Silver nanoparticles based on sulfobutylether-β-cyclodextrin functionalized graphene oxide nanocomposite: Synthesized, characterization, and antibacterial activity.
In this work, an effective method was explored to prepare silver nanoparticles/graphene oxide-sulfobutylether-β-cyclodextrin (AgNPs/GO-SBE-β-CD) antibacterial nanocomposite. Dopamine (DA) was used as a green and mild reductant to directly in situ reduce silver nitrate on Sulfobutylether-β-cyclodextrin (SBE-β-CD) modified graphene oxide (GO-SBE-β-CD). Its synthesized, antibacterial properties and biocompatibility were studied. Results showed that silver nanoparticles with an average size of 73 nm were uniformly distributed on the GO-SBE-β-CD sheets. In addition, AgNPs/GO-SBE-β-CD were proved an effective antibacterial material against both gram-negative and gram-positive, reduced the viability of E. coli and S. aureus by 90 % at 40 µg/mL. At the same time, AgNPs/GO-SBE-β-CD co-cultured with L929 cells did not show cytotoxicity. In vivo experiment, AgNPs/GO-SBE-β-CD showed good biocompatibility. Collectively, AgNPs/GO-SBE-β-CD is a promising material to prevent bacterial infection, expecting to be applied in wound healing.


Contrasting properties of medial septal neurons projecting to hippocampus or interpeduncular nucleus in the rat.
The properties of neurons of the medial septal nucleus and of the nucleus of the diagonal band of Broca which project to hippocampus or to interpeduncular nucleus were compared in rats anesthetized with urethane. Neurons projecting to the interpeduncular nucleus had a slower conduction velocity and a lower spontaneous discharge rate. In contrast, their responses to various putative neurotransmitters (glutamate, GABA, acetylcholine) were similar. In a few cases, neurons projecting to both structures (i.e., with branched axons) were observed. Both septohippocampal and septointerpeduncular pathways are known to be partly cholinergic. Our results show that they originate from two independent populations of medial septal-nucleus of the diagonal band of Broca neurons with different physiologic properties.


Characterization of hepatic lactogen receptor. Subunit composition and hydrodynamic properties.
The structure of the membrane-bound and Triton X-100-solubilized female rat liver prolactin receptor has been studied by affinity cross-linking/sodium dodecyl sulfate-polyacrylamide gel electrophoresis, gel filtration, and sucrose/H2O and sucrose/D2O density gradient centrifugation. Hydrodynamic characterization revealed that the 125I-human growth hormone receptor-detergent complex represents a molecular species with a Stokes radius of 61 A, a sedimentation coefficient of 5.0 s, and a calculated molecular weight of 158,000. The molecular weight of the receptor was calculated to be 92,000. Three lactogenic hormone-binding species with Mr values of 87,000, 40,000, and 35,000, respectively, were repeatedly found when detergent-solubilized preparations were analyzed using an affinity cross-linking technique. Estrogen treatment of female rats increased the intensity of these bands. Occasionally, an Mr 165,000 hormone-binding species was also found. Two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis studies (first dimension, nonreducing; second dimension, reducing) demonstrated that disulfide- and nondisulfide-linked hormone-binding species with Mr values of 40,000 and 35,000 are contained within the Mr 87,000 species. It is concluded that the Triton X-100-solubilized female rat liver prolactin receptor has a molecular weight of about 90,000. This molecular species contains Mr 40,000 and Mr 35,000 hormone-binding subunits. It cannot be determined whether these subunits are combined with each other or with as yet undetected subunit(s) to make up the Mr 90,000 species, or whether each one of these subunits is a proteolytic fragment of the Mr 90,000 species.


Long-Term Safety and Efficacy of Fractional CO2 Laser Treatment in Post-Menopausal Women with Vaginal Atrophy.
We have previously reported improvement of clinical symptoms of genitourinary syndrome of menopause (GSM) at 3 and 6 months following three CO2 laser treatments. The current paper presents the results of long term follow up at 12, 15- and 18-months post laser treatment. Twenty subjects (mean age 60.65 ± 6.34 years) who had completed the core study participated in follow-up. Subjects were evaluated at 12, 15, and 18 months following final laser therapy. An optional maintenance treatment was offered during Month 12 and Month 15 to those women who failed to increase their Vaginal Health Index Score (VHIS) by more than 34% from their individual baseline, or if the subject desired an additional treatment. At each study visit, VHIS and vulvovaginal atrophy (VVA) symptom severity were recorded. Sexual function was assessed using the Female Sexual Function Index (FSFI). Fifteen subjects were eligible for a single maintenance treatment (N = 2, at 12 months, and N = 13 at 15 Months). The mean VHIS (± standard deviation) remained significantly improved at 12 months following their last laser treatment (16.3 ± 4.5 vs. Baseline 12.4 ± 4.0; p < 0.05) and at the 15- and 18-months follow up visits as well (16.9 ± 4.6 and 17.1 ± 4.6, respectively; p < 0.05 compared to Baseline). Almost all VVA symptoms were significantly improved at 12 months following the third treatment compared to Baseline and this improvement was sustained at 15 and 18 months. At the 12 Months visit, the total FSFI score increased significantly (N = 15, 24.4 ± 6.9; p < 0.05), and at the 15- and 18-month follow-up visits, the total FSFI remained significantly higher than Baseline (22.2 ± 6.7, 25.8 ± 6.6). Fractional CO2 laser treatments are effective in alleviating symptoms of VVA and sexual dysfunction in post-menopausal women, and that effects are sustained over the long-term.


miR-181c protects CsA-induced renal damage and fibrosis through inhibiting EMT.
Cyclosporine A (CsA), a widely used immunosuppressive drug in organ transplantation and autoimmune disorders, frequently induces renal damage and fibrosis. Recent evidence has implicated epithelial-mesenchymal transition (EMT) in CsA-induced nephrotoxicity. Microarray analysis disclosed miR-181c as the microRNA most dramatically repressed by CsA. Downregulation of miR-181c expression at the transcriptional level by CsA is dependent on the transcription factor Nrf2. miR-181c mimics or inhibitors attenuate or aggravate CsA-induced EMT gene changes, respectively. Importantly, in Nrf2-/- mice, CsA-induced renal damage, fibrosis, and EMT gene changes are restored by miR-181c mimics. Mechanistically, we identified Notch2 as a potential target of miR-181c. Collectively, our data support the notion that miR-181c may serve as an important factor for protecting renal tissues from CsA-induced nephrotoxicity.


A contribution to the improvement of Listeria monocytogenes enumeration in cold-smoked salmon.
For the enumeration of Listeria monocytogenes in food, a sensitive enumeration method based on membrane filtration followed by transfer of the filter to a selective medium has been developed. This study was carried out with cold-smoked salmon, a product likely to be contaminated with L. monocytogenes. The operating protocol utilizes three filtration runs in parallel (5, 15 and 30 ml) of a 1 in 10 dilution of the salmon suspension through 0.45-microm pore-size cellulose ester membranes, and then culture of the filters on Aloa agar (AES Laboratoires, Combourg, France). The results obtained with the technique were compared with those from the reference EN ISO 11290-2 method and found to provide more precise results in the enumeration of L. monocytogenes from both artificially and naturally contaminated cold-smoked salmon. Moreover, for several samples contaminated at low levels, L. monocytogenes could be recovered only by the filtration method. The examination of increasing volumes of salmon suspension enabled readable results to be obtained for all levels of L. monocytogenes and competitive microflora investigated. In most cases, the optimised operating protocol enabled 5.1 g of salmon to be examined, instead of 0.01-0.1 g with the reference EN ISO 11290-2 method, thus improving the sensitivity of the method.


[Experiences in 130 operations of carotid elongation (author's transl)].
A report on 130 operations of carotid elongation is presented. Indications for reconstruction are based on angiography, neurologic symptoms, and recently, on ultrasonography (Doppler's). Several surgical methods have been performed: 25 resections of the internal carotid artery, 5 resections of the common carotid artery, 3 resections of loop aneurysms. The main operative techniques were resection and neoimplantation, the latter with patch-plastic surgery. Usually, a shunt was used. Mortality was 0%, lethality, 2%. During a follow-up period of 6 weeks to 2 years, 86% of the patients were found to be free of complaints, and 14% were without change of the neurologic symptoms. The good neurologic results are convincing.


Adherence to national exercise guidelines by patients attending emergency departments: A multi-site survey.
The proportion of adults in Australia meeting or exceeding the national guidelines for physical activity has remained relatively static over the past 10 years. The research objective was to measure self-reported physical activity and sedentary behaviour among ED patients in accordance with Australia's current physical activity and sedentary behaviour guidelines, revised in 2014. A convenience sample of participants was recruited from three EDs in Melbourne between February and May 2016. Eligible participants were administered the International Physical Activity Questionnaire - Short Form plus researcher-derived questions. Participants were assessed as whether meeting the physical activity guidelines or not, using pre-defined criteria. The proportion of 18-64 year olds meeting all of the physical activity guidelines was 19.0% (95% confidence interval [CI] 15.2-22.8). A majority of participants (63.1%, 95% CI 58.5-67.7) met the aerobic component of the guidelines although only 28.9% (95% CI 24.5-33.3) of participants reported undertaking strength building exercises two or more times per week. Adults in the oldest age group were found to be less likely to engage in muscle strengthening exercises (23.3%, n = 30) than those in the youngest age group (40.0%, n = 60, P = 0.005). Average daily sitting time (minutes) did not differ between men (median = 300) and women (median = 360, P = 0.118). Overall adherence with physical activity guidelines is low among adults attending the ED. All adults need to be encouraged to undertake muscle strengthening activities, especially adults in older age groups.


