Maternal occupation and term low birth weight in a predominantly latina population in los angeles, california.
Focusing on Latinas, we investigated whether maternal occupations during pregnancy increase term low birth weight (TLBW) (less than 2500 g; 37 weeks or more). In a case-control study (n = 1498) nested within a 2003 birth cohort (n = 58,316) in Los Angeles County, California (65% Latina), we assessed the influence of maternal occupation on TLBW, using Occupational Codes based on the 2000 US Census Occupational Classification System. Odds ratios (ORs) for TLBW were increased among women working during pregnancy in "transportation and material moving operations" (adjusted OR = 3.28; 95% confidence interval = 1.00 to 10.73), "food preparation and serving occupations" (adjusted OR = 3.03, 95% confidence interval = 1.21 to 7.62), or "production occupations" (adjusted OR = 2.63, 95% confidence interval = 1.01 to 6.82) compared with "office occupations;" 73% to 93% of women working in these higher-risk jobs were immigrant Latinas. Working conditions in various jobs held mainly by first-generation immigrant Latinas increase risks for TLBW and need to be addressed to develop strategies to reduce TLBW.


Lentiviral-based BMP4 in vivo gene transfer strategy increases pull-out tensile strength without an improvement in the osteointegration of the tendon graft in a rat model of biceps tenodesis.
The present study aimed to develop a rat model of biceps tenodesis and to assess the feasibility of a lentiviral (LV)-based bone morphogenetic protein (BMP) 4 in vivo gene transfer strategy for healing of biceps tenodesis. A rat model of biceps tenodesis was developed with an interference-fit open surgical technique. A LV vector expressing a BMP4 gene or β-galactosidase (β-gal) control gene was applied to the bone tunnel and the tendon graft before its insertion into the bone tunnel. Osteointegration was assessed by histology and pull-out tensile strength was measured by a biomechanical test suitable for small rat biceps tendon grafts. Neo-chondrogenesis was seen at the tendon-bone interface of LV-BMP4-treated but not control rats. The LV-BMP4-treated rats showed 32% (p < 0.05) more newly-formed trabecular bone at the tendon-bone junction than the LV-β-gal-treated controls after 3 weeks. However, the sites of neo-chondrogenesis and new bone formation in the LV-BMP4-treated tenodesis were highly spotty. Although the LV-BMP4 strategy did not promote bony integration of the tendon graft, it yielded a 29.5 ± 11.8% (p = 0.066) increase in improvement the pull-out strength of rat biceps tendons compared to the LV-β-gal treatment after 5 weeks. Although the LV-BMP4 in vivo gene transfer strategy did not enhance osteointegration of the tendon graft, it yielded a marked improvement in the return of the pull-out strength of the tendon graft. This presumably was largely a result of the bone formation effect of BMP4 that traps or anchors the tendon graft onto the bony tunnel.


Comparison of the levels of depression and anxiety in elderly aortic stenosis patients treated with surgical or transcatheter aortic valve replacement.
Currently, only a few studies have been conducted on the mental status recovery in elderly aortic stenosis (AS) patients after treatment. How transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR) differentially impinge on the mental status of elderly AS patients is completely unknown. The present prospective study aims to investigate this question by comparing the post-treatment levels of depression and anxiety, quality of life and frailty. A total of 120 elderly patients (age above 70) with symptomatic AS were included, where 78 of them were treated with TAVR and 42 of them were treated with SAVR. Levels of depression and anxiety, quality of life and frailty were assessed by the Chinese version of Hospital Anxiety and Depression Scale (HADS), World Health Organization Quality of Life Instrument-Older Adults Module (WHOQOL-OLD) and clinical frailty scale, respectively. Scores were recorded and compared at admission, 1 month, 4 months and 8 months after treatment. Before treatment, both patient groups had similar baseline characteristics and all mental parameters. During the follow-up period, patients in the TAVR group demonstrated significant improvement in all assessed mental parameters to certain extent compared to the SAVR group. Specifically, frailty was significantly improved in the TAVR-treated patients at all three follow-up time points. Levels of depression and anxiety were significantly improved 8 months after treatment, although the remaining patient number is limited. Quality of life was only significantly improved 1 month after treatment. TAVR may provide a better mental recovery outcome in elderly AS patients.


Flumazenil may attenuate some subjective effects of nitrous oxide in humans: a preliminary report.
Two double-blind, randomized, crossover trials were conducted to study whether the benzodiazepine antagonist, flumazenil, would interact with the subjective and psychomotor effects of nitrous oxide in healthy volunteers. In both experiments, eight subjects inhaled 30% nitrous oxide in oxygen for 35 min and were challenged, 10 min into the inhalation, with flumazenil. Experiment 1 tested a range of flumazenil doses used clinically (0, 0.25, 0.5, and 1.0 mg/70 kg) whereas Experiment 2 tested a supraclinical flumazenil dose (0 and 5.0 mg/70 kg). Nitrous oxide increased mood ratings of "high," "drunk," and "tingling," and decreased psychomotor performance as assessed by the Digit Substitution Test. Flumazenil, at the supraclinical dose, significantly lowered the mood rating of "high." Decreases, though not significant (p < 0.10), were also obtained on the ratings "drunk," "elated," and "drug liking". Flumazenil, in both experiments, did not interact with the psychomotor effects of nitrous oxide. It appears that flumazenil, at a dose higher than that used clinically, may antagonize some of the subjective effects produced by nitrous oxide in humans.


Local infiltration of the surgical wound with levobupivacaine, ibuprofen, and epinephrine in postoperative pain: An experimental study.
The body areas from where sutures are removed later, where wound healing is delayed. Epidural analgesia is the most effective method but could not be used for postoperative pain. Peripheral nerve blockers also provided excellent analgesia but are not effective in postoperative pain. Infiltration of the surgical wound with local anesthetics is decreased postoperative pain by inhibiting transmission of noxious impulses at the site. The objective of the study was to explore the effect of the local infiltration of the surgical wounds with low-dose of levobupivacaine, ibuprofen, and epinephrine over the sutured muscle wound in postoperative pain. Laparotomy was performed in adult rats under isoflurane anesthesia. During surgery, the surgical wounds were infiltrated with 50μL solution containing 0.3% w/v levobupivacaine, 2mg/mL ibuprofen, and 8mg/mL epinephrine (treatment group) and compared to infiltration of that of water for injection (vehicle group) over the sutured muscle wound before skin closing. Postoperative pain was assessed by rodent grimace scales scoring. The study also carried out for measurement for histopathological examinations and the tensile strength of wound. The one-way ANOVA following the Dunnett Multiple comparisons test was used to show significant differences between parameters at 95% level of confidence. The fall in pain started with three-hour post-surgery in the treatment group. At 24h after the end of the successful infiltration, the treatment group had significant reduction of a pain than vehicle group (p=0.048; q=3.527). After three weeks of the wound were closed, a significant improvement of angiogenesis process (p=0.021) and the tensile strength (p=0.019) for the treatment group as compared to baseline. The experimental study was reported that local infiltration of the surgical wound with levobupivacaine, ibuprofen, and epinephrine combination was effective in the postoperative pain and healing of the surgical wounds.


Variants in nucleotide excision repair core genes and susceptibility to recurrence of squamous cell carcinoma of the oropharynx.
Genetically determined capacity for NER may modulate both cancer risk and prognosis. Thus, we evaluated associations of seven selected variants in the NER core genes with recurrence risk in 658 squamous cell carcinoma of the oropharynx (SCCOP) patients treated principally by radiation. The seven polymorphisms in the core NER genes (XPC-rs2228000, XPC-rs2228001, XPD-rs1799793, XPD-rs13181, XPG-rs17655, ERCC1-rs3212986 and XPA-rs1800975) were genotyped using PCR-RFLP method and log-rank test and multivariable Cox models were used to evaluate the associations in both dominant and recessive genetic models. In a dominant model, we found that polymorphisms of XPC-rs2228000, XPD-rs1799793 and XPG-rs17655 were significantly associated with disease-free survival (log-rank, p = 0.014; p = 0.00008; p = 0.0007, respectively), and these polymorphisms were significantly associated with recurrence risk of SCCOP (hazard ratio (HR) = 1.6, 95% confidence interval (CI) 1.1-2.3 for XPC-rs2228000; HR = 0.4, 95% 0.3-0.6 for XPD-rs1799793 and HR = 0.5, 95% CI 0.4-0.8 for XPG-rs17655) after multivariable adjustment. Moreover, the borderline significant or significant associations were also found for these three polymorphisms in HPV16/18-positive SCCOP patients (HR = 1.6, 95% CI 1.0-4.1 for XPC-rs2228000; HR = 0.2, 95% CI 0.1-0.5 for XPD-rs1799793 and HR = 0.1, 95% CI 0.0-0.9 for XPG-rs17655). However, similarly significant associations were not found for these polymorphisms in a recessive model. These findings suggest that polymorphisms of XPC-rs2228000, XPD-rs1799793 and XPG-rs17655 in the NER core genes may contribute to recurrence risk of SCCOP, particularly HPV-positive SCCOP, in a dominant but not in a recessive model. However, validation of these results is warranted.


Lung Cancer in Patients With Lynch Syndrome: Association or Coincidence?
Lynch syndrome (LS), also known as hereditary nonpolyposis colorectal cancer (HNPCC) occurs due to microsatellite instability (MSI) caused by mutations in one of the mismatch repair genes leading to deficient mismatch repair proteins (dMMR). Although lung cancer is very common there is no established association between LS and lung cancer. In this manuscript we describe a case of lung cancer in a LS patient and then summarize available literature on this topic. Sixty seven y/o female patient with history of stage I colon and urothelial cancer, meeting the Amsterdam criteria, was diagnosed with LS on genetic testing. Sixteen years after the diagnosis of colon cancer, she was found to have adenocarcinoma of the lung with Next-generation sequencing (NGS) testing revealing the presence of germline mutation in MSH2 in the tumor cells indicating the possibility of LS driven lung cancer. However, subsequent immunohistochemistry (IHC) on tumor cells indicated proficient mismatch repair genes confirming the sporadic nature of lung cancer. On review of literature, we found that the coincidental presence of lung cancer in patients with LS can sometimes be mistaken for causation and may lead to confusion. Lynch syndrome associated tumors which are microsatellite instable (MSI) can be treated effectively with immunotherapy with durable responses, however, not all tumors in patient with LS are MSI impacting the choice of therapy.


Human milk feeding.
This article examines the factors to be considered in providing optimal nutritional care to the infant fed human milk. These factors include the nutrient and non-nutrient composition of human milk, nutrient requirements of full-term and premature infants, the timing and need for supplementary or complementary foods, and the role of milk-based formulas.


