In vitro study of sirolimus release from a drug-eluting stent: Comparison of the release profiles obtained using different test setups.
In this study drug release from the CYPHER™ stent, the gold standard in drug-eluting stent therapy until the end of its marketing in 2011/2012, was systematically evaluated using different in vitro release tests. The test systems included incubations setups, the reciprocating holder apparatus (USP7), the flow-through cell apparatus (USP4) and the vessel-simulating flow-through cell (vFTC) specifically designed for stent testing. The results obtained show a large variability regarding the fractions released into the media after 7d ranging from 38.6% ± 4.5% to 74.6% ± 1.2%. The lowest fraction released was observed in the vFTC and the highest in an incubation setup with frequently changed media of a volume of 2 mL. Differences were even observed when using fairly similar and simple incubations setups with mere changes of the media volume, under maintenance of sink conditions, and of the vessel geometry. From these data it can be concluded, that in vitro release even from a slow releasing drug-eluting stent is greatly influenced by the experimental conditions and care must be taken when choosing a suitable setup. Comparison of the obtained in vitro release profiles to published in vivo data did not result in a distinct superiority of any of the tested methods regarding the predictability for the situation in vivo due to large differences in the reported in vivo data. However, this comparison yielded that the release observed in vitro using the 2 mL incubation setup and the reciprocating holder apparatus may be faster than the reported in vivo release. The results of this study also emphasize the necessity to use highly standardized release tests when comparisons between results from different experiments or even different labs are to be performed. In this context, the compendial methods are most likely offering the highest degree of standardization.


Early stimulation and responsive care: A mediator of caregivers' depression on the suspected developmental delay of left-behind children in China.
Due to multiple factors, left-behind children in rural areas suffer from neurodevelopment delay and their caregivers suffer from depressive symptoms. This study aimed to analyze the effect of caregivers' depressive symptoms on left-behind children's neurodevelopment, with early stimulation and responsive care mediating. We conducted a cross-sectional survey in five counties in China. A total of 904 left-behind children aged 0-3 and their primary caregivers were enrolled. The Zung Self-rating Depression Scale (ZSDS) was used to measure caregivers' depressive symptoms. The Ages and Stages questionnaires-third edition (ASQ-3), which contains five domains: communication (CM), gross motor (GM), fine motor (FM), problem-solving (CG), and personal social (PS), was used to screen children for suspected developmental delay (SDD). 31.4 % of left-behind children suffered from SDD, while 39.7 % of left-behind children's caregivers experienced depressive symptoms. Caregivers' ZSDS scores were positively correlated with the SDD on four domains (FM, GM, CG, and PS), while Early stimulation and responsive care was negatively correlated with the SDD on four domains (CM, FM, CG, and PS). The cross-sectional design limited the ability to ascertain causal relations. Besides, the findings may not be generalized to all regions of China due to the heterogeneity of the study population. Left-behind children under three years old in rural China were at high risk of SDD, while a substantial proportion of their caregivers had depressive symptoms. Caregivers' depressive symptoms may negatively affect the SDD of left-behind children through caregivers providing less early stimulation and responsive care.


Reversal of autoimmune hemolytic anemia associated with chronic lymphocytic leukemia following high-dose immunoglobulin.
An 85-year-old man with chronic lymphocytic leukemia developed severe warm antibody-type autoimmune hemolytic anemia. Initial therapy with high-dose corticosteroids had no discernible effect on the hemolytic process. Following treatment with high-dose intravenous immunoglobulin (0.4 g/kg/d for 5 consecutive days) there was an immediate and sustained increase in hematocrit accompanied by a progressive decline in reticulocyte count. A review of the literature reveals that some patients with steroid-resistant immune hemolysis may benefit from high-dose immunoglobulin. This approach should be considered in elderly patients with severe anemia whose medical status precludes splenectomy.


Variation of modulation and expression of biomarkers associated with inflammation in bariatric surgery patients: A systematic review and meta-analysis.
Bariatric surgery is an effective intervention that causes a series of metabolic changes related to inflammatory processes; however, the variation of biomarkers related to these processes is not entirely understood. Our objective was to investigate the variation of modulation and expression of biomarkers associated with inflammation in patients who underwent bariatric surgery. We searched the MEDLINE (via PubMed), EMBASE (via Elsevier), Cochrane Central Register of Controlled Trials, Latin American and Caribbean Literature on Health Sciences (via virtual health library), Cumulative Index to Nursing and Allied Health Literature (via EBSCO), Web of Science core collection, and Scopus (via Elsevier) databases, and the gray literature was examined from inception to January 2022. Three pairs of reviewers performed data screening, extraction, and quality assessment independently. Meta-analysis with random effects models was used for general, subgroup, and sensitivity analyses. The I2 statistic was used to assess heterogeneity between studies. In total, 96 articles were included in this systematic review; of these, 87 studies met the criteria for the meta-analysis, involving 3,533 participants. Five biomarkers were included in the meta-analysis (tumor necrosis factor alpha; interleukin 6; leptin; interleukin 1 beta, and lipopolysaccharides). Only leptin showed a significant decrease in the first month after surgery (mean difference -20.71; [95% confidence interval: -28.10 to -13.32, P < .0001; I2 = 66.7%), with moderate heterogeneity. The 12 months after surgery showed a significant decrease in tumor necrosis factor alpha (mean difference -0.89; [95% confidence interval: -1.37 to -0.42], P = .0002; I2 = 94.7%), interleukin 6 (mean difference -1.62; [95% confidence interval: -1.95 to -1.29], P < .0001; I2 = 94.9%), leptin (mean difference -28.63; [95% confidence interval: -34.02 to -23.25], P < .0001; I2 = 92.7%), and interleukin 1 beta (mean difference -2.46; [95% confidence interval: -4.23 to -0.68], P = .006; I2 = 98.3%), all with high heterogeneity. The type of surgery did not show significant differences for the biomarkers at the first month and 12 months, and the results have not changed with high-quality studies. In the 12-month measurement, variations in tumor necrosis factor alpha and leptin were associated with body mass index. The findings of this meta-analysis suggest that Roux-en-Y gastric bypass and sleeve gastrectomy bariatric surgeries are associated with a significant reduction in leptin at 1 month after bariatric surgical intervention and tumor necrosis factor alpha, leptin, and interleukin 1 beta after 12 months.


A three-part system for refining intraocular lens power calculations.
A three-part system that determines the correct power for an intraocular lens (IOL) to achieve a desired postoperative refraction is presented. The three components are (1) data screening criteria to identify improbable axial length and keratometry measurements, (2) a new IOL calculation formula that exceeds the current accuracy of other formulas for short, medium, and long eyes, and (3) a personalized "surgeon factor" that adjusts for any consistent bias in the surgeon's results, from any source, based on a reverse solution of the new formula; the reverse solution uses the postoperative stabilized refraction, the dioptric power of the implanted IOL, and the preoperative corneal and axial length measurements to calculate the personalized surgeon factor. The improved accuracy of the new formula was proven by performing IOL power calculations on 2,000 eyes from 12 surgeons and comparing the results to seven other currently used formulas.


New European Society of Cardiology Guidelines on diabetes; prediabetes, and cardiovascular diseases - a truly strong base for the major paradigm shift in clinical practice?


The effect of electronic medical record system sophistication on preventive healthcare for women.
To observe the effect of electronic medical record (EMR) system sophistication on preventive women's healthcare. Providers in the National Ambulatory Medical Care Survey (NAMCS), 2007-8, were included if they had at least one visit by a woman at least 21 years old. Based on 16 questions from NAMCS, the level of a provider's EMR system sophistication was classified as non-existent, minimal, basic, or fully functional. A two-stage residual-inclusion method was used with ordered probit regression to model the level of EMR system sophistication, and outcome-specific Poisson regressions to predict the number of examinations or tests ordered or performed. Across the providers, 29.23%, 49.34%, 15.97%, and 5.46% had no, minimal, basic, and fully functional EMR systems, respectively. The breast examination rate was 20.27%, 34.96%, 37.21%, and 44.98% for providers without or with minimal, basic, and fully functional EMR systems, respectively. For breast examinations, pelvic examinations, Pap tests, chlamydia tests, cholesterol tests, mammograms, and bone mineral density (BMD) tests, an EMR system increased the number of these tests and examinations. Furthermore, the level of sophistication increased the number of breast examinations and Pap, chlamydia, cholesterol, and BMD tests. The use of advanced EMR systems in obstetrics and gynecology was limited. Given the positive results of this study, specialists in women's health should consider investing in more sophisticated systems. The presence of an EMR system has a positive impact on preventive women's healthcare; the more functions that the system has, the greater the number of examinations and tests given or prescribed.


[Breech Presentation: CNGOF Guidelines for Clinical Practice - Maternal Benefits and Risks of Planned Cesarean Delivery compared to Planned Vaginal Delivery].
To evaluate maternal risks and benefits associated with planned mode of delivery in case of breech presentation at term. MedLine and Cochrane Library databases search and review of the main foreign guidelines. To analyze maternal complications according to the planned mode of delivery for breech singleton at term, only one study of high quality is available, a randomized controlled trial- the Term Breech Trial, having found a similar maternal morbidity rate with planned cesarean delivery compared to planned vaginal delivery (LE2). This trial found at 3 months postpartum a decreased risk of urinary incontinence and perineal pain, and an increased risk of abdominal pain in case of planned cesarean delivery compared to planned vaginal delivery (LE2). This trial found at 2 years postpartum, a similar rate of maternal morbidity according to planned mode of delivery, in the absence of subsequent pregnancy (LE2). In studies with fetus in cephalic presentation, previous cesarean delivery exposes women in subsequent pregnancies at serious risk of uterine rupture, abnormalities of placental insertion and hysterectomy (LE2). For breech singleton at term, short and long term maternal complications appear similar in case of planned vaginal delivery compared to planned cesarean delivery without subsequent pregnancy. In subsequent pregnancies, women with previous cesarean section are at risk for serious complications (uterine rupture, abnormalities of placental insertion).


"You are Not Alone": Linking Peer Support to Information and Resources for Mental Health Concerns in Advocacy Groups' Social Media Messaging.
The pervasive stigmatization of mental health concerns has caused a public health crisis in the United States, as it prevents individuals from seeking treatment for such concerns. Grassroots mental health advocacy groups working to mitigate this stigma and promote treatment largely do so through social media messaging strategies to provide audiences with information, resources, and peer support. Yet, scholars have not fully explicated what constitutes information, resources, or support. Further, little is known about mental health advocacy groups' goals for and perceived effectiveness of these strategies or how audience members understand these messaging strategies. By employing a case study approach with two grassroots mental health advocacy groups, this study provides a nuanced understanding of the strategies involved in providing information, resources, and peer support in social media messaging. This study also demonstrates that both content creators and audience members agree on the importance of linking support strategies - specifically peer support - with information and resources to achieve the organizations' primary goals. Theoretical and practical implications for the strategies used by both organizations are discussed.