Galanin receptors in the hippocampus and entorhinal cortex of aged Fischer 344 male rats.
Galanin (GAL) has been proposed to be an inhibitory modulator of cholinergic memory pathways because it acts within the hippocampus to inhibit the release and antagonize the postsynaptic actions of acetylcholine. Here we have used: 1) slice binding and quantitative autoradiography to assess the density and occupancy of GAL receptors; and 2) in situ hybridization histochemistry to assess expression of the GALR1 receptor subtype in the ventral hippocampus of 3-month-old and 21-month-old Fischer 344 male rats. We detected a small but significant (p < or = 0.0003) age-related reduction in 125I-GAL binding-site density in the ventral hippocampus and entorhinal cortex under standard binding conditions. Post-hoc analysis indicated that this reduction with age persisted in the CA1 radiatum and entorhinal cortex following GTP-induced desaturation to unmask pre-existent GAL receptors occupied by endogenous ligand. It was not associated with a significant change in peak GALR1 gene expression in the hippocampus. Because a portion of GAL receptors in this region have been postulated to function as presynaptic auto-receptors on cholinergic fiber terminals, the reduction in GAL binding sites with age may be a consequence of age-related alterations in GAL receptor expression by basal forebrain cholinergic neurons which project to the ventral hippocampus.


Prevalence of Disability and Disability Types by Urban-Rural County Classification-U.S., 2016.
In the U.S., disability affects approximately 61.4 million (25.7%) adults, with mobility disability being the most prevalent type, affecting about 1 in 7 U.S. adults. However, little is known about the prevalence of disability and functional disability types by urbanization level. Data from the 2016 Behavioral Risk Factor Surveillance System were analyzed. The prevalences of disability, overall and by functional disability type, were estimated among U.S. adults across 6 levels of urban-rural county categories based on the 2013 National Center for Health Statistics Urban-Rural Classification Scheme for Counties. Adjusted prevalence ratios with 95% CIs were estimated by conducting log-linear regression analyses with robust variance estimator while adjusting for study covariates. Data analyses were conducted in 2018. The prevalences of having any disability, functional disability type, or multiple disabilities were lowest in large metropolitan centers and fringe metropolitan counties and highest in noncore (rural) counties. After controlling for age, sex, race/ethnicity, education, and federal poverty level, adults living in noncore counties were 9% more likely to report having any disability, 24% more likely to report having 3 or more disabilities, and 7% (cognition) to 35% (hearing) more likely to report specific disability types than the adults living in large metropolitan centers. Results of this study suggest that significant disparities in the prevalence of disability exist by level of urbanization, with rural U.S. residents having the highest prevalence of disability. Public health interventions to reduce health disparities could include people with disabilities, particularly in rural counties.


Some observations on the gastric effects of phentolamine in rats.
The effects of graded doses of phentolamine on gastric secretion, gastric emptying rate, gastric mucosal mucus content and gastric mucosal lesion incidence were studied in conscious rats 2 h after intramuscular administration. In pylorus-occluded rats, phentolamine (5, 10 or 20 mg/kg) produced dose-dependent decreases in the gastric secretory volume and total acid output. Similar doses of the drug also produced dose-dependent decreases in the gastric emptying rate in animals without pylorus occlusion (intact rats), but did not affect the gastric mucosal mucus content. The incidence of gastric mucosal lesions in pylorus-occluded or intact animals rose with increasing doses. The findings are discussed in the light of the possibility that phentolamine, in the dose range examined, possesses a sympathomimetic action which would underlie the gastric lesions observed.


Steroid hormones enhanced sister-chromatid exchange in cultured CHO cells.
The influence of steroid hormones on the induction of sister-chromatid exchange (SCE) in cultured CHO cells was studied. It was observed that estradiol-17 beta, estriol, estrone and ethynyl estradiol treatments enhanced SCE rates compared to the controls. Overall, these compounds produced a dose response effect. The importance of a detailed study on the long-term genetic effects of steroids on mammalian cells is emphasized.


Corrigendum to "Actin Alpha 2 (ACTA2) Downregulation Inhibits Neural Stem Cell Migration through Rho GTPase Activation".
[This corrects the article DOI: 10.1155/2020/4764012.].


Dissimilatory Fe(III) reduction by an electrochemically active lactic acid bacterium phylogenetically related to Enterococcus gallinarum isolated from submerged soil.
The isolation and identification of a glucose-oxidizing Fe(III)-reducing bacteria (FRB) with electrochemical activity from an anoxic environment, and characterization of the role of Fe(III) in its metabolism. A Gram-positive (Firmicutes), nonmotile, coccoid and facultative anaerobic FRB was isolated based on its ability to reduce Fe(III). Using the Vitek Gram-positive identification card kit and 16S rRNA gene sequence analysis, the isolate was identified as Enterococcus gallinarum, designated strain MG25. On glucose this isolate produced lactate plus small amounts of acetate, formate and CO2 and its growth rates were similar in the presence and absence of Fe(O)OH. These results suggest that MG25 can couple glucose oxidation to Fe(III) reduction, but without conservation of energy to support growth. Cyclic voltammetry showed that strain MG25 was electrochemically active. An electrochemically active and FRB, E. gallinarum MG25, was isolated from submerged soil. Fe(III) is used in the bacterial metabolism as an electron sink. This is the first report concerning the electrochemical activity of glucose-oxidizing FRB, E. gallinarum. This organism and others like it could be used as new biocatalysts to improve the performance of a mediator-less microbial fuel cell.


Successful treatment of necrobiosis lipoidica and associated retinal vasculitis with tumor necrosis factor (TNF)-alpha inhibitor.
To report the clinical and histopathologic features of necrobiosis lipoidica and associated retinal vasculitis and describe successful treatment of both skin and eye manifestations with adalimumab, a tumor necrosis factor (TNF)-alpha inhibitor. A 35-year-old patient with bipolar disorder and ocular hypertension was referred for evaluation of bilateral retinal vasculitis. Fluorescein angiography revealed bilateral occlusive retinal vasculitis. Physical exam was notable for multiple annular and round erythematous hyperpigmented and atrophic patches and plaques on both lower extremities. Skin biopsy revealed a diagnosis of necrobiosis lipoidica, a rare granulomatous skin disease. Both the patient's retinal vasculitis and skin patches responded favorably to treatment with adalimumab, a TNF-alpha inhibitor. This case highlights the importance of obtaining a complete history and physical exam in patients who present with ocular inflammation, as extraocular manifestations of disease may be present. It also demonstrates the effectiveness of a multidisciplinary approach to evaluation and management of these patients, as both skin and eye involvement were successfully treated with adalimumab, a TNF-alpha inhibitor.


A mouse monoclonal antibody with HLA-DR4 associated specificity.
A mouse monoclonal antibody is described which reacts with HLA-DR4 positive cells. Gel analysis of the immunoprecipitated antigen is consistent with it being a DR molecule.


Involvement of dysregulated IKCa and SKCa channels in preeclampsia.
Excessive constriction of placental chorionic plate arteries (CPAs) may be associated with preeclampsia (PE). Nitric oxide (NO) as well as intermediate and small Ca2+-activated K+ channels (IKCa and SKCa) plays vital roles in vasodilation of CPAs. We hypothesized that dysregulated IKCa and SKCa channels may be involved in the pathogenesis of PE mediated by the impaired NO system on CPAs. The location of IKCa and SKCa channels, activities of NO synthases (NOS), and expression levels of these molecules were studied on CPAs from 30 normal pregnancies and 30 PE. The vasodilating function of CPAs was measured under openers or blockers of IKCa/SKCa channels in the presence or absence of NO donor or inhibitor. IKCa and SKCa channels were located both on endothelium and on smooth muscles of CPAs and the expressions of them were downregulated in PE women comparing to those in normal pregnant women. The protein expressions of endothelial NOS (eNOS) and inducible NOS (iNOS) were downregulated on CPAs in PE accompanied by decreased activity of eNOS. Notably, the vasodilatory functions mediated by IKCa/SKCa channels and by NO were aberrant on preeclamptic CPAs. In addition, IKCa and SKCa channels were responsible for nitric oxide (NO)-attributable vasorelaxation and activity modulation of NO synthases. This study provides evidence that dysregulated IKCa and SKCa channels might contribute to fetal pathogenesis of PE through direct promotion of vascular constriction of CPAs and through affecting functions of NO and activities of NOS.


Can the impact of bed closure in intensive care units be reliably monitored?
To assess the properties of various indicators aimed at monitoring the impact on the activity and patient outcome of a bed closure in a surgical intensive care unit (ICU). Comparison before and after the intervention. A surgical ICU at a university hospital. All patients admitted to the unit over two periods of 10 months. Closure of one bed out of 17. Activity and outcome indicators in the ICU and the structures upstream from it (emergency department, operative theater, recovery room) and downstream from it (intermediate care units). After the bed closure, the monthly medians of admitted patients and ICU hospital days increased from 107 (interquartile range 94-112) to 113 (106-121, P=0.07) and from 360 (325-443) to 395 (345-436, P=0.48), respectively, along with the linear trend observed in our institution. All indicators of workload, patient severity, and outcome remained stable except for SAPS II score, emergency admissions, and ICU readmissions, which increased not only transiently but also on a mid-term basis (10 months), indicating that the process of patient care delivery was no longer predictable. Health care systems, including ICUs, are extraordinary flexible, and can adapt to multiple external constraints without altering commonly used activity and outcome indicators. It is therefore necessary to set up multiple indicators to be able to reliably monitor the impact of external interventions and intervene rapidly when the system is no longer under control.


The effect of estrus synchronization treatment on somatic cell count of transitional-anestrus local-Damascus cross breed goats' milk.
An experiment was conducted to examine the effect of estrus synchronization protocols and steroid hormones concentrations on somatic cell count (SCC) of transitional-anestrus local-Damascus cross goats' milk. Fifty-six goats (2-4-year old) were randomly assigned to three groups: fluorogestone acetate (FGA, n = 19), FGA-Prostaglandin (FGA-PGF, n = 19) and control (n = 18) groups. Intravaginal sponge containing 40 mg FGA was inserted for 13 days and an injection of 600 IU equine chorionic gonadotropin (eCG) was administered for goats of FGA and FGA-PGF groups at the time of sponge removal (day 0). In addition, goats of FGA-PGF group were injected with 10 mg dinoprost tromethamine (PGF2alpha) on day 0. Five fertile local-Damascus cross bucks were turned-in with all goats on day 0. Blood and milk samples were collected from all goats on days -13 (beginning of experiment), -6, 0, 1, 2, 7, 13 and 20 (end of the experiment). Four-year old and second-parity goats had significantly higher (p < 0.05) SCC of both udder halves than 2- and 3-year old and first-parity goats, respectively. There was a significant effect (p < 0.05) for treatment and number of kids born in the last kidding season on SCC of both udder halves. Neither estradiol nor progesterone concentrations were correlated with SCC in goats in this experiment. The SCC of both udder halves and left udder halves in goats of the control and FGA groups, respectively, increased significantly (p < 0.05) after sponge removal and buck introduction when compared with day 0, with no differences in the FGA-PGF group. This increase in SCC of the control and FGA groups coincided with peak estrus behavior. However, SCC was far below the upper limit of the current standard for normal milk. In conclusion, induction of estrus with progestagen based programs and buck introduction may cause temporary significant increase in SCC. However, the SCC values during this period of temporary increase were still in the range of acceptable values for normal milk. With the current standards for SCC of 1,000,000/ml as legal limit for abnormal milk control programs in goats, estrus synchronization programs and the estrus status should not be considered when bulk-tank milk SCC is being investigated.