Imaging of elbow disorders.
Numerous modalities are available for imaging the elbow. Radiographs should be the first imaging procedure performed for evaluation of an elbow abnormality. The use of advanced imaging modalities such as MR imaging, CT, and sonography also is discussed in this article.


Influence of algal farming on fish assemblages.
We examined the influence of algal farming on fish assemblages in two shallow coastal lagoons in Zanzibar, Tanzania. Fish assemblages were visually investigated using a belt transect method and the line-intercept technique was used to examine the substrate composition. 101 species of fish belonging to 31 families were recorded. Algal farming affected the associated fish fauna in terms of abundance, species richness, trophic identity and fish community composition. However, the impact differed between the lagoons. Algal farms in one lagoon hosted a more abundant and diversified fish fauna than controls, whereas farms in the other lagoon exhibited lower fish densities and similar species diversity compared to controls. The discrepancies between lagoons may be an effect of differences in farming intensity and character of the substratum.


Insulin subcutaneous application vs. continuous infusion for postoperative blood glucose control in patients with non-insulin-dependent diabetes mellitus.
Frequently, the use of insulin is considered for metabolic control in postoperative patients with non-insulin-dependent diabetes mellitus (NIDDM). We sought to determine the best method for control of glucose in NIDDM non-insulin patients during postoperative care. Two algorithms were developed: subcutaneous administration of insulin (SC), and continuous intravenous infusion (IV). A randomized, controlled clinical trial was designed. In addition, both experimental groups were compared with a non-concurrent routinely managed group (RM) with insulin administration under no predetermined algorithm. Eligible patients were those subjected to major surgery under general anesthesia or spinal blockade. They were followed for 48 h after surgery. Target variables were capillary and central blood glucose, insulin dose administered, urine glucose and ketone strip determination, and development of hyper- or hypoglycemia. A total of 62 patients were studied (RM = 25, SC = 19, IV = 18). Results for both experimental algorithms were similar except for the IV group that required less insulin per hour compared to SC (0.64 vs. 0.34 U/h; p = 0.0003). The RM control group showed poor control in all capillary glucose measurements (194.9 +/- 26.8 mg/dL) compared with the two experimental algorithms (SC = 129.9 +/- 21; IV = 131.6 +/- 20.4) (p <0.05). More hyperglycemia events appeared in the RM group (p = 0.016). Only one hypoglycemia event occurred in the IV group. Postoperative control of NIDDM is similar with both tested methods. The use of any of the algorithms studied improves metabolic control substantially because it standardizes postoperative management of the diabetic patient with timely determination of capillary blood glucose and insulin administration. However, IV administration has the advantage of accomplishing adequate control with a smaller insulin dose.


Plantar pressure distribution in hallux valgus feet after a first metatarsal proximal crescentic osteotomy with a lesser metatarsal proximal shortening osteotomy.
Plantar pressure distribution after the first metatarsal proximal crescentic osteotomy (FMPCO) with lesser metatarsal proximal shortening osteotomy (LMPSO) for hallux valgus with metatarsalgia has not been previously described. The pre- (Pre) and postoperative (Post) groups comprised of 18 patients who underwent unilateral FMPCO with LMPSO; fifteen healthy volunteers constituted the control (C) group. For each of the 10 regions, peak pressure (Peak-P), maximum force (Max-F), contact time (Con-T), contact area (Con-A), and force-time integral (FTI) were measured. The mean Peak-P of the second metatarsal head was significantly lower in the Post group than the Pre group. The mean Peak-P, Max-F, Con-T, and FTI were not significantly different between the Post and C groups. The mean Con-A was significantly lower in the Post group than the C group. FMPCO with LMPSO may improve the plantar pressure of the central forefoot comparable to healthy subjects.


Sorption and pH determine the long-term partitioning of cadmium in natural soils.
The bioavailability of metals in soil is a dynamic process. For a proper extrapolation to the field of laboratory studies on fate and effects, it is important to understand the dynamics of metal bioavailability and the way it is influenced by soil properties. The aim of this study was to assess the parallel (concurrent) effect of pH and aging time on the partitioning of cadmium in natural LUFA 2.2 soil. Cadmium nitrate-spiked pH-amended LUFA 2.2 soils were incubated under laboratory conditions for up to 30 weeks. Measured pHpw was lower after 3 weeks and decreased only slightly toward the end of the test. Cadmium concentrations in the pore water increased with time for all soil pH levels, while they decreased with increasing pH. Freundlich kf values ranged between 4.26 and 934 L kg(-1) (n = 0.79 to 1.36) and were highest at the highest pH tested (pH = 6.5). Multiple linear regression analysis, based on a soil ligand modeling approach, resulted in affinity constants of 2.61 for Ca(2+) (log KCa-SL) and 5.05 for H(+) (log KH-SL) for their binding to the active sites on the soil surface. The results showed that pH and aging time are two important factors which together affect cadmium partitioning and mobility in spiked natural soils.


Sinonasal fibrosarcoma: analysis of the Surveillance, Epidemiology, and End Results database.
Primary fibrosarcoma of the sinonasal region is an infrequently occurring malignant neoplasm. Fibrosarcomas are most commonly found in the extremities, with only 1% of fibrosarcomas reported in the head and neck region. This study analyzes the demographic, clinicopathologic, and survival characteristics of sinonasal fibrosarcoma (SNFS). The Surveillance, Epidemiology, and End Results (SEER) database (1973 to 2012) was queried for SNFS cases. Data were analyzed with respect to various demographic and clinicopathologic factors. Survival was analyzed using the Kaplan-Meier model. Fifty-one cases of fibrosarcoma were identified in the sinonasal region. The mean age at diagnosis was 54.5 years and the mean survival was 119.7 months. There was no gender predilection with a male-to-female ratio of 1.04:1. The maxillary sinus was the most common site of involvement (54.9%), followed by the nasal cavity (23.5%). Five-year survival analysis revealed an overall survival rate of 71.7%, disease-specific survival rate of 77.8%, and relative survival (RS) rate of 78.8%. Disease-specific survival was better among those treated with surgery (with [76.2%] or without [87.5%] adjuvant radiotherapy) than those treated with primary radiotherapy alone (33.3%) (p = 0.0069). SNFS is a rare entity. This study represents the largest series of SNFS to date. The mainstay of treatment for this tumor is surgical resection with or without radiotherapy.


Peripheral venous bullet embolization to the heart. Case report and review of the literature.
Peripheral venous bullet embolization to the heart is a rare event. We report our experience with one patient who suffered peripheral venous bullet embolization to the right ventricle and review the 38 patients with this phenomenon previously reported in the literature. The clinical presentation of patients with peripheral venous bullet embolization to the right ventricle is discussed. In addition, the indications for surgery and the therapeutic approaches available to patients with bullet embolization are discussed.


Pharmacokinetic and pharmacodynamic studies of infusions with [Sar 1, Val5, Ala8] angiotensin II (saralasin).
A modification of the infusion test with saralasin, an angiotensin II antagonist for the detection of renin-dependent high blood pressure was studied in renal hypertensive rats and in normotensive and hypertensive subjects. Infusion was started at a rate of 0.01 microgram/kg x min saralasin and the dose was increased ten-fold at 15 min intervals. A significant fall of diastolic blood pressure was observed at the dose of 0.1 microgram/kg x min in renal hypertensive rats, in healthy subjects treated with diuretics, and in patients with renovascular hypertension (saralasin responders). Plasma concentrations of angiotensin I, angiotensin II and of saralasin as well as plasma renin activity were measured. At the lowest infusion rate of 0.01 microgram/kg x min, saralasin plasma levels were 40-fold higher than plasma angiotensin II levels. The decrease in arterial blood pressure occurred at lower doses of saralasin than the increase of plasma renin due to inhibition of feedback on the renin secreting cells. It is concluded that if the saralasin test is performed by a stepwise increase of the infusion rate, potentially dangerous complications such as hypo- or hypertensive reactions can be avoided. The diagnostic reliability is improved by such a procedure since false positive and false negative responses may be prevented. The pressor effect of saralasin in non-renin dependent patients is an advantage since it causes a more marked difference of blood pressure change between saralasin responders and non-responders.


Comparison of speed of sound and ultrasound attenuation in the os calcis to bone density of the radius, femur and lumbar spine.
Broadband ultrasonic attenuation (BUA) between 0.1 and 0.6 MHz and speed of sound (SOS) were measured on the os calcis in normal women (n = 40), and women who had mild osteoporosis (n = 36). Comparisons were made between the ultrasonic properties and bone mineral densities (BMD) obtained using photon absorptiometry on the lumbar spine, proximal femur and radius shaft. In the osteoporotic women, whose spine BMD was significantly reduced, BUA and SOS were lower, to about the same degree of significance as radius BMD; ROC analysis demonstrated that for discrimination of spinal osteopenia, the area under the ROC curve was similar for radius BMD, SOS, and BUA. There was a modest correlation (r about 0.65) between either SOS or BUA on the os calcis and BMDs of the spine and radius. Correlations of the SOS and BUA with femoral neck BMD were lower (r about 0.4 to 0.5). The standard error of estimate for both spine and femoral neck BMD was too high (about 0.14 g cm-2) for os calcis measurements to be substituted clinically for densitometry at these fracture sites.


Early identification of promiscuous attributes of aldose reductase inhibitors using a DMSO-perturbation assay.
Aldose reductase (AR) inhibitors are used clinically to treat long-term diabetic complications. Previous studies reported a series of AR inhibitory candidates, but unfortunately the mode of inhibition was poorly described due mainly to the lack of readily available methods for evaluating the specificity. The present study examined the AR inhibitory effects of novel synthetic hydantoins and their structural relatives, some of which were obtained from chemically engineered extracts of natural plants, and discovered several novel AR inhibitors with moderate inhibitory activity. The identified inhibitors were then subjected to a two-step mechanistic characterization using a detergent-addition assay and our novel dimethyl sulfoxide (DMSO)-perturbation assay. The detergent-addition assay revealed aggregation-based inhibitors, and the subsequent DMSO-perturbation assay identified nonspecific binding inhibitors. Thus, the present study demonstrates the usefulness of the DMSO-perturbation screen for identifying nonspecific binding characteristics of AR inhibitors.