Food insecurity and SNAP use among sexual minority people: analysis of a population-based sample from National Health Interview Survey, 2017.
Food insecurity is a pressing public health problem. Lesbian, gay, and bisexual (LGB) people are at increased risk for food insecurity, yet this issue remains grossly understudied among this population. The purpose of this study was to add to the existing literature surrounding food insecurity and the use of federal food assistance programs (SNAP) among LGB people. This study used publicly available, de-identified data from the 2017 National Health Interview Survey (NHIS). Primary variables were sexual orientation, food security status, and receipt of SNAP. Food security was assessed using the 10-item USDA Family Food Security measure. In our sample, people who identified as bisexual had the highest rates of food insecurity (23.8%, n = 76). Female sexual minorities were 52% more likely to experience food insecurity (aOR = 1.518, 95% CI 1.105-2.087, p = .01) and 44% more likely to report household SNAP assistance than their heterosexual counterparts (aOR = 1.441, 95% CI 1.025-2.028, p = .03). SNAP partially mediated the association between sexual orientation and food insecurity for LGB females. Our findings add to the growing empirical evidence documenting food insecurities among sexual minority adults. Our results reiterate the need for sexual orientation to be included in nationally representative federal food security measures.


Lipid oxidation and gel to liquid-crystalline transition temperatures of synthetic polyunsaturated mixed-acid phosphatidylcholines.
Synthetic preparations of the polyunsaturated phosphatidylcholines 1-stearoyl-2-linoleoyl-sn-glycero-3-phosphocholine (SLPC) and 1-stearoyl-2-alpha-linolenoyl-sn-glycero-3-phosphocholine (SLnPC) were observed to undergo autooxidation sometimes during synthesis and also on storage. Oxidation was also induced by treatment of unoxidized SLPC with ultraviolet irradiation. Oxidation was estimated by thin layer chromatographic, fatty acid and ultraviolet spectral analyses. With limited oxidation, the gel to liquid-crystalline transition temperatures of aqueous dispersions of these lipids were seen to increase. Extensive oxidation led to a reduction in the enthalpies of the transitions. The increases in transition temperatures were consistent with the presence of conjugated double bonds, as shown by increased absorption at 230 nm, and trans double bonds, in the oxidized lipids leading to the creation of more rigid domains within the bilayer. Some of the changes in the transitions, especially the decreasing enthalpy after extensive oxidation, may have occurred because of the presence of small amounts of lysophosphatidylcholine and other oxidation intermediates or breakdown products seen by thin layer analysis. Thermograms of mixtures of unoxidized SLPC with amounts of lysostearoylPC found in the oxidized samples showed, however, that lysoPC likely did not contribute significantly to the increase in transition temperatures. Thin layer analysis suggested that the presence of cross-linked products could have contributed to the observed thermotropic properties.


Purging tumor cells from bone marrow by use of antibody and complement: a critical appraisal.
This review highlighted several problems associated with the use of antibody and complement in the elimination of tumor cells from bone marrow that was to be used for transplantation, and it discussed some of the difficulties encountered in developing this approach in model systems. These problems should be seriously considered by any clinician contemplating this method for bone marrow purging.


Colorimetric and Raman spectroscopic array for detection of hydrogen peroxide and glucose based on etching the silver shell of Au@Ag core-shell nanoparticles.
Gold-silver core-shell nanoparticles (Au@Ag NPs) were prepared by two successive reductions in a seed-growth method. The Au@Ag NPs are used as both a colorimetric and Raman spectroscopic probe for ultrasensitive determination of H2O2 and glucose. It is found that H2O2 (as produced from glucose by the action of glucose oxidase) can directly oxidize and gradually corrode the silver shell of the Au@Ag NPs. This results in a drop in the surface plasmon resonance absorbance at 400 nm, and the color of the solution changes from brownish yellow to purple. Without adding any additional chromogenic agents, the color change can be visually observed and detected photometrically. Silver NPs also are an excellent surface-enhanced Raman scattering (SERS) substrate. Due to corrosion of the silver shell, the SERS intensity (measured at 1083 cm-1) gradually decreases with increasing glucose concentration. The detection limits are 300 nM of glucose for the colorimetric assays, and 20 nM for the SERS assay. Graphical abstractSchematic representation of the method for glucose determination. H2O2 can oxidize and gradually corrode the silver shell of the gold-silver core-shell nanoparticles. This results in a distinct color change of the solution from brownish yellow to purple, and a drop in SERS intensity. The effect is applied in colorimetric and Raman spectroscopic assays for glucose.


Neurotrophin receptors expression and JNK pathway activation in human astrocytomas.
Neurotrophins are growth factors that regulate cell growth, differentiation and apoptosis in the nervous system. Their diverse actions are mediated through two different transmembrane - receptor signaling systems: Trk receptor tyrosine kinases (TrkA, TrkB, TrkC) and p75NTR neurotrophin receptor. Trk receptors promote cell survival and differentiation while p75NTR induces, in most cases, the activity of JNK-p53-Bax apoptosis pathway or suppresses intracellular survival signaling cascades. Robust Trk activation blocks p75NTR -induced apoptosis by suppressing the JNK-p53-Bax pathway. The aim of this exploratory study was to investigate the expression levels of neurotrophin receptors, Trks and p75NTR, and the activation of JNK pathway in human astrocytomas and in adjacent non-neoplastic brain tissue. Formalin-fixed paraffin-embedded serial sections from 33 supratentorial astrocytomas (5 diffuse fibrillary astrocytomas, WHO grade II; 6 anaplastic astrocytomas, WHO grade III; 22 glioblastomas multiforme, WHO grade IV) were immunostained following microwave pretreatment. Polyclonal antibodies against TrkA, TrkB, TrkC and monoclonal antibodies against p75NTR and phosphorylated forms of JNK (pJNK) and c-Jun (pc-Jun) were used. The labeling index (LI), defined as the percentage of positive (labeled) cells out of the total number of tumor cells counted, was determined. Moderate to strong, granular cytoplasmic immunoreactivity for TrkA, TrkB and TrkC receptors was detected in greater than or equal to 10% of tumor cells in the majority of tumors independently of grade; on the contrary, p75NTR receptor expression was found in a small percentage of tumor cells (approximately 1%) in some tumors. The endothelium of tumor capillaries showed conspicuous immunoreactivity for TrkB receptor. Trk immunoreactivity seemed to be localized in some neurons and astrocytes in non-neoplastic tissue. Phosphorylated forms of JNK (pJNK) and c-Jun (pc-Jun) were significantly co-expressed in a tumor grade-dependent manner (p < 0.05). Interestingly, a statistically significant (p < 0.05) reverse relationship between Trk receptors LIs and pc-Jun/pJNK LIs was noted in some glioblastomas multiforme. In the context of astrocytomas, Trk receptors (TrkA, TrkB, TrkC) expression may promote tumor growth independently of grade. Furthermore, activation of JNK pathway may contribute to progression towards malignancy. Considering the fact that regional tumor heterogeneity may be a limiting factor for immunohistochemical studies, the significance of the reverse relationship between Trk receptors and pc-Jun/pJNK LIs with respect to biological behavior of human astrocytomas requires further evaluation.


Adaptation of the myelin sheath during axonal atrophy.
Distal axonal atrophy was produced by proximal constriction of the tibial nerve in the rabbit. Single fibres were teased from the distal tibial nerve, and a selected internode from each fibre was measured and then cut transversely for electron microscopy, so that axon area and perimeter, myelin lamellar number and periodicity, and myelin spiral length could be related to the length of the internode which had been sectioned. When sections from atrophic and control internodes of similar length were compared, there was no difference in the mean number of myelin lamellae or their periodicity in the two groups, in spite of a mean reduction in axon cross-sectional area of 60% in the atrophic group. Mean values for axon perimeter and myelin spiral length were reduced by 14%-15% in atrophic fibres, compared with controls. The reduction in mean myelin spiral length might seem to imply that myelin had been lost from the atrophic internodes. However, there was also an increase in the length of individual lamellae in the long axis of the internode, due to the irregular folding of the sheath, and it is uncertain whether any overall change in internodal myelin volume had occurred.


Coronary angiography of Kawasaki disease with the coronary vasodilator dipyridamole: assessment of distensibility of affected coronary arterial wall.
The authors evaluated the distensibility of the coronary arterial wall by pharmacoangiography with intravenous administration of dipyridamole in 38 patients with Kawasaki disease. In the acute stage of the illness, the coronary arteries were evaluated for aneurysms by two-dimensional echocardiography. After the acute stage of the illness, selective coronary cineangiographies were performed by Seldinger's method under general anesthesia before and after intravenous administration of 0.6 mg/kg of dipyridamole for four minutes. The calibers of aneurysms and normal appearing segments of coronary arteries, at most 7 segments in 1 patient, were measured before and after dipyridamole administration on the high-quality cineangioanalyzer and percentages of coronary arterial dilatation were calculated. In 14 cases without evidence of coronary arterial lesions, the distensibility was 10.2 +/- 4.7% (mean +/- SD). The distensibility of 32 aneurysms in 16 cases was 0.6 +/- 1.1% and was significantly decreased (p less than 0.001). In 24 cases with coronary arterial lesions, aneurysms, stenosis, or obstruction, the distensibility of normal appearing segments of coronary arteries was 4.5 +/- 4.9% and was significantly decreased (p less than 0.001). This method is useful in evaluating distensibility and appears to be effective in detecting pathologic changes of the coronary arterial wall, even if it appears normal in shape. The patient with previously diseased coronary arteries should be kept under careful longterm surveillance.


Characteristics of Hearts at Necropsy in Patients Treated Chronically With Prednisone (The Corticosteroid Heart).
It is known that long-term corticosteroid therapy increases fatty deposits in several human tissues. To quantify the quantity of fatty deposits in the heart in patients on prednisone, we examined the heart at necropsy in 37 patients who had received long-term corticosteroid therapy (prednisone in 34) and compared certain findings in them to those in 194 (steroid-naïve) patients also studied at necropsy at Baylor University Medical Center, Dallas, in a 3-year period (2013, 2014, and 2015). Significant differences between the 2 groups were found in age, gender, and frequency of coronary artery disease but not in body mass index, frequency of massive cardiac adiposity, heart weight, or frequency of systemic hypertension or diabetes mellitus. Furthermore, no significant differences were observed in the patients taking ≤20 mg versus those taking >20 mg daily of prednisone. In conclusion, this study observed no significant differences in body mass index, frequency of cardiac adiposity (floating heart), heart weight, or frequencies of systemic hypertension or diabetes mellitus in the patients receiving or not receiving prednisone for a long term, but the prednisone-treated patients were younger, more often women, and had a lower frequency of severe narrowing of ≥1 major coronary arteries.