Treatment Responsiveness in CIDP Patients with Diabetes Is Associated with Higher Degrees of Demyelination.
Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is one of several chronic treatable acquired demyelinating neuropathies. To explore the association between the degree of demyelination in CIDP, and treatment responsiveness. A retrospective chart review of CIDP subjects assessed between 1997 and 2013 was performed to compare treatment responsiveness using different sets of criteria. 99 CIDP patients were included, 34 with diabetes mellitus (DM). Treatment responsiveness was higher in CIDP-DM fulfilling 1 or more EFNS/PNS criteria, (63% vs. 31%, p = 0.03), and in CIDP+DM fulfilling 2 or more criteria (89% vs. 36%, p = 0.01). Nonetheless, treatment responsiveness in CIDP+DM had the highest odds ratio (3.73, p = 0.01). Similar results were also shown in simplified uniform study criteria, with 10% cut off values for CIDP-DM, compared to 30% for CIDP+DM. In CIDP+DM, higher degrees of demyelination are associated with treatment responsiveness, implying the need to adjust current criteria in these patients.


Factors affecting optical coherence tomography angiography signal strength index in patients receiving intravitreal injection treatment.
To investigate the clinical factors affecting optical coherence tomography angiography (OCTA) signal strength index (SSI) and its change after intravitreal injection treatment in patients with retinal disorders. OCTA data from 186 eyes of 166 patients with various retinal disorders including age-related macular degeneration, diabetic macular edema (DME), and retinal vein occlusions who received intravitreal injections were analyzed. The associations between SSI and clinical factors, including age, best-corrected visual acuity (BCVA), media opacity severity, and central macular thickness (CMT), were evaluated both before and after injection. After injection, BCVA improved and CMT decreased significantly, and SSI increased significantly (p = 0.030). BCVA showed a significant positive correlation with media opacity severity before and after injection and with CMT only before injection. In the multivariate analysis, age, presence of DME, BCVA, and media opacity severity were negatively associated with SSI both before and after injection, while CMT was negatively associated with SSI only before injection. After injection, a negative correlation was found between SSI change and both BCVA and CMT change. Our findings suggest that OCTA SSI is influenced by various clinical factors, including age, visual acuity, media opacity severity, and macular thickening, especially in cases of DME. The results also indicate that SSI may decrease in patients with macular disorders due to the presence of macular edema and the associated decrease in visual acuity. Therefore, it is crucial to consider these factors when interpreting OCTA data and ensure an adequate level of SSI.


Vitamin D in rheumatoid arthritis.
The discovery of the vitamin D receptor (VDR) in the cells of the immune system and the fact that activated dendritic cells produce the vitamin D hormone suggested that vitamin D could have immunoregulatory properties. VDR, a member of the nuclear hormone receptor superfamily, was identified in mononuclear cells, dendritic cells, antigen-presenting cells, and activated T-B lymphocytes. In synthesis, the most evident effects of the D-hormone on the immune system seem to be in the downregulation of the Th1-driven autoimmunity. Low serum levels of vitamin D3 might be partially related, among other factors, to prolonged daily darkness (reduced activation of the pre vitamin D by the ultra violet B sunlight), different genetic background (i.e. vitamin D receptor polymorphism) and nutritional factors, and explain to the latitute-related prevalence of autoimmune diseases such as rheumatoid arthritis (RA), by considering the potential immunosuppressive roles of vitamin D. 25(OH)D3 plasma levels have been found inversely correlated at least with the RA disease activity showing a circannual rhythm (more severe in winter). Recently, greater intake of vitamin D was associated with a lower risk of RA, as well as a significant clinical improvement was strongly correlated with the immunomodulating potential in vitamin D-treated RA patients.


Surgical treatment of the pilonidal disease: primary closure or flap reconstruction after excision.
Controversy still exists regarding the best surgical technique for the treatment of pilonidal disease in terms of minimizing disease recurrence and patient discomfort. The present study analyzes the results of excision with primary closure and excision with flap reconstruction in the surgical treatment of sacrococcygeal pilonidal disease. From January 2003 to January 2006, 60 consecutive patients with primary pilonidal sinus disease received surgical treatment in the form of either excision and primary closure (group I, n = 20 patients) or excision and flap reconstruction (group II, n = 40 patients; modified Limberg flap n = 20, classic Limberg flap n = 10 and adipo-fasciocutaneous flap n = 10). Times for complete healing and return to work were recorded. To evaluate patient comfort, all patients were asked to complete a questionnaire including visual analog scale, time to sitting on toilet without pain, and time to walking without pain 3 months after surgery. Mean follow-up was 21 months. A significant difference was observed between the two groups in terms of length of hospital stay (P < 0.003), time to complete healing (P < 0.001), time off work (P < 0.001), wound infection (P < 0.01), recurrence rates (P < 0.01), times to sitting on toilet without pain (P < 0.002), and walking without pain (P < 0.001). The mean (standard deviation) postoperative visual analog scale scores were 6.1 (1.2) in the primary closure group vs. 7.4 (1.3) in the flaps groups (P < 0.001). In the modified Limberg flap, no wound infection, wound breakdown, or recurrence of the disease occurred. Flap reconstructions were superior to primary closure after excision of pilonidal sinus and that modified Limberg flap was superior with regard to wound infection and recurrence.


Identifying C. elegans lifespan mutants by screening for early-onset protein aggregation.
Genetic screens are widely used to identify genes that control specific biological functions. In Caenorhabditis elegans, forward genetic screens rely on the isolation of reproductively active mutants that can self-propagate clonal populations. Screens that target post-reproductive phenotypes, such as lifespan, are thus challenging. We combine microfluidic technologies and image processing to perform high-throughput automated screening for short-lived mutants using protein aggregation as a marker for aging. We take advantage of microfluidics for maintaining a reproductively active adult mutagenized population and for performing serial high-throughput analysis and sorting of animals with increased protein aggregation, using fluorescently-labeled PAB-1 as a readout. We demonstrate that lifespan mutants can be identified by screening for accelerated protein aggregation through quantitative analysis of fluorescently labeled aggregates while avoiding conditional sterilization or manual separation of parental and progeny populations. We also show that aged wildtypes and premature aggregation mutants differ in aggregate morphology, suggesting aggregate growth is time-dependent.


False-positive human immunodeficiency virus antibody test in a dialysis patient.
A patient developed end-stage renal disease secondary to p-anti-neutrophil cytoplasmic antibody (p-ANCA) positive rapidly progressive glomerulonephritis. He subsequently had human immunodeficiency virus (HIV)-1 antibody screening performed as part of a pre-transplant evaluation. The HIV-1 enzyme immunoassay (EIA) antibody test was repeatedly reactive. The HIV-1 western blot was indeterminate. The western blot pattern revealed "non-specific staining obscuring bands in that region." Another sample of serum was sent and the results were identical to the first result. An HIV-1 proviral qualitative polymerase chain reaction test was then performed several months later and no HIV-1 DNA was detected. One year later, an HIV-1 RNA test was negative. Thus, the positive antibody EIA test and the indeterminate western blot represent a false-positive result, most likely due to cross-reacting antigens in the patient's serum with various HIV antibodies. Throughout this period and thereafter, the patient has exhibited no symptoms of HIV infection.


Impact of bacterial infections and spontaneous bacterial peritonitis prophylaxis on phage-bacterial dynamics in cirrhosis.
Gut microbiota, including bacteria and phages, are altered in cirrhosis, but their role during infections and spontaneous bacterial peritonitis (SBP) prophylaxis is unclear. Our aim was determine metagenomic changes in gut bacteria; phages and their linkages centered around Gram-negative and Gram-positive pathobionts in patients with cirrhosis with/without infections or SBP prophylaxis. We included uninfected (n = 231) and infected (n = 30, SBP n = 19 and urinary tract infection n = 11 before antibiotics) patients who gave stool for bacterial and phage metagenomics. We matched uninfected to infected patients 1:1 on a model for end-stage liver disease (MELD). We also analyzed subgroups of patients with ascites matched on an MELD (n = 73) to patients on SBP prophylaxis (n = 7) and then to SBP infection. Phage and bacterial taxa differences (DESeq2) and correlation networks centered around Escherichia coli and Enterococcus faecium were analyzed. Infections were mostly due to Enterobacteriaceae and Enterococcus spp. On metagenomics, higher fold changes of Enterobacteriaceae members, Enterococcus and Streptococcus spp., and Escherichia phages were seen in infected patients. Correlation networks showed more complex bacteria-phage linkages in infected patients compared with uninfected ones overall and centered around E. coli and E. faecium. SBP prophylaxis induced higher Gram-positive bacteria. In SBP, Enterococcus and Escherichia were higher versus ascites. Correlation networks around E. coli were complex in ascites but sparse with SBP prophylaxis, whereas the reverse was seen with E. faecium. Lytic phages and those associated with antibiotic resistance were correlated with E. faecium. In cirrhosis, there are significant changes in phage-bacterial linkages in infected patients and those on SBP prophylaxis compared to the remaining patients. SBP prophylaxis enriches complexity of E. faecium-centered but induces a collapse in E. coli-centered phage-bacterial correlations.