A Triazolium-Anchored Self-Immolative Linker Enables Self-Assembly-Driven siRNA Binding and Esterase-Induced Release.
The increased importance of RNA-based therapeutics comes with a need to develop next-generation stimuli-responsive systems capable of binding, transporting and releasing RNA oligomers. In this work, we describe triazolium-based amphiphiles capable of siRNA binding and enzyme-responsive release of the nucleic acid payload. In aqueous medium, the amphiphile self-assembles into nanocarriers that can disintegrate upon the addition of esterase. Key to the molecular design is a self-immolative linker that is anchored to the triazolium moiety and acts as a positively-charged polar head group. We demonstrate that addition of esterase leads to a degradation cascade of the linker, leaving the neutral triazole compound unable to form complexes and therefore releasing the negatively-charged siRNA. The reported molecular design and overall approach may have broad utility beyond this proof-of-principle study, because the underlying CuAAC "click" chemistry allows bringing together three groups very efficiently as well as cleaving off one of the three groups under the mild action of an esterase enzyme.


Cerebral blindness and encephalopathy with cyclosporin A toxicity.
We observed acute cerebral blindness and encephalopathy complicating cyclosporin A (CyA) toxicity in a 5-year-old transplantation patient. Serum CyA level was 1,704 ng/ml (normal, less than 300 ng/ml). Additional neurologic complications of CyA toxicity will be reviewed.


xPM: Enhancing exogenous data visibility.
Process mining is a well-established discipline with applications in many industry sectors, including healthcare. To date, few publications have considered the context in which processes execute. Little consideration has been given as to how contextual data (exogenous data) can be practically included for process mining analysis, beyond including case or event attributes in a typical event log. We show that the combination of process data (endogenous) and exogenous data can generate insights not possible with standard process mining techniques. Our contributions are a framework for process mining with exogenous data and new analyses, where exogenous data and process behaviour are linked to process outcomes. Our new analyses visualise exogenous data, highlighting the trends and variations, to show where overlaps or distinctions exist between outcomes. We applied our analyses in a healthcare setting and show that clinicians could extract insights about differences in patients' vital signs (exogenous data) relevant to clinical outcomes. We present two evaluations, using a publicly available data set, MIMIC-III, to demonstrate the applicability of our analysis. These evaluations show that process mining can integrate large amounts of physiologic data and interventions, with resulting discrimination and conversion to clinically interpretable information.


Adiponectin is associated with poor prognosis in carcinoma patients: evidence from a meta-analysis.
Studies have come to conflicting conclusions about whether adiponectin (APN) expression is associated with cancer prognosis. To help resolve this question, we meta-analyzed the available evidence. PubMed, EMBASE, the Cochrane Library, the Chinese Biological Medical Database and the Chinese National Knowledge Infrastructure Database were systematically searched to identify all eligible studies examining APN expression and prognosis for patients with any type of cancer. Pooled hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) related to overall survival (OS) or disease-free survival (DFS) were calculated. Ten studies involving 999 patients were meta-analyzed. Analysis across all patients revealed no significant association between high/positive APN expression and DFS, but they did show a significant association between high/positive APN expression and OS (HR 1.51, 95 %CI 1.21 to 1.89). Subgroup analysis showed that high/positive APN expression in non-Asians was significantly associated with both DFS (HR 1.36, 95% CI 1.03 to 1.80) and OS (HR 1.53, 95 %CI 1.20 to 1.96), but no such associations were observed in Asians. In addition, high/positive APN expression was significantly associated with OS across all patients with hepatocellular carcinoma (HR 1.89, 95 %CI 1.20 to 2.98). The available evidence suggests that high/positive APN expression is associated with poor prognosis for patients with various carcinomas, especially for non-Asian cancer patients and for all patients with hepatocellular carcinoma. These findings should be confirmed and extended in large, well-designed studies.


Understanding the Symptom Burden and Impact of Myasthenia Gravis from the Patient's Perspective: A Qualitative Study.
Patients with generalized myasthenia gravis (gMG) experience functional impairment due to MG symptoms. This study aimed to assess, from the patient perspective, the symptoms, impacts, and treatment goals of individuals diagnosed with gMG. Semi-structured, in-depth concept-elicitation interviews were conducted with 28 individuals diagnosed with gMG in the United States. Participants reported gMG symptoms that affected many body regions and functions, with an average of 16 symptoms per participant. The most frequently reported symptoms were eyelid drooping (93%), physical fatigue (89%), symptoms affecting the legs (82%), difficulty breathing (82%), and difficulty holding head up (82%). Nearly all participants (96%) reported fluctuations in symptoms and severity. Participants' most bothersome symptoms were blurry/double vision (43%), breathing difficulties (36%), all-over fatigue (36%), and swallowing problems (29%). Impacts on physical functioning included an inability to participate in hobbies/sports, need for increased planning, and difficulties performing activities of daily living. All participants reported emotional impacts and impacts on their work and finances. Their treatment goals included reduced fatigue and weakness, improved symptom stability, and minimization of the impact of symptoms, in particular the emotional impact. The fluctuating and unpredictable nature of gMG symptoms was found to have a substantial impact on patients' emotional, social, and economic well-being. Participants' goals for symptom management suggest that greater focus is needed to help them quickly resume a normal lifestyle by achieving symptom stability. Impacts of fluctuating and unpredictable symptoms are difficult to measure, but it is important to consider symptom fluctuation as well as ongoing symptomatology when making treatment decisions, and to recognize the impact of uncontrolled symptoms on patients, their partners/caregivers, and family/friends. These factors are often not reflected in burden/cost-of-illness studies.


Pelvic endometriosis: infertility and pelvic pain.
A multifactorial approach was used by the authors to analyze data from 119 women with endometriosis and infertility. Conservative surgical procedures afforded a mean pregnancy rate of 37.7 per cent for those women with significant disease. Only 6.7 per cent became pregnant when the proposed surgery was declined. There was an inverse relationship in severity of endometriotic involvement and pregnancy rate. The mean pregnancy rate among 17 patients with minimal disease for whom surgery was discouraged was 64.7 per cent; all pregnancies occurred within the first 2 years of follow-up. Relief of pelvic pain was dramatic, especially following presacral neurectomy. Laparoscopic selection of cases further reinforces the importance of grading severity of endometriosis prior to embarking on restorative surgery. Presacral neurectomy, despite reinforcement of pain relief, did not appear to contribute significantly to the occurrence of pregnancy.


Levels of thiobarbituric acid reactive substances and the cytocidal potential of gammalinolenic and docosahexaenoic acids on ZR-75-1 and CV-1 cells.
To clarify the mechanism by which gammalinolenic acid (GLA) is more tumoricidal than docosahexaenoic acid (DHA), we have compared the incorporation of the respective exogenously added ethyl esters GLAe and DHAe into the phospholipids of tumorigenic ZR-75-1 and non-tumorigenic CV-1 cells relative to the ability of the cells to survive and to accumulate thiobarbituric acid reactive substances (TBARS). GLA and DHA were incorporated in the phospholipids to the same extent, but GLA disappeared more rapidly than DHA in both cell lines. GLAe induced about twice as much intracellular TBARS as DHAe in both cell lines, but killed ZR-75-1 cells four times more effectively than DHAe. DHAe induced 11-15 fmoles malondialdehyde-equivalents (MDA-eq)/cell in both ZR-75-1 and CV-1 cells, whereas GLAe induced 5-6 times more TBARS in ZR-75-1 cells (26-30 fmoles MDA-eq/cell) than in CV-1 cells (5-6 fmoles MDA-eq/cell). The results show that there is no difference in GLA and DHA incorporation into phospholipids, but that their metabolism differs in the two cell types. The data also suggest that the cytocidal potential is related to TBARS levels in a nonlinear fashion. The relationship between excess prostaglandin production and excessive cell death due to GLA is discussed.


Integrating electronic health data records to develop and validate a predictive model of hospital-acquired acute kidney injury in non-critically ill patients.
Models developed to predict hospital-acquired acute kidney injury (HA-AKI) in non-critically ill patients have a low sensitivity, do not include dynamic changes of risk factors and do not allow the establishment of a time relationship between exposure to risk factors and AKI. We developed and externally validated a predictive model of HA-AKI integrating electronic health databases and recording the exposure to risk factors prior to the detection of AKI. The study set was 36 852 non-critically ill hospitalized patients admitted from January to December 2017. Using stepwise logistic analyses, including demography, chronic comorbidities and exposure to risk factors prior to AKI detection, we developed a multivariate model to predict HA-AKI. This model was then externally validated in 21 545 non-critical patients admitted to the validation centre in the period from June 2017 to December 2018. The incidence of AKI in the study set was 3.9%. Among chronic comorbidities, the highest odds ratios (ORs) were conferred by chronic kidney disease, urologic disease and liver disease. Among acute complications, the highest ORs were associated with acute respiratory failure, anaemia, systemic inflammatory response syndrome, circulatory shock and major surgery. The model showed an area under the curve (AUC) of 0.907 [95% confidence interval (CI) 0.902-0.908), a sensitivity of 82.7 (95% CI 80.7-84.6) and a specificity of 84.2 (95% CI 83.9-84.6) to predict HA-AKI, with an adequate goodness-of-fit for all risk categories (χ2 = 6.02, P = 0.64). In the validation set, the prevalence of AKI was 3.2%. The model showed an AUC of 0.905 (95% CI 0.904-0.910), a sensitivity of 81.2 (95% CI 79.2-83.1) and a specificity of 82.5 (95% CI 82.2-83) to predict HA-AKI and had an adequate goodness-of-fit for all risk categories (χ2 = 4.2, P = 0.83). An online tool (predaki.amalfianalytics.com) is available to calculate the risk of AKI in other hospital environments. By using electronic health data records, our study provides a model that can be used in clinical practice to obtain an accurate dynamic and updated assessment of the individual risk of HA-AKI during the hospital admission period in non-critically ill patients.


Sclerosing cholangitis epidemiology and etiology.
Sclerosing cholangitis represents a spectrum of chronic biliary diseases that either has an unknown etiology (i.e., primary) or is caused by identifiable insults to the biliary tree (i.e., secondary). To date, the epidemiology of primary sclerosing cholangitis has been appraised; however, its etiology continues to be unclear. In contrast, the etiology of secondary sclerosing cholangitis is always known, but the epidemiology of this clinical entity is difficult to study.