A rare genetic variant in the manganese transporter SLC30A10 and elevated liver enzymes in the general population.
A genetic variant in the manganese transporter SLC30A10 (rs188273166, p.Thr95Ile) was associated with increased plasma alanine transaminase (ALT) in a recent genome-wide association study in the UK Biobank (UKB). The aims of the present study were to test the association of rs188273166 with ALT in an independent cohort, and to begin to assess the clinical, hepatic, and biochemical phenotypes associated with the variant. We included n = 334,886 white participants from UKB, including 14,462 with hepatic magnetic resonance imaging (MRI), and n = 113,612 individuals from the Copenhagen City Heart Study and the Copenhagen General Population Study combined. Genotyping SLC30A10 p.Thr95Ile identified 816 heterozygotes in the UKB and 111 heterozygotes in the Copenhagen cohort. Compared to noncarriers, heterozygotes had 4 and 5 U/L higher levels of ALT in the UKB and Copenhagen cohort, respectively, and 3 U/L higher plasma aspartate transaminase and gamma-glutamyl transferase in the UKB. Heterozygotes also had higher corrected T1 on liver MRI, a marker of hepatic inflammation (p = 4 × 10-7), but no change in MRI-quantified steatosis (p = 0.57). Plasma manganese was within the normal range in nine heterozygotes that provided new blood samples. SLC30A10 p.Thr95Ile heterozygotes had an eightfold increased risk of biliary tract cancer in UKB (p = 4 × 10-7), but this association was not replicated in the Copenhagen cohort. SLC30A10 p.Thr95Ile was associated with elevated liver enzymes in two large general population cohorts, and with MRI-quantified hepatic inflammation. A rare genetic variant (p.Thr95Ile) in the manganese transporter SLC30A10 is associated with elevated plasma alanine transaminase (ALT) and higher corrected T1 on liver MRI, markers of liver inflammation. These data support that the variant may increase the risk of liver disease.


Nuclear Cell-Free DNA Predicts Adverse Events After Pediatric Cardiothoracic Surgery.
Preoperative risk stratification in cardiac surgery includes patient and procedure factors that are used in clinical decision-making. Despite these tools, unidentified factors contribute to variation in outcomes. Identification of latent physiologic risk factors may strengthen predictive models. Nuclear cell-free DNA (ncfDNA) increases with tissue injury and drops to baseline levels rapidly. The goal of this investigation is to measure and to observe ncfDNA kinetics in children undergoing heart operations with cardiopulmonary bypass (CPB), linking biomarkers, organ dysfunction, and outcomes. This is a prospective observational study of 116 children <18 years and >3 kg undergoing operations with CPB. Plasma ncfDNA samples were collected and processed in a stepwise manner at predefined perioperative time points. The primary outcome measure was occurrence of postoperative cardiac arrest or extracorporeal membrane oxygenation. Data were available in 116 patients (median age, 0.9 years [range, 0-17.4 years]; median weight, 7.8 kg [range, 3.2-98 kg]). The primary outcome was met in 6 of 116 (5.2%). Risk of primary outcome was 2% with ncfDNA <20 ng/mL and 33% with ncfDNA >20 ng/mL (odds ratio, 25; CI, 3.96-158; P = .001). Elevated ncfDNA was associated with fewer hospital-free days (P < .01). This study analyzes ncfDNA kinetics in children undergoing operations with CPB for congenital heart disease. Elevated preoperative ncfDNA is strongly associated with postoperative arrest and extracorporeal membrane oxygenation. Further studies are needed to validate this technology as a tool to predict morbidity in children after cardiac surgical procedures.


Effect of nafenopin (SU-13,437) on liver functions. Hepatic uptake and biliary excretion of ouabain in the rat.
Pretreatment of rats for 2 days with the hypolipidemic drug, nafenopin, 0.5 g/kg, results in an increase in liver weight and bile flow. Despite these changes, hepatic transport of ouabain is reduced. This was demonstrated in the isolated perfused liver as well as in vivo. Although net uptake into liver is diminished in treated rats, the initial rapid phase of the plasma disappearance curve is unaffected. This suggests that the primary uptake process is unaffected by nafenopin or is altered in a manner that is not reflected in this phase of plasma disappearance. Alternatively, nafenopin may increase ouabain efflux from liver to plasma. Biliary excretion of ouabain is markedly suppressed after nafenopin pretreatment and higher liver levels of ouabain were encountered after the first 20 min in treated animals. The inference is drawn that liver to bile transport of ouabain is also suppressed by nafenopin pretreatment.


Subunit dissociation and activation of wild-type and mutant glucocorticoid receptors.
Apparent molecular weights of wild-type and nti ('increased nuclear transfer') mutant glucocorticoid receptors were obtained from Stokes radii and sedimentation coefficients. At low salt concentrations molecular forms of Mr 328,000 and 298,000 of the wild-type and mutant, respectively, were predominant. Increasing ionic strength resulted in receptor dissociation. Dissociated forms of Mr 130,000 and 63,000 of the wild-type and mutant, respectively, were obtained at 300 mM KCl and above. Some metal oxi-anions prevented dissociation. Receptor activation to allow DNA binding produced the dissociated forms which could be separated from non-activated receptors by filtration through DNA-cellulose or by DEAE-cellulose chromatography. Non-activated wild-type and nti receptors eluted from DEAE-cellulose under identical conditions while activated wild-type and nti receptors eluted differently. Partially proteolyzed wild-type receptors behaved identically to nti receptors. We conclude that the large forms of wild-type and nti receptors are heteromeric and contain only one hormone-building polypeptide per complex.


Gender difference in a subpopulation of rat superior cervical ganglion neurons.
The number of superior cervical ganglion (SCG) neurons is equivalent in males and females on the day of birth. By 15 days, after most of the normal neuron death has occurred, males have 20-30% more neurons than females; and this difference persists in the adult. The present study was undertaken to determine whether this difference exists uniformly throughout the ganglion, or only in a subpopulation of these neurons. To study subpopulations of SCG neurons, bilateral transection of the internal carotid nerve, the external carotid nerve, or both postganglionic nerves was performed on neonatal male and female Sprague-Dawley rats on the day of birth. Littermate sham operates served as controls. Numbers of neurons were counted in SCGs of animals on either postnatal day 4 or 15, before or after normal development of the SCG sex difference. At 4 days, the number of SCG neurons in sham-operated males had females were not different, while at 15 days, sham-operated males had more SCG neurons than did sham-operated females. The number of neurons remaining in the SCG following neonatal transection of the internal carotid nerve were not different in males and females at either 4 or 15 days postnatal. The number of SCG neurons remaining following neonatal transection of the external carotid nerve was greater in males than in females at both 4 and 15 days postnatal. It was concluded that the gender difference in survival of SCG neurons lies in neurons projecting through the internal carotid nerve. The number of neurons projecting out the external carotid nerve is equivalent in males and females.


Phospholipase A2-interacting weak neurotoxins from venom of monocled cobra Naja kaouthia display cell-specific cytotoxicity.
The molecular weights of two phospholipase A(2) (PLA(2))-interacting polypeptides (kaouthiotoxins (KTXs)-KTX-A and KTX-B) purified from the venom of monocled cobra Naja kaouthia, were estimated by mass spectrometry as 7722 and 7627Da, respectively. Binary sequence alignment showed that both KTXs share substantial sequence homology with weak neurotoxins from cobra venom and they were devoid of any enzymatic activity. Their pI was determined at pH 8.1 showing basic nature of these proteins. KTXs displayed cell-specific cytotoxicity on mammalian and insect cells.


Anti-fibrotic effects of Salvia miltiorrhiza and Ligustrazine Injection on LX-2 cells involved with increased N-myc downstream-regulated gene 2 expression.
To investigate the effects of Salvia miltiorrhiza and Ligustrazine Injection (SML) on proliferation and apoptosis of human hepatic stellate cell LX-2 and the expression of N-myc downstreamregulated gene 2 (NDRG2, a tumor suppressor gene). HSCs from the LX-2 cell line were cultured in vitro. The proliferative state of different initial LX-2 cell numbers was measured using a 3-(4,5-dimethylthiazol- 2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assay. LX-2 cells were plated in 96-well plates at an approximate density of 2.50×104 cells/mL and cultured for 24 h followed by the application of different concentrations of SML (1, 2, 4 and 8 μL/mL). Cell proliferation was measured using the MTT assay at 24 and 48 h. Apoptosis was detected by flow cytometry at 24 h. LX-2 cells were treated with different concentrations of SML and extracted with protein lysis buffer. The levels of NDRG2 and β-catenin were measured by Western blot. With the exception of the 1 and 2 μL/mL concentrations, 4 and 8 μL/mL SML inhibited cell proliferation in a concentration-dependent manner at 24 and 48 h (P<0.05). With the exception of the 1 and 2 μL/mL concentrations, the NDRG2 expression level was greatly increased in a concentration-dependent manner. However, the level of β-catenin was unaffected. SML inhibit LX-2 cell proliferation in a concentration-dependent manner, and the mechanism may be associated with NDRG2 over-expression.


Postoperative bronchopleural fistula: endoscopic closure in 12 patients.
Twelve consecutive patients with postresectional bronchopleural fistula were treated with endoscopic application of tissue glue adhesive (methyl-2-cyanoacrylate). Eight patients had associated empyema. Endoscopic gluing was successfully accomplished in 10 cases (success rate of 83%). The two failures both had fistulas of 0.5 cm or larger. Bronchopleural fistulas developed in 8 patients early after the intervention (< 15 days): of the 4 patients without associated empyema, 3 had their fistula definitely closed after endoscopic treatment. Similarly, 3 of the 4 patients with early bronchopleural fistulas and empyema were cured after endoscopic closure of the fistula and appropriate management of the empyema. Four bronchopleural fistulas occurred late after the operation (> 15 days) and all had associated empyema. Successful endoscopic closure of the fistula was accomplished in all. Resolution of the empyema occurred in 1. We conclude that endoscopic application of tissue adhesive may be a valid therapeutic measure in selected patients with postresectional bronchopleural fistula. In late bronchopleural fistula with empyema, the closure of the fistula can be achieved, but empyema may persist and require additional surgical procedures.