Longitudinal trajectories of BMI z-score: an international comparison of 11,513 Australian, American and German/Austrian/Luxembourgian youth with type 1 diabetes.
BMI fluctuations during puberty are common. Data on individual change in BMI from childhood to young adulthood are limited in youth with type 1 diabetes. To compare longitudinal trajectories of body mass index z score (BMIz) from childhood to adolescence across three registries spanning five countries. Data sources: T1DX (USA), DPV (Germany/Austria/Luxembourg) and ADDN (Australia). The analysis included 11,513 youth with type 1 diabetes, duration >1 year, at least one BMI measure at baseline (age 8-10 years) and >5 aggregated BMI measures by year of age during follow-up until age 17 years. BMIz was calculated based on WHO charts. Latent class growth modelling was used to identify subgroups following a similar trajectory of BMIz over time. Five distinct trajectories of BMIz were present in the T1DX and ADDN cohorts, while six trajectories were identified in the DPV cohort. Boys followed more often a low/near-normal pattern while elevated BMIz curves were more likely in girls (ADDN; DPV). For T1DX cohort, no sex differences were observed. Comparing the reference group (BMIz ~0) with the other groups during puberty, higher BMIz was significantly associated with older age at T1D onset, racial/ethnic minority and elevated HbA1c (all p<0.05). This multinational study presents unique BMIz trajectories in youth with T1D across three continents. The prevalence of overweight and the longitudinal persistence of overweight support the need for close monitoring of weight and nutrition in this population. The international and individual differences likely result from diverse genetic, environmental and therapeutic factors.


Evidence for the retention of genetic variation in Erodium seed dormancy by variable rainfall.
The periodic occurrence of summer/early autumn precipitation in the California annual grassland can result in the formation of early and late emerging cohorts of Erodium botrys and E. brachycarpum. The occurrence of early rainfall and the timing of such rainfall are highly variable from year to year. A series of field watering experiments in 1980-81 were used to simulate early emergence conditions that would result from significant rainfall (1 cm) occurring in mid-July, late August, and mid-September. Net reproduction was used to estimate fitness differentials between Erodium cohorts emerging in response to a watering treatment (early emerging cohorts) and Erodium cohorts emerging with the onset of winter rains in mid-October (late emerging cohorts). Survival was lower and gross reproduction was higher among early emerging cohorts than late emerging cohorts. For both species, net reproduction of the early cohort was lower than that of the late cohort under the July watering treatment and higher than that of the late cohort under the August watering treatment.Early cohorts, formed in response to rainfall in mid-September, 1982, were also compared demographically to later cohorts emerging in October. Compared to late cohorts, net reproduction, gross reproduction and survival were higher for the early cohorts.Common garden experiments indicate that differences in the duration of seed dormancy between the progenies of early and late emerging plants reflect a significant genetic component. Progency produced by early cohorts of E. brachycarpum from all three watering treatments possessed more extended seed dormancy than progeny of late cohorts. In E. botrys, progeny from early cohorts emerging in response to the July watering treatment were also more dormant than late progeny. In contrast, early cohorts of E. botrys emerging in response to the September watering treatment produced seed less dormant than seed produced by late cohorts. When combined with demographic data, indicating that fitness differentials between early and late cohorts varied with changes in the date of early emergence, genetic results suggest that year to year variation in early rainfall may act to retain genetic variation in the duration of seed dormancy.


The role and significance of chondroitin sulfate in the development of otosclerosis.
Chondroitin sulfate is a sulfated glycosaminoglycan that predominates in the ground substance of cartilage. Using monoclonal antichondroitin sulfate in 61 specimens of human otosclerotic lesions, we studied the distribution of this glucosaminoglycan in various stages of otosclerosis. Our findings show that chondroitin sulfate plays an important role in the development of otosclerosis. In addition, the distribution of chondroitin sulfate clearly delineates the stage of otosclerosis referred to as active into two distinct histologic stages. Dividing the active stage into "osteolytic" and "sponge-chondroid" would be reasonable based on our findings.


A unified model for the combined temporal and spatial Broca-Sulzer effect.
A briefly pulsed light is brighter than a pulse of longer duration. For a brief flash of fixed duration and small area, enlarging a target results initially in an increase in brightness. Beyond some critical area, the target dims with further increases in size. These two phenomena are the temporal and the spatial Broca-Sulzer effect respectively. Each effect can be modeled using a generalization of the Hartline-Ratliff equation. The resulting analysis produces a mathematically unified treatment of both effects.


Care of the patient with Alzheimer's disease living at home.
Although the majority of people with Alzheimer's disease and related disorders are cared for in the home for most of their illness, there are few resources available on a consistent basis for nursing interaction. Nurses employed in a variety of settings provide ongoing information and support for families and caregivers in order to provide well-informed care. Because of the complexity of symptom presentation and care, the use of a simple conceptual model can be a valuable aid, helping families to understand behavioral alterations. The evaluation of behaviors as stress related assists both families and caregivers in determining the cause and effect of activities and environment to assist in enhancing comfort and life quality for both.


Comparative advantages and limitations of the fallout radionuclides (137)Cs, (210)Pb(ex) and (7)Be for assessing soil erosion and sedimentation.
The fallout radionuclides (FRNs) (137)Cs, (210)Pb(ex) and (7)Be are increasingly being used as a means of obtaining quantitative information on soil erosion and sediment redistribution rates within agricultural landscapes, over a range of different timescales, and they are frequently seen to represent a valuable complement to conventional measurement techniques. The recent development of the (7)Be method has greatly extended the timescale over which FRNs can be used, by permitting assessment of short-term soil erosion linked to individual events and changing soil management practices. This paper aims to review the advantages and limitations of each of the three FRNs and to identify key knowledge gaps linked to their use. In addition, guidelines for selecting the most appropriate FRN and associated approach, in order to deal with a range of spatial and temporal scales and to investigate specific sets of agro-environmental problems, are provided. Key requirements for future work, related to the application of FRNs in soil erosion investigations, are also identified. These include the upscaling of the approach to the catchment scale and a shift from use of the approach as a research tool to a decision support tool.


Effects of phosphatidylcholine and betaine supplements on women's serum choline.
Maternal phosphatidylcholine supplements have shown benefit in the development of the human fetal brain, as assessed both by newborn physiological measurements and by a related decrease in later childhood behavioral abnormalities. However, the relatively low choline component of phosphatidylcholine mandates high doses that are difficult for pregnant women to consume. Betaine can substitute for some choline effects. The hypothesis was that betaine supplementation would significantly increase women's serum choline. A three-arm crossover clinical trial was used to assess serum concentrations of choline after betaine supplements at two doses, in comparison with phosphatidylcholine supplementation. The effects of both a single dose and of one-week twice-daily doses were assessed in normal non-pregnant women. Betaine supplements at two doses failed to increase serum choline concentrations after single administration or one-week twice-daily dosing. Phosphatidylcholine supplements raised choline concentrations after both single doses (mean change from baseline 8.34 ± 7.29 ng/ml, paired t = 3.24, df 7, p = 0.014, range 1-21 ng/ml, d' = 1.15) and one-week twice-daily doses (mean change from baseline 4.58 ± 3.68 ng/ml standard deviation; paired t = 3.51, df 7, p < 0.001, range 2-13 ng/ml, d' = 2.65). Betaine concentrations rose after both betaine and phosphatidylcholine supplementation. Betaine supplements did not substitute for phosphatidylcholine supplements, which raise serum choline concentrations both after a single dose and after repeated administration. However, serum betaine concentrations did rise after both betaine and phosphatidylcholine consumption and, therefore, betaine may be a stable indicator of choline intake.


Formulation and evaluation of gastro-retentive floating bilayer tablet for the treatment of hypertension.
The paper aimed to progress an ideal gastro retentive drug delivery system intended for directing Losartan and Hydrochlorothiazide as a fixed-dose combination for anti-hypertensive therapy. The bilayer tablets were primed through direct compression method. Losartan was formulated by means of a floating layer expending hydrophilic swellable polymer Hydroxy Propyl Methyl Cellulose K4M, ethyl cellulose (4cps) as a buoyancy enhancer, sodium bicarbonate as a gas spawning agent. The amount of polymer blends remains optimized using 23 full factorial designs. The clout of experimental factors such as swelling agent concentration, buoyancy enhancer and gas generating agent on floating lag time, total floating time, T50% and % drug release remain investigated to get optimized formulation. The responses remain analyzed using Analysis of variance, and polynomial equation stood created for every retort using Multiple linear regression analysis. Entirely preparations floated for more than 12 h. The release pattern of losartan stood fitted to diverse models based on the coefficient of correlation (r). All the formulations, except F2, showed the Korsemeyer-Peppas model as the best fit model. Formulation F2 showed the zero-order model. Diffusion exponents (n) remained indomitable designed for entirely formulations (0.45-0.89), accordingly the chief drug discharge mechanism was non-fickian (anamolous) transport. Formulation F4 containing 20% w/w Hydroxy Propyl Methyl Cellulose K4M, 15% Sodium bicarbonate and 5% ethyl cellulose (4cps) was the best formulation as per the range of drug release remain institute to be more than 95 % in 12h and floating lag time was 20.15 s. The immediate-release layer stood optimized using crospovidone and Indion 414 as a super disintegrant. Formulation A8 containing 2% Indion 414 was considered as optimized formulation as it released 99% drug within 35 min and possessed less disintegration time. Optimized formulation F4 from the controlled-release layer and A8 from immediate-release layer was used to formulate bilayer tablet. The optimized formulation was imperilled to stability reading for three months at 40○C/75% relative humidity. The stability revision exhibited no substantial alteration in the appearance of tablets, floating characteristics, drug content and in-vitro drug dissolution. Consequently, a biphasic drug release design was effectively accomplished over the formulation of floating bilayer tablets.


Lower limb oedema following distal arterial bypass grafting.
Lower-limb oedema following arterial bypass surgery for ischemia is a common sequela which can complicate wound healing or delay resumption of mobility. Its exact pathogenesis remains uncertain but many theories have been proposed. Lymphatic disruption during arterial exposure, and endothelial damage from atrophy of the media and oxygen-derived free radical release are currently favoured hypotheses. Infrequently, deep vein thrombosis follows surgery and may exacerbate the condition. Efforts aimed at reducing the oedema, such as the use of lymphatic preserving incisional approaches or the use of antioxidants, have given conflicting results. The use of compression hosiery and leg elevation appear to be the most effective measures in reducing postoperative lower limb oedema.


