in vitro model of cerebral ischemia.
An in vitro model of ischemia was developed and characterized using the acute rat hippocampal slice preparation. Neuroprotective concentrations of several competitive and noncompetitive glutamate subtype-selective antagonists (CGS-19755, MK-801, YM90K and GYKI-52466) were initially determined in anoxia-enhanced agonist-induced excitotoxicity experiments. Concentrations which proved to be effective in these studies were subsequently tested for their effectiveness against an ischemic episode. Ischemia was defined as a 30-min exposure to aglycemic media ending in 5 min of concurrent anoxia, a protocol which was arrived at by empirically determining the effect of various hypoglycemic and anoxic insults on the ability of hippocampal slices to retain their electrophysiological viability. Exposure to such an ischemic episode resulted in a loss of viability by most slices, an effect which was strongly dependent on extracellular calcium. AMPA antagonists applied alone produced no neuroprotective effect in the present model of in vitro ischemia, while NMDA antagonists applied alone had a modest neuroprotective effect. In contrast, the coapplication of 10 microM MK-801 and 300 microM GYKI-52466, noncompetitive NMDA and AMPA receptor antagonists, respectively, resulted in almost complete neuroprotection. This protection was comparable to that obtained by withholding extracellular calcium, indicating that the toxic effects of glutamate receptor overstimulation can be accounted for solely by calcium influx. The effect of this combination treatment on the survival rate of hippocampal slices was synergistic, that is greater than the sum of the effects of the individual compounds. The results indicate that neuroprotection against acute ischemic insults may require a combination therapy approach.


Directional spread of activity in synaptic networks of the human lateral amygdala.
Spontaneous epileptiform activity has previously been observed in lateral amygdala (LA) slices derived from patients with intractable-temporal lobe epilepsy. The present study aimed to characterize intranuclear LA synaptic connectivity and to test the hypothesis that differences in the spread of flow of neuronal activity may relate to spontaneous epileptiform activity occurrence. Electrical activity was evoked through electrical microstimulation in acute human brain slices containing the LA, signals were recorded as local field potentials combined with fast optical imaging of voltage-sensitive dye fluorescence. Sites of stimulation and recording were systematically varied. Following recordings, slices were anatomically reconstructed using two-dimensional unitary slices as a reference for coronal and parasagittal planes. Local spatial patterns and spread of activity were assessed by incorporating the coordinates of electrical and optical recording sites into the respective unitary slice. A preferential directional spread of evoked electrical signals was observed from ventral to dorsal, rostral to caudal and medial to lateral regions in the LA. No differences in spread of evoked activity were observed between spontaneously and non-spontaneously active LA slices, i.e. basic properties of evoked synaptic responses were similar in the two functional types of LA slices, including input-output relationship, and paired-pulse depression. These results indicate a directed propagation of synaptic signals within the human LA in spontaneously active epileptic slices. We suggest that the lack of differences in local and in systemic information processing has to be found in confined epileptiform circuits within the amygdala likely involving well-known "epileptic neurons".


Human chromosome 16 conservation in primates.
A study was made of the organization of the chromosome orthologous to HSA16 in primates using a panel of 8 BAC probes spanning human chromosome 16. The probes were used in FISH experiments on great apes and on representatives of the Old World monkeys, New World monkeys, and lemurs. The domestic cat was used as an outgroup. The results indicate that 16p and 16q were separate chromosomes in a primate ancestor. They fused in a Catarrhini ancestor giving rise to the present day form found in HSA, great apes, and Old World monkeys. Several rearrangements were found in New World monkeys.


Hilar and mediastinal adenopathy caused by bacterial abscess of the lung.
Enlargement of hilar and mediastinal lymph nodes commonly accompanies a lung abcess. Of 27 patients with lung abscesses, 14 had hilar or mediastinal adenopathy or both. The problem resolved promptly with clearing of the abcesses and was absent on clinical and radiographic follow-up.


Mutations and expressions of breast cancer 1/2 in lung cancer.
Breast cancer 1 (BRCA1) and breast cancer 2 (BRCA2) tumor suppressor genes play crucial roles in DNA repair and regulation of transcription. Mutations in these genes are closely associated with the occurrence of cancers. However, the mutation status of BRCA gene in central south Chinese lung cancer patients remains unclear, and its expression levels in lung cancer also need to be further explored. In this study, we use next-generation sequencing (NGS) technology to analyze the BRCA genes mutations in 462 central south Chinese lung cancer patients. Public databases including cBioportal, Catalogue Of Somatic Mutations In Cancer (COSMIC), The Cancer Genome Atlas (TCGA), Human Protein Atlas (HPA) and Expression Profiling Interactive Analysis (GEPIA) are also applied to explore the expression level and mutation status of BRCA in lung cancer patients and their relationships with the prognosis. We found that the mutation rate of BRCA1/2 in central south Chinese lung cancer patients is 4.3% and 6.5% respectively, and missense mutations account for the majority in both BRCA1/2, which are similar to the international status of BRCA1/2 from public databases. In addition, 45 novel mutations of BRCA1/2 in lung cancer are reported in this study. Furthermore, we find that the BRCA2 mutations are negatively correlated with overall survival rate in lung cancer using cBioportal. Last, we demonstrate that both of the mRNA and protein levels of BRCA1/2 are upregulated in lung cancer, and the elevated mRNA expression levels are positively linked with poor prognosis. In general, our study better complements knowledge of the BRCA1/2 mutation status in the Chinese lung cancer patients, and firstly reveals the association between BRCA1/2 expression levels and prognosis of lung cancer patients, which may provide great value for the early diagnosis and clinical treatment of lung cancer.


Neural H₂ Control Using Continuous-Time Reinforcement Learning.
In this article, we discuss continuous-time H2 control for the unknown nonlinear system. We use differential neural networks to model the system, then apply the H2 tracking control based on the neural model. Since the neural H2 control is very sensitive to the neural modeling error, we use reinforcement learning to improve the control performance. The stabilities of the neural modeling and the H2 tracking control are proven. The convergence of the approach is also given. The proposed method is validated with two benchmark control problems.


[Practical follow-up of a patient treated with finasteride in screening for prostate cancer].
The following conclusions can be made on the practical follow up of a patient receiving finasteride in screening for prostate cancer from an analysis of the literature and, particularly, the Prostate Cancer Prevention Trial (PCPT). Prostate volume fells by an average of 17 to 19%. The average fall in PSA after one year of finastéride treatment was 50%. This fall continued over time, at an average of 5% per year. An adjustment factor of x 2 at 1 year was used to return to a PSA value of a group of untreated men. The ratios of free PSA/total PSA and complexed PSA/total PSA remained unchanged and were interpreted as usual. The risk of cancer was low if the PSA fell by > or = 50% and raised if it fell by < 33%. Prostate cancer was associated with an average 15% rise in PSA on finasteride. This change still needs to be validated. The sensitivity of PSA and rectal examination was greater in detecting all grades of cancer in people receiving finasteride than on placebo. These findings have the benefit of reducing the indications for biopsy during follow up. Finasteride does not appear to cause high grade cancers. Despite the 25% reduction in the risk of cancer on finasteride there was insufficient information, particularly on the impact on mortality to allow chemoprevention to be proposed. Patients started on finasteride to treat BPH must be informed of the possible benefits, side effects and follow up arrangements to screen for prostate cancer.


Strapping a benzaldehyde-appended 2,2'-bis-dipyrrin Zn(ii) double-stranded helicate using imine bond formation.
A novel linear binuclear Zn(ii)/2,2'-bis-dipyrrin double-stranded helicate bearing peripheral p-benzaldehyde moieties has been strapped by formation of imine bonds upon reaction with m-xylylenediamine and characterized by 1H- and 13C-NMR spectroscopy, UV-Visible spectroscopy and high-resolution mass spectrometry.


Analysis of anti-apoptotic PVT1 oncogene and apoptosis-related proteins (p53, Bcl2, PD-1, and PD-L1) expression in thyroid carcinoma.
An aberrant expression of long non-coding RNA PVT1 has been associated with apoptosis in various cancer types. We aimed to explore the PVT1 and four apoptosis-related proteins (p53, Bcl2, and PD-1/PD-L1) signature in thyroid cancer (TC). The PVT1 expression level was measured in 64 FFPE TC paired samples by real-time quantitative PCR. Overall and stratified analyses by different clinicopathological features were done. The apoptotic proteins were evaluated by immunohistochemistry staining. Overall analysis showed significant PVT1upregulation in TC tissues (p < 0.001). Similarly, subgroup analysis by BRAFV600E mutation showed consistent results. Lower expression of p53 was associated with mortality (p = 0.001). Bcl2 overexpression was associated with greater tumor size (p = 0.005). At the same time, HCV-positive cases were associated with repressed Bcl2 expression levels (54.3% in HCV-negative vs. 6.9% in HCV-positive cases, p = 0.011). PD-1 expression was associated with lymph node metastasis (p = 0.004). Enhanced PD-L1 expression in the tumor was associated with a higher tumor stage, lymphovascular invasion, and mortality risk. Kaplan-Meier curves for overall survival showed that low p53 and high PD-L1 expressions were associated with lower survival time. The p53-positive staining is associated with a 90% decreased mortality risk (HR = 0.10, 95%CI = 0.02-0.47, p = 0.001), while patients with high PD-L1 were five times more likely to die (HR = 4.74, 95%CI = 1.2-18.7, p = 0.027). Our results confirm the upregulation of PVT1 in TC. The apoptosis-related proteins (p53, Bcl2, and PD-1/PD-L1) showed different prognostic utility in TC patients; in particular, low p53 and high PD-L1 expressions associated with low survival times. Further large-scale and mechanistic studies are warranted.