Analysis of Experimental Ligature-Induced Periodontitis Model in Mice.
Periodontitis is one of the most prevalent chronic inflammatory diseases in humans. However, the disease has been hard to study, majorly because it has been difficult to establish a reproducible animal model. Nonetheless, the ligature-induced periodontitis model in rodent has shown some promise. Here we describe a simplified systematic method to analyze periodontal pathogenesis using quantitative polymerase chain reaction, immunohistochemistry, and bone phenotype in ligature-induced periodontitis murine model. We provide detailed experimental methods and also provide notes that will help to carry out the procedure successfully.


Role of intravenous immunoglobulin in severe steroid-dependent asthma.
Subgroups of asthma patients have extremely severe respiratory symptoms that require chronic use of steroids for disease control. These patients are at risk of significant side-effects from chronic exposure to high doses of oral steroids. Intravenous immunoglobulin (IVIG) has immunomodulatory properties as shown by its use in some immune disorders. A few trials have suggested a possible benefit in individuals with severe asthma. To evaluate the role of IVIG as an adjunctive therapy in steroid-dependent asthma, monitoring the outcomes of lung function and measured reduction in oral steroid requirement. Seven patients with severe steroid-dependent asthma were given IVIG at a dose of 1 g/kg each month for 6 months. Baseline pulmonary function tests and immunoglobulin levels were obtained. At the end of 6 months, the end-points observed were lung function and the degree of reduction in the dose of oral steroids. The number of hospital admissions during the 12 months following commencement of IVIG was compared with the preceding 12 months. There was a significant reduction in daily prednisolone dose from 56 +/- 31 mg to 39 +/- 35 mg (P=0.04, Wilcoxon rank sum test) and a decrease in the number of hospital admissions from 5.9 +/- 2.9 to 3.6 +/- 3.5 (P=0.04). No significant improvement occurred in lung function. IVIG provides a potentially important adjunctive therapy in severe steroid-dependent asthma, reducing steroid requirement and decreasing hospital admissions, but not improving lung function.


Cervical Stand-Alone Polyetheretherketone Cage versus Zero-Profile Anchored Spacer in Single-Level Anterior Cervical Discectomy and Fusion : Minimum 2-Year Assessment of Radiographic and Clinical Outcome.
We compared the clinical and radiographic outcomes of stand-alone polyetheretherketone (PEEK) cage and Zero-Profile anchored spacer (Zero-P) for single level anterior cervical discectomy and fusion (ACDF). We retrospectively reviewed 121 patients who underwent single level ACDF within 2 years (Jan 2011-Jan 2013) in a single institute. Total 50 patients were included for the analysis who were evaluated more than 2-year follow-up. Twenty-nine patients were allocated to the cage group (m : f=19 : 10) and 21 for Zero-P group (m : f=12 : 9). Clinical (neck disability index, visual analogue scale arm and neck) and radiographic (Cobb angle-segmental and global cervical, disc height, vertebral height) assessments were followed at pre-operative, immediate post-operative, post-3, 6, 12, and 24 month periods. Demographic features and the clinical outcome showed no difference between two groups. The change between final follow-up (24 months) and immediate post-op of Cobb-segmental angle (p=0.027), disc height (p=0.002), vertebral body height (p=0.033) showed statistically better outcome for the Zero-P group than the cage group, respectively. The Zero-Profile anchored spacer has some advantage after cage for maintaining segmental lordosis and lowering subsidence rate after single level anterior cervical discectomy and fusion.


Discontinuous-flow plasmapheresis and patent foramen ovale: a possible cause of paradoxical embolism.
A 68-year-old woman was admitted for a subacute polyradiculoneuropathy and submitted to PE. A central right jugular venous access was placed after the third PE procedure due to a failing peripheral blood access. During the fourth PE, performed with a discontinuous-flow system (continuous-flow used for 3 procedures), she developed multiple embolic ischemic lesions in the left middle cerebral artery (MCA) territory. A thorough cerebrovascular screening showed only a patent foramen ovale (PFO). In our case, a possible increase of the right atrium blood pressure induced by the positive flux of the discontinuous-flow PE could have been responsible for a paradoxical embolism through the PFO. Plasma exchange (PE) is used in several neurologic disorders. It is commonly thought to be a relatively safe procedure. However, a number of adverse events may occur: paradoxical embolism has not been reported to occur.


p53 and metabolism: Inside the TIGAR.
The p53 tumor suppressor pathway coordinates DNA repair, cell-cycle arrest, apoptosis, and senescence to preserve genomic stability and prevent tumor formation. The discovery of three new target genes for p53 reveals unexpected functions for this tumor suppressor in the regulation of glucose metabolism and autophagy.


Extravascular fluid dynamics of the embryonic chick wing bud.
While a number of models of positional information in the chick wing bud have involved the diffusion of morphogens to establish chemical gradients of morphogenetic activity, only recently have there been attempts to characterize the milieu in which such diffusion must take place. We report an analysis of the fluid dynamics of the extravascular (interstitial) spaces of stage 22-25 chick wing buds, into which aqueous aniline blue dye was microinjected as a visible, unreactive tracer. Six sites along the antero-posterior (A-P) and proximo-distal (P-D) axes were chosen for study. Injections of dye into the posterior half of the wing bud exhibited marked directionality of extravascular transport (mean of all posterior sites = 68%), while anterior injections showed little or no directionality (mean of all anterior sites = 13%). All instances of directed dye movement were disto-proximal, the same direction as the blood flow through the marginal veins. In embryos gassed in situ with CO2, which reversibly stopped the heartbeat and vascular flow, directionality was abolished, yet diffusion rates were unaffected. Posterior disto-proximal extravascular dye movement was correlated with the greater diameter, flow velocity, and volume flow rate of the posterior marginal vein, compared to the anterior marginal vein. Radial diffusion rates were measured, and posterior disto-proximal rates were corrected for measured disto-proximal directionality by the use of a simple diffusion-translation model. Three-way analysis of variance showed that directionality-uncorrected disto-proximal rates in posterior sites were not significantly different from anterior radial rates, but that directionality-corrected posterior rates did differ significantly (P less than 0.0001). A significant stage effect (P less than 0.005) and a significant interaction between the A-P axis and stage (P less than 0.05) were also found. We hypothesize that the spatial arrangement and flow patterns of the vasculature physically determine the fluid dynamics of the interstitium. Based on these observations, we also suggest that disto-proximal extravascular fluid movement in the posterior wing bud presents a barrier to the free diffusion of aqueous molecules, including morphogens originating in the "zone of polarizing activity."


Finnish Allergy Programme 2008-2018--time to act and change the course.
The prevalence of allergic diseases has grown in Finland, similarly to many other western countries. Although the origin of allergy remains unresolved, increasing body of evidence indicates that the modern man living in urban built environment is deprived from environmental protective factors (e.g. soil microorganisms) that are fundamental for normal tolerance development. The current dogma of allergen avoidance has not proved effective in halting the 'epidemic', and it is the Finnish consensus that restoring and strengthening tolerance should more be in focus. The national 10-year programme is aimed to reduce burden of allergies. The main goals are to (i) prevent the development of allergic symptoms; (ii) increase tolerance against allergens; (iii) improve the diagnostics; (iv) decrease work-related allergies; (v) allocate resources to manage and prevent exacerbations of severe allergies and (vi) decrease costs caused by allergic diseases. For each goal, specific tasks, tools and evaluation methods are defined. Nationwide implementation acts through the network of local co-ordinators (primary care physicians, nurses, pharmacists). In addition, three nongovernmental organizations (NGOs) take care of the programme implementation. The 21 central hospital districts carry out a three step educational process: (i) healthcare personnel; (ii) representatives and educators of NGOs and (iii) patients and the general population. For outcome evaluation, repeated surveys are performed and healthcare registers employed at the beginning, at 5 years, and at the end of the programme. The process will be evaluated by an independent external body. The Finnish initiative is a comprehensive plan to reduce burden of allergies. The aim is to increase immunological tolerance and change attitudes to support health instead of medicalizing common and mild allergy symptoms. It is time to act, when allergic individuals are becoming a majority of western populations and their numbers are in rapid increase worldwide. The Programme is associated with the Global Alliance of Chronic Respiratory Diseases (GARD), WHO.


Correction to: Exhaled nitric oxide is not a biomarker for idiopathic pulmonary arterial hypertension or for treatment efficacy.
Following publication of the original article [1], the authors flagged that name of the author 'Batoul Khoundabi' had been provided with an incorrect spelling: 'Batoutl' was given in place of 'Batoul'.


Non-invasive determination of zero-pressure geometry of arterial aneurysms.
Arterial aneurysms are in a pre-deformed state in vivo under non-zero pressure. The ability to determine their zero pressure geometry may help in improving accuracy of determination of stress distribution and reverse estimation of material properties from dynamic imaging data. An approximate method to recover the zero pressure geometry of the AAA is proposed. This method is motivated by the observation that the patterns in displacement field for a given AAA are strikingly consistent in an AAA under all physiological pressures. The basic principle is to leverage this observation to iteratively identify the geometry that when subjected to the in vivo pressure, will recover the geometry reconstructed from in vivo imaging. The methodology is demonstrated and validated using patient-specific AAA models.


GC-MS-based metabolic signatures reveal comparative steroidogenic pathways between fetal and adult mouse testes.
Previous studies on gonadal steroidogenesis have not compared metabolic pathways between fetal and adult mouse testes to date. To evaluate comparative metabolic signatures of testicular steroids between fetus and adult mice using gas chromatography-mass spectrometry (GC-MS)-based steroid profiling. GC-MS with molecular-specific scan modes was optimized for selective and sensitive detection of 23 androgens, 7 estrogens, 14 progestogens, and 13 corticoids from mouse testes with a quantification limit of 0.1-5.0 ng/mL and reproducibility (coefficient of variation: 0.3%-19.9%). Based on 26 steroids quantitatively detected in testes, comparative steroid signatures were analyzed for mouse testes of 8 fetuses on embryonic day 16.5 and 8 adults on postnatal days 56-60. In contrast to large amounts of steroids in adult testes (P < .0002), all testicular levels per weight unit of protein were significantly increased in fetal testes (P < .002, except 6β-hydroxytestosterone of P = .065). Both 11β-hydroxyandrostenedione and 7α-hydroxytestosterone were only measurable in fetal testes, and metabolic ratios of testosterone to androstenediol and androstenedione were also increased in fetal testes (P < .05 for both). Testicular steroid signatures showed that both steroidogenic Δ4 and Δ5 pathways in the production of testosterone were activated more during prenatal development. Both 7α- and 11β-hydroxylations were predominant, while hydroxylations at C-6, C-15, and C-16 of testosterone and androstenedione were decreased in the fetus. The present GC-MS-based steroid profiling may facilitate understanding of the development of testicular steroidogenesis.