Reducing the psychological distress of family caregivers of home-based palliative care patients: short-term effects from a randomised controlled trial.
Palliative care is expected to incorporate comprehensive support for family caregivers given that many caregivers suffer psychological morbidity. However, systematically implemented evidence-based psychological support initiatives are lacking. The objective of this study was to prepare caregivers for the role of supporting a patient with advanced cancer receiving home-based palliative care by offering a one-to-one psycho-educational intervention. We hypothesised that primary family caregivers who participated in the intervention would report decreased psychological distress (primary outcome), fewer unmet needs and increased levels of perceived preparedness, competence and positive emotions. A three-arm randomised controlled trial was conducted comparing two versions of the intervention (one face-to-face visit versus two visits) plus standard care to a control group (standard care) across four sites in Australia. A total of 298 participants were recruited; 148 were in the Control condition, 57 in Intervention 1 (one visit) and 93 in Intervention 2 (two visits). Relative to participants in the control group; the psychological well-being of participants in the intervention condition was improved by a small amount but non-significantly. No significant reduction in unmet needs or improvements in positive aspects of caregiving amongst the intervention group were identified. However, the intervention demonstrated significant improvements in participants' levels of preparedness and competence for Intervention 2. This research adds to accumulating body of evidence demonstrating that relatively short psycho-educational interventions can enable family caregivers to feel more prepared and competent in the role of supporting a dying relative. Further investigation is required to determine the longer term outcomes of such interventions.


Environmental contributions to otitis media requiring tympanostomy tubes.
Otitis media requiring tympanostomy tubes (OMwTT) is a prevalent disease process that has been previously shown to have a strong familial link. The impact from the environmental versus genetic contributions to this link is unknown. The objective was to determine the environmental involvement in the development of OMwTT. Using an extensive genealogical database linked to medical records, we evaluated the risk of OMwTT in children of probands as compared to children of controls, individually matched 5:1 on sex and birth year, from a conditional logistic regression model. The model included adjustments for geographic and socioeconomic environmental risk factors mapped to residence location of study subjects within 63 small health statistical areas of ∼33,500 persons each. 37,814 case probands diagnosed with OMwTT and 181,339 controls were included in our analysis. Children of probands with OMwTT had an overall 2.5× higher risk of also having OMwTT as compared to the children of controls (p < 10-9), independent of environmental factors (PM2.5 [particulate matter] air pollution, education level of parents, and density of primary care providers). After accounting for geographic and socioeconomic differences that may influence risk between cases and controls, our findings suggest evidence of a genetic predisposition in families of OMwTT patients. Further characterization of high-risk pedigrees is needed for future genomic studies.


[Kidney function study of healthy persons by the 131I-hippuran renography method under prolonged hypokinesia].
The paper describes renography studies (using I131-hippurane) of the renal function of 28 test subjects who participated in 30- and 120-day bed rest experiments. Typical changes in the vascular, secretory and evacuatory segments of renograms were noted. The delay in the isotope absorption and excretion from the blood and kidneys was mostly expressed by the end of bed rest. A relationship between renographic changes and renal blood flow as well as between renal excretion of water and sodium at different experimental stages was established. The above changes in the renal function were functional and associated with changes in the systems controlling the fluidelectrolyte metabolism.


Prevalence and associations of external punctal stenosis in a general population in Spain.
To determine the prevalence of external punctal stenosis (EPS) and to investigate its associations in a general adult population in northwestern Spain. A total of 1155 subjects ≥ 40 years were selected by an age-stratified random sample procedure in O Salnés (Spain). An interview was carried out to collect history of systemic diseases and lifestyle details, and a comprehensive ophthalmic evaluation in which EPS was recorded. The prevalence of EPS and its relationship with demographic, lifestyle, and systemic and ocular factors was investigated. All calculations were weighted to give unbiased estimates. From 937 eligible subjects, 621 (66.3%) participated [mean age (SD), 63.4 (14.5) years; range, 40-96 years; 37.0% men). The prevalence of EPS was 17.3% [95% confidence interval (CI), 14.8-19.8). This prevalence increased significantly with aging (P = 0.000) and was 13.8% (95% CI, 10.3-18.3) in men and 19.4% (95% CI, 16.1-23.2) in women. After controlling for age and sex, EPS was associated with outdoor occupational activity (age and sex adjusted odd ratio [ORa], 2.22; 95% CI, 1.31-3.37) and with degenerative disorders such as pinguecula (ORa, 1.48; 95% CI, 1.15-1.89) but not with inflammatory disorders such as blepharitis or dry eye. A multivariable analysis in which sex differences also became significant (P = 0.024) confirmed these associations. External punctual stenosis is a common disorder associated with outdoor occupational activity. Processes associated with tissue degeneration but not with inflammation are highly prevalent among subjects with EPS. Modifiable factors, such as sun exposure, must be addressed to reduce the impact of this disorder.


The protein binding of vinblastine in the serum of normal subjects and patients with Hodgkin's disease.
The protein binding of vinblastine was measured in the serum from 6 normal subjects and 9 patients with Hodgkin's disease. Cellulose acetate electrophoresis showed that the predominant binding protein fractions were the alpha 1- and alpha 2-globulins with little binding to albumin and beta- and gamma-globulins. At a serum concentration of 10 nM a significantly lower percentage bound was found in the patient group (p = 0.001). Binding to both groups was very high at 99.7% bound in the normal subjects and 98.9% bound in the patient group. Binding in both groups was best described by a two class protein binding model with higher and lower affinity binding sites. No significant difference was found on inter-group comparisons of binding parameter values.


Geographic Differences in Rates of Primary Total Knee Arthroplasty in Young and Older Adults: A Comparison of 3 US States.
Rates of total knee arthroplasty (TKA) among Medicare beneficiaries (adults aged ≥ 65 yrs) vary across the United States, with higher rates in the Midwest and West than in the South. It is not known if a similar variation is present among younger patients, or if findings in Medicare reflect selective postponement of TKA in some regions. Data on all primary TKA performed in adults aged ≥ 20 years in 3 states (Iowa, Utah, and Florida) in 2016 were obtained from state inpatient databases. Rates of TKA were computed based on population census data. Age-, sex-, and race-standardized rates were compared between Iowa and Florida, and between Utah and Florida, among adults aged 20-64 years and adults aged ≥ 65 years. There were 10,074, 8954, and 43,908 primary TKAs in Iowa, Utah, and Florida, respectively. Standardized rates were higher in Iowa and Utah than in Florida among both adults aged 20-64 years (Iowa:Florida rate ratio [RR] 1.89, 95% CI 1.79-1.99; Utah:Florida RR 2.31, 95% CI 2.18-2.45) and those aged ≥ 65 years (Iowa:Florida RR 1.41, 95% CI 1.35-1.47; Utah:Florida RR 1.77, 95% CI 1.70-1.85). Results were similar in sensitivity analyses limited to White patients, urban residents, and those with a diagnosis of knee osteoarthritis. TKA rates were higher in Iowa and Utah than in Florida among both younger adults and those aged ≥ 65 years, indicating that geographic differences are not specific to elderly patients.


Distribution of plantar pressure during jogging barefoot or in minimalistic shoes in people who used to run in cushioned shoes.
In recent years, an increasing number of runners prefer jogging barefoot or in minimalistic shoes. The aim of this study was to compare the distribution of plantar pressure during jogging barefoot, in minimalistic shoes, or in shoes with cushioned soles, as these forces modulate the risk of injury. The study included nine men aged between 24 and 25 years, who engaged in long-distance running. The plantar pressure of three foot zones (forefoot, midfoot, and hindfoot) was examined with WIN-POD electronic podometer during running barefoot, in minimalistic shoes, or in shoes with cushioned soles. Individuals who ran barefoot showed the greatest forefoot pressure, followed by those running in minimalistic shoes and cushioned shoes. In contrast, the heel pressure in individuals running in cushioned shoes was significantly greater than in those using minimalistic shoes or running barefoot. Switching from running in cushioned shoes to jogging barefoot is associated with the accumulation of greatest pressure in the forefoot and midfoot. The accumulation of the greatest pressure at the insertion of plantar aponeurosis can lead to the injuries of musculoskeletal system, in particular plantar aponeurositis. Even distribution of pressure among various parts of the foot in persons running in minimalistic shoes is associated with lower risk of injury than in the case of running barefoot.


How many people with type 2 diabetes fulfil the eligibility criteria for randomized, controlled trials of insulin glargine 300 U/mL in a real-world setting?
Randomized controlled trial (RCT) populations often do not reflect those typically seen in clinical practice. This retrospective, observational cohort study analysed the real-world data of people with type 2 diabetes (T2DM) prescribed basal insulin analogues from electronic medical records (EMRs) in the Explorys database, which includes data from 39 integrated healthcare systems in the United States, to determine how representative selected RCTs investigating insulin glargine 300 U/mL (Gla-300) are of T2DM populations in a real-world setting. Applying eligibility criteria derived from the EDITION 1, 2 and 3 (Gla-300 vs. insulin glargine 100 U/mL [Gla-100]) and BRIGHT (Gla-300 vs. insulin degludec) RCTs, we observed that only 17% (33 345/191 218) of people captured in the real-world database would have been eligible for such trials. Those who were ineligible tended to be older, had more comorbidities and a higher baseline hypoglycaemia rate than the eligible group. Using another large US EMR database (Optum Humedica) as corroboration, we found that 15% (36 285/235 697) would have been eligible to participate in the EDITION/BRIGHT RCTs. Furthermore, only 7% (1734/24 547) would have been eligible for the CONCLUDE (insulin degludec vs. Gla-300) RCT. Our findings remind us of the value of real-world data studies, complementing the results of RCTs, and providing additional insights into groups who would typically be excluded from RCTs.