Adsorption of bisphenol A and 2,4-dichlorophenol onto cetylpyridinium chloride-modified pine sawdust: a kinetic and thermodynamic study.
Using biomass wastes as adsorbents is a promising option for organic waste reclamation, but unfortunately, their adsorption capacity is usually limited, especially for hydrophobic organic pollutants. To address this issue, this work prepared cetylpyridinium chloride (a cationic surfactant)-modified pine sawdust (CPC-PS) and further demonstrated their performance for hydrophobic bisphenol A (BPA) and 2,4-dichlorophenol (DCP) adsorption. Compared to the PS, the CPC-PS improved the maximum adsorption capacity for BPA and DCP by approximately 98% and 122%, respectively. The kinetic and thermodynamic analyses showed that the BPA and DCP adsorption onto the CPC-PS fitted the pseudo-second-order kinetics and the Freundlich model. After regeneration using NaOH, the adsorption capacity of the CPC-PS for BPA still maintained 80.2% of the initial value after five cycles. Based on the experimental results, the CPC-PS was proposed to enhance the BPA and DCP adsorption through the solubilization of hemimicelles for hydrophobic organic pollutants, the π-π stacking between benzene-ring structures, and the hydrogen binding between the adsorbents and the pollutants. This work provides a viable method to use surfactant-modified pine sawdust as effective adsorbents to remove hydrophobic pollutants.


Mice lacking integrin β3 expression exhibit altered response to chronic stress.
Recent studies indicate multiple roles for integrin αvβ3 in adult neurons, including response to pharmacological agents such as cocaine and selective serotonin reuptake inhibitors. In this study, we examined the role of the integrin β3 gene (Itgb3) in the response to environmental stimuli by subjecting Itgb3+/+ and Itgb3-/- mice to unpredictable chronic mild stressors. We found that genetic abrogation of integrin β3 expression elicits an exaggerated vulnerability to chronic unpredictable stress in the open field test. In this test, chronic stress elicited significant decreases in stereotypic behavior and horizontal locomotor activity, including increases in anxiety behaviors. Mild chronic stress led to reductions in dopamine turnover in midbrains of Itgb3+/+, but not Itgb3-/- mice, suggesting a disruption of stress-dependent regulation of DA homeostasis. Chronic stress elicited altered synaptic expression of syntaxin and synaptophysin in midbrains of Itgb3-/- mice, when compared to Itgb3+/+. Semi-quantitative Western blot studies revealed that the synaptic expression, but not total tissue expression, of multiple signaling proteins is correlated with integrin αv levels in the midbrain. Moreover, loss of integrin β3 expression modifies this correlation network. Together, these findings demonstrate that Itgb3-/- mice display a pattern of changes indicating disrupted regulation of midbrain synaptic systems involved in conferring resilience to mild stressors.


Characterisation of a monoclonal antibody capable of neutralising the haemorrhagic activity of West African Echis carinatus (carpet viper) venom.
A murine monoclonal antibody (SV-1/F10) was highly specific immunologically for West African E.carinatus venom both by ELISA and immunoblotting. In cross-protection tests in vivo, it possessed strong antihaemorrhagic activity. This IgGl monoclonal antibody recognised an epitope present in a protein band of 124,000 mol. wt using immunoblotting of non-reduced Nigerian and Ghanaian E.carinatus venoms, as well as in a second protein band of 105,000 mol. wt in Ghanaian E.carinatus venom. The SV-1/F10 monoclonal antibody is of potential use for the isolation of West African E.carinatus venom haemorrhagin from whole venom, allowing the possibility of elucidation of the mechanism of its actions as well as its interactions with antibody.


Pulsed linear acceleration as a vestibular stimulus in electrophysiological investigations.
A simple method of generating precisely defined pulsed linear acceleration stimuli was developed and used to study vestibular responses to cranial acceleration. Electromechanical shakers were coupled to a stimulus platform. The platform, in turn, was used to couple stimuli to the skull. Movements were controlled by a voltage waveform (V(t] applied to shakers. Software algorithms were used to synthesize voltage functions (V(t]. The resulting acceleration was monitored [a(t)] and used to generate velocity [v(t)] and position [x(t)] functions (first and second integrals of a(t), respectively). The characteristics of stimuli used in physiological experiments are described. The system provides precise control of the timing and amplitude of acceleration, velocity and position pulses to the cranium and has proved to be valuable in developing noninvasive electrophysiological measures of peripheral and central vestibular function.


EraSOR: a software tool to eliminate inflation caused by sample overlap in polygenic score analyses.
Polygenic risk score (PRS) analyses are now routinely applied across biomedical research. However, as PRS studies grow in size, there is an increased risk of sample overlap between the genome-wide association study (GWAS) from which the PRS is derived and the "target sample," in which PRSs are computed and hypotheses are tested. Despite the wide recognition of the sample overlap problem, its potential impact on the results from PRS studies has not yet been quantified, and no analytical solution has been provided. Here, we first conduct a comprehensive investigation into the scale of the sample overlap problem, finding that PRS results can be substantially inflated even in the presence of minimal overlap. Next, we introduce a method and software, EraSOR (Erase Sample Overlap and Relatedness), which eliminates the inflation caused by sample overlap (and close relatedness) in almost all settings tested here. EraSOR could be useful in PRS studies (with target sample >1,000) similar to those investigated here, either (i) to mitigate the potential effects of known or unknown intercohort overlap and close relatedness or (ii) as a sensitivity tool to highlight the possible presence of sample overlap before its direct removal, when possible, or else to provide a lower bound on PRS analysis results after accounting for potential sample overlap.


[The effect of insulin on the function of the lysosomal apparatus of the neutrophilic leukocytes during the formation of a stress syndrome].
In experiments on male rabbits with the lack of insulin it is been revealed violations after the past immobilization the intensivity and duration of neutrophilic leukocytosis decrease, contents of lysosomes in neutrophils, activity of acid phosphatase. By lysosomal ferments don't determine the can observer discordance of processes of coagulation, fibrinolysis, kininogenesis.


The IL-10 promoter polymorphism at position -592 is correlated with susceptibility to occult HBV infection.
Occult hepatitis B infection (OBI) is characterized as a form of hepatitis in which detectable amounts of HBV-DNA can be monitored in the peripheral blood of patients whereas the hepatitis B surface antigen is undetectable. The main aim of this study was to investigate whether there is a relationship between OBI and single nucleotide polymorphisms in the -592 region of the IL-10 gene. In this study, the polymorphism at position -592 of the IL-10 promoter of 57 OBI cases was compared and correlated to that of 100 healthy controls by PCR-RFLP techniques. Our results showed that patient and control groups had significant differences regarding genotypes and alleles of the -592 polymorphism in the IL-10 gene. Based on our results, it can be concluded that the -592 polymorphism within the promoter of the IL-10 gene is associated with OBI.


[Intrathyroidal iodine concentration after application of non-ionic contrast media with and without prophylactic application of perchlorate].
This study was designed to show the effect of a nonionic contrast medium (Iomeprol-300; CM) on the intrathyroidal iodine concentration with and without a concomitant medication with perchlorate (1380 mg/d) to block the thyroidal iodine uptake. Twelve volunteers recieved 100 ml Iomeprol-300 intravenously and the perchlorate prophylaxis mentioned above. Another 12 volunteers got 100 ml Iomeprol-300 only. By means of X-ray-fluorescence-analysis the intrathyroidal iodine concentration was determined in advance as well as 0.2, 1, 3, 5, 7, 24, 48, 72, and 96 hours after the application of the CM. The intrathyroidal iodine concentration did not change in the group of volunteers on perchlorate medication. Without perchlorate the intrathyroidal iodine concentration decreased after the application of the CM when it was initially high (722 +/- 66 microg/ml before, 670 +/- 65 microg/ml after CM; p = 0.046) and increased in case of a low initial concentration (327 +/- 40 microg/ml before, 381 +/- 25 microg/ml after CM; p = 0.046). The effect is significant but its magnitude is too small to be harmful for a patient with a healthy thyroid. The oral application of 1.4 g/d perchlorate inhibits the thyroidal iodine uptake and the intrathyroidal iodine concentration is unaffected by the application of a CM.


Cysteine: depolarization-induced release from rat brain in vitro.
Compounds released on depolarization in a Ca2+-dependent manner from rat brain slices were screened to identify candidates for neuroactive substances. Lyophilized superfusates were analyzed by reversed-phase HPLC after derivatization with 9-fluorenyl N-succinimidyl carbonate. One of the compounds that showed an increase of concentration in superfusates in the presence of iodoacetamide was identified as the cysteine (Cys) derivative, S-carboxamidomethylcysteine, by fast atom bombardment mass spectrometry and other methods. This stable Cys derivative originates from endogenous, extracellular Cys. The finding led to a method for quantification of Cys in superfusates by immediate cooling of the superfusates to 0 degrees C and reaction of Cys with N-ethylmaleimide. Depolarization-induced Ca2+-dependent release of Cys was most prominent in the neocortex, followed by the mesodiencephalon, striatum, and cerebellum. This suggests that Cys is released from a neuronal compartment and might be involved in neurotransmission.


Personality self-reports are concurrently reliable and valid during acute depressive episodes.
It is alleged that depression distorts the assessment of general personality traits. To test that hypothesis, we examined scores on the Revised NEO Personality Inventory (NEO-PI-R) administered to acutely depressed patients at baseline and 14 to 26 weeks after treatment with antidepressant medication. Two hundred and fifty patients completed the NEO-PI-R at baseline, 109 patients after 14 to 26 weeks of antidepressant pharmacotherapy. 48 patients (49.5%) were identified as responders while 49 (50.5%) were identified as non-responders. The remaining 12 patients were excluded because they met HRSD response criteria but not the SCID-I MDD criteria at treatment completion. At baseline, NEO-PI-R scales showed high internal consistency and replicated the normative factor structure, suggesting that psychometric properties were preserved. Among non-responders, retest correlations were uniformly high (rs=.50 to .88) and mean levels showed little change, providing evidence for the consistency of personality self-reports during an acute depressive episode. NEO-PI-R scales showed construct validity in the concurrent prediction of a number of clinical criteria. Effective treatment had significant effects on the mean levels of neuroticism, which decreased, and extraversion, openness, and conscientiousness, which increased. The participants were from a clinical database and were not randomly assigned for the treatment. The results suggest that the effect of acute depression is to amplify somewhat the personality profile of people prone to depression. Rather than regard these depression-caused changes in assessed personality trait levels as a distortion, we interpret them as accurate reflections of the current condition of the individual. Personality traits have biological bases, and when they are changed (by disease or therapeutic interventions) trait levels change.


Hydroaminoalkylation of alkenes using transition metals complexes grafted on silica SBA15 as catalysts.
The gas-phase hydroaminoalkylation reaction of propene catalyzed by group 4 (M = Ti, Zr and Hf) metal amido complexes [(≡Si-O-)(M(-NMe2)3] was investigated by using PBE0-D3/SVP//TZVP level of theory. The geometrical analysis traced the formation of the metallaaziridines and the azametallacyclopentanes as key intermediates in these reactions. The metallaaziridines were simulated through the activation of α-C-H bonds of the amido groups; while the azametallacyclopentanes were configured by slotting the propene double bond onto the M - C bonds of the metallaaziridines. The latter reaction was considered the rate-determining step. Thermochemical calculations showed that the order of catalytic activity is: Ti ≥ Zr > Hf; while the preference of the azametallacyclopentanes is: Hf > Zr ≥ Ti.