Popliteal artery damage during total knee arthroplasty.
Injury of popliteal artery during total knee arthroplasty is a relatively rare complication. We report on one case of transverse semi-dissection of the popliteal artery during the tibial cut and one case of popliteal pseudoaneurysm formation caused by Hohmann retractors. Diagnosis was made early in the first case but it was delayed in the second due to misdiagnosis of deep vein thrombosis. Both injuries were managed eventually by open surgery. Postoperative clinical examination and ultrasound imaging confirmed the successful restoration of the blood flow. This case report also describes the classification system of the type of vascular damage and describes the mechanism, the clinical presentation, diagnostic modalities and treatment options for these rare complications of total knee arthroplasty surgery.


AA amyloid in human food chain is a possible biohazard.
AA amyloidosis can be transmitted experimentally in several mammalian and avian species as well as spontaneously between captive animals, even by oral intake of amyloid seeds. Amyloid seeding can cross species boundaries, and fibrils of one kind of amyloid protein may also seed other types. Here we show that meat from Swedish and Italian cattle for consumption by humans often contains AA amyloid and that bovine AA fibrils efficiently cross-seed human amyloid β peptide, associated with Alzheimer's disease.


Engineering microbial diagnostics and therapeutics with smart control.
Microbes have become an increasingly powerful chassis for developing diagnostic and therapeutic technologies. While many of the earlier engineering efforts used microbes that expressed relevant proteins constitutively, more microbes are being engineered to express them with region-selectivity and disease-responsiveness through biosensors. Such 'smart' microbes have been developed to diagnose and treat a wide range of disorders and diseases, including bacterial infections, cancers, inflammatory disorders, and metabolic disorders. In this review, we discuss synthetic biology technologies that have been applied to engineer microbes for biomedical applications, focusing on recent reports that demonstrate microbial sensing by using animal models or clinical samples. Advances in synthetic biology will enable engineered microbes to significantly improve the medical field.


The role of renal resistive index measures in the diagnostic work up of congenital hydronephrosis.
To evaluate the role of renal resistive index (RI) measures in the diagnostic work up of congenital hydronephrosis. Seventeen neonatal pigs were randomized to either left-sided partial unilateral ureteral obstruction (n=12) or sham operation (n=5) at 2 weeks of age. Serial investigations including B-mode ultrasound, RI measures and combined clearance/renographic evaluations were performed at 4, 12 and 24 weeks of age under light sedation. Results were analysed statistically, and receiver operating characteristic (ROC) curves were generated in order to evaluate the diagnostic efficacy of RI. In all, 15 animals completed the study protocol. In the obstructed group, hydronephrosis and significant compromise of renal function developed on the subject side, whereas sham-operated pigs had stable renal morphology and function throughout the study. There were however no significant differences in RI or DeltaRI between the two groups at any age, or between right and left RIs in the obstructed group at any point. RI and DeltaRI had no prognostic or diagnostic value as judged by ROC curve analysis. RI and DeltaRI were not affected by partial unilateral ureteral obstruction induced in the immature neonatal porcine kidney. The results of this study do not support the clinical use of Doppler ultrasound studies in the diagnostic work up of congenital hydronephrosis.


Carcinoma of prostate metastatic to parotid gland.
A rare case of prostate cancer with metastasis to the parotid salivary gland is reported. The prostatic origin of the mass was proven by incisional biopsy and immunohistochemical staining for prostate-specific antigen. Additional studies of the tumor included ultrastructural and quantitative deoxyribonucleic acid (DNA) analysis.


Weifuchun alters tongue flora and decreases serum trefoil factor I levels in gastric intestinal metaplasia: A CONSORT-compliant article.
To explore the molecular mechanisms of Weifuchun in the treatment of gastric intestinal metaplasia (GIM), we designed a preclinical pilot study to examine potential markers of disease progression based on alterations in the tongue flora. Total 27 patients with GIM were treated with Weifuchun for 4 weeks and 26 volunteers as controls. Tongue coating bacteria were profiled using 16S rDNA high-throughput sequencing. Serum pepsinogen I and II levels were detected using the latex immunoturbidimetric assay. The levels of serum trefoil factor I was detected by ELISA. Microplate-based quantification was used to detect serum total bile acid (TBA). After treatment, the relative abundance of 4 dominant tongue coating genera (Granulicatella, Gemella, Lachnoanaerobaculum, and Neisseria) increased significantly wheras Alloprevotella, [Eubacterium] nodatum group, Prevotell, and Ruminococcaceae UCG-014 decreased (P < .05). The results showed that Alloprevotella and 3 rare tongue coating genera (Lautropia, Treponema 2, and Aliihoeflea) might be potential markers or target flora for the treatment of GIM. Kyoto encyclopedia of genes and genomes (KEGG) function prediction analysis showed that Weifuchun may regulate bile secretion and folate biosynthesis in patients with GIM. The level of serum trefoil factor I decreased significantly in response to Weifuchun treatment, which was consistent with the decrease in folate biosynthesis predicted by KEGG. Weifuchun may restore the balance of tongue flora by decreasing the levels of serum trefoil factor I, thereby providing a new way to measuring the underlying effectiveness and potential mechanisms of action of this traditional Chinese medicinal compound in the treatment of GIM.


[Experience gathered through a sociological analysis within the framework of a gerontological longitudinal study (author's transl)].
The authors present the results of a sociological analysis within the framework of a longitudinal study and discuss their relevance.


Feeding cycles entrain circadian rhythms of locomotor activity in CS mice but not in C57BL/6J mice.
The effects of periodic, restricted feeding (RF) for two hours at a fixed time of day on the circadian rhythms of locomotor activity were examined in CS and C57BL/6J mice, kept under continuous dim, red lights (LLdim). In C57BL/6J mice, free-running rhythms were not affected by an RF schedule, although anticipatory behavior prior to the food access period was observed. On the other hand, the free-running rhythms of CS mice did entrain to an RF schedule, exhibiting anticipatory behavior. The free-running rhythms of none of the control animals in either strain exhibited any effects resulting from the periodic disturbances occurring concurrently with the performance of RF. These results indicate that the circadian pacemaker couples with the food entrainable oscillator (FEO) in CS mice, but that such coupling may not exist, or may be very weak, in C57BL/6J mice.


Mechanical confinement regulates cartilage matrix formation by chondrocytes.
Cartilage tissue equivalents formed from hydrogels containing chondrocytes could provide a solution for replacing damaged cartilage. Previous approaches have often utilized elastic hydrogels. However, elastic stresses may restrict cartilage matrix formation and alter the chondrocyte phenotype. Here we investigated the use of viscoelastic hydrogels, in which stresses are relaxed over time and which exhibit creep, for three-dimensional (3D) culture of chondrocytes. We found that faster relaxation promoted a striking increase in the volume of interconnected cartilage matrix formed by chondrocytes. In slower relaxing gels, restriction of cell volume expansion by elastic stresses led to increased secretion of IL-1β, which in turn drove strong up-regulation of genes associated with cartilage degradation and cell death. As no cell-adhesion ligands are presented by the hydrogels, these results reveal cell sensing of cell volume confinement as an adhesion-independent mechanism of mechanotransduction in 3D culture, and highlight stress relaxation as a key design parameter for cartilage tissue engineering.


Multiple bilateral fibroadenomas of the breasts requiring mastectomy in a renal transplant patient.
Fibroadenomas of the breast have been reported in female renal graft recipients and associated with the use of cyclosporin A (CsA). We report the case of a young patient given CsA who developed multiple bilateral fibroadenomas of the breasts 3 years after renal transplantation, leading to bilateral mastectomy. We discuss the association of CsA with fibroadenomas, the mechanisms by which the drug can act and review the literature. Based on these observations, an early conversion from CsA to tacrolimus should be considered; further observations are needed to assess the reversibility of the breast(s) lesions after such immunosuppressive regimen switch.


An update on familial pancreatic cancer and the management of asymptomatic relatives.
Families of patients with pancreatic adenocarcinoma (PC) often ask about their own risk of developing this disease. There is now a sufficient body of evidence to inform relatives of their relative risk of developing PC. The purpose of this review is to provide practical advice for the clinician when confronted with questions about the risk of PC in relatives, and the role of genetic testing and screening in high-risk individuals.