P11: a potential biomarker for posttraumatic stress disorder.
Posttraumatic stress disorder (PTSD) is a chronic and disabling anxiety disorder that occurs after a traumatic event. It is associated with an increased risk of suicide and marked deficits in social and occupational functioning. Currently, the diagnosis for PTSD is established on the basis of a patient's clinical history, mental status examination, duration of symptoms, and clinician administered symptom checklist or patient self-report. However, there are no available laboratory biomarker tests for PTSD. To begin intervention at the earliest possible time, priority must be given to developing objective approaches to determine the presence of PTSD. Thus, using cutting-edge technology and skill to develop a simple blood test or a biomarker to detect PTSD at its earliest and most treatable stage would benefit both physician and patient. Several technologies and skills have been used in the identification biomarker research. We discuss three major methods in this chapter (blood RNA and DNA purification, chromatin immunoprecipitation, and Western blot), which have been used in our study to determine whether p11 is a potential biomarker for PTSD. Using these procedures will not only enhance the study of the molecular mechanisms of PTSD but also help the translation of basic science to a clinical setting.


Solid phase synthesis of selective caspase-3 peptide inhibitors.
A robust method for the solid phase synthesis of a series of selective caspase-3 peptide inhibitors is described. The inhibitors can be obtained after cleavage from the solid support without further purification.


Prenatal exposure to nanoparticulate titanium dioxide enhances depressive-like behaviors in adult rats.
Titanium dioxide nanoparticles (TiO2 NPs) have the potential to produce reactive oxygen species and can be transferred from the mother to the fetal brain. The central nervous system exhibits remarkable plasticity in early life and can be altered significantly by environmental stressors encountered during fetal period. Additionally, prenatal stressors are involved with emotional problems in adulthood. The purpose of the current study is to evaluate whether prenatal exposure to TiO2 NPs could induce oxidative damage in the offspring brain and eventually affect the emotional behaviors in adulthood. The results showed that prenatal exposure to TiO2 NPs impaired the antioxidant status, caused a significant oxidative damage to nucleic acids and lipids in the brain of newborn pups, and enhanced the depressive-like behaviors during adulthood in the force swimming test and the sucrose preference test. These results suggest that the stress during fetal life induced by prenatal exposure to TiO2 NPs could be implicated in depressive-like behaviors in adulthood.


"Labia Majora Fasciocutaneous Flap Reconstruction in Complex Urogynecological Fistulas With Vaginal Deficit - A Versatile Approach".
To appraise the pivotal points of different modifications of labia majora fasciocutaneous flap in combating the challenges of complex urogynecological fistula repair in the form of 7 cases. Seven patients with complex urogynecological fistulas with vaginal deficit were treated over last 3 years. The challenges associated with them were non-capacious rigid vagina, irradiated and inflamed surrounding tissues, inelasticity, long-standing fistula with radiation-induced vesicovaginal fistula(VVF), an iatrogenic urethrovaginal fistula with anterior vaginal wall loss with vaginal stenosis, and a case of vesicolabial fistula with a history of forceps delivery and transvaginal VVF repair. Transvaginal repair with labia majora fasciocutaneous flap along with fat pad with relevant technical modifications was contemplated in all. All radiation-induced VVF patients demonstrated no leak in the postoperative period barring one who became dry after transvaginal colpocleisis later. The patient with urethrovaginal fistula and vaginal stenosis was continent, had capacious vagina, and without any leak with regular menstrual periods. The female with vesicolabial fistula remained dry at the end of 6-month follow-up. Transvaginal repair using the labia majora fasciocutaneous flap and the demonstrated technical modifications can be a feasible option in repairing complex urogynaecological fistulas associated with vaginal wall deficit.


Patient-level meta-analysis of the EDITION 1, 2 and 3 studies: glycaemic control and hypoglycaemia with new insulin glargine 300 U/ml versus glargine 100 U/ml in people with type 2 diabetes.
To conduct a patient-level meta-analysis of the EDITION 1, 2 and 3 studies, which compared the efficacy and safety of new insulin glargine 300 U/ml (Gla-300) with insulin glargine 100 U/ml (Gla-100) in people with type 2 diabetes (T2DM) on basal and mealtime insulin, basal insulin and oral antihyperglycaemic drugs, or no prior insulin, respectively. The EDITION studies were multicentre, randomized, open-label, parallel-group, phase IIIa studies, with similar designs and endpoints. A patient-level meta-analysis of the studies enabled these endpoints to be examined over 6 months in a large population with T2DM (Gla-300, n = 1247; Gla-100, n = 1249). No significant study-by-treatment interactions across studies were found, enabling them to be pooled. The mean change in glycated haemoglobin was comparable for Gla-300 and Gla-100 [each -1.02 (standard error 0.03)%; least squares (LS) mean difference 0.00 (95% confidence interval (CI) -0.08 to 0.07)%]. Annualized rates of confirmed (≤3.9 mmol/l) or severe hypoglycaemia were lower with Gla-300 than with Gla-100 during the night (31% difference in rate ratio over 6 months) and at any time (24 h, 14% difference). Consistent reductions were observed in percentage of participants with ≥1 hypoglycaemic event. Severe hypoglycaemia at any time (24 h) was rare (Gla-300: 2.3%; Gla-100: 2.6%). Weight gain was low (<1 kg) in both groups, with less gain with Gla-300 [LS mean difference -0.28 kg (95% CI -0.55 to -0.01); p = 0.039]. Both treatments were well tolerated, with similar rates of adverse events. Gla-300 provides comparable glycaemic control to Gla-100 in a large population with a broad clinical spectrum of T2DM, with consistently less hypoglycaemia at any time of day and less nocturnal hypoglycaemia.


Effects of gut microbiota disturbance induced in early life on the expression of extrasynaptic GABA-A receptor α5 and δ subunits in the hippocampus of adult rats.
Previous studies have demonstrated that gut microbiota disturbance significantly increases the risk of emotional disorders via the gut-brain axis, but the mechanism is unclear. Furthermore, gamma-aminobutyric acid (GABA) deficits were reported to be implicated in the development of depression and amnesia, but the alterations in the GABA-A receptor subunits that are involved in the pathogenetic process have not been fully elucidated. This study used juvenile rats that were fed ampicillin-Na to establish degree III dysbiosis of the intestinal flora and examined emotional change via the tail suspension test, forced swim test and Morris water maze. Additionally, our study investigated the expression of GABA-A receptor α5 and δ subunits in the hippocampus in adulthood via q-PCR and immunohistochemistry. We focused on the role of GABA-A receptor α5 and δ subunit changes induced by juvenile gut microbiota disturbance in the pathogenesis of emotional disorders in adulthood. In addition, we investigated the protective effects of probiotics and benzodiazepine (clonazepam). Findings showed that juvenile gut microbiota disturbances induced chronic depression and memory loss and reduced the expression of GABA-A receptor α5 and δ subunits in the hippocampus of the adult rat. Furthermore, moderate probiotic administration led to a significant improvement compared to short-term BZ treatment. However, we are aware that these results have been established with a single animal experiment and will require further confirmation with a larger group of individuals. Future directions for the exploration of the effects of gut microbiota disturbance on GABA-A receptor α5 and δ subunits are discussed.


Nanoparticles for Inducing Antigen-Specific T Cell Tolerance in Autoimmune Diseases.
Autoimmune diseases affect many people worldwide. Current treatment modalities focus on the reduction of disease symptoms using anti-inflammatory drugs which can lead to side effects due to systemic immune suppression. Restoration of immune tolerance by down-regulating auto-reactive cells in an antigen-specific manner is currently the "holy grail" for the treatment of autoimmune diseases. A promising strategy is the use of nanoparticles that can deliver antigens to antigen-presenting cells which in turn can enhance antigen-specific regulatory T cells. In this review, we highlight some promising cell targets (e.g. liver sinusoidal endothelial cells and splenic marginal zone macrophages) for exploiting natural immune tolerance processes, and several strategies by which antigen-carrying nanoparticles can target these cells. We also discuss how nanoparticles carrying immunomodulators may be able to activate tolerance in other antigen-presenting cell types. Finally, we discuss some important aspects that must be taken into account when translating data from animal studies to patients.


Detection of human in vitro hapten specific antibody responses.
A microculture and radioimmunoassay is described which is capable of generating and detecting very small levels of human anti-DNP antibody. The antibody produced is hapten specific and the response is T-cell dependent. The microculture system described avoids the need for high serum supplements, mitogens, in vivo immunisation or large cell numbers. As this system is simple, sensitive and reproducible it has considerable potential in the study of human immune response regulation and especially the role of lymphokines in human antibody responses.


Psychiatry to dermatology; panic disorder.
Anxiety is commonly observed together with skin diseases and can aggravate them, while skin diseases can increase anxiety. The relationship of skin diseases observed in panic disorder with quantitative electroencephalography (QEEG) findings has not been investigated yet. The aim of this study is to compare the absolute alpha and delta power of panic disorder patients with and without skin disease. 246 panic disorder patients, 19 of whom had skin disease and 227 of whom did not have skin disease, were included in the study. Panic disorder severity scale (PDSS) scores of patients were recorded, and QEEG recording was performed. Absolute alpha and delta power and PDSS scores were compared between the two groups. It was found that the absolute delta power in the left hemisphere was lower and PDSS scores were higher in the patients with skin diseases compared to the control group. In the patients with skin disease, decreased delta power in the left hemisphere may cause impairment in the processing of positive emotions and may cause trait anxiety. Trait anxiety may increase susceptibility to skin diseases by disrupting cutaneous homeostasis resulting from the prolonged sympathetic nervous system activation.