Effect of Dynamic Neuromuscular Stabilization and Vojta Therapy on Respiratory Complications in Neuromuscular Diseases: A Literature Review.
The purpose of this study was to review the literature on the effect of dynamic neuromuscular stabilization (DNS)/Vojta on respiratory complications of neuromuscular diseases. The search strategy was conducted, based on the population, intervention, comparison, and outcome method, in the PubMed, Embase, ISI Web of Knowledge, ProQuest, and Scopus databases from inception to August 2021. The quality assessment of included papers was performed through the Physiotherapy Evidence Database scale. A narrative analysis was performed since a meta-analysis could not be conducted. A total of 7 papers were chosen for the final assessment. All studies, except 1, evaluated individuals with neurological disease. Three studies evaluated Vojta therapy effects, and 4 studies evaluated DNS effects on respiratory parameters. Although the studies had limitations in their methodology according to the Physiotherapy Evidence Database scale, 4 were identified as level 1 evidence. None of the studies reported any adverse effects of Vojta therapy or DNS on respiratory parameters. However, not enough clinical trials were found to examine the effect of DNS on respiratory disease. Although the studies were weak in internal and external validity, this review suggests that Vojta therapy and DNS may influence respiratory parameters, such as blood gases, diaphragm movements, and functional respiratory parameters, in patients with neuromuscular diseases.


Differentiated HL-60 cells are a valid model system for the analysis of human neutrophil migration and chemotaxis.
We have carried out a detailed comparison of the motile properties of differentiated HL-60 cells and human peripheral blood neutrophils. We compared the effects of chemotactic stimuli and of inhibitors of signalling proteins on morphology, chemokinesis and chemotaxis of neutrophils and differentiated HL-60 cells using videomicroscopy and a filter assay for chemotaxis. We also assessed expression of signalling and cytoskeletal proteins using Western blotting. Chemotactic peptide induced a front-tail polarity in HL-60 cells comparable to that of neutrophils. Chemokinetic and chemotactic responses to chemotactic peptide were also very similar for both cell types, concerning mean speed of migration, the fraction of migrated cells and the concentration of stimulus optimal for activation. The cytokine interleukin-8 was in contrast clearly less effective in activating motile responses of differentiated HL-60 cells as compared to neutrophils. An important functional role of Rho-activated kinases and phosphatidylinositol 3-kinase in motile responses of HL-60 cells, consistent with their upregulation during differentiation, could be confirmed using inhibitors with specificity for the corresponding enzymes. The only difference observed here between HL-60 cells and neutrophils concerned the differential effects of a protein kinase C inhibitor.In summary, the results presented here show that differentiated HL-60 cells, stimulated with chemotactic peptide, are a valid model system to study molecular mechanisms of neutrophil emigration.


Association between interleukin-1, interleukin-6, and tumor necrosis factor-alpha polymorphisms and juvenile idiopathic arthritis: a meta-analysis.
In juvenile idiopathic arthritis (JIA), interleukin (IL)-1, IL-6, and tumor necrosis factor-alpha (TNF-α) are associated with development and progression of JIA. We investigated whether IL-1, IL-6, and TNF-α polymorphisms were associated with susceptibility to JIA. A meta-analysis was conducted on the associations between IL-1α-899 C/T, IL-1β-511 C/T, IL-6-174 G/C, and TNF-α-308 G/A and -238 G/A polymorphisms, and JIA (PubMed and Embase). A total of 27 studies involving 4678 JIA patients and 7634 controls were considered in the meta-analysis. There was no association between the IL-1α-899 C/T, IL-1β-511 C/T, IL-6-174 G/C, and TNF-α-308 G/A and -238 G/A polymorphisms, and JIA in allele contrast or any other genetic models. In subgroup analysis based on subtype, except for the dominant model of TNF-α-238 G/A, systemic JIA was not significantly associated with IL-6 and TNF-α polymorphisms. In Caucasians, the dominant and additive models of IL-1β-511 C/T were significantly associated with JIA (odds ratio [OR] 1.48, 95% confidence interval [CI] 1.09-2.00, P=0.01; OR 1.46, 95% CI 1.05-2.03, P=0.02, respectively). This meta-analysis showed no association between IL-1, IL-6, and TNF-α polymorphisms, and JIA, but the TT genotype of IL-1β -511 C/T was associated with higher prevalence of JIA in Caucasians.


Functional models of nonheme diiron enzymes: kinetic and computational evidence for the formation of oxoiron(iv) species from peroxo-diiron(iii) complexes, and their reactivity towards phenols and H2O2.
The reactivity of the previously reported peroxo adducts [Fe2(μ-O2)(L(1))4(CH3CN)2](2+), and [Fe2(μ-O2)(L(2))4(CH3CN)2](2+), (L(1) = 2-(2'-pyridyl)benzimidazole and L(2) = 2-(2'-pyridyl)-N-methylbenzimidazole) towards H2O2 as catalase mimics, and towards various phenols as functional RNR-R2 mimics, is described. Kinetic, mechanistic and computational studies gave direct evidence for the involvement of the (μ-1,2-peroxo)diiron(iii) intermediate in the O-H activation process via formation of low-spin oxoiron(iv) species.


[The average cell size as a factor reflecting the interaction of the CHO cells during process of proliferation].
Changes in the cell area during cultivation of the CHO line cells were studied using time-lapse technique (start of registration in one day after cell plating). It was established that the size of the daughter cells after mitosis remains lees than the size of the mother cell for a long time (up to 6 h). Nevertheless, the average cell area of the whole population is constant throughout the observation period (up to 18 h). We assume that this phenomenon could be a result of interaction among dividing and not-dividing cells. The experimental data confirming this conclusion are presented.


Railway mortality for several mammal species increases with train speed, proximity to water, and track curvature.
Railways are a major source of direct mortality for many populations of large mammals, but they have been less studied or mitigated than roads. We evaluated temporal and spatial factors affecting mortality risk using 646 railway mortality incidents for 11 mammal species collected over 24 years throughout Banff and Yoho National Parks, Canada. We divided species into three guilds (bears, other carnivores, and ungulates), compared site attributes of topography, land cover, and train operation between mortality and paired random locations at four spatial scales, and described temporal patterns or mortality. Mortality risk increased across multiple guilds and spatial scales with maximum train speed and higher track curvature, both suggesting problems with train detection, and in areas with high proximity to and amount of water, both suggesting limitations to animal movement. Mortality risk was also correlated, but more varied among guilds and spatial scales, with shrub cover, topographic complexity, and proximity to sidings and roads. Seasonally, mortality rates were highest in winter for ungulates and other carnivores, and in late spring for bears, respectively. Our results suggest that effective mitigation could address train speed or detectability by wildlife, especially at sites with high track curvature that are near water or attractive habitat.


Dapsone as Second-Line Treatment for Cutaneous Lupus Erythematosus? A Retrospective Analysis of 34 Patients and a Review of the Literature.
A variety of therapeutic options have been reported for cutaneous lupus erythematosus (CLE); one of these is dapsone. However, no high priority has been given to this drug. To determine whether dapsone is an effective and safe treatment alternative in patients with LE. We reviewed the literature and analyzed retrospectively 34 CLE patients who were treated with dapsone as monotherapy or combined with antimalarials. We assessed the course of the disease under treatment, response, concomitant treatment and side effects. Six patients went into remission, 14 patients improved, and in 6 patients disease remained constant during the observation period. Dapsone was discontinued in 9 patients: in 4 due to reversible side effects and in 5 patients due to poor efficacy. Our data confirm that dapsone with/without antimalarials is effective in more than 50% of patients with CLE and could be used as second-line therapy for CLE.


Information theoretic measures of network coordination in high-frequency scalp EEG reveal dynamic patterns associated with seizure termination.
How a seizure terminates is still under-studied and, despite its clinical importance, remains an obscure phase of seizure evolution. Recent studies of seizure-related scalp EEGs at frequencies >100 Hz suggest that neural activity, in the form of oscillations and/or neuronal network interactions, may play an important role in preictal/ictal seizure evolution (Andrade-Valenca et al., 2011; Stamoulis et al., 2012). However, the role of high-frequency activity in seizure termination, is unknown, if it exists at all. Using information theoretic measures of network coordination, this study investigated ictal and immediate postictal neurodynamic interactions encoded in scalp EEGs from a relatively small sample of 8 patients with focal epilepsy and multiple seizures originating in temporal and/or frontal brain regions, at frequencies ≤ 100 Hz and >100 Hz, respectively. Despite some heterogeneity in the dynamics of these interactions, consistent patterns were also estimated. Specifically, in several seizures, linear or non-linear increase in high-frequency neuronal coordination during ictal intervals, coincided with a corresponding decrease in coordination at frequencies <100 Hz, suggesting a potential interference role of high-frequency activity, to disrupt abnormal ictal synchrony at lower frequencies. These changes in network synchrony started at least 20-30s prior to seizure offset, depending on the seizure duration. Opposite patterns were estimated at frequencies ≤ 100 Hz in several seizures. These results raise the possibility that high-frequency interference may occur in the form of progressive network coordination during the ictal interval, which continues during the postictal interval. This may be one of several possible mechanisms that facilitate seizure termination. In fact, inhibition of pairwise interactions between EEGs by other signals in their spatial neighborhood, quantified by negative interaction information, was estimated at frequencies ≤ 100 Hz, at least in some seizures.