Interaction of metal ions with nucleic acids. Interaction of copper(II) with guanosine and its derivatives.
Interaction of copper(II) with guanosine, 2'-deoxyguanosine, 1-methylguanosine, 7-methylguanosine and GMP was studied withe use of spectroscopic and magneto-chemical methods. The main site of copper(II) binding in guanosine is nitrogen N-7; participation of N-1 is not excluded. The involvement of carbonyl oxygen in copper binding or copper chelation to N-7 and 0-6 is rather unlikely. A crystalline complex of copper(II) with GMP [Cu(C10H12O8N5P) .(H2O)3] was obtained, and it was demonstrated that copper(II) is bound with N-7 and the phosphate group.


Emerging treatments in Neurogastroenterology: Perspectives of guanylyl cyclase C agonists use in functional gastrointestinal disorders and inflammatory bowel diseases.
Functional gastrointestinal disorders (FGID) and inflammatory bowel diseases (IBD) are the most frequent pathologic conditions affecting the gastrointestinal (GI) tract and both significantly reduce patients' quality of life. Recent studies suggest that guanylyl cyclase C (GC-C) expressed in the GI tract constitutes a novel pharmacological target in the treatment of FGID and IBD. Endogenous GC-C agonists - guanylin peptides: guanylin and uroguanylin, by the regulation of water and electrolyte transport, are involved in the maintenance of homeostasis in the intestines and integrity of the intestinal mucosa. Linaclotide, a synthetic agonist of GC-C was approved by Food and Drug Administration and European Medicines Agency as a therapeutic in constipation-predominant irritable bowel syndrome (IBS-C) and chronic idiopathic constipation (CIC). Lately, several preclinical and clinical trials focused on assessment of therapeutic properties of synthetic agonists of uroguanylin, plecanatide, and SP-333. Plecanatide is currently tested as a potential therapeutic in diseases related to constipation and SP-333 is a promising drug in ulcerative colitis treatment. Here, we discuss the most recent findings and future trends on the development of GC-C agonists and their use in clinical trials.


Stimulatory effect of prolactin on human placental progesterone secretion at term in vitro: possible inhibitory effect on oestradiol secretion.
Maternal and fetal circulating prolactin (PRL) increases 10-fold compared with the non-pregnant state. We examined the effect of PRL upon placental steroidogenesis. It had a significant (P less than 0.05) time-dependent stimulatory effect upon placental explants/P4 accumulation and secretion into the medium. The maximal stimulatory effect (two-fold) in dose-dependent experiments was found to be 200 ng/ml. The effect of PRL upon oestradiol secretion was mainly inhibitory. This inhibition was most pronounced at 200 ng/ml. In conclusion, placental steroid secretion is modulated by PRL. This effect occurs mainly at concentrations seen in the placenta at term, suggestive of its physiologic role.


A case series on the potential effect of omega-3-fatty acid supplementation on 24-h heart rate variability and its circadian variation in children with attention deficit (hyperactivity) disorder.
Attention deficit disorder with and without hyperactivity (ADHD) in children is associated with decreased 24-h heart rate variability (HRV). Previous research has shown that supplementation of omega-3-fatty acid increases HRV. Here, we aimed to investigate whether the supplementation of omega-3-fatty acids would increase 24-h HRV in an uncontrolled case series of children with ADHD. HRV was recorded in 18 children and adolescents (age 13.35 ± 2.8 years) before and after omega-3 supplementation. Preliminary results indicate that omega-3 supplementation in children with AD(H)D may reduce mean heart rate and increase its variability. Future studies would do well to implement randomized, placebo-controlled designs with greater methodological rigor.


CXCR2 antagonism promotes oligodendrocyte precursor cell differentiation and enhances remyelination in a mouse model of multiple sclerosis.
Multiple sclerosis (MS) is a chronic autoimmune demyelinating disease characterized by the autoimmune attack of oligodendrocytes, leading to demyelination and progressive functional deficits. CXC chemokine receptor 2 (CXCR2) is recently reported to orchestrate the migration, proliferation and differentiation of oligodendrocyte precursor cells (OPCs), which implies its possible involvement in the demyelinating process. Here, we used a CXCR2 antagonist, compound 2, as a tool to investigate the role of CXCR2 in demyelination and the underlying mechanism. The primary cultured oligodendrocytes and cuprizone (CPZ)-intoxicated mice were applied in the present study. The results showed that compound 2 significantly promoted OPC proliferation and differentiation. In the demyelinated lesions of CPZ-intoxicated mice, vigorous OPC proliferation and myelin repair was observed after compound 2 treatment. Subsequent investigation of the underlying mechanisms identified that upon inhibition of CXCR2, compound 2 treatment upregulated Ki67, transcription factor 2 (Olig2) and Caspr expression, activated PI3K/AKT/mTOR signaling, ultimately promoted OPCs differentiation and enhanced remyelination. In conclusion, our results demonstrated that CXCR2 antagonism efficiently promoted OPC differentiation and enhanced remyelination in CPZ-intoxicated mice, supporting CXCR2 as a promising therapeutic target for the treatment of chronic demyelinating diseases such as MS.


Global Chang's Conjecture and singular cardinals.
We investigate the possibilities of global versions of Chang's Conjecture that involve singular cardinals. We show some ZFC limitations on such principles and prove relative to large cardinals that Chang's Conjecture can consistently hold between all pairs of limit cardinals below ℵ ω ω .


Computed tomographic presentation of granulomatous reaction from intraventricular shunt.
A case is presented in which the patient was diagnosed as having a large mass lesion arising in the region of the quadrigeminal plate. The patient had been shunted in the past for hydrocephalus. The computed tomographic picture was that of a primary brain neoplasm. At surgery extensive granulation tissue was found. The similarity between the CT presentation of this inflammatory mass and a neoplasm is emphasized.


Active Surveillance with Delayed Intervention for Recurrent Low Risk Bladder Cancer.
Active surveillance with delayed intervention aims to minimize the discomfort, potential complications and costs associated with immediate treatment of recurrent low grade Ta tumors of the bladder. We reviewed the data supporting this management strategy for low risk bladder cancer. A PubMed® query was performed to identify relevant literature on the topic of active surveillance for low risk bladder cancer. English language publications were reviewed and select data presented. Available data suggest that only 5% to 10% of patients diagnosed with a low grade appearing papillary bladder tumor will have progression in stage or grade. Coupled with the discomfort and potential for complications associated with transurethral resection, this supports the role of active surveillance for patients with small, recurrent, low risk bladder cancer. In addition, this management strategy stands to benefit the health care system by reducing the costs associated with caring for patients with bladder cancer. Active surveillance with delayed intervention represents a safe and cost-effective strategy for patients with recurrent low risk bladder cancer.


Factors associated with rural doctors' intention to continue a rural career: a survey of 3072 doctors in Japan.
To show the relationship between the personal and educational backgrounds of rural doctors and their intention to continue a rural career. Nationwide postal survey. Public clinics or hospitals in municipalities that are classified as 'rural' by the national government. A total of 4896 doctors working for 828 public clinics and hospitals. A questionnaire was mailed. The questionnaire inquired about the subject's age, sex, hometown, exposure to rural practice in undergraduate education, postgraduate training, continuing medical education, current position and affiliation status with a medical school, as well as his or her intention to continue a rural career. Response rate was 64%; 26% answered that they intended to continue a rural career. Postgraduate training in general internal medicine, general surgery, anaesthesiology, paediatrics and gastroenterology were positively related with the intention to continue a rural career (odds ratio = 2.045, 1.59, 1.30, 1.48, 1.38). Rural background, undergraduate exposure to rural practice, multispecialty-rotation in postgraduate training and current administrative position had positive correlations with the intention to continue in logistic regression analysis (odds ratio = 1.80, 2.47, 1.54, 2.17). Affiliation with a medical school department was negatively related with the intention to continue (odds ratio = 0.45). In addition to the rural background of physicians, some undergraduate and postgraduate factors were independently associated with the intention to continue a rural career.


Ethylene oxide potential toxicity.
The future of ethylene oxide (EO) sterilization has been questioned, owing to its associated toxicity. EO has been around for more than 60 years, mainly due to its recognized characteristics of reliability and effectiveness, coupled with the process flexibility, as well as its compatibility with most mechanical devices. Despite the well-known EO toxicity, the undesirable effects of medical devices' EO residues on the patient's health have not yet been well established. There are limitations related to the current risk-assessment studies. To overcome these drawbacks, demands on greater safety are increasing, which lead to improvements in sterilizers and aeration equipment, as well as the design of the processes. The paper under evaluation highlights risks related to EO sterilization of materials used during processing of stem cells for transplantation, but is an example of a study where the dose of the residues in the devices is not considered.


Solid-phase synthesis of the non-calcium-binding loop of cod allergen M. Direct evidence of the reactivity of the amino-terminal segment.
The synthesis of the non-calcium-binding AB loop of the assembly 13-32 of cod Allergen M (Mr 2122.1) was accomplished by solid-phase peptide synthesis. This peptide and the previously synthesized ones [12, 13, 14] have significant amino acid sequence homology. The synthetic crude preparation was obtained at relatively high recovery and purity. Further purification on a Bio-Gel P-2 column and a reversed-phase high-performance liquid chromatography column improved the grade of homogeneity, as demonstrated by high-voltage electrophoresis, end-terminal analysis, and amino acid composition. The peptide could, although to a much weaker extent than the intact Allergen M, directly bind IgE antibodies from the sera of cod-allergic individuals. At identical molar concentrations, a ratio of 1:6 for the in vitro reactivity of the peptide relative to the intact Allergen M was obtained. A similar reactivity was shown in the in vivo system used. The peptide also reacted with rabbit anti-Allergen M antibodies in rocket immunoelectrophoresis. The peptide appears to function as a divalent molecule in its primary interaction with antibodies.