Gene expression dose-response changes in microarrays after exposure of human peripheral lung epithelial cells to nickel(II).
Occupational exposure to nickel compounds is associated with lung cancer risk; both genotoxic and epigenetic mechanisms have been proposed. For comprehensive examination of the acute effects of nickel(II) acetate on gene expression in cultured human peripheral lung epithelial HPL1D cells, microarray analyses were carried out with cDNA chips (approximately 8000 cDNAs). Cells were exposed for 24 h to nontoxic (50, 100, and 200 microM) or toxic (400, 800, and 1600 microM) nickel(II) concentrations. Cluster analysis was applied to the 868 genes with > or = 2-fold change at any concentration. Two main clusters showed marked up- or down-regulation at the highest, toxic concentrations. The data further subdivided into 10 highly cohesive clusters with high probability, and of these only 2 had the same response trend at low nontoxic as at high concentrations, an observation of clear relevance to the process of high- to low-dose extrapolation in risk assessment. There were 113 genes showing > or = 2-fold change at the three lower nontoxic concentrations, those most relevant to in vivo carcinogenesis. In addition to expected responses of metallothionein, ferritin, and heat-shock proteins, the results revealed for the first time changed expression of some potential cancer-related genes in response to low-dose Ni(II): RhoA, dyskerin, interferon regulatory factor 1, RAD21 homologue, and tumor protein, translationally controlled. Overall, most of the genes impacted by nontoxic concentrations of nickel(II) acetate related to gene transcription, protein synthesis and stability, cytoskeleton, signaling, metabolism, cell membrane, and extracellular matrix.


Aggressive Cutaneous Lymphomas and Their Mimics.
Cutaneous lymphomas encompass a heterogeneous group of neoplasms with a wide spectrum of clinical presentations, histopathologic features, and prognosis. Because there are overlapping pathologic features among indolent and aggressive forms and with systemic lymphomas that involve the skin, clinicopathologic correlation is essential. Herein, the clinical and histopathologic features of aggressive cutaneous B- and T-cell lymphomas are reviewed. Indolent cutaneous lymphomas/lymphoproliferative disorders, systemic lymphomas, and reactive processes that may mimic these entities are also discussed. This article highlights distinctive clinical and histopathologic features, increases awareness of rare entities, and presents new and evolving developments in the field.


[Exploring the Prognostic Features of Hepatocellular Carcinoma via Text Mining and Data Analysis].
Transcatheter arterial chemoembolization is one of the interventional treatments for hepatocellular carcinoma (HCC). This treatment is generally used for patients with intermediate to advanced hepatocellular carcinoma, and identifying the role of HCC-related genes can help improve the efficiency of transcatheter arterial chemoembolization. To investigate the role of HCC-related genes and to provide valid evidence for transcatheter arterial chemoembolization treatment, we performed a comprehensive bioinformatics analysis. Through text mining ("hepatocellular carcinoma") and microarray data analysis (GSE104580), we obtained a standard gene set, which was followed by gene ontology and Kyoto Gene and Genome Encyclopedia analysis. The significant 8 genes clustered in protein-protein interactions network were chosen to be used in the follow-up analysis. Through survival analysis low expression of the key genes were found to be strongly associated with survival in HCC patients in this study. The correlation between the expression of the key genes and tumor immune infiltration was assessed by Pearson correlation analysis. As a result, 15 drugs targeting seven of the eight genes have been identified, and therefore can be considered as potential components for transcatheter arterial chemoembolization treatment of HCC.


Negotiating and bidding for good results.
When determining a method of procurement, the purchasing manager must remember his goals. Whether it be by bidding, negotiating, or open-ended contracts, the method chosen is a means of obtaining savings for the hospital and, ultimately, for the patient.


General Severity of Illness Scoring Systems and COVID-19 Mortality Predictions: Is "Old Still Gold?"
How to cite this article: Siddiqui SS, Patnaik R, Kulkarni AP. General Severity of Illness Scoring Systems and COVID-19 Mortality Predictions: Is "Old Still Gold?" Indian J Crit Care Med 2022;26(4):416-418.


Improved Doppler signal intensity in coronary arteries after intravenous peripheral injection of a lung-crossing contrast agent (SHU 508A)
We tested the hypothesis that SHU 508A, a new lung-crossing contrast agent capable of increasing the Doppler signal to noise ratio in the right heart as well as left heart cavities after intravenous injection, could increase Doppler signal intensity in coronary arteries, thus improving the feasibility and quality of transesophageal Doppler echocardiographic evaluation of coronary blood flow velocity. Coronary blood flow velocity can be evaluated by transesophageal Doppler echocardiography. However, an adequate Doppler tracing is obtainable in a relatively low percent of patients. Transesophageal Doppler echocardiography of coronary arteries was performed in 35 patients before and after SHU 508A injection at four different dosages (200 mg/ml in 5 ml, 200 mg/ml in 10 ml, 300 mg/ml in 5 ml and 300 mg/ml in 10 ml). Color Doppler mapping of coronary flow and pulsed wave Doppler measurement of coronary blood flow velocity were attempted in all patients. Color Doppler flow mapping of 105 evaluated coronary segments (left main, left anterior descending and circumflex in 35 patients) was not detectable or was weak in 88% of patients before and 33% of patients after echo contrast injection (p < 0.0001); it was optimal (that is, well delineated with complete flow mapping of the explored vessel) in only 11% of patients before and 67% after echo contrast injection (p < 0.0001). In addition, pulsed wave Doppler signal quality improved after echo contrast injection: Pulsed wave Doppler recording of coronary blood flow velocity was not obtainable or was weak in 78% of cases before and 34% after echo contrast injection (p < 0.0001); pulsed wave Doppler recording of coronary blood flow velocity was optimal (that is, there was a complete and well defined outline of diastolic coronary blood flow velocity in 23% of cases before and 66% after echo contrast injection [p < 0.0001]. Both length and width of color Doppler mapping in the left anterior descending coronary artery increased after SHU 508A injection (from 5.75 +/- 5.32 and 1.51 +/- 1.17 to 17.04 +/- 8.76 and 4.21 +/- 1.78 mm, respectively, mean +/- SD, p < 0.0001). The feasibility and quality of recording coronary blood flow velocity by transesophageal Doppler echocardiography are considerably improved by intravenous injection of SHU 508A. The improved feasibility of this new semi-invasive method for evaluating coronary blood flow velocity and flow reserve can considerably increase its research and clinical utilization.


CDKD: a clinical database of kidney diseases.
The main function of the kidneys is to remove waste products and excess water from the blood. Loss of kidney function leads to various health issues, such as anemia, high blood pressure, bone disease, disorders of cholesterol. The main objective of this database system is to store the personal and laboratory investigatory details of patients with kidney disease. The emphasis is on experimental results relevant to quantitative renal physiology, with a particular focus on data relevant for evaluation of parameters in statistical models of renal function. Clinical database of kidney diseases (CDKD) has been developed with patient confidentiality and data security as a top priority. It can make comparative analysis of one or more parameters of patient's record and includes the information of about whole range of data including demographics, medical history, laboratory test results, vital signs, personal statistics like age and weight. The goal of this database is to make kidney-related physiological data easily available to the scientific community and to maintain & retain patient's record. As a Web based application it permits physician to see, edit and annotate a patient record from anywhere and anytime while maintaining the confidentiality of the personal record. It also allows statistical analysis of all data.


Connections of the ventral granular frontal cortex of macaques with perisylvian premotor and somatosensory areas: anatomical evidence for somatic representation in primate frontal association cortex.
In macaque monkeys with injections of tritiated amino acids or horseradish peroxidase in the ventrolateral granular frontal cortex, we observed extensive anterograde and retrograde labeling of the premotor and somatosensory cortex in and around the lateral sulcus. Comparable labeling was not present with large and small control injections of the dorsal granular cortex. Cytoarchitectonic evaluation of the perisylvian cortex in the three cases examined in detail indicated that labeled areas included the ventral premotor cortex (area 6V); the precentral opercular and orbitofrontal opercular areas (PrCO and OFO); the second somatosensory area (S-II); the opercular cortex immediately anterior to S-II, possibly corresponding to area 2 of the S-I complex; and the central part of the insular cortex, including portions of the granular and dysgranular insular fields (Ig, Idg). Labeling was particularly dense and extensive in areas 6V, S-II, and OFO. Lighter labeling was also present in the rostral inferior parietal lobule (areas 7b and POa). The distribution of label within perisylvian areas was not uniform: certain parts were heavily labeled, while other parts were lightly labeled or unlabeled. Comparison of label distribution with published accounts of the somatotopy of these areas indicates that forelimb and orofacial representations were selectively labeled. Further, our results, taken together with other recent anatomical findings (e.g., Matelli et al.: Journal of Comparative Neurology 251:281-298, 1987; Barbas and Pandya: Journal of Comparative Neurology 256:211-228, 1987) suggest strongly that there is a network of interconnected forelimb and orofacial representations in macaque cortex, involving the ventral granular frontal cortex, area 6V, OFO, opercular area 2, S-II, the central insula, and area 7b. Each injection of frontal cortex which labeled the perisylvian somatic cortex involved the cortex of the ventral rim of the principal sulcus (PSvr). The cortex surrounding the PSvr does not stand out as a distinct area in Nissl-stained material. However, examination of myelin-stained sections prepared from uninjected hemispheres with the Gallyas technique revealed the existence of a distinct zone centered on the PSvr. This myeloarchitectonic area, which we term area 46vr, is more heavily myelinated than the ventral bank and fundus of the principal sulcus (area 46v) but is less heavily myelinated than the ventral (inferior) convexity (area 12). Involvement of area 46vr in our injections was probably responsible for the strong labeling observed in perisylvian somatic areas.(ABSTRACT TRUNCATED AT 400 WORDS)


Spatial distribution, temporal variation and risks of parabens and their chlorinated derivatives in urban surface water in Beijing, China.
The occurrence and distribution of 13 target compounds, including eight parabens, four chlorinated parabens and p-hydroxybenzoic acid (PHBA), were detected in surface water samples at 35 sampling sites in the Beijing River system, China. The surface water samples were collected from the main rivers and lakes in the urban area monthly from July 2013 to June 2014 (except the frozen period). Laboratory analyses revealed that parabens were ubiquitous in the surface water of Beijing. PHBA was the predominant compound in the surface water samples, with the average concentration of 239ngL(-1), followed by the total amount of chlorinated parabens (average 50.1ng/L) and parabens (average 44.3ng/L). It is noteworthy that octylparaben with longer chain was firstly detected in the surface water. Significant difference was observed for paraben concentrations from different sampling sites, and the highest level of parabens was found in the Xiaotaihou River, which was mainly due to the untreated sewage discharge. Seasonal variation of target compounds in the urban surface water was also studied, and parabens exhibited a different temporal variation from chlorinated derivatives. A combination of factors including high residual chlorine level and water temperature as well as intense ultraviolet radiation might enhance the persistence of chlorinated parabens in chlorinated water during the wet season. Risk assessment showed that parabens and their chlorinated derivatives are not likely to produce biological effects on aquatic ecosystems at current levels in the surface water of Beijing.