Predominant expression of T helper 2 cytokines and altered expression of T helper 1 cytokines in long-term allograft survival induced by intrathymic immune modulation with donor class I major histocompatibility complex peptides.
We have recently demonstrated that three synthetic peptides corresponding to the alpha-helices of the alpha1 and alpha2 domains of the donor class I RT1.Aa molecule served as efficient CD4+ T-cell epitopes for indirect recognition of this molecule during cardiac allograft rejection in the PVG.R8-toPVG.1U rat strain combination. These peptides induce long-term graft survival when injected into the thymus 7 days before transplantation under the cover of transient immunosuppression with anti-rat lymphocyte serum. In this study, we analyzed intragraft cytokine gene expression to test whether immune deviation to the T helper (Th) 2 response is associated with long-term allograft survival in this model. Intragraft cytokine gene expression was analyzed using a competitive reverse transcription polymerase chain reaction method we developed for this study. Cytokine gene expression was quantified in control allografts (n=5) with acute rejection and allografts from intrathymically manipulated recipients with acute rejection (n=5), delayed rejection (n=7), or no rejection (n=8). Long-surviving allografts expressed high levels of interleukin (IL)-4, IL-10, transforming growth factor (TGF)-beta, interferon (IFN)-gamma, and undetectable levels of IL-2. Allografts that were rejected in a delayed fashion expressed mostly IL-2, IFN-gamma, and TGF-beta with low or undetectable levels of IL-4 and IL-10. Acutely rejected allografts from unmanipulated controls or peptide-manipulated recipients expressed high levels of IL-2, IFN-gamma, TGF-beta and undetectable levels of IL-4 or IL-10. All allografts also expressed T-cell receptor Cbeta gene, providing evidence for the presence of T-cell infiltrates in the grafts. These observations demonstrate that acute graft rejection in this model is associated with the expression of Th1 cytokines, IL-2, and IFN-gamma, whereas long-term survival is associated with predominant expression of Th2 cytokines, IL-4, and IL-10. The expression of IFN-gamma in long-surviving allografts in the absence of IL-2 provides evidence for altered activation of the Th1 response in this intrathymic immune modulation model.


Autotoxicity and chemical defense: nicotine accumulation and carbon gain in solanaceous plants.
We quantified the accumulation of and tolerance to exogenously-fed nicotine by monitoring photosynthetic capacity and growth in two nicotine producing species of Solanaceous plants (Nicotiana sylvestris andN. glauca) as well as two Solanaceous species (Datura stramonium andLycopersicon esculentum) that do not produce nicotine to examine the relationship between tolerence and the ability to produce nicotine in defensive quantities. SinceN. sylvestris uses nicotine as an inducible defense, we examined whether nicotine tolerance is induced by damage to examine further the relationship between nicotine tolerence and synthesis. All species were grown in a 1 mM nicotine-containing hydroponic solution. Reductions in the photosynthetic capacity of nicotine-fed plants were found in all species tested. Nicotine-producing species showed no greater tolerance as measured by photosynthetic capacity than the two non-producing species. Leaf damage marginally increased the tolerence ofN. sylvestris to exogeneouslyfed nicotine suggesting that photosynthetic tolerance is coordinated with nicotine production in this nicotine-producing species.N. glauca plants regained photosynthetic capacity after their accumulated nicotine was demethylated to form nornicotine. Leaf nicotine pools in the other three species did not decrease, suggesting that for these species alkaloid metabolism does not play a major role in tolerance. Tolerance, as measured by biomass gained, was higher in the two non-producing species than in the nicotine-producing species suggesting that nicotine may also be functioning as a growth regulator. These results do not support the hypothesis that tolerance is as important as biosynthetic ability in determining which species accumulate defensively significant quantities of nicotine.


Effect of neonatal thyroidectomy on nucleic acids and protein contents of the developing rat brain.
(1) Thyroidectomy at birth caused a temporal reduction of the DNA content only in the cerebellum during the periods from 7 to 21 days after birth, but not in the cerebrum and brain stem. (2) The ratio of RNA to DNA in cerebrum from the thyroidectomized rats was underwent a marked decrease from 14 to 56 days as compared with those of the normal controls. On the other hand, the effect of thyroid deficiency on the ratios of cerebellum and brain stem as a whole was very small. (3) The ratios of protein to DNA generally declined in the three brain regions during the periods from 14 to 56 days as a result of throid deprivation.


Surgical management of urethrovaginal and vesicovaginal fistulas.
This report reviews a 50 year period during which 157 vesico- and 24 urethrovaginal fistulas were managed. Although the etiologic factors have changed, there has not been a dramatic decrease in the incidence of this complication. In the last 17 years we have noted an increased number of both types of fistula, primarily related to the increased frequency of gynecologic operative procedures. Only 11 (6%) of the fistulas reported in this series resulted from surgical procedures performed in our department. In this series 96% were repaired vaginally but the abdominal approach was used for certain complicated fistulas. Our initial cure rate was 89% and the final success rate in 157 vesicovaginal fistulas was 94.3%. The urethrovaginal fistulas represent a special problem because of the location, scarring, and lack of sufficient fascia for a second-layer closure. In such instances we have successfully used the bulbocavernous fat pad. The success rate for 24 patients with this type of fistula was 87.5%.


Impairment of beta chemokine and cytokine production in patients with HIV related Pneumocystis jerovici pneumonia.
Pneumocystis jerovici pneumonia (PJP) remains a frequent opportunistic infection in HIV infected patients which markedly upregulates HIV replication by mechanisms so far poorly elucidated. PJP triggers the production of proinflammatory mediators with activating effects on HIV. However, anti-inflammatory factors with inhibiting effects on HIV are normally produced in parallel. We postulated that an imbalance of mediators normally controlling HIV replication could underlie its marked increase during PJP. The production of tumour necrosis factor alpha (TNFalpha), interleukins IL-6 and IL-10, and beta-chemokine by bronchoalveolar lavage (BAL) cells recovered from HIV infected patients with and without PJP was compared. The pulmonary viral load was determined and correlations with cytokine and chemokine production were examined. TNFalpha and IL-6 release was similar in patients with and without PJP but IL-10 and beta-chemokine release was markedly lower in the PJP group (IL-10: p<10(-2), RANTES, MIP-1alpha and MIP-1beta: p<0.001). The pulmonary viral load was markedly higher in patients with PJP (p<0.001) and correlated negatively with levels of MIP-1alpha, RANTES and IL-10 in BAL fluid cells (p<0.05). Pulmonary IL-10 and beta-chemokine production is markedly defective in HIV infected patients with PJP, while pulmonary TNFalpha and IL-6 levels are normal. The resulting excess of these latter factors, which are known to upregulate HIV replication, might contribute to the increase in pulmonary viral load and to the more rapid HIV disease progression observed in patients with PJP.


Isolation of synaptic junction-enriched fraction from the forebrain of day-old chickens. Preparation and characterization of chick forebrain subcellular fractions.
Synaptosomal plasma membrane (SPM) and other subcellular fractions were isolated from the forebrain of 1-day-old chickens by a procedure based on that of Davis and Bloom (16) and Cotman and Taylor (13). The procedure involves the centrifugation through a discontinuous sucrose gradient of a crude synaptosomal-mitochondrial fraction which has been lysed and weighed with iodonitrotetrazolium. SPM isolated by this method contains only small amounts of lysosomal or mitochondrial membranes and is practically devoid of contaminating microsomal membranes, as estimated by enzyme marker assays. The purity of chick-brain SPM prepared by this method is compared to the purity of chick-brain fractions obtained by two other laboratories, using different methods (4, 59). The SPM were extracted with Triton X-100 and all fractions solubilized in sodium dodecyl sulfate (sds). The delipidated proteins of all fractions were subjected to SDS-polyacrylamide electrophoresis on slab gels and stained for protein. A distinct difference was observed between the patterns given by the Triton-soluble and -insoluble fractions. Electron microscopy of the synaptic junction fraction showed numerous junctional complexes.


Orientation on understanding interpersonal influence.
Everyone influences and is influenced by others. Are you satisfied with the impact your influence has on others? If not, it can be changed by examining and working on the dimensions of your "style of influence," such as activity, visibility, involvement, and productivity. The author analyzes some of the opposites on a spectrum or "wheel of influence," showing how they may be melded by moderation to achieve the kind of impact you may wish. For instance, there is the analyzer vs. the performer, the leader vs. the follower, the experimenter vs. the organizer, and the asserter vs. the listener. As modes of influence, extremes in any dimension are self-defeating, but by balancing aspects of both sides, desirable "compromises" can be developed. Should you wish to change your style of influence, helfpful procedures to follow are suggested, which, hopefully, will result in satisfying interpersonal relationships and understanding.


Sensitivity of Escherichia coli acrA mutants to psoralen plus near-ultraviolet radiation.
The sensitivity to psoralen plus near-ultraviolet radiation (PUVA) was compared in a pair of E. coli strains differing at the acrA locus. Survival was determined for both bacteria and phage lambda. AcrA mutant cells were 40 times more sensitive than wild type to the lethal effect of PUVA. Free lambda phage exposed to PUVA survived as well when plated on acrA mutants as on wild type. In contrast, prophage lambda CI857 ind carried in lysogenic acrA strains was hypersensitive to PUVA. The enhanced sensitivity of bacterial and lambda DNA, when inside acrA cells, was paralleled by an increased photobinding of radiolabelled psoralens in the mutant. Binding was increased specifically to DNA rather than to nucleic acids in general. The difference in psoralen-binding ability determined by the acrA gene persisted after permeabilizing treatment of the cells. The results suggest that the acrA mutation causes an alteration specifically in the environment of the cellular DNA so as to allow increased intercalation and photobinding of psoralens.


Formate dehydrogenase.
Formate is a substrate, or product, of diverse reactions catalyzed by eukaryotic organisms, eubacteria, and archaebacteria. A survey of metabolic groups reveals that formate is a common growth substrate, especially among the anaerobic eubacteria and archaebacteria. Formate also functions as an accessory reductant for the utilization of more complex substrates, and an intermediate in energy-conserving pathways. The diversity of reactions involving formate dehydrogenases is apparent in the structures of electron acceptors which include pyridine nucleotides, 5-deazaflavin, quinones, and ferredoxin. This diversity of electron acceptors is reflected in the composition of formate dehydrogenase. Studies on these enzymes have contributed to the biochemical and genetic understanding of selenium, molybdenum, tungsten, and iron in biology. The regulation of formate dehydrogenase synthesis serves as a model for understanding general principles of regulation in anaerobic organisms.


Insight into the selection of oxidant in persulfate activation system: The effect of the target pollutant properties.
As a rising branch of advanced oxidation processes, persulfate activation has attracted growing attention. Unlike catalysts that have been widely studied, the selection of persulfate is previously overlooked. In this study, the affecting factors of persulfates were studied. The effect of target pollutant properties on superior persulfate species (the species with a higher degradation efficiency) was investigated by multiwalled carbon nanotube (MWCNT)/persulfate catalytic systems. Innovatively, the EHOMO (or vertical ionization potential (VIP)) value of the target pollutant was proposed to be an index to judge the superior persulfate species, and the threshold is VIP= 6.397-6.674 eV, EHOMO= -8.035∼- 7.810 eV, respectively. To be specific, when the VIP of phenolic compounds is higher (or EHOMO of phenolic compounds is lower) than the threshold, the catalytic performance of peroxymonosulfate would be higher than that of peroxydisulfate. Moreover, the effects of coexisting cations on peroxydisulfate superior species were further investigated. It was illustrated that the hydrated cation radius of coexisting cations would influence the pollutant degradation efficiency under some circumstances. This study provides a new approach to improve the cost of persulfate activation systems and promotes the underlying downstream application of persulfate activation systems.