S100A7 enhances invasion of human breast cancer MDA-MB-468 cells through activation of nuclear factor-κB signaling.
S100A7 signaling plays a critical role in the pathogenesis and progression of human breast cancers but the precise role and mechanism of S100A7 for tumor invasion remains unclear. in the present study, we investigated whether S100A7 overexpression could be mechanistically associated with the up-regulation of NF-κB, VEGF and MMP-9, resulting in the promotion of breast cancer cell invasion and growth, and vice versa. pcDNA3.1-S100A7 cDNA plasmid was constructed and transfected into the MDA-MB-468 cells. 4,5-dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay was used to detect cell proliferation, Matrigel was used to detect cell mobility and invasion in vitro.The MMP-9 and VEGF expression and levels was detected by western blot and ELISA assay. NF-κB DNA binding activity was detected by Electrophoretic mobility shift assay. Up-regulation of S100A7 by stable S100A7 cDNA transfection increased cell invasion and proliferation, whereas downregulation of S100A7 by small interfering RNA in S100A7 cDNA-transfected MDA-MB-468 cells decreased cell invasion and proliferation. Consistent with these results, we found that the up-regulation of S100A7 increased NF-κB DNA-binding activity and MMP-9 and VEGF expression. Down-regulation of S100A7 in S100A7 cDNA -transfected decreased NF-κB DNA-binding activity and MMP-9 and VEGF expression. Our data demonstrate that the S100A7 gene controls the proliferation and invasive potential of human MDA-MB-468 cells through regulation of NF-κB activity and its target genes, such as MMP-9 and VEGF expression. Down-regulation of S100A7 could be an effective approach for the down-regulation and inactivation of NF-κB and its target genes, such as MMP-9 and VEGF expression, resulting in the inhibition of invasion and growth.


[Percutaneous nephrostomy and temporary immunosuppression in treatment of idiopathic retroperitoneal fibrosis (Ormond disease)].
Our experiences in the diagnostics, treatment and follow-up-course of 10 patients suffering from idiopathic retroperitoneal fibrosis are reported. The ureterolysis and temporary nephrostomy, initially as percutaneous nephrostomy, and a long-term immunosuppressive therapy is the treatment of choice. In the follow-up control ultrasonography and computerized tomography are valuable and the prognosis of the disease quoad functionem is good.


Effects of various periods of food deprivation on serotonin turnover in the lateral hypothalamus.
Preliminary results indicated enhanced serotonin turnover in the lateral hypothalamus of 24 hr food deprived rats as compared to non-deprived rats. In the present study, the periods of food deprivation were extended in ordered that the effects of 0. 24, 48 and 72 hr of food deprivation on serotonin turnover could be measured. One hr following an infusion of 3H-5-hydroxytryptamine the lateral hypothalamus was perfused with physiological bacteriostatic saline for 40 min. Samples of perfusate, which corresponds to 75--90 min post-infusion, were analyzed by thin layer chromatography for estimation of 3H-labelled precursor and metabolites. The results indicate that serotonin turnover is enhanced as a function of hours of food deprivation.


Resolvability of Adair constants from oxygenation curves measured at low hemoglobin concentration.
Analyses of low concentration oxygenation curves for apparent Adair constants in which the effects of dimers is ignored have been explored using recently determined values of the overall energy coupling parameters. For high affinity systems and favorable energy distributions, it is found that the errors in estimated binding free energies may be less than one kcal provided the measurement errors are strictly random and of small magnitude. These errors are nevertheless quite substantial as compared with the differences between values for the successive binding steps.


Retrospective evaluation of osseointegrated implants for treatment of partial and full edentulism at Walter Reed Army Medical Center: Part I: Patient recall.
A retrospective study was done on patients treated with dental implants at Walter Reed Army Medical Center. An extensive recall of patients treated was accomplished. Each patient was clinically evaluated, radiographs were made, and the patients were asked to complete a survey. The results were not statistically analyzed but are reported simply as raw data.


Enhanced recovery principles applied to revision hip and knee arthroplasty leads to better patient outcomes.
There is very little published literature on Enhanced Recovery Principles (ERP) used in primary joint replacements applied to revision hip and knee arthroplasty (rTHA, rTKA). Retrospective series of 268 rTHA and rTKA surgeries from 2010 -2018, treated with ERP, focusing on multimodal pain management, blood management and early functional recovery. No patients from the latest cohort required readmission within 6 weeks. Only 20 patients (7.5%) required a blood transfusion. Surgical site local anaesthetic infiltration was associated with lower PCA use in aseptic rTHA and rTKA (p<0.001; p<0.001). Revisions for infection had a longer length of stay (LOS) and increased PCA usage in both rTHA (6.5 vs. 5.2 days) and rTKA (10.1 vs. 5.3 days), similar to our previous study.1 Use of an intra-articular catheter for analgesia in rTKA showed reduced PCA use. Tourniquets were not beneficial for blood loss in rTKA and had greater PCA use post-operatively (p<0.001). The application of ERP to revision THA and TKA surgery is safe and effective.


Effect of cyclic AMP, db-cyclic AMP and phosphodiesterase inhibitors on histamine inhibition of the contractile response of the mouse vas deferens.
Histamine inhibited the contractile response of the mouse vas deferens to various frequencies of stimulation, and the inhibition was inversely related to the frequency of stimulation. This effect of histamine was mimicked by cyclic AMP, db-cyclic AMP and various phosphodiesterase inhibitors (IBMX, aminophylline and theophylline). Histamine-produced inhibition, but not that produced by the other compounds, was blocked by cimetidine. The low concentrations (10-100 microM) of various phosphodiesterase inhibitors caused inhibition but failed to potentiate the inhibitory response to histamine. The basal cyclic AMP levels of the tissues were unaffected at these concentrations of aminophylline. At higher concentrations (1 and 5 mM), however, aminophylline significantly elevated the basal cyclic AMP levels of the tissues and markedly inhibited the contractile response to various frequencies of stimulation but still failed to enhance or potentiate the inhibitory response to histamine. In fact, the inhibitory response to histamine at these concentrations of aminophylline was reduced. Based on these and earlier [3] findings, it is concluded that, although histamine increases the accumulation of cyclic AMP in the mouse vas deferens and although its inhibitory effect on the preparation can be mimicked by both the cyclic nucleotides and phosphodiesterase inhibitors, the involvement of cyclic AMP in the mediation of its inhibitory response is still unresolved.


Click synthesized dianthryl-TTFV: an efficient fluorescent turn-on probe for transition metal ions.
Tetrathiafulvalene vinylogue (TTFV) was functionalized with two anthryl fluorophores via Cu(I)-catalyzed alkyne-azide [3 + 2] cycloaddition, forming a dianthryl-TTFV hybrid to show fluorescent turn-on sensing behaviour for Cu(2+), Fe(2+), and Cd(2+) ions in THF with remarkably low detection limit down to the sub-ppm level.


[Inhibition of rat heart and kidney allograft rejection by photochemical treatment of the recipient].
After temporary posttransplant PUVA treatment of graft recipients the survival time of rat heart and kidney allografts was significantly prolonged. In the semiallogeneic F1 model all kidney transplant recipients survived without rejection signs. The mechanism of action should be cleared especially the role of cis-urocanic acid and the introduction of the method into clinical organ transplantation is discussed.


A conjugated fatty acid present at high levels in bitter melon seed favorably affects lipid metabolism in hepatocytes by increasing NAD(+)/NADH ratio and activating PPARα, AMPK and SIRT1 signaling pathway.
α-Eleostearic acid (α-ESA), or the cis-9, trans-11, trans-13 isomer of conjugated linolenic acid, is a special fatty acid present at high levels in bitter melon seed oil. The aim of this study was to examine the effect of α-ESA on hepatic lipid metabolism. Using H4IIEC3 hepatoma cell line, we showed that α-ESA significantly lowered intracellular triglyceride accumulation compared to α-linolenic acid (LN), used as a fatty acid control, in a dose- and time-dependent manner. The effects of α-ESA on enzyme activities and mRNA profiles in H4IIEC3 cells suggested that enhanced fatty acid oxidation and lowered lipogenesis were involved in α-ESA-mediated triglyceride lowering effects. In addition, α-ESA triggered AMP-activated protein kinase (AMPK) activation without altering sirtuin 1 (SIRT1) protein levels. When cells were treated with vehicle control (VC), LN alone (LN; 100μmol/L) or in combination with α-ESA (LN+α-ESA; 75+25μmol/L) for 24h, acetylation of forkhead box protein O1 was decreased, while the NAD(+)/NADH ratio, mRNA levels of NAMPT and PTGR1 and enzyme activity of nicotinamide phosphoribosyltransferase were increased by LN+α-ESA treatment compared to treatment with LN alone, suggesting that α-ESA activates SIRT1 by increasing NAD(+) synthesis and NAD(P)H consumption. The antisteatosis effect of α-ESA was confirmed in mice treated with a high-sucrose diet supplemented with 1% α-ESA for 5weeks. We conclude that α-ESA favorably affects hepatic lipid metabolism by increasing cellular NAD(+)/NADH ratio and activating PPARα, AMPK and SIRT1 signaling pathways.