The role of oxygen in the biosynthesis of cytochrome c oxidase of yeast mitochondria.
The formation of cytochrome c oxidase in yeast is dependent on oxygen. In order to examine the oxygen-dependent formation of the active enzyme, the effect of oxygen on the synthesis and the assembly of cytochrome c oxidase subunits was studied. Pulse-labeling experiments revealed that oxygen has no significant immediate effect on the synthesis of the three mitochondrially made subunits I to III; however, its presence causes subunits I and II to form a complex with the cytoplasmically made subunits VI and VII. This "assembly-inducing" effect can be demonstrated with intact yeast cells as well as with isolated mitochondria. It is independent of cytoplasmic or mitochondrial protein synthesis. After anaerobic growth for 10 or more generations, the intracellular concentrations of individual cytochrome c oxidase subunits drop 10- to 100-fold. Most of these residual subunits are not assembled within a functional cytochrome c oxidase molecule.


Automated urinalysis with expert review for incidental identification of atypical urothelial cells: An anticipated bladder carcinoma diagnosis.
The most common diagnostic technique for the detection of malignant/atypical urothelial cells (m/AUC) is urinary cytology (Ucytol). Urinary sediment (Used) examination, often prescribed for asymptomatic, healthy subjects, can incidentally identify suspicious/AUC (s/AUC) in routine daily practice. Unstained, unfixed and uncentrifuged urine samples were analyzed with an automated intelligent microscopy (AIM) system. From January 2010, any incidental identification of s/AUC through expert revision of unclassified cell images was reported, according to internal protocols, as an additional note on the patients' laboratory report. Patients' symptomatology or previous history was unknown to the pathologist. All referrals from January 2010 to December 2014, with the s/AUC note, were reviewed and cross-referenced with Ucytol and histology data from a central database. Of the 162 patients identified with s/AUC (0.1/1000 samples), 84% (n=136) performed further Ucytol and/or histological examinations. The sensitivity of the identification of non-transitory AUC at Used was 87.5%. Positive histological examinations were 91.2% classified as high-grade urothelial carcinoma. Routine Used examination, with an AIM and expert revision, can identify the presence of AUC in a clinical laboratory setting, and for some subjects, may anticipate bladder carcinoma diagnosis.


Essential hypertension is lymphatic: a working hypothesis.
Lymphatics, a third component of the circulation, may be deranged by the same factors as veins and arteries. Malfunctioning through overload or dyscrasia, they may foster high blood pressure. It is hypothesized that essential hypertension is caused by lymphatic system aberrations.


A case of transvaginal NOTES partial gastrectomy using new techniques and devices.
The latest technique of transvaginal NOTES partial gastrectomy is described in detail. The procedure involves new "over-tube steering" technique and usage of two newly developed endoscopic accessories. The technique is feasible, safe, and practical, since all devices used in the case are off-the-shelf products.


Antitumoral effect of maintained neutrophilia induced by rhG-CSF in a murine model of pancreatic cancer.
Although the protumoral functions of polymorphonuclear neutrophils are well known, some now-forgotten studies report antitumoral roles for these cells. The present work examines the antitumoral effect of maintained neutrophilia induced via the injection of recombinant human granulocyte colony stimulating factor (rhG-CSF, 100 μg/kg/day) in a Panc-1 subcutaneous xenograft murine model of pancreatic cancer. This treatment was compared with gemcitabine administration (120 mg/kg every two days) and a saline control (n = 6-7 mice per group). Compared to the controls, both the rhG-CSF- and gemcitabine-treated mice showed significantly suppressed tumor growth by day 4 (p < 0.001 and p = 0.013 respectively). From a mean starting volume of 106.9 ± 3.1 mm3 for all treatment groups, the final mean tumor volumes reached were 282.0 ± 30.7 mm3 for the rhG-CSF-treated mice, 202.6 ± 18.1 mm3 for the gemcitabine-treated mice and 519.4 ± 62.9 mm3 for the control mice (p < 0.004 and p < 0.01, respectively, vs. control). The rhG-CSF-treated tumors showed higher percentage necrosis than those treated with gemcitabine (37.4 ± 4.6 vs. 7.5 ± 3.0; p < 0.001). This is the first report of a clear anti-tumoral effect of rhG-CSF when used in monotherapy against pancreatic cancer. Since rhG-CSF administration is known to be associated with very few adverse events, it may offer an attractive alternative in the clinical treatment of pancreatic cancer.


An examination of a contaminated seminal stain using absorption-elution and enzyme-linked immunosorbent assay (ELISA).
A semen stain, apparently contaminated with a detergent cleanser, was received for examination. The contamination interfered with the normal biochemical reactions of such stains. Treatment of the sample enabled ABO groups to be determined.


Serotyping and genotyping of encapsulated Escherichia coli K1 sepsis isolates with a monoclonal IgG anti K1 antibody and K1 gene probes.
Among infectious diseases caused by E. coli the capsular type K1 plays a predominant role. E. coli K1 isolates account for 80% of cases of E. coli neonatal meningitis and 30% of E. coli sepsis strains. Serotyping of K1 strains has conventionally relied upon the use of K1-specific bacteriophages or serum agar methods with polyvalent anti K1 serum. In the study present here, 187 E. coli sepsis isolates have been analysed for production of the K1 antigen using K1 phages, K1 serum agar plates and Latex agglutination and ELISA using an IgG2a anti K1 monoclonal antibody. In total, 33 sepsis isolates (about 18%) were identified as K1 positive, with three of these strains proving negative in all tests except those exploiting the monoclonal antibody. That these three strains elaborate the K1 antigen was confirmed by Southern blot experiments using cloned K1 antigen production genes as probes. The failure of the three strains in all the tests except those that use monoclonal antibody could be explained by apparent disruption of K1 gene sequences that encode functions essential for the export of capsular material to the cell surface. The superiority of tests based on monoclonal antibodies above the conventional methods for detection of K1 antigen is evident.


9-Amino-1,2,3,4-tetrahydroacridine (THA) blocks agonist-induced potassium conductance in rat hippocampal neurones.
The actions of 9-amino-1,2,3,4-tetrahydroacridine (THA) were studied on rat CA1 pyramidal neurones under voltage-clamp in transverse slices of hippocampus maintained in vitro. As previously reported, THA reduced the resting conductance of cells; THA also suppressed inward rectification activated by hyperpolarization by up to 75% (The dose of THA which reduced the response by 50% (IC50) was 300 microM). More sensitive to the action of THA was the outward K+ current activated in CA1 neurones by 5-HT, adenosine and baclofen. This was completely blocked by THA (IC50 = 28 microM). The cooperativity of this latter action of THA with its well-known anticholinesterase activity is discussed in relation to the therapeutic effects of THA in treating Alzheimer's disease.


Pseudomembranous colitis in cystic fibrosis.
Cystic fibrosis (CF) patients may require frequent courses of antibiotics and repeated hospital admissions. Although children with CF have high carriage rate for C.difficile, they rarely develop colitis. Pseudomembranous colitis is more common in adult post lung transplant CF patients. Although rare, paseudomembranous colitis should be considered in CF patients presenting with abdominal symptoms even in the absence of diarrhoea.


Gorilla diet in the Lopé Reserve, Gabon: : A nutritional analysis.
The results of an analysis of gorilla diet in the Lopé Reserve, Gabon are presented. Samples were assayed for nutrients and plant secondary compounds (total phenols, condensed tannins and alkaloids) in an attempt to explain gorilla food choice. The diet is the most diverse so far analysed for gorillas; it seems to be a balance between sugary fruit, proteinaceous leaves, and relatively fibrous stems. Most fruits and herbaceous stems are succulent, but some drier, fibrous fruit and bark is also consumed. Seeds are another component of the diet, including unripe ones. Fruit, seeds, leaves and bark may all contain very high levels of total phenols and condensed tannins; but all herbaceous stems assayed contain low levels of these compounds. Alkaloids are not apparently a significant component of gorilla foods, and may be avoided. Gorillas at Lopé tend to avoid fatty fruit, and select leaves which are high in protein and low in fibre compared to the general vegetation. When fruit and preferred young leaves are scarce, proteinaceous barks and mature leaves, and sugary pith, are important sources of nutrients. We conclude that gorillas exploit the broad frugivore niche in West African lowland forests, and are part of the frugivore community there. What distinguishes them is their ability to eat large fibrous fruit, mature leaves and stems, and to overcome high levels of phenolics (we use "phenolics" as an umbrella term for both total phenols and condensed tannins). Gorilla diet at Lopé overlaps greatly with that of sympatric, frugivorous, primates, and resembles more closely that of chimpanzees than it does gorilla diet studied elsewhere in Africa.


Plasma methotrexate levels in patients with gestational trophoblastic neoplasia treated by two methotrexate regimens.
Plasma methotrexate levels were measured in six patients with nonmetastatic and three patients with "low-risk" metastatic gestational trophoblastic neoplasia who were treated by two different methotrexate regimens. Five patients were treated with 16 cycles consisting of methotrexate, 1 mg/kg (days 1, 3, 5, and 7) followed in 24 hours by citrovorum factor, 0.1 mg/kg (days 2, 4, 6, and 8). Cycles alternated between intravenous and intramuscular administration. Statistical differences in plasma levels were found at 1 and 48 hours between the two routes of administration but probably were not of clinical importance. The plasma levels at the time of citrovorum factor administration were below that necessitating citrovorum factor rescue. Four patients were treated with alternating cycles of intravenous or intramuscular methotrexate, 0.5 mg/kg for 5 consecutive days without citrovorum factor. A total of 15 cycles demonstrated no difference in plasma levels at 1, 12, and 24 hours between intravenous and intramuscular administration. Statistical differences in plasma methotrexate levels were noted between the two methotrexate regimens only with intramuscular administration but were not of clinical importance. The reduced toxicity of the methotrexate-citrovorum factor may be due to the scheduling of the methotrexate and not to the citrovorum factor.


Coronary heart disease: epidemiology of smoking and intervention studies of smoking.
Smoking is a strong risk factor for myocardial infarction (MI) and sudden coronary death, but not for angina pectoris that is not complicated by a MI. Even light cigarette and pipe and cigar smokers run an increased risk for MI and sudden coronary death. Smoking potentiates other risk factors such as lipid abnormalities and hypertension. Smoking increases blood pressure acutely, but smokers have generally had lower blood pressures than nonsmokers in epidemiologic studies. Smoking adversely affects the prognosis in patients who have suffered a MI and those with angina pectoris. Of great importance regarding community risk of smoking are the many light and moderate smokers. These persons should be addressed more vigorously in intervention efforts.