Toxoplasma gondii vaccine candidates: a concise review.
Toxoplasma gondii is an obligate intracellular parasite that causes toxoplasmosis. It has been shown that the severity of symptoms depends on the functioning of the host immune system. Although T. gondii infection typically does not lead to severe disease in healthy people and after infection, it induces a stable immunity, but it can contribute to severe and even lethal Toxoplasmosis in immunocompromised individuals (AIDS, bone marrow transplant and neoplasia). The antigens that have been proposed to be used in vaccine candidate in various studies include surface antigens and secretory excretions that have been synthesized and evaluated in different studies. In some studies, secretory antigens play an important role in stimulating the host immune response. Various antigens such as SAG, GRA, ROP, ROM, and MAG have been from different strains of T. gondii have been synthesized and their protective effects have been evaluated in animal models in different vaccine platforms including recombinant antigens, nanoparticles, and DNA vaccine. Four bibliographic databases including Science Direct, PubMed Central (PMC), Scopus, and Google Scholar were searched for articles published up to 2020.The current review article focuses on recent studies on the use and usefulness of recombinant antigens, nanoparticles, and DNA vaccines.


Human umbilical cord vein allograft arteriovenous fistula for chemotherapy access.
Seven patients who received chronic chemotherapy and required vascular access underwent construction of an arteriovenous fistula of the leg using gluteraldehyde-tanned human umbilical cord vein allografts. No wound or graft complications have occurred and patient tolerance of the operative procedure and subsequent use of the fisulas for chemotherapy has been excellent. Our preliminary results suggest that the use of umbilical vein allograft arteriovenous fistulas is quite satisfactory for long-term chemotherapy access.


Erlotinib, erlotinib-sulindac versus placebo: a randomized, double-blind, placebo-controlled window trial in operable head and neck cancer.
The EGF receptor (EGFR) and COX2 pathways are upregulated in head and neck squamous cell carcinoma (HNSCC). Preclinical models indicate synergistic antitumor activity from dual blockade. We conducted a randomized, double-blind, placebo-controlled window trial of erlotinib, an EGFR inhibitor; erlotinib plus sulindac, a nonselective COX inhibitor; versus placebo. Patients with untreated, operable stage II-IVb HNSCC were randomized 5:5:3 to erlotinib, erlotinib-sulindac, or placebo. Tumor specimens were collected before and after seven to 14 days of treatment. The primary endpoint was change in Ki67 proliferation index. We hypothesized an ordering effect in Ki67 reduction: erlotinib-sulindac > erlotinib > placebo. We evaluated tissue microarrays by immunohistochemistry for pharmacodynamic modulation of EGFR and COX2 signaling intermediates. From 2005-2009, 47 patients were randomized for the target 39 evaluable patients. Thirty-four tumor pairs were of sufficient quality to assess biomarker modulation. Ki67 was significantly decreased by erlotinib or erlotinib-sulindac (omnibus comparison, two-sided Kruskal-Wallis, P = 0.04). Wilcoxon pairwise contrasts confirmed greater Ki67 effect in both erlotinib groups (erlotinib-sulindac vs. placebo, P = 0.043; erlotinib vs. placebo, P = 0.027). There was a significant trend in ordering of Ki67 reduction: erlotinib-sulindac > erlotinib > placebo (two-sided exact Jonckheere-Terpstra, P = 0.0185). Low baseline pSrc correlated with greater Ki67 reduction (R(2) = 0.312, P = 0.024). Brief treatment with erlotinib significantly decreased proliferation in HNSCC, with additive effect from sulindac. Efficacy studies of dual EGFR-COX inhibition are justified. pSrc is a potential resistance biomarker for anti-EGFR therapy, and warrants investigation as a molecular target.


Implicit Changes of Model Uses in Astrophysics, Illustrated on the Paris-Durham Shock Model.
This paper explores the epistemic status of models and simulations between theory, on the one hand, and observations, on the other. In particular, I will argue that the interpretation of an essentially invariant astrophysical model structure can change substantially over time. I will illustrate this claim using as an example the first 20 years (1985-2004) of development of the Paris-Durham shock code-a numerical model of slow interstellar shock waves (i.e. a disturbance of the medium that travel faster than the local speed of sound). I will show that the model's interpretation and, in particular, its underlying representational ideal-the modeler's (often implicit) goal governing the development and the use of the model-changed notably during this period. Whereas the code was originally used in a purely exploratory fashion, it was later taken to represent and encompass the target phenomenon as completely as possible. It is noteworthy that during this transition the model's change of epistemic status was never explicitly acknowledged or in any way articulated. However, the impetus for the change can, I claim, be found in the role that observational data came to play in the later publications.


A mechanism of differential expression of GLUT2 in hepatocyte and pancreatic beta-cell line.
DNase I footprinting assay using liver nuclear extracts revealed six protected regions between nucleotide -600 and +110 and hence named Box I-VI. Upstream promoter element (UPE), a DNA element playing crucial role in transcriptional control of the tissue specific expression of pancreatic beta-cell, has been detected within the proximal region of rat GLUT2 promoter. This region is included in Box VI. The protein-DNA interaction in this region (Box VI) was confirmed by mobility shift assay using liver nuclear extracts. Deletion of the region between -585 bp and -146 bp resulted in dramatic changes in promoter activity when they were expressed in liver and beta-cell derived cell line. When -585/-146 construct was expressed in liver, the activity was decreased to 46%, whereas the activity in beta-cell line, HIT-T15 cell, was increased by 84% when compared to -146/+190 construct. These opposing phenomena can be explained by the fact that beta-cell specifically expresses the UPE binding protein. Assuming that there may be Box VI-binding protein playing negative roles both in hepatocyte and beta-cell, and that the protein acts as a negative regulator of GLUT2 gene, the UPE binding protein in the beta-cell may overcome the inhibition by binding to the protein.


To stay or re-migrate after the pandemic shock? Labor re-migration intention to the coastal areas of Thừa Thiên Huế province in Vietnam.
This study applied the extended theory of planned behavior (ETPB) to explore factors that shape the behavioral intention of migrant laborers returning to the coastal region of Thừa Thiên Huế province during the peak of the COVID-19 pandemic to remigrate. Data collection included 210 interviews with returned migrants aged 18 and above in 4 coastal communes of Thừa Thiên Huế province, in-depth interviews (8 key informants) and a group discussion (5 persons). Exploratory factor analysis and a multivariate linear regression model were applied to analyze the data. Results showed that in addition to individual socio-demographic characteristics (i.e. level of education, age, income level and sex), attitudes, subjective norms, perceived behavioral control, and perceived risk were also determinant factors of migrants' intention to remigrate. This research suggested that in order to build resilience of rural migration workers, related departments should seriously consider the following recommendations: (i) raise awareness and encourage young rural people to complete their education and necessary skills; (ii) organize related psychological training programs for rural laborers; (iii) raise awareness about the necessity to participate in social insurance; (iv) promote rural job creation programs suitable for low education and low-skilled rural laborers; (v) raise awareness for local people, particularly school children, about the value and opportunities of being smart farmers in the context of 4.0 technology and social risks at the destination for low education and low-skilled laborers; (vi) digitalize migration labor management and provide digital information services regarding job opportunities for rural laborers.


The Kaplan and Meier and the Nelson estimate for the probability of ulcer recurrence 10 and 15 years after parietal cell vagotomy.
The use of a nonparametric estimate from incomplete observations is demonstrated on ulcer recurrence 10-15 years after parietal cell vagotomy in 339 patients with duodenal ulcer. The median period of observation was 108 months (range: 1-197 months). Proven recurrent ulcer developed in 62 patients. The life-table method as described by Kaplan and Meier and Nelson's modification are demonstrated. The calculated risk of recurrence after 10 years was 23% (+/- 3.8%) and after 15 years was 27% (+/- 4.3%). The rate of recurrence seemed to decline toward the end of the trial time.


Highly host-linked viromes in the built environment possess habitat-dependent diversity and functions for potential virus-host coevolution.
Viruses in built environments (BEs) raise public health concerns, yet they are generally less studied than bacteria. To better understand viral dynamics in BEs, this study assesses viromes from 11 habitats across four types of BEs with low to high occupancy. The diversity, composition, metabolic functions, and lifestyles of the viromes are found to be habitat dependent. Caudoviricetes species are ubiquitous on surface habitats in the BEs, and some of them are distinct from those present in other environments. Antimicrobial resistance genes are identified in viruses inhabiting surfaces frequently touched by occupants and in viruses inhabiting occupants' skin. Diverse CRISPR/Cas immunity systems and anti-CRISPR proteins are found in bacterial hosts and viruses, respectively, consistent with the strongly coupled virus-host links. Evidence of viruses potentially aiding host adaptation in a specific-habitat manner is identified through a unique gene insertion. This work illustrates that virus-host interactions occur frequently in BEs and that viruses are integral members of BE microbiomes.


Cortical "stress tests" in schizophrenia: regional cerebral blood flow studies.
A total of 261 regional cerebral blood flow (rCBF) studies were carried out on 34 medication-free patients with chronic schizophrenia and 50 normal subjects. rCBF, an indicator of local cortical metabolism and activity, was measured during the resting state and also during four cognitive activation tasks or "cortical stress tests." The latter included the Wisconsin Card Sort (WCS), a test of prefrontal lobe function; a simple numbers matching task, and two versions of a visual Continuous Performance Task (CPT). Multivariate comparisons of the two subject groups were performed for each of the five testing conditions, and discriminant function analyses for each condition were carried out to define mathematical models that differentiated normal subjects from medication-free patients. The best such model was determined and was then applied to another group of patients who had diagnoses other than schizophrenia or for whom the diagnosis was unclear. This group included two patients with clinical "frontal lobe syndrome" and radiological evidence of frontal lobe damage. The most robust differences between the groups were seen in frontal rCBF during the WCS. In the discriminant function analysis, rCBF during the WCS was the best discriminator between the two groups, retrospectively classifying 85% of the subjects correctly. rCBF during the resting state and one of the CPTs correctly classified subjects at a rate only marginally better than chance. When the model derived from WCS rCBF was applied to a second group of patients, the two patients with known frontal lobe disease were classified as "schizophrenic" with 100% certainty. Three other patients with psychotic illnesses were also assigned to this group with greater than 80% certainty, whereas a patient with character disorder (rule-out affective disorder) was classified as "normal" with a high level of confidence. These data suggest (1) that schizophrenia is characterized by a deficit in prefrontal function that is revealed when regionally specific demand exceeds the physiological capacity, and (2) that functional brain imaging studies, such as rCBF, can best identify brain abnormalities during "cortical stress tests."