[Skin, bonding and partnership in atopic dermatitis and psoriasis].
On the basis of attachment, the study combines results in relationship and psychosomatic research. A buffering hypothesis of a secure attachment in patients with chronic skin diseases is checked. Patients with atopic dermatitis (n = 21) and psoriasis (n = 22) were tested with various questionnaires: the German questionnaire for partnership attributes (PFB) and problem list (PL), questionnaire for psychosomatic complaints (BEB), Relationship Scales Questionnaire (RSQ), and a self-designed questionnaire. Unsecurely attached patients with atopic dermatitis feel mentally more disturbed and report more coherence between mental strains and changes in skin surface than securely attached psoriasis patients. There are tendencies to the assumed buffering effects. The study shows hints of the importance of attachment theory in psychosomatic skin diseases. In the treatment of patients with chronic skin diseases psychosocial aspects should be taken into consideration. Partnership factors might be used as a resource.


Prospective Observational Study of Patient-Controlled Intrathecal Analgesia: Impact on Cancer-Associated Symptoms, Breakthrough Pain Control, and Patient Satisfaction.
Although data exist for the efficacy of intrathecal therapy (ITT), there are no prospective data on patient-controlled intrathecal analgesia (PCIA) in refractory cancer pain. This study examines the effect of PCIA on cancer symptom scores, patient satisfaction, and analgesic efficacy with an emphasis on breakthrough pain (BTP). Ninety-eight patients with refractory cancer pain prospectively completed questionnaires including the MD Anderson Symptom Inventory and a BTP survey before and after the implantation of an intrathecal pump. Fifty-eight patients were included in the study group. Average "worst" pain scores decreased from 8.32 (SD, 1.73) pre-ITT to 4.98 (SD, 2.92) post-ITT, P < 0.001. Severe pain (numerical rating score ≥7) decreased from 84.2% to 35.2% (P < 0.001). Mean daily morphine equivalent dosing decreased from 805.3 mg/d to 128.2 mg/d, with 65.5% of patients discontinuing all nonintrathecal opioids. The mean MD Anderson Symptom Inventory symptom severity score decreased from 4.98 to 3.72 (P < 0.0001), and the symptom interference score from 6.53 to 4.37 (P < 0.001). Pain reduction was 46.8% with pre-ITT breakthrough medications and 65.2% with PCIA (P < 0.001). Median time to onset was 30 minutes with pre-ITT breakthrough medications and 10 minutes with PCIA (P < 0.001). Patient-controlled intrathecal analgesia, compared with conventional BTP medications, was "a lot better" in 60.7% and "a little better" in 28.6%. Overall pain control satisfaction was also improved, with 78.2% "a lot better" and 10.9% "I have no pain." In patients with poorly controlled cancer pain, PCIA is associated with improved pain control, improved cancer-related symptoms, and high satisfaction. Compared with conventional BTP regimens, PCIA provides superior analgesia and a 3-fold faster onset of action.


Measuring Verbal Psychotherapeutic Techniques-A Systematic Review of Intervention Characteristics and Measures.
Language is one of the most important "tools" of psychotherapists. The working mechanisms of verbal therapeutic techniques, however, are still marginally understood. In part, this is due to the lack of a generally acknowledged typology as well as a gold standard for the assessment of verbal techniques, which limits the possibility of conducting studies focusing this topic. The present study reviews measures used in clinical research which assess directly observable dimensions of verbal interventions in a reliable manner. All measures were evaluated with respect to their theoretical foundation, research goals, assessment modes, and various psychometric properties. A systematic search in databases (PubMed, PsycInfo, PsycArticles, PSYNDEX, Web of Science, Embase) followed by an additional "snowballing" search covering the years 1940-2013 yielded n = 179 publications eligible for review. Within these publications, 34 measures were identified showing great heterogeneity regarding the aspects under study. Only two measures reached the highest psychometric standards and can be recommended for clinical use without any reservation. Central problems include deficiencies in the systematization of techniques as well as their partly ambiguous and inconsistent definitions. To promote this field of research, it will be important to achieve a consensus concerning the terminology, conceptions and measures of verbal interventions.


Nondestructive optical feedback systems for use during infrared laser sealing of blood vessels.
High-power infrared lasers are capable of sealing blood vessels during surgery. A real-time diagnostic feedback system utilizing diffuse optical transmission is characterized by nondestructive identification of vessel seals. For real-time diffuse optical transmission experiments, two approaches were studied. First, a low-power (1.2 mW) visible aiming beam (635 nm) was used for diagnostics, co-aligned with the therapeutic high-power infrared beam (1470 nm). Second, the 1470 nm beam was used simultaneously for both therapy and diagnostics. For both studies, the 1470-nm laser delivered 5 W for 5 seconds for unsuccessful seals (control) versus 30 W for 5 seconds for successful seals, using a linear beam profile (8.4 × 2 mm). Diffuse optical transmission signals were correlated with vessel burst pressures measured using a standard burst pressure setup. Diffuse optical transmission studies using the low-power, 635-nm aiming beam were promising. A decrease in the visible transmitted signal of 59 ± 11% was measured for successful seals versus 23 ± 8% for failed seals (p = 5.4E-8). The use of the high-power, 1470-nm infrared laser for simultaneous therapeutics and diagnostics proved inconsistent and unreliable, due in part to the dynamic and rapid changes in water content and absorption during the seal. A low-power, visible aiming beam, integrated with the therapeutic high-power infrared diode laser, may be used as a real-time diagnostic system for indicating successful laser seals, based on significant changes in optical scattering and diffuse optical transmission between native and coagulated compressed vessels. With further development, this simple and inexpensive optical feedback system may be integrated into a laparoscopic device for laser de-activation upon successful vessel sealing.


Multimodal imaging of capsid and cargo reveals differential brain targeting and liver detargeting of systemically-administered AAVs.
The development of gene delivery vehicles with high organ specificity when administered systemically is a critical goal for gene therapy. We combine optical and positron emission tomography (PET) imaging of 1) reporter genes and 2) capsid tags to assess the temporal and spatial distribution and transduction of adeno-associated viruses (AAVs). AAV9 and two engineered AAV vectors (PHP.eB and CAP-B10) that are noteworthy for maximizing blood-brain barrier transport were compared. CAP-B10 shares a modification in the 588 loop with PHP.eB, but also has a modification in the 455 loop, added with the goal of reducing off-target transduction. PET and optical imaging revealed that the additional modifications retained brain receptor affinity. In the liver, the accumulation of AAV9 and the engineered AAV capsids was similar (∼15% of the injected dose per cc and not significantly different between capsids at 21 h). However, the engineered capsids were primarily internalized by Kupffer cells rather than hepatocytes, and liver transduction was greatly reduced. PET reporter gene imaging after engineered AAV systemic injection provided a non-invasive method to monitor AAV-mediated protein expression over time. Through comparison with capsid tagging, differences between brain localization and transduction were revealed. In summary, AAV capsids bearing imaging tags and reporter gene payloads create a unique and powerful platform to assay the pharmacokinetics, cellular specificity and protein expression kinetics of AAV vectors in vivo, a key enabler for the field of gene therapy.


The essential role for c-Ski in mediating TGF-beta1-induced bi-directional effects on skin fibroblast proliferation through a feedback loop.
The bi-directional regulation of TGF-beta1 (transforming growth factor-beta1) on fibroblast proliferation with stimulation at low concentration, but inhibition at high concentration, has important significance during tissue repair. The mechanism has not been defined. c-Ski is a major co-repressor of TGF-beta1/Smad3 signalling; however, the exact role of c-Ski in the bi-directional regulation of fibroblast proliferation remains to be determined. In the present study, we established a dose-effect relationship of bi-directional regulation of TGF-beta1-mediated proliferation in rat skin fibroblasts, and found that c-Ski overexpression promoted fibroblast proliferation by inhibiting Smad3 activity. Importantly, c-Ski expression was decreased at the high concentration of TGF-beta1, but increased at the low concentration of TGF-beta1. This dose-dependent change in TGF-beta1 action did not affect Smad3 phosphorylation or nuclear translocation, but altered Smad3 DNA-binding activity, transcriptional activity and expression of the downstream gene p21 that both increased at the high concentration and decreased at the low concentration. Furthermore, c-Ski overexpression exerted synergistic stimulation with TGF-beta1 at the low concentration, but reversed the inhibitory effect of TGF-beta1 at high concentrations, while knockdown of c-Ski by RNA interference abrogated bi-directional role of TGF-beta1 on fibroblast proliferation. Thus our data reveal a new mechanism for this bi-directional regulation, i.e. c-Ski expression change induced by low or high TGF-beta1 concentration in turn determines the promoting or inhibiting effects of TGF-beta1 on fibroblast proliferation, and suggests an important role of c-Ski that modulates the local availability of TGF-beta1 within the wound repair microenvironment.