A state affiliate's utilization of ASHP's Practice Advancement Initiative 2030 to identify current state of practice and a process to prioritize goal achievement.
The American Society of Health-System Pharmacists (ASHP) has been a long-standing supporter of advancing pharmacy practice, specifically in the area of pharmacy practice models. In 2019, ASHP began the planning to launch PAI (Practice Advancement Initiative) 2030. PAI 2030 describes and details a bold vision for patient care, medication use, and pharmacy practice over the next decade. This work represents an ambitious goal to continue to advance the profession of pharmacy for the betterment of our patients. While much has been accomplished with the PAI, there is little literature on PAI 2030 (the authors are unaware of any published examples). The purpose of the article is to explain a novel state affiliate's prioritization of ASHP's PAI 2030 recommendations. In the spring of 2020, the North Carolina Association of Pharmacists (NCAP), the North Carolina state affiliate of ASHP, began discussions around PAI 2030. In the fall of 2020, prior to the NCAP Annual Convention, health system pharmacy leaders within NCAP developed a questionnaire to serve as a PAI 2030 self-assessment. This approach allowed a state affiliate to implement an innovative program to act on the recommendations from PAI 2030. After the prioritization, health system pharmacy leaders engaged in discussion to comment on what recommendations have been identified. The goal of this discussion was to provide NCAP a direction to pursue focused efforts to support recommendations of PAI 2030. Ultimately, NCAP seeks that this statewide approach would help advance pharmacy practice, and improve pharmacy practice across the state of North Carolina in collaboration with NCAP. This discussion illustrates how a state affiliate has pursued implementing PAI 2030. This approach provides a strategy for state affiliates in addressing the recommendations within PAI 2030. A novel statewide approach can help marshal resources to advance practice when health systems partner with a state affiliate.


Human umbilical cord-derived mesenchymal stromal cells ameliorate aging-associated skeletal muscle atrophy and dysfunction by modulating apoptosis and mitochondrial damage in SAMP10 mice.
Skeletal muscle mass and function losses in aging individuals are associated with quality of life deterioration and disability. Mesenchymal stromal cells exert immunomodulatory and anti-inflammatory effects and could yield beneficial effects in aging-related degenerative disease. We investigated the efficacy of umbilical cord-derived mesenchymal stromal cells (UC-MSCs) on sarcopenia-related skeletal muscle atrophy and dysfunction in senescence-accelerated mouse prone 10 (SAMP10) mice. We randomly assigned 24-week-old male SAMP10 mice to a UC-MSC treatment group and control group. At 12 weeks post-injection, the UC-MSC treatment had ameliorated sarcopenia-related muscle changes in performance, morphological structures, and mitochondria biogenesis, and it enhanced the amounts of proteins or mRNAs for myosin heavy chain, phospho-AMP-activated protein kinase, phospho-mammalian target of rapamycin, phospho-extracellular signal-regulated kinase1/2, peroxisome proliferator-activated receptor-γ coactivator, GLUT-4, COX-IV, and hepatocyte growth factor in both gastrocnemius and soleus muscles, and it reduced the levels of proteins or mRNAs for cathepsin K, cleaved caspase-3/-8, tumor necrosis factor-α, monocyte chemoattractant protein-1, and gp91phox mRNAs. The UC-MSC treatment retarded mitochondria damage, cell apoptosis, and macrophage infiltrations, and it enhanced desmin/laminin expression and proliferating and CD34+/Integrin α7+ cells in both types of skeletal muscle of the SAMP10 mice. In vitro, we observed increased levels of HGF, PAX-7, and MoyD mRNAs at the 4th passage of UC-MSCs. Our results suggest that UC-MSCs can improve sarcopenia-related skeletal muscle atrophy and dysfunction via anti-apoptosis, anti-inflammatory, and mitochondrial biogenesis mechanisms that might be mediated by an AMPK-PGC1-α axis, indicating that UC-MSCs may provide a promising treatment for sarcopenia/muscle diseases.


[Socioeconomic status and hygiene habits of the members of a rural community from the province of Habana].
A study is made of the socioeconomic conditions, environmental sanitation, and hygienic habits in the members of a rural community in Havana province. This was compared with the results of a stool culture analysis made to all inhabitants of this locality in order to determine the degree of infestation by intestinal parasites. It was found that sanitation conditions are good, which explains the low prevalence of helminths. The greatest proportion of parasitized people show inappropriate habits of personal hygiene, which explains that most of them are due to protozoa.


New and old diagnostic markers of meningitis in cerebrospinal fluid (CSF).
Five new markers (tumor necrosis factor TNF-alpha, interleukin IL-1 beta, IL-6, IL-8, lipopolysaccharide binding protein (LBP)) and 11 old classical markers were evaluated in 180 cerebrospinal fluid (CSF) and serum pairs to discriminate acute bacterial meningitis (BM) on admission from aseptic (viral) meningitis (AM), bacterial meningitis treated with antibiotics (TM) from AM, and AM from multiple sclerosis (MS). Statistical tests were computed which classified correctly > or =90% of the patients with BM, TM, AM at a sum minimum of false positive plus false negative results, and which reached additionally > or =90% sensitivity and specificity. To discriminate BM from AM, CSF IL-6 test > or =500 ng/l and CSF IL-1 beta test > or =8 ng/l besides CSF lactate test > or =3.5mM/l and CSF granulocyte test > or =150 M/l were revealed. CSF lactate test > or =3.2 mmol/l discriminated TM from AM. CSF leukocyte test > or =35 M/l discriminated AM from MS. Tests with the new markers were more laborious, expensive, and time consuming compared to CSF lactate test. Test candidates, detecting > or =80% of patients with > or =80% sensitivity and specificity, were evaluated with CSF TNF-alpha, IL-8 and LBP, serum IL-6, CSF leukocytes, lymphocytes and monocytes, Qglucose, CSF total protein, albumin, and Qalbumin. All tests should be reviewed in context of clinical findings to diagnose BM reliably.


A stochastic approach in the evaluation of plasma curves with enterohepatic recycling.
The precision of the existing methods for evaluation of compartmental models may not be warranted if the plasma curve is irregular due to enterohepatic recycling of the substance during its elimination. In this work a new approach is proposed which involves the assessments of rate-constants using combined cross-sectional and time-series data. As (C0-Cpl) means the concentration of the drug in the environmental compartment, the (Formula: see text) equation is valid for the change in the plasma concentration level. Calculating the correlation coefficients (r) for the Cpl and (C0-Cpl) data-pairs from the cross-sectional data, in this case the time-derivatives of these correlation coefficients are equal to the rate constants.


Reduced activity of Candida detachment factors in the saliva of the elderly.
Saliva in healthy human subjects contains protenaceous factors that detach Candida albicans cells from plastic plates. To investigate the physiological role of the detachment activity of human saliva, we compared the activity of salivary specimens collected from the elderly (who are at greater risk of oral candidiasis) to the activity of specimens collected from children and nonelderly adults. C. albicans cells were cultured and attached to the bottoms of the wells of a 96-well plate, and saliva preparations were then added to each well. After 3 h of incubation, Candida cells attached to the bottoms of the wells were counted, using the crystal violet staining method. The results showed that the activity of salivary detachment factors was significantly lower among the elderly than among nonelderly adults and children. Furthermore, the activity of salivary detachment factors was reduced in 12 of the 43 elderly subjects (27.9%), a significantly higher proportion relative to that in the children and nonelderly adults. However, there was no significant difference in the level of salivary proteins between the samples collected from elderly subjects displaying low and high salivary detachment activity. These results suggest that the increased number of people with lower salivary detachment activity among the elderly may be one of the reasons that oral candidiasis is more common among the elderly than in nonelderly adults and children.


A potential skin substitute constructed with hEGF gene modified HaCaT cells for treatment of burn wounds in a rat model.
This study aimed to investigate the feasibility of using an immortal keratinocyte cell line, HaCaT cells, to effectively deliver epidermal growth factor (EGF) in a skin substitute to treat burn wounds. The skin equivalent was constructed with human EGF (hEGF) gene modified HaCaT cells obtained through stable gene transfection; these were applied to full thickness burn wounds in a rat model. The results showed that the hEGF gene modified HaCaT cells produced more than 390ng/l of bioactive hEGF in the culture supernatant. K19 and integrin-β1 as keratinocyte differentiation markers were elevated in the hEGF gene modified HaCaT cells which were shown to be non-tumorigenic. The skin equivalent constructed with hEGF gene modified HaCaT cells demonstrated improved epidermal morphogenesis with a thick and compact epidermis. Wound healing was accelerated noticeably when applied with this skin substitute seeded with hEGF gene modified HaCaT cells in vivo. The results suggest that HaCaT cells modified with hEGF gene might be promising seed cells for construction of genetically modified skin substitute which can effectively secrete hEGF to accelerate wound repair and regeneration.


An unbiased seed-based RNAi selection screen identifies small RNAs that inhibit androgen signaling and prostate cancer cell growth.
Blocking androgen receptor signaling is the mainstay of therapy for advanced prostate cancer (PCa). However, acquired resistance to single agents targeting this pathway results in the development of lethal castration-resistant PCa. Combination therapy approaches represent a promising strategy for the treatment of advanced disease. Here, we explore a therapeutic strategy for PCa based on the ability of shRNAs/siRNAs to function essentially as miRNAs and, via seed sequence complementarity, induce RNA interference of numerous targets simultaneously. We developed a library that contained shRNAs with all possible seed sequence combinations to identify those ones that most potently reduce cell growth and viability when expressed in PCa cells. Validation of some of these RNAi sequences indicated that the toxic effect is associated with seed sequence complementarity to the 3' UTR of AR coregulatory and essential genes. In fact, expression of siRNAs containing the identified toxic seed sequences led to global inhibition of AR-mediated gene expression and reduced expression of cell-cycle genes. When tested in mice, the toxic shRNAs also inhibited castration-resistant PCa and exhibited therapeutic efficacy in pre-established tumors. Our findings highlight RNAi of androgen signaling networks as a promising therapeutic strategy for PCa.


High- and low-affinity states of striatal D2 receptors are not affected by 6-hydroxydopamine or chronic haloperidol treatment.
Specific D2 binding in rat striatum was characterized and then the effects of chronic disruption of dopaminergic activity on antagonist and agonist binding to these sites were studied. D2 receptors were defined as those sites capable of binding [3H]spiperone in the presence of cinanserin, a 5-HT2 antagonist, but not in the presence of (+)-butaclamol, a D2 and 5-HT2 blocker. Saturation, competition, and kinetic analyses suggested that D2 receptors are a homogeneous population exhibiting more complex interactions with agonists than antagonists. Antagonist binding was monophasic and guanine nucleotide-insensitive whereas agonist binding was biphasic and guanine nucleotide-sensitive. D2 receptor density was elevated by more than 40% following dopamine depletion by 6-hydroxydopamine or chronic receptor blockade by haloperidol. However neither treatment altered the affinities or magnitudes of the high- and low-affinity components associated with agonist binding to the D2 receptor.