Spontaneous disappearance of gallstones.
A case of spontaneous disappearance of gallstones in a 55-year-old woman is presented. Examination of biliary lipids after the stones had disappeared revealed supersaturated bile with cholesterol. This suggests that the stones migrated from the gallbladder to the small intestine via the biliary ductal system.


Higher bacterial DNAemia can affect the impact of a polyphenol-rich dietary pattern on biomarkers of intestinal permeability and cardiovascular risk in older subjects.
Aging can be characterized by increased systemic low-grade inflammation, altered gut microbiota composition, and increased intestinal permeability (IP). The intake of polyphenol-rich foods is proposed as a promising strategy to positively affect the gut microbiota-immune system-intestinal barrier (IB) axis. In this context, we tested the hypothesis that a PR-dietary intervention would affect the presence of bacterial factors in the bloodstream of older adults. We collected blood samples within a randomized, controlled, crossover intervention trial in which older volunteers (n = 51) received a polyphenol-enriched and a control diet. We quantified the presence of bacterial DNA in blood by qPCR targeting the 16S rRNA gene (16S; bacterial DNAemia). Blood DNA was taxonomically profiled via 16S sequencing. Higher blood 16S levels were associated with higher BMI and markers of IP, inflammation, and dyslipidemia. PR-intervention did not significantly change bacterial DNAemia in the older population (P = 0.103). Nonetheless, the beneficial changes caused by the polyphenol-enriched diet were greatest in participants with higher bacterial DNAemia, specifically in markers related to IP, inflammation and dyslipidemia, and in fecal bacterial taxa. Finally, we found that the bacterial DNA detected in blood mostly belonged to γ-Proteobacteria, whose abundance significantly decreased after the polyphenol-rich diet in subjects with higher bacterial DNAemia at baseline. This study shows that older subjects with higher bacterial DNAemia experienced a beneficial effect from a polyphenol-rich diet. Bacterial DNAemia may be a further relevant marker for the identification of target populations that could benefit more from a protective dietary treatment. This trial was retrospectively registered at www.isrctn.org (ISRCTN10214981) on April 28, 2017.


Correlation between the coexpression of zinc finger and SCAN domain-containing protein 31 and transcriptional activator with PDZ-binding motif and prognosis in hepatocellular carcinoma.
Transcriptional coactivator with PDZ binding motif (TAZ) regulates multiple biological processes and has been found to be related to hepatocellular carcinoma (HCC). However, common signaling pathways downstream after TAZ knockdown may also be important. TAZ was knocked down in an HCC cell line, and its potential target genes were analyzed. A decrease in the expression of zinc finger and SCAN domain-containing protein 31 (ZSCAN31) was observed. The difference in ZSCAN31 expression was evaluated, and its effect on survival in HCC patients who received surgical resection was determined. ZSCAN31 was over-expressed in HCC tissues and was associated with low overall survival (OS) in HCC patients after surgical resection. Analysis of tissue samples from 83 HCC patients who underwent surgical resection in our hospital produced similar results. High ZSCAN31 expression was significantly associated with tumor size. High expression levels of both TAZ and ZSCAN31 were related to poor OS. A positive correlation was identified between ZSCAN31 expression and TAZ expression, and the protein binding of ZSCAN31 and TAZ was confirmed by co-immunoprecipitation (Co-IP) assay using an HCC cell line. ZSCAN31 is associated with TAZ expression in HCC cells, and the targeting of ZSCAN31 and TAZ may represent a novel therapeutic approach in HCC.


Neoadjuvant intralesional methotrexate in cutaneous squamous cell carcinoma: a comparative cohort study.
Intralesional methotrexate (MTX-il) has been used as neoadjuvant therapy for keratoacanthoma but has only been utilized in a few isolated cases of cutaneous squamous cell carcinoma as neoadjuvant therapy (cSCC). The objective of this study was to evaluate the effectiveness in clinical practice of presurgical MTX-il infiltration to reduce the size of the cSCC. Safety and the impact on subsequent reconstructive surgical techniques was also assessment. Single, retrospective, observational study of two historical cohorts differentiated in time. Subjects included were diagnosed with infiltrating cSCC. Patients included in group-A received neoadjuvant MTX-il and patients included in group-B underwent scheduled surgery without prior infiltration. Univariate and multivariate analyses were performed. Group-A patients (n = 43) showed an average reduction in the tumour area of 0.52 cm(2) , while in group-B (n = 43), the area increased by 0.49 cm(2) . A multivariate linear regression analysis demonstrated that MTX-il was the only independent variable that significantly reduced the tumour size [mean 42.6% (95% CI: 31.17-54.03)]. Tumours ≥2 cm in size required significantly a lower percentage of complex reconstructions (P = 0.026). Lower lip tumours showed a higher reduction in group treated with MTX-il (P = 0.045). The only complication observed was discomfort during methotrexate infiltration (60.47%). Neoadjuvant MTX-il reduced the presurgical size of cSCC lesions and could simplify their subsequent surgery.


Interventions delivered in secondary or tertiary medical care settings to improve routine vaccination uptake in children and young people: a scoping review protocol.
The objective of this review is to identify and collate the available evidence, and to produce an overview of interventions delivered in secondary and tertiary healthcare settings with the aim of improving vaccination uptake in children and young people. Vaccine hesitancy appears in the World Health Organization's Ten Threats to Global Health in 2019. Time spent in secondary or tertiary healthcare settings with a child or young person may present an opportunity to deliver vaccination-focused interventions. National Institute for Health and Care Excellence guidance highlights a gap in the evidence of the effectiveness of different interventions aimed at increasing immunization uptake among children and young people. Quantitative studies that describe interventions delivered in secondary and tertiary care settings will be included. Participants will include children and young people aged less than 16 years and/or their parents/carers (potentially interventions could be delivered to the child-parent/carer dyad) present in a secondary or tertiary care setting as either a patient or relative. This scoping review will be conducted using MEDLINE, CINAHL, Cochrane Library, Embase, Web of Science, as well as gray literature. The scoping review will exclude publications not available in English and any publication older than 30 years. Two reviewers will independently select articles using the inclusion criteria, based on their title and abstract. Data will be extracted from selected full text articles using a data extraction tool based on JBI recommendations. Study findings will be presented in tabular form detailing the interventions identified in the literature.


C-Jun N-terminal kinase regulates adenosine A1 receptor-mediated synaptic depression in the rat hippocampus.
Adenosine A1 receptors are ubiquitous mediators of presynaptic inhibition of neurotransmission in the central nervous system, yet the signalling pathway linking A1 receptor activation and decreased neurotransmitter release remains poorly resolved. We tested the contribution of c-Jun N-terminal kinase (JNK) to adenosine A1 receptor-mediated depression of field excitatory postsynaptic potentials (fEPSPs) in area CA1 of the rat hippocampus. We found that inhibition of JNK with SP600125 or JNK inhibitor V, but not an inactive analogue, attenuated the depression of fEPSPs induced by adenosine, hypoxia, and the A1 receptor agonist N(6)-cyclopentyladenosine (CPA). In contrast, the JNK inhibitor SP600125 did not inhibit GABA(B)-mediated synaptic depression. In support of our electrophysiological findings, Western blot analysis showed that A1 receptor stimulation resulted in a transient increase in JNK phosphorylation in the membrane fraction of hippocampal lysates. The total amount of JNK in the membrane fraction was unchanged by CPA treatment. The increase in phosphorylated JNK induced by A1 receptor stimulation was blocked by the A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), indicating that A1 receptors specifically activate JNK in the hippocampus. Together with functional data indicating that JNK inhibition decreased CPA-induced paired pulse facilitation, these results suggest that JNK activation is necessary for adenosine A1 receptor-mediated synaptic depression occurring at a presynaptic locus The adenosine A1 receptor-JNK signalling pathway may represent a novel mechanism underlying inhibition of neurotransmitter release in the CNS.


Comparison of state legislation regarding professional liability.
The so-called malpractice crisis of the mid-1970s alerted physicians to the need for legislative involvement in order to achieve needed malpractice tort reform. There has been a positive effort to modify the medical liability situation in each of our 50 states. A review of this legislative activity from 1975 through 1977 is presented. It is anticipated that a new malpractice crisis may develop during the early 1980s. Actuarial data now being collected plus the effects of such innovations as arbitration, pretrial screening panels, collateral source rules, and periodic funding of malpractice claims may provide an equitable approach to any future malpractice tort reform.


Evaluation and Management of Acne.
Acne is a common complaint in the primary care clinics. It has not only physical implications but also psychological. This article discusses the epidemiology, pathophysiology, and criteria for making the diagnosis. It also discusses endocrine disorders that may be the cause of acne. Treatment and management are discussed by subtype. Acne mechanica or sports-related acne is also discussed.


Determination of trace levels of phenol and cresols in rain by continuous liquid-liquid extraction and high-performance liquid chromatography.
Trace levels of phenol and methylphenols (cresols) in aqueous samples were determined by continuous liquid-liquid extraction and normal-phase high-performance liquid chromatography with UV-fluorescence detection. The recovery of phenol from water at a concentration of 1.6 micrograms l-1 was 70 +/- 6%. The method successfully measured traces of phenol and cresols extracted from rainwater without further clean-up. The average reproducibility of the method for rain samples was +/- 16%. The results compared well with those obtained by high-resolution gas chromatography-mass spectrometry.


Music predictability and liking enhance pupil dilation and promote motor learning in non-musicians.
Humans can anticipate music and derive pleasure from it. Expectations facilitate the learning of movements associated with anticipated events, and they are also linked with reward, which may further facilitate learning of the anticipated rewarding events. The present study investigates the synergistic effects of predictability and hedonic responses to music on arousal and motor-learning in a naïve population. Novel melodies were manipulated in their overall predictability (predictable/unpredictable) as objectively defined by a model of music expectation, and ranked as high/medium/low liked based on participants' self-reports collected during an initial listening session. During this session, we also recorded ocular pupil size as an implicit measure of listeners' arousal. During the following motor task, participants learned to play target notes of the melodies on a keyboard (notes were of similar motor and musical complexity across melodies). Pupil dilation was greater for liked melodies, particularly when predictable. Motor performance was facilitated in predictable rather than unpredictable melodies, but liked melodies were learned even in the unpredictable condition. Low-liked melodies also showed learning but mostly in participants with higher scores of task perceived competence. Taken together, these results highlight the effects of stimuli predictability on learning, which can be however overshadowed by the effects of stimulus liking or task-related intrinsic motivation.