Impact of recommendations and new therapies on the prognosis of colon cancer with synchronous liver metastasis.
To assess the prognostic impact of the new therapies recommended over the past twenty years for colonic cancers with synchronous hepatic metastasis (hmCC). From 1995 to 2016, 802 hmCC were identified in a tumor registry. An univariate and multivariate analysis looked for the impact of the different recommendations over three periods: chemotherapy without targeted therapy (p1CH), chemotherapy with targeted agent in 2nd line (p2TA2), chemotherapy with TA in 1st line (p3TA1) depending on anatomoclinical criteria and therapeutic sequences: chemotherapy then resection of the primary tumor (CR) (n = 100), resection of the primary tumor then chemotherapy (RC) (n = 541), chemotherapy alone with or without TC (onlyCH) (n = 161). The rates of onlyCH, CR and RC had varied respectively during these 3 periods from 12% to 26%, 6% to 21% and from 82% to 53% (p = 0.001). The medians of p1CH, p2TA2 and p3TA1 survival were 20.2, 22.7 and 23.6 months, respectively (p = 0.12). The independent factors of poor prognosis were age ≥ 75 years (1.6 [1.35; 1.9] p = 0.0001), chemotherapy only 2.3 [1.6; 3.5] p = 0.0001), p1CH 1.7 [1.4; 2.1] p<0.0001), p2TA2 1.2 [1.02;1.6] p = 0.04. The p2TA2 period had a worse prognosis than p3TA1 (1.25 [1.01; 1.5] p = 0.03). In public health point of view, the recommendation of first-line TA improved survival and increased rate of primary tumor resection after chemotherapy.


Effect of an intraoperative periradicular application of platelet-rich fibrin (PRF) on residual post-surgical neuropathic pain after disc herniation surgery: study protocol for NeuroPRF, a randomized controlled trial.
The prevalence of post-surgical lumbar neuropathic radiculopathy is approximately 30%. Poor response to the recommended treatments for neuropathic pain, namely antidepressants and/or gabapentinoids, requires the development of new techniques to prevent chronic pain. One such well-tolerated technique is the administration of autologous plasma enriched in platelets and fibrin (PRF). This approach is largely used in regenerative medicine owing to the anti-inflammatory and analgesic properties of PRF. It could also be an interesting adjuvant to surgery, as it reduces neurogenic inflammation and promotes nerve recovery, thereby reducing the incidence of residual postoperative chronic pain. The aim of the present study is to evaluate the benefit of periradicular intraoperative application of PRF on the residual postsurgical neuropathic pain after disc herniation surgery. A randomized, prospective, interventional, controlled, single-blind study with evaluation by a blind outcome assessor will be performed in Strasbourg University Hospital. We will compare a control group undergoing conventional surgery to an experimental group undergoing surgery and periradicular administration of PRF (30 patients in each arm). The primary outcome is the intensity of postoperative neuropathic radicular pain, measured by a visual analog scale (VAS) at 6 months post-surgery. The secondary outcomes are the characteristics of neuropathic pain (NPSI), the quality of life (SF-12 and PGIC), the presence of anxiety/depression symptoms (HAD), and the consumption of analgesics. We will also carry out transcriptomic analysis of a panel of pro- and anti-inflammatory cytokines in blood samples, before surgery and at 6 months follow-up. These gene expression results will be correlated with clinical data, in particular, with the apparition of postoperative neuropathic pain. This study is the first randomized controlled trial to assess the efficacy of PRF in the prevention of neuropathic pain following surgery for herniated disc. This study addresses not only a clinical question but will also provide information on the physiopathological mechanisms of neuropathic pain. This study is registered at ClinicalTrials.gov: NCT05196503 , February 24, 2022.


Human Neural Stem Cells for Ischemic Stroke Treatment.
Ischemic stroke is the second most common cause of death worldwide and a major cause of disability. It takes place when the brain does not receive sufficient blood supply due to the blood clot in the vessels or narrowing of vessels' inner space due to accumulation of fat products. Apart from thrombolysis (dissolving of blood clot) and thrombectomy (surgical removal of blood clot or widening of vessel inner area) during the first hours after an ischemic stroke, no effective treatment to improve functional recovery exists in the post-ischemic phase. Due to their narrow therapeutic time window, thrombolysis and thrombectomy are unavailable to more than 80% of stroke patients.Many experimental studies carried out in animal models of stroke have demonstrated that stem cell transplantation may become a new therapeutic strategy in stroke. Transplantation of stem cells of different origin and stage of development has been shown to lead to improvement in experimental models of stroke through several mechanisms including neuronal replacement, modulation of cellular and synaptic plasticity and inflammation, neuroprotection and stimulation of angiogenesis. Several clinical studies and trials based on stem cell delivery in stroke patients are in progress with goal of improvements of functional recovery through mechanisms other than neuronal replacement. These approaches may provide therapeutic benefit, but generation of specific neurons for reconstruction of stroke-injured neural circuitry remains ultimate challenge. For this purpose, neural stem cells could be developed from multiple sources and fated to adopt required neuronal phenotype.


Reproductive abnormalities in adult male mice following preimplantation exposures to estradiol or pesticide methoxychlor.
Adult females of ICR strain of mice were bred, separated into different experimental groups, and treated as follows. On Days 2-4 of pregnancy, the mice received daily subcutaneous injections of either 0.05 ml sesame oil (vehicle) or same volume of 5.0mg of purified methoxychlor (MXC) suspended in the vehicle. Another group received a single subcutaneous injection of 1.0 microg of estradiol-17beta (E) on Day 2 of pregnancy only. Male offspring were tested at 3 and 6 months of age. At 3 months, E or MXC did not alter the weights of seminal vesicles, preputial glands, or testes, although after exposure for 30 min to a female in estrus behind a partition, testosterone levels were significantly reduced in treated males in comparison to control males exposed to the same partition test. At 6 months, the preputial glands and testes weight remained unchanged, while the seminal vesicles were significantly heavier in E- and MXC-treated males. Same partition tests again revealed that in E and MXC groups, testosterone levels remained significantly lower in comparison to control males. MXC or E exposures during preimplantation appear to induce long-term effects on the sexual development in 3 and 6 month-old-males by compromising their sexual arousal and altering seminal vesicles weights in the older group.


Accuracy of measuring tape and vertebral-level methods to determine shoulder internal rotation.
Goniometers can be used to assess shoulder ROM with reasonable accuracy, but not internal rotation. Vertebral level, as determined by the hand-behind-the-back method, is used frequently but its reproducibility is questionable. We therefore devised a new measuring tape-based method for determining vertebral level. We (1) compared the accuracy of a measuring tape-based and conventional vertebral-level method; (2) determined whether BMI affects their accuracy; and (3) devised a formula for converting distances measured using a measuring tape to vertebral levels. We assessed internal rotation in 61 patients with shoulder pain. An electrode was taped to the skin where the thumb reached maximally behind the back. The vertebral-level method involved determining the vertebral level of the electrode by palpating bony landmarks whereas the measuring tape method involved measuring the distance between the C7 spinous process and the electrode. True vertebral levels of the electrode were confirmed by radiography. In nonobese patients, the accuracies of the upper thoracic and lumbar-level measurements were better for the measuring tape method than the vertebral-level method (r = 0.861 and 0.700, respectively in upper thoracic; 0.913 and 0.710, respectively in lumbar). Patient BMI affected the accuracy of the vertebral-level method but not that of the measuring tape method. The distances obtained using the measuring tape method could be converted into vertebral-level units using the formula: estimated vertebral level = 0.031 × [distance between C7 spinous process and thumb behind back] - 0.044 × [patient height] + 7.277. The measuring tape-based method reflected shoulder internal rotation with higher accuracy than the vertebral-level method, and unlike the vertebral-level method, the measuring tape method was not affected by obesity. Level II, diagnostic study. See Guidelines for Authors for a complete description of levels of evidence.


A detailed view on the constituents of EPs 7630.
Extracts of PELARGONIUM SIDOIDES, commonly known as EPs 7630, are produced by extraction of milled roots with 11 % (w/w) ethanol in water. This solvent leads to a spectrum of constituents which differs significantly from extracts obtained by extraction with non-polar solvents. EPs 7630 is composed of six main groups of constituents, namely unsubstituted and substituted oligomeric prodelphinidins, monomeric and oligomeric carbohydrates, minerals, peptides, purine derivatives and highly substituted benzopyranones. The oligoprodelphinidins, frequently supposed to be compounds with unspecific tanning interactions, show, in contrast to other polyphenols, an amazing variety of substructures and connectivities which results in an uncommon diversity even at a low degree of polymerization. Three distinct purine derivatives, second messengers and probably intermediates of DNA synthesis, were identified and characterized by phytochemical means. The main benzopyranones of EPs 7630 are highly oxygenated at the phenyl moiety (three to four oxygens) and in addition sulfated at distinct positions. A disulfate of 6,7,8-trihydoxybenzopyranone has been identified for the first time in plants. Taken together, these constituents amount to about 70 to 80 % of the total weight of EPs 7630, the active ingredient of the phytopharmaceutical Umckaloabo (Iso Arzneimittel Ettlingen).