Simultaneous transcatheter tricuspid and mitral valve-in-valve replacement for the treatment of degenerated bioprosthetic valves.
Transcatheter valve-in-valve replacement has become a viable option for patients with degenerated bioprosthetic valves at high risk for redo surgery. We report a case of a patient who had degenerated mitral and tricuspid bioprosthesis causing severe tricuspid and mitral regurgitation. We performed simultaneous mitral and tricuspid valve-in-valve replacement via a transfemoral approach. Although the data on performing both valve-in-valve procedures are limited, this case demonstrated that these procedures can be safely done as a single procedure.


Unusual finding of encapsulated nematode larvae (Spiruroidea) in Bartramia longicauda and Numenius americanus (Charadriiformes) in western Canada.
Third-stage spiruroid larvae were found encapsulated on the serosa of the small and large intestines and in the mesentery of one of 15 adult upland sandpipers (Bartramia longicauda) from Manitoba, Canada, and three of 18 adult long-billed curlews (Numenius americanus) from Alberta, Canada. The larvae resemble third-stage larvae of Physocephalus sexalatus and birds may serve as a paratenic host of this unidentified spiruroid species.


Quality of life of Tunisian patients with lung cancer: descriptive study.
No previous study has set as primary goal the evaluation of the quality of life (QOL) of Tunisian patients with lung cancer (LC). To evaluate the QOL of Tunisian patients with LC. This was a cross-sectional descriptive study. QOL of 100 patients with LC (90 men) was evaluated via the QLQ-C30 and QLQ-LC13 questionnaires. QLQ-C30 data were compared with international reference values. 40, 38, 7 and 15% of patients had, adenocarcinoma, squamous cell carcinoma, large cell and small cell LC, respectively. 72, 20 and 8% of patients had received chemotherapy, combination of chemotherapy and surgery or radiotherapy, respectively. The means±SDs of the QLQ-C30 were 3717 (QOL), 5121 (physical activity), 3921 (life role activity), 9113 (cognitive activity), 6622 (emotional activity), 2720 (social activity), 5517 (fatigue), 5120 (pain), 820 (nausea/vomiting), 4221 (dyspnea), 6623 (insomnia), 5125 (anorexia), 4932 (constipation), 1021 (diarrhea) and 7173 (financial problems). The scores means±SDs of dyspnea, cough, hemoptysis, sore mouth and tongue, dysphagia, peripheral neuropathy, alopecia, chest pain, pain in arm or shoulder, and other pain sites were, 5116, 4523, 1319, 1819, 1017, 3430, 1522, 4720, 4534, and 1419, respectively. Comparison of QLQ-C30 data with international reference values showed an alteration of all scores except of those of emotional activity, nausea/vomiting, dyspnea and diarrhea. Tunisian patients with LC had poor QOL.


A cluster randomised intervention trial of asthma clubs to improve quality of life in primary school children: the School Care and Asthma Management Project (SCAMP).
To evaluate the effectiveness of a programme of asthma clubs in improving quality of life in primary school children with asthma. A cluster randomised intervention trial was undertaken in 22 primary schools within the urban area of south and east Belfast, Northern Ireland. Schools were randomised in pairs to immediate or delayed groups. The study subjects comprised 173 children aged 7-11 years whose parents had notified the school of their asthma diagnosis. Children attended school based weekly clubs over an 8 week period. The main outcome measures were the interview administered Paediatric Quality of Life Questionnaire scores, ranging from 1 (worst) to 7 (best), spirometry, and inhaler technique. Over 15 weeks, small but non-significant improvements in the overall quality of life score (mean 0.20; 95% confidence interval (CI) -0.20 to 0.61) and in each of its three components, activity limitation (0.20; -0.43 to 0.84), symptoms (0.23; -0.23 to 0.70), and emotional function (0.17; -0.18 to 0.52), were observed in the immediate compared with the delayed group. Inhaler technique at week 16 was markedly better in the immediate group, with 56% having correct technique compared with 15% in the delayed group. No significant effect of the intervention on spirometry results could be demonstrated. This primary school based asthma education programme resulted in sustained improvements in inhaler technique, but changes in quality of life scores were not significant.


Basic study of nasal provocative test. Second report: assessment method on provocative reaction.
Because no simple and precise method is available to test intensity of the reaction resulted from a nasal provocative test in diagnosis of nasal allergy, comparisons were made among the conventional test methods of rhinoscopy (RS), rhinomanometry (RM) and the carbon powder elimination test (CET) devised by the authors. The rhinoscopy shows high positive rates and has advantages being free from any special equipment, prolonged time or the patients' cooperation, but also had disadvantages such as requirement of skill of examiner and problems in objectivity. The carbon powder elimination test is a preferable method in that it is not only equipped with the advantages of the rhinoscopy but also makes up for its disadvantages, but a disadvantage of CET is requirement of longer time than RS. Rhinomanometry had lower positive rates and requires a special equipment, prolonged time and the skillful patients' cooperation. The disadvantage is that its impracticableness in many patients--26% impracticableness even in adult patients, but the method is fully objective. From these findings the value of Carbon Powder Elimination Test in judging provoked reactions is recognized.


A novel and facile synthesis of carbon quantum dots via salep hydrothermal treatment as the silver nanoparticles support: Application to electroanalytical determination of H2O2 in fetal bovine serum.
A simple, low-cost, and green process was used for the synthesis of carbon quantum dots (CQDs) through the hydrothermal treatment of salep as a novel bio-polymeric carbon source in presence of only pure water. The silver nanoparticles (AgNPs) were embedded on the surface of CQDs by ultra-violate (UV) irradiation to the CQDs and silver nitrate mixture solution. The as-synthesized CQDs and AgNPs decorated CQDs nanohybrid (AgNPs/CQDs) were characterized by UV-vis and photoluminescence spectroscopy, Fourier transform-infrared spectroscopy, transmission electron microscopy, atomic force microcopy, X-ray diffraction, and field emission scanning electron microscopy. Then, the AgNPs/CQDs nanohybrid was casted on the glassy carbon electrode in order to prepare an amperometric hydrogen peroxide (H2O2) sensor. The electrochemical investigations show that the AgNPs/CQDs nanohybrid possesses an excellent performance toward the H2O2 reduction. In the optimum condition, the linear range of H2O2 determination was achieved from 0.2 to 27.0μM with high sensitivity (1.5μA/µM) and the limit of detection was obtained about 80nM (S/N=3). Finally, the prepared nanohybrid modified electrode was effectively applied to the H2O2 detection in the disinfected fetal bovine serum samples, and the recovery was obtained about 98%. The achieved results indicate that the AgNPs/CQDs nanohybrid with high reproducibility, repeatability, and stability has a favorable capability in electrochemical sensors improvement.


High-Throughput Screening for Insulin Secretion Modulators.
The application of forward chemical genetics to insulin secretion in high-throughput has been uncommon because of high costs and technical challenges. However, with the advancement of secreted luciferase tools, it has become feasible for small laboratories to screen large numbers of compounds for effects on insulin secretion. The purpose of this chapter is to outline the methods involved in high-throughput screening for small molecules that chronically impact pancreatic beta cell function. Attention is given to specific points in the protocol that help to improve the dynamic range and reduce variability in the assay. Using this approach in 384-well format, at least 48 and as many as 144 plates can theoretically be processed per week. This protocol serves as a guideline and can be modified as required for alternate stimulation paradigms and improved upon as new technologies become available.


Sexual dimorphism in gastric cancer: tumor-associated neutrophils predict patient outcome only for women.
Tumor-associated neutrophils (TANs) are part of the tumor immune microenvironment (TIME) and may contribute to gastric cancer (GC) biology. We hypothesized that TAN are enriched in the TIME, show sex-specific differences, and correlate with patient outcome. We analyzed the distribution and putative tumor biological significance of TANs in a well-characterized, therapy-naïve, European GC cohort using immunohistochemical staining of myeloperoxidase (MPO), and digital image analysis using Definiens Tissue Studio®. Different tumor compartments were examined, and TAN densities were correlated with various clinicopathological patient characteristics. TAN density showed a large interindividual variability ranging from 0 to 6711.0 TANs/mm2. Intratumoral distribution patterns were inhomogeneous (tumor surface vs. tumor center vs. invasion front) and correlated significantly with Laurén phenotype, tumor grade, and microsatellite status in the tumor center and invasion front. In the multivariate analysis, TAN density in the invasion front was an independent predictor of tumor-specific survival only for women (HR = 2.77, p < 0.001). In men, no correlation was found between TAN density and survival. With regard to TANs, our study independently validates sexual dimorphism in GC biology.


Multiprofessional guidelines for the management of the patient with primary cutaneous squamous cell carcinoma.
These guidelines for management of primary cutaneous squamous cell carcinoma present evidence-based guidance for treatment, with identification of the strength of evidence available at the time of preparation of the guidelines, and a brief overview of epidemiological aspects, diagnosis and investigation.


Pilot scale oxidative fast pyrolysis of sawdust in a fluidized bed reactor: A biorefinery approach.
Oxidative fast pyrolysis of sawdust was performed in a pilot scale fluidized bed system (3 kg/h) under stabilized experimental conditions (0.20 equivalence ratio and 550 °C). Experiments were performed in non-catalytic and catalytic (ZSM-5) mode. During non-catalytic fast pyrolysis, bio-oil (∼38 wt%), bio-char (∼12 wt%) and pyro-gas (∼50 wt%) were obtained; in contrast, for catalytic fast pyrolysis bio-oil, bio-char and pyro-gas yields were ∼44 wt%, ∼4 wt% and ∼52 wt% respectively. The obtained bio-oil was characterized through CHNSO, NMR (1H and 13C NMR), FT-IR and GC-MS techniques. GC-MS analysis of the bio-oil shows it is a mixture of ∼21 chemical compounds. Furthermore, NMR (1H and 13C NMR) and FT-IR results indicates presence of hydrocarbon, alcohol, phenol and aldehyde in the bio-oil. The TGA of bio-char shows that it is stable up to 950 °C. The activation energies (Ea) of sawdust and bio-char are found to be 112.3 kJ/mol and 46.92 kJ/mol respectively. FT-IR analysis of bio-char clearly revealed removal of functionalized organic compounds during devolatilization of sawdust. In addition, GC analysis of pyro-gas suggests that it is a mixture of N2 (35.55 vol%), CO (34.49 vol%), CO2 (16.80 vol%), H2 (4.54 vol%), O2 (4.25 vol%), and CH4 (4.41 vol%).