Paracoccidioides species present distinct fungal adherence to epithelial lung cells and promote different IL-8 secretion levels.
Fungi that belong to the genus Paracoccidioides are the etiologic agents of paracoccidioidomycosis, a human systemic mycosis, which occurs in Latin America. Epithelial cell is one of the first cells that interact with these fungi and responds by secreting inflammatory mediators such as cytokines. In the present study, we demonstrate that yeasts of different isolates of Paracoccidioides brasiliensis (Pb18 and Pb03) and Paracoccidioides lutzii (Pb01) distinctly promoted interleukin (IL)-8 secretion by the lung epithelial cell line A549. Depending on the isolate, this cytokine release may rely on the epithelial cell interaction with fungal secreted components or direct contact with the pathogen. In addition, adhesion of yeasts to the pulmonary epithelial cells was also different among Paracoccidioides isolates, and the highest percentage of A549 cells with adhered fungi was observed with P. lutzii. All Paracoccidioides isolates induced an expression increase of α3 and α5 integrins in A549 cells and, using small interfering RNA, we observed that the integrin silencing promoted a reduction of P. lutzii adhesion, which suggests the involvement of integrins in this event. Together, these results indicate that host epithelial cell response may depend on the isolate of Paracoccidioides.


The importance of surgical treatment in encrusted cystitis and pyelitis: A case report.
Encrusted cystitis and Encrusted pyelitis are rare chronic inflammatory diseases. Those conditions are commonly caused by the Corynebacterium spp. especially the type D2 which is a gram positive, aerobic, slow-growing, and urea-sliting bacteria with a multi-antibiotic resistant profile. We report the case of a 62-year-old man with a past history of chronic obstructive pulmonary disease. He was referred to the department of urology for urosepsis. Bacterial culture results were positive to Corynebacterium urealyticum. The diagnosis of encrusted cystitis and pyelitis were highly considered. An adapted antibiotherapy was undertaken using vancomycin during 3 weeks. The patient presented two acute peritonitis : the first was caused by a spontaneous bladder dome rupture which was surgically repaired and the second was caused by a total bladder rupture which required cysto-prostatectomy and bilateral ureterostomy. The post operative outcomes were uneventful. Bacterial urinalysis was negative and total recovery was obtained. In the majority of the reported cases, there were no sepsis or peritonitis conditions. Medical treatment by the glycopeptides and urine acidification was sufficient. However in this case, the sepsis condition and the bladder rupture with acute peritonitis made exclusively medical treatment by antibiotics insufficient. Therefore cystectomy associated to conventional antibiotics were able to limit the systemic dissemination of the bacteria and save the patient's life. Glycopeptides antibiotics are currently the preferential treatment of encrusted cystitis. In some complicated conditions such as bladder rupture and urosepsis as in this case, radical surgical treatment by cystectomy must be realized early to avoid peritonea and septic shock.


Patellar tendon bearing orthosis--application as adjunctive treatment in healing of lower-limb tissue loss.
To assess the efficacy of the patellar tendon bearing orthosis (PTBO) as adjunctive treatment of patients with significant lower-limb ischaemia and tissue loss complicated by neuropathy. Twelve consecutive patients (14 legs) with a variety of underlying conditions causing extensive lower limb tissue loss are described. Seven patients were diabetic. Six patients (seven legs) underwent vascular reconstruction procedures. Wound healing and amputation rate. Eight patients had ulcer healing within 5 months, one at 18 months (patient with alcoholic neuropathy who was poorly compliant with treatment), one stopped using the PTBO at 3 months and was converted to protective footwear with healing, one died of a myocardial infarct 1 month after the PTBO was fitted (the ulcer was showing signs of healing), and one has just had surgery and been fitted with a PTBO. Early results from this anecdotal series are encouraging and a prospective study to determine the application of the PTBO in patients with neuropathic and neuropathic/ischaemic tissue loss is planned.


Transverse volar skin laceration of the finger: Sign of volar plate injury.
Transverse tears of the volar skin of a finger with a hyper-extension injury is associated with frequent volar plate tears or avulsions. Recognition is essential for surgical exploration of the volar plate and supporting joint structures and, if injured, surgical repair should be carried out at the time of skin suturing.


Fatal hydrofluoric acid poisoning: histologic findings and review of the literature.
Hydrofluoric acid (HF), the inorganic acid of elemental fluorine, is a highly dangerous substance and death can result from a very small exposure. In addition to local toxicity, HF can trigger fatal systemic reactions by its high affinity for calcium and magnesium. The authors report the autopsy case of a male worker who was exposed to 50% HF while repairing the leakage from an HF tank valve in a semi-conductor washing factory. His colleagues found blisters on his neck after 6 h of work and he was sent to the hospital. However, he expired from cardiac arrest despite an immediate calcium gluconate injection. At autopsy, burns with eschar covering less than 5% of the total body surface were identified on the neck and around both ears, and microscopic examination of the affected skin revealed extensive necrosis of the epidermis and dermis with pustule formation. In chemical analysis, no fluoride ions were detected in blood, vitreous humor, urine, pleural fluid, bile, or skin tissue from the neck. Considering the chemical burns on the neck and the circumstantial information, the cause of death was determined to be HF poisoning. This article presents the clinical manifestations of local and systemic toxicity after the accidental exposure to a high concentration of HF, with histologic demonstrations of chemical burns.


Endobronchial ultrasonography in a patient with a mediastinal thoracic duct cyst.
Mediastinal thoracic duct cysts are rare clinical findings. We report the case of a symptomatic 58-year-old woman in whom a thoracic duct cyst was successfully treated with surgical resection. Preoperative endobronchial ultrasonography revealed an oval-shaped hypoechoic area with a distinct, thick pedicle, gradual intermittent flux of the fluid content within the lesion, and endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) revealed lymphocyte predominant serous fluid without malignancy, which is consistent with features of a mediastinal thoracic duct cyst. We postulate that EBUS-TBNA can be used as a preoperative diagnostic tool for patients with possible mediastinal thoracic duct cysts.


[Effect of vinblastine on the proliferative and immune responses of the lymphoid cells of the draining lymph node and spleen in mice undergoing regional immunization with ram erythrocytes].
It was found that vinblastine administered 48 hours after immunization of mice by sheep red cells produced a long-term (for up to 3 days) suppression of 3H-thymidine inclusion into lymphoid cells following a 8-12-hour latent period. This was accompanied with a complete elimination of humoral response of the draining lymph node and a five-fold decrease of the number of antibody-forming cells in the spleen.


Severe Combined Immunodeficiency Disorders.
Severe combined immunodeficiency disorders represent pediatric emergencies due to absence of adaptive immune responses to infections. The conditions result from either intrinsic defects in T-cell development (ie, severe combined immunodeficiency disease [SCID]) or congenital athymia (eg, complete DiGeorge anomaly). Hematopoietic stem cell transplant provides the only clinically approved cure for SCID, although gene therapy research trials are showing significant promise. For greatest survival, patients should undergo transplant before 3.5 months of age and before the onset of infections. Newborn screening programs have yielded successful early identification and treatment of infants with SCID and congenital athymia in the United States.


Clinical features and outcomes of nonocclusive mesenteric ischemia after cardiac surgery: a retrospective cohort study.
Nonocclusive mesenteric ischemia after cardiac surgery is a life-threatening complication requiring emergent intervention. However, because of its rarity, the clinical features and outcomes of nonocclusive mesenteric ischemia remain unknown. The present study aimed to clarify patients' backgrounds, clinical features and mortality of nonocclusive mesenteric ischemia after cardiac surgery, using a Japanese national inpatient database. We identified patients undergoing cardiac or thoracic aortic surgery between July 2010 and March 2017, using the Japanese Diagnosis Procedure Combination database. We calculated the incidence proportion of nonocclusive mesenteric ischemia and examined treatment options (bowel resection and interventional radiology) and patients' discharge status (in-hospital mortality and destination of discharge). We identified 221,900 eligible patients to find 568 (0.26%) patients with bowel ischemia in the same admission. Of these, 124 (0.06%) patients developed nonocclusive mesenteric ischemia, and in-hospital mortality after nonocclusive mesenteric ischemia was 77%. Treatment options for nonocclusive mesenteric ischemia included bowel resection alone (n = 34), interventional radiology (n = 15), or both (n = 15); 27, 10, and 8 patients died, respectively. Seven patients (5.6%) were discharged to home. Among 60 patients without bowel resection or interventional radiology, 50 patients died. In multivariable regression analysis, older age, preoperative hemodialysis, preoperative circulatory support, and hypothermic cardiopulmonary bypass were associated with NOMI. The present study showed that nonocclusive mesenteric ischemia after cardiac surgery was very rare. Mortality following nonocclusive mesenteric ischemia was very high even if patients underwent bowel resection or interventional radiology.


Sorption of quaternary ammonium compounds in soils: implications to the soil microbial activities.
Despite their widespread use in household activities and various industries, information on the toxicity of quaternary ammonium compounds (QACs) to microbial activities in soil is scant. This study investigated the effect of three commonly used QACs namely hexadecyltrimethyl ammonium bromide (HDTMA), octadecyltrimethyl ammonium bromide (ODTMA) and Arquad on dehydrogenase and potential nitrification activities in three different soils. The toxicity of QACs on the dehydrogenase activity and potential nitrification in these soils followed the order: HDTMA>ODTMA>Arquad and Arquad>HDTMA>ODTMA, respectively. HDTMA, ODTMA and Arquad exhibited toxicity to dehydrogenase activity at concentration of 50, 100 and 750 mg kg(-1) soil, respectively, whereas potential nitrification was inhibited by HDTMA and ODTMA even at 50 mg kg(-1) soil. Arquad exhibited toxicity to potential nitrification at comparatively higher concentration of 250 mg kg(-1) soil, with the severity of toxicity very intense at higher concentrations. The nature of QACs and soil properties influenced the toxicity. The toxic effect of QACs on soil microbial activities was more influenced by the relative release of sorbed QACs in soils. This study provides valuable information on the toxicological properties of some widely used QACs on important soil microbial activity parameters. To our knowledge, this is the first report.