Processing of autobiographical memory retrieval cues in borderline personality disorder.
Affective dysregulation in borderline personality disorder (BPD) in response to both external stimuli and memories has been shown to be associated with functional alterations of limbic and prefrontal brain areas. This study aimed to examine neuronal networks involved in autobiographical memory retrieval using standardized stimuli that gain autobiographical significance by illustrating marked solitary and social situations of human life. Using event-related functional Magnetic Resonance Imaging (fMRI), we examined the processing of pictures from the Thematic Apperception Test (TAT) in 14 BPD patients and 14 controls. In both groups, TAT stimuli activated brain areas known to be involved in autobiographical memory retrieval. BPD subjects lacked differential amygdala, orbitofrontal and cingulate activations for TAT versus neutral stimuli. In the TAT condition, compared to controls, BPD subjects displayed increased BOLD responses in the bilateral orbitofrontal and insular regions, in the left anterior cingulate and medial prefrontal cortex, as well as in the parietal and parahippocampal areas, consistent with a more aversive and arousing experience assessed by self-reports. Increased BOLD responses during TAT processing in BPD subjects were in line with previously reported changes in anterior cingulate and orbitofrontal cortices, which are known to be involved in memory retrieval. However, BPD subjects displayed hyperactivation in these areas for both TAT and neutral stimuli. The deficit of selective activation of areas involved in autobiographical memory retrieval suggests a general tendency towards a self-referential mode of information processing in BPD, or a failure to switch between emotionally salient and neutral stimuli.


The relationship of hormones to arterial glycosaminoglycans and atherosclerosis.
Glycosaminoglycan fractions were measured in representative large and medium sized arteries of normal, hypophysectomized and hormone treated young beagles. Hyaluronate, heparan sulphate, dermatan sulphate and the isomeric chondroitin sulphates were determined in the aortic arch, thoracic and abdominal segments, in the external iliac, superior mesenteric, renal, common carotid and coronary arteries. The hormones used for replacement therapy of hypophysectomized animals were growth hormone, thyroxine, cortisone and the sex hormones testosterone, estrogen and progesterone. The sensitivity to an individual hormone was found to differ in various segments of the arterial tree; the thoracic and abdominal aorta were most responsive but renal and superior mesenteric arteries were relatively inert. The hypothesis is advanced that arteries with a GAG metabolism highly sensitive to hormones are more prone to develop atherosclerosis than arteries that have a limited sensitivity to alterations in endocrine balance.


Monoclonal antibodies localize changes on myosin heavy chain isozymes during avian myogenesis.
Monoclonal antibodies were used to identify and localize by immunoelectron microscopy epitopes on myosin isozymes. An antibody that reacts with an amino-terminal fragment of the myosin heavy chain maps on the myosin head 140 A distal to the head-rod junction. It identifies an epitope that is shared on adult and embryonic myosin, and detects two transitions in myosin expression during avian pectoralis myogenesis. Another antibody maps to the carboxyl terminus of the myosin rod. It is specific for an adult fast myosin epitope that is not detected in early developing pectoralis muscle. In contrast, an epitope that is present throughout development is identified by an antibody that reacts with a myosin light chain. This light chain epitope is localized at the head-rod junction. These results demonstrate structural changes in widely separated regions of the myosin molecule accompanying the sequential expression of developmental myosin isozymes.


Clinical intestinal transplantation.
The advent of tacrolimus allowed clinical intestinal transplantation to become a feasible procedure for patients with irreversible intestinal failure. Over last 5 years, 71 patients underwent intestinal transplantation. Forty-one recipients were children, and 30 recipients were adults. Twenty-five patients received an isolated intestinal graft, 34 patients received a combined liver-intestinal graft, and 12 received a multivisceral graft. The colon was included the intestinal graft in 29 patients. One-year, 2-year, and 4-year actuarial patient survival is 72%, 57%, and 45%, respectively. Our experience has shown that infectious, and immunological problems have caused significant morbidity and mortality. In this paper, we present our clinical experience and overview with intestinal transplantation.


Cooperativity between remote sites of ectopic spiking allows afterdischarge to be initiated and maintained at different locations.
Many symptoms of nerve damage arise from ectopic spiking caused by hyperexcitability. Ectopic spiking can originate at the site of axonal damage and elsewhere within affected neurons. This raises the question of whether localized damage elicits cell-wide changes in excitability and/or if localized changes in excitability can drive abnormal spiking at remote locations. Computer modeling revealed an example of the latter involving afterdischarge (AD)--stimulus-evoked spiking that outlasts stimulation. We found that AD originating in a hyperexcitable region of axon could shift to the soma where it was maintained. This repositioning of ectopic spike initiation was independent of distance between the two sites but relied on the rate and number of ectopic spikes originating from the first site. Nonlinear dynamical analysis of a reduced model demonstrated that properties which rendered the axonal site prone to initiating AD discouraged it from maintaining AD, whereas the soma had the inverse properties thus enabling the two sites to interact cooperatively. A first phase of AD originating in the axon could, by providing sufficient drive to trigger somatic AD, give way to a second phase of AD originating in the soma such that spiking continued when axonal AD failed. Ectopic spikes originating from the soma during phase 2 AD propagated successfully through the defunct site of axonal spike initiation. This novel mechanism whereby ectopic spiking at one site facilitates ectopic spiking at another site is likely to contribute to the chronification of hyperexcitability in conditions such as neuropathic pain.


Mixed-ligand Ru(II) complexes with 2,2'-bipyridine and tetradentate Schiff bases auxiliary ligands: Synthesis, physico-chemical study, DFT analysis, electrochemical and Na+ binding properties.
cis-Bis(2,2'-bipyridyl)dichlororuthenium(II)dihydrate complexed with Schiff bases salen (L1H2) and salophen (L2H2) provides complexes of compositions [Ru(L1)(bpy)2] 1 and [Ru(L2)(bpy)2] 2, respectively with cavity. The structure of these complexes characterized by spectroscopic studies were supported by their optimized geometries based on DFT calculations. Complexes 1 and 2 were then allowed to interact with methanolic solution of sodium perchlorate separately providing corresponding complexes 3 and 4 with the compositions 1.NaClO4 and 2.NaClO4, respectively. The formation constants were then evaluated by monitoring the changes in their UV-visible spectral features upon addition of different amount of sodium salts in the presence of a fixed concentration of the ruthenium complexes at a wavelength 294 nm. Emission (solution), luminescence microscopic and cyclic voltammetric studies of these complexes have also been made.


HPLC-NMR for tissue-specific analysis of phenylphenalenone-related compounds in Xiphidium caeruleum (Haemodoraceae).
HPLC-(1)H NMR has been used to study the tissue-specific distribution of phenylphenalenones, polyphenolic natural products of Xiphidium caeruleum, a neotropical member of the Haemodoraceae plant family. The present results provide insight into the occurrence of phenylphenalenone-related compounds in root segments of whole plants and different in vitro culture lines of the same species.


The use of a 51Cr technique to detect gastrointestinal microbleeding associated with nonsteroidal antiinflammatory drugs.
Of techniques used to evaluate gastrointestinal (GI) bleeding, use of radiochromium (51Cr)-tagged erythrocytes is the most quantitative and scientifically acceptable method. The value of this technique as well as systematic errors possible with its use are discussed. The medical literature concerning 51Cr evaluation of GI microbleeding with naproxen therapy is critically reviewed. We suggest that future studies using this technique be parallel, randomized, double-blind, and include a 1-week placebo baseline phase for all subjects. Treatment with nonsteroidal antiinflammatory drugs (NSAIDs) should last 3 to 4 weeks. A parallel group of subjects should receive placebo throughout the study. For valid statistical analyses, randomization must achieve baseline comparability of weight, height, age, and sex in the treatment groups. Data transformations may be necessary to satisfy the assumptions of the statistical model. Following these guidelines will enable investigators to better evaluate GI microbleeding during treatment with naproxen or other NSAIDs, and, hopefully, to establish the safety profiles of these drugs.


Lhx2 regulates the timing of β-catenin-dependent cortical neurogenesis.
The timing of cortical neurogenesis has a major effect on the size and organization of the mature cortex. The deletion of the LIM-homeodomain transcription factor Lhx2 in cortical progenitors by Nestin-cre leads to a dramatically smaller cortex. Here we report that Lhx2 regulates the cortex size by maintaining the cortical progenitor proliferation and delaying the initiation of neurogenesis. The loss of Lhx2 in cortical progenitors results in precocious radial glia differentiation and a temporal shift of cortical neurogenesis. We further investigated the underlying mechanisms at play and demonstrated that in the absence of Lhx2, the Wnt/β-catenin pathway failed to maintain progenitor proliferation. We developed and applied a mathematical model that reveals how precocious neurogenesis affected cortical surface and thickness. Thus, we concluded that Lhx2 is required for β-catenin function in maintaining cortical progenitor proliferation and controls the timing of cortical neurogenesis.


Occurrence, spatial distributions, and ecological risk of pyrethroids in coastal regions of South Yellow and East China Seas.
Pyrethroids are increasingly receiving attention as aqueous micropollutants, but their presence has been reported only in a few small coastal areas. In this study, we investigated the distribution, sources, and risks of nine pyrethroids in large marine zones. The 40 seawater samples were collected from the South Yellow Sea (SYS) and East China Sea (ECS) in China, during the spring of 2020, using a high-volume, solid-phase extraction method. The total pyrethroid concentrations ranged from 0.72 to 1.82 ng L-1 in the SYS and from 0.02 to 11.0 ng L-1 in the ECS. We used cluster analysis to classify pollutant sources into five categories, and discussed the influence of sources on the transport and distribution of pyrethroids in each group. Ecological risk assessment indicated that pyrethroids pose a high risk to crustaceans and a negligible risk to others. These results are important for understanding the behavior of pyrethroids in marine environments.


Good evidence for effectiveness of analgesics most commonly prescribed by UK dentists. What is the relative efficacy of single-dose oral analgesics after third molar extraction?
Dental trials were sought among systematic reviews of randomised, double-blind studies of analgesics in acute pain, which were identified from the Cochrane Library, Biological Abstracts, MEDLINE, PubMed and the Oxford Pain Relief database. Data were extracted independently by two reviewers. Dichotomous information from active and placebo treatments was used, first to calculate the statistical significance using relative risk, and then to evaluate the clinical relevance using number-needed-to-treat (NNT). Nonsteroidal anti-inflammatory drugs (NSAID) and cyclooxygenase (COX)-2 inhibitors had the lowest (best) NNT for the outcome of pain at least halved over 4-6 h compared with placebo. With the best performing analgesics, 50-70 patients out of 100 had good pain relief compared with about 10 out of 100 with placebo. Only paracetamol (600/650 mg) plus codeine (60 mg) was associated with any significant increase in any patient experiencing an adverse event. NSAID and COX-2 inhibitors have the lowest (best) NNT. These may also have fewer adverse effects after third molar surgery, but conclusive evidence is lacking. At least 80% of analgesic prescribing by UK dentists is in line with the best available evidence on efficacy and safety.


The influence of various aetiopathogenetic factors on testicular function.
Three hundred and seventy-one patients with azoospermia were examined by means of testicular biopsy. The patients were assigned to seven histological groups according to the degree of damage found in their germinative epithelium. The degree of damage to the germinative epithelium was correlated with the aetiopathogenetic factors.


The interleukin-10-1082 G/A polymorphism: allele frequency in different populations and functional significance.
Genotypic variation in the human interleukin-10 (IL-10) promoter may account for marked inter-individual variation in IL-10 production and may influence susceptibility to autoimmune diseases. The G/A polymorphism at position -1082 has been linked to high/low IL-10 producer status. We directly tested the functional significance of this polymorphism using DNA-binding assays and reporter gene assays, examined allele frequencies in two geographically distinct populations and assessed intra- and inter-individual variation in IL-10 production in vitro according to genotype. Functional analyses showed that the -1082 region contains a putative ETS-like transcription factor-binding site, and nuclear factors from a monocyte cell line bind to this region. Transient transfection studies in an Epstein-Barr virus-transformed B cell line indicated that the -1082 A allele confers a two fold increase in transcriptional activity of the IL-10 promoter compared to the G allele. There was marked inter-individual variation in IL-10 production by peripheral blood mononuclear cells in vitro, with no consistent effect of genotype.


Prospective evaluation of drug eluting self-apposing stent for the treatment of unprotected left main coronary artery disease: 1-year results of the TRUNC study.
To assess long-term safety and efficacy of the Xposition S self-apposing stent in the treatment of unprotected left main coronary artery (ULMCA) disease. Percutaneous intervention with stents has emerged as a valid alternative to surgical revascularization to treat ULMCA disease. Conventional balloon-expandable stents face technical challenges, particularly in large left main diameter requiring extensive optimization and side branch access in distal bifurcation. Xposition S allows for optimal apposition, bridging diameter differences, and allows expansion to vessel diameters up to 6.0 mm. Between June 2016 and July 2017, 205 patients were enrolled in this international, prospective, multicenter registry. Patients with SYNTAX score ≥ 33 or recent STEMI were excluded. IVUS during procedure was performed in a prespecified subgroup of 50 patients. The primary clinical endpoint was 12 months Target lesion failure (TLF) and the primary efficacy endpoint was angiographic success. Distal left main bifurcation was involved in 92.7%, treated with provisional approach in most cases (79.4%). TLF rate at 12 months was 8.3%, which was defined as a composite of cardiac death (2.0%), target-vessel MI (2.9%), and TLR (5.4%). Most revascularizations occurred at SB ostium. IVUS analysis demonstrated optimal stent apposition with only one reported malapposition and promising poststenting minimal stent area measures. The TRUNC study confirms that Xposition S self-apposing stent is a valid and feasible option for the treatment of ULMCA disease. Such results were reached without the systematic need of stent optimisation techniques, focusing mainly on lesion treatment.


Angiographic and magnetic resonance imaging evaluation of in-hospital delay in primary percutaneous intervention delivery on myocardial salvage.
Shortening symptom-to-reperfusion time improves prognosis in patients with ST-segment elevation myocardial infarction. Accordingly, current guidelines target a door-to-balloon time <90 minutes, irrespective of symptom-to-door time; nevertheless, the relation between door-to-balloon and symptom-to-door time and its potential impact on myocardial salvage remains largely unknown. We investigated the influence of door-to-balloon guideline fulfillment on myocardial salvage in patients presenting with different symptom-to-door times. Contrast-enhanced magnetic resonance study was performed acutely to measure infarct size in 172 patients admitted for primary percutaneous coronary intervention of their first ST-segment elevation myocardial infarction to 2 tertiary hospitals. The Bari score was adapted to quantify the angiographic area at risk, and the myocardial salvage index (MSI) was computed as percent area at risk that spared necrosis. Increased symptom-to-balloon time was associated with a significant decrease in MSI only within the first 5 hours (p <0.001). Accomplishment of a target door-to-balloon <90 minutes was associated with a significant increase in MSI only in patients presenting within the first hour of symptom onset (48.5 ± 30.9 vs 29.6 ± 22.3%, p <0.05). Achieving a door-to-balloon time <60 minutes further increased MSI in patients presenting within the second hour of symptoms (43.5 ± 8.6 vs 26.3 ± 20.5%, p <0.01). In conclusion, myocardial salvage progressively decreases up to 5 hours after symptom onset. However, the benefit of the recommended door-to-balloon time appears to be confined to patients presenting within 1 hour of symptom onset.


Detecting compensatory movements of stroke survivors using pressure distribution data and machine learning algorithms.
Compensatory movements are commonly employed by stroke survivors during seated reaching and may have negative effects on their long-term recovery. Detecting compensation is useful for coaching the patient to reduce compensatory trunk movements and improving the motor function of the paretic arm. Sensor-based and camera-based systems have been developed to detect compensatory movements, but they still have some limitations, such as causing object obstructions, requiring complex setups and raising privacy concerns. To overcome these drawbacks, this paper proposes a compensatory movement detection system based on pressure distribution data and is unobtrusive, simple and practical. Machine learning algorithms were applied to classify compensatory movements automatically. Therefore, the purpose of this study was to develop and test a pressure distribution-based system for the automatic detection of compensation movements of stroke survivors using machine learning algorithms. Eight stroke survivors performed three types of reaching tasks (back-and-forth, side-to-side, and up-and-down reaching tasks) with both the healthy side and the affected side. The pressure distribution data were recorded, and five features were extracted for classification. The k-nearest neighbor (k-NN) and support vector machine (SVM) algorithms were applied to detect and categorize the compensatory movements. The surface electromyography (sEMG) signals of nine trunk muscles were acquired to provide a detailed description and explanation of compensatory movements. Cross-validation yielded high classification accuracies (F1-score>0.95) for both the k-NN and SVM classifiers in detecting compensation movements during all the reaching tasks. In detail, an excellent performance was achieved in discriminating between compensation and noncompensation (NC) movements, with an average F1-score of 0.993. For the multiclass classification of compensatory movement patterns, an average F1-score of 0.981 was achieved in recognizing the NC, trunk lean-forward (TLF), trunk rotation (TR) and shoulder elevation (SE) movements. Good classification performance in detecting and categorizing compensatory movements validated the feasibility of the proposed pressure distribution-based system. Reliable classification accuracy achieved by the machine learning algorithms indicated the potential to monitor compensation movements automatically by using the pressure distribution-based system when stroke survivors perform seated reaching tasks.


Treatment of extensive aortic aneurysms by a new multiple-stage approach.
A new multiple-stage approach to extensive aneurysmal disease of the aorta is presented. The method is designed to obviate the proximal graft-to-aorta anastomosis in second-stage and third-stage aortic replacement to simplify and facilitate these operative steps. Since 1981 a total of 17 such procedures were performed in seven patients with dissecting and nondissecting aneurysms without deaths or complications related to the method.