Progressive pneumoperitoneum increases the length of abdominal muscles.
The aim of this prospective observational study was to determine the effects of progressive preoperative pneumoperitoneum (PPP) on the size of large incisional hernia (IH) and abdominal muscles by abdominal computed tomography (CT) scan. PPP was performed in 18 patients. All IH were large. A mean volume of 12.8 l was insufflated over a mean period of 14.8 days. Respectively, before and after PPP, the mean IH height and width was 117 and 130 mm (P < 0.05) and 101 and 115 mm (P < 0.05), the mean width of the right and left rectus abdominis was 99 and 109 mm (P < 0.05) and 100 and 113 mm (P < 0.05), and the length of the right and left anterolateral muscles was 198 and 233 mm (P < 0.05) and 185 and 210 mm (P < 0.01). In conclusion, PPP increases the abdominal wall muscle length and has the same impact on the IH orifice. PPP would facilitate the fascial repair of otherwise untreatable large IH.


Predicting intensive care unit admission and death for COVID-19 patients in the emergency department using early warning scores.
To identify the most accurate early warning score (EWS) for predicting an adverse outcome in COVID-19 patients admitted to the emergency department (ED). In adult consecutive patients admitted (March 1-April 15, 2020) to the ED of a major referral centre for COVID-19, we retrospectively calculated NEWS, NEWS2, NEWS-C, MEWS, qSOFA, and REMS from physiological variables measured on arrival. Sensitivity, specificity, positive (PPV) and negative predictive value (NPV), and the area under the receiver operating characteristic (AUROC) curve of each EWS for predicting admission to the intensive care unit (ICU) and death at 48 h and 7 days were calculated. We included 334 patients (119 [35.6%] females, median age 66 [54-78] years). At 7 days, the rates of ICU admission and death were 56/334 (17%) and 26/334 (7.8%), respectively. NEWS was the most accurate predictor of ICU admission within 7 days (AUROC 0.783 [95% CI, 0.735-0.826]; sensitivity 71.4 [57.8-82.7]%; NPV 93.1 [89.8-95.3]%), while REMS was the most accurate predictor of death within 7 days (AUROC 0.823 [0.778-0.863]; sensitivity 96.1 [80.4-99.9]%; NPV 99.4[96.2-99.9]%). Similar results were observed for ICU admission and death at 48 h. NEWS and REMS were as accurate as the triage system used in our ED. MEWS and qSOFA had the lowest overall accuracy for both outcomes. In our single-centre cohort of COVID-19 patients, NEWS and REMS measured on ED arrival were the most sensitive predictors of 7-day ICU admission or death. EWS could be useful to identify patients with low risk of clinical deterioration.


An Alu insertion in compound heterozygosity with a microduplication in GNPTAB gene underlies Mucolipidosis II.
Mucolipidosis type II (ML II) is a fatal, autosomal recessive, lysosomal storage disorder characterized by severe clinical and radiologic features. ML II results from mutations in alpha and beta subunits, encoded by the GlcNAc-1-phosphotransferase gene (GNPTAB). Most of the 40 different GNPTAB mutations reported so far are insertions and deletions predicting diverse types of aberrant proteins. Alu mobile elements have however never been involved in these events up to now. The Italian ML II patient of our study showed an Alu retrotrasposition in GNPTAB exon 5. The Alu insertion mutation (NM_024312.3:c.555_556insHSU14569) generated a transcript with a skipping of the target exon 5 and a frameshift p.S122fs, causing a premature translation termination codon at position 123. This insertion mutation was found in compound heterozygosity with the frameshift p.S887KfsX33, resulting from a new mono-nucleotide duplication (c.2659dupA) that occurred in GNPTAB exon 13. A possible involvement of cis-splicing elements having an exonic location, such as exon enhancers (ESEs), is discussed as mechanism that led to the production of the aberrant mRNA splicing.


Endoscopic total parathyroidectomy by the anterior chest approach for renal hyperparathyroidism.
During the past 3 years, minimally invasive procedures have been adopted for the surgical treatment of primary hyperparathyroidism, and we have tried to perform endoscopic total parathyroidectomy for renal hyperparathyroidism. Five 5-mm trocars were inserted through the skin of the anterior chest under a general anesthesia. Carbon dioxide was then insufflated up to 4 mmHg, and the endoscopic surgery was performed. Endoscopic procedure was successfully performed in five patients. The mean duration of total parathyroidectomies was 236 min. No evidence of injury to the recurrent laryngeal nerve was observed in any cases. At follow-up, the serum calcium and parathyroid hormone levels had returned to within the normal range in all patients. Postoperative cosmetic status was excellent. We believe that endoscopic total parathyroidectomy by the anterior chest approach will find a role in the treatment of renal hyperparathyroidism.


Subcortical lobar hematomas: clinico-computed tomographic correlations.
Eighteen patients with subcortical lobar hematomas were reviewed. Arterial hypertension was the leading cause and three had arteriovenous malformation and were treated surgically. More than half of cases had hematomas of either the temporooccipital or occipital lobes. Common neurologic findings were headaches, vomiting, alertness, dysarthria, hemiparesis and hemianopsia. All patients survived and had better resolution of neurological deficits, suggesting that surgical intervention is not necessary.


Maternal estimates of neonatal birth weight in diabetic patients.
No consensus exists on estimation of birth weight or prediction of fetal macrosomia in the diabetic population. We compared intrapartum clinical, maternal, and ultrasonographic estimates of birth weight in diabetic patients. Diabetic patients at term had clinical, maternal, and ultrasonographic estimations of fetal weight. The mean absolute error, standardized error, and percentage of estimates within 10% of actual birth weight were determined for the three estimates. Effects of maternal weight, parity, and recent ultrasonography were assessed, and statistical analysis was done. With 32 women enrolled, no statistical difference was seen among clinical (11%), maternal (8.8%), and ultrasonographic (8.0%) birth weight estimates. No difference was seen in accuracy of the three estimates. Estimates were within 10% of actual birth weight in 69% of clinical and maternal estimations and 75% of ultrasonographic estimations. Maternal weight, parity, and recent ultrasonographic evaluation did not affect accuracy of predictions. Intrapartum maternal estimation of fetal weight in diabetic patients is as accurate as clinical and ultrasonographic predictions.


The influence of age and metformin treatment status on reported gastrointestinal side effects with liraglutide treatment in type 2 diabetes.
Treatment of type 2 diabetes with glucagon-like peptide-1 (GLP-1) receptor agonists may be limited by gastrointestinal side effects (GISE) in some patients. Risk factors for developing GISE are not known. We analysed patient characteristics that were associated with GISE among patients treated with the GLP-1 receptor agonist liraglutide. Data was obtained from an audit database of liraglutide use based in clinical practice in the UK. Patients were grouped into those who did not report GISE, those who reported GISE but continued liraglutide and those who discontinued liraglutide due to GISE within 26 weeks of treatment. Baseline variables of age, diabetes duration, HbA1c, weight, BMI, blood pressure, lipids, gender, ethnicity, alanine transaminotransferase, estimated glomerular filtration rate (eGFR) and diabetes treatment types were tested for possible associations with GISE outcome. Significant variables in univariate analyses were entered into ordinal logistic regression analyses. A total of 4442 patients were suitable for analysis. A total of 3905 (87.9%) did not report GISE, 297 (6.7%) and 240 (5.4%) had GISE and continued and discontinued treatment, respectively. Age, weight, eGFR, metformin status and insulin status were associated with GISE outcome in univariate analyses (P all <0.05). In the final regression model, age (adjusted OR 1.15 [95%CI 1.05,1.26], P=0.002) and non-metformin use (adjusted OR 0.76 [95%CI 0.60,0.96], P=0.020) were associated with worse GISE outcome. Older age and non-metformin use were associated with more significant GISE leading to discontinuation of liraglutide treatment. The reasons for these findings are unclear and warrant further investigation.


Technology and ethics: three scenarios for the 1990s.
The 1990s will be a critical decade for medical technology. An irresistible force (an aging population that requires more medical care) will meet an immovable object (limited resources). Technology will be the centerpiece of debates about the efficiency and efficacy of the health system in the United States, which currently has the best medical technology in the world and the highest medical costs, with much of the cost attributable to technology. Faced with the possibilities of maintaining our current health system, or going to other systems (Medical Break-throughs, Reregulation, or a National Health System), the United States needs a national health policy that cost-effectively raises health levels for all people. Technology can be the strong point of such a system. However, we must plan for and manage technology effectively. If managed care is unsuccessful in holding health inflation to below 10%, more radical solutions to the ethical issues involving the cost and availability of technology become increasingly necessary.


A co-culture model of the hippocampal neurogenic niche reveals differential effects of astrocytes, endothelial cells and pericytes on proliferation and differentiation of adult murine precursor cells.
The niche concept of stem cell biology proposes a functional unit between the precursor cells and their local microenvironment, to which several cell types might contribute by cell-cell contacts, extracellular matrix, and humoral factors. We here established three co-culture models (with cell types separated by membrane) for both adherent monolayers and neurospheres to address the potential influence of different niche cell types in the neurogenic zone of the adult hippocampus of mice. Astrocytes and endothelial cells enhanced precursor cell proliferation and neurosphere formation. Endothelial factors also led to a prolonged increase in proliferation after growth factor withdrawal, which otherwise induces differentiation. All niche cell types enhanced cell survival in monolayer cultures, endothelial cells also stimulated neuronal differentiation. A parallel trend elicited by astrocytes did not reach conventional statistical significance. Pericytes had variable effects here. We did not observe changes in differentiation in neurosphere co-cultures. In summary, our data indicate that in precursor cell culture protocols survival could be improved by adding as yet unknown factors physiologically contributed by astrocytes and endothelial cells. Our findings also underscore the complexity of the niche and the differential impact of factors from the different sources on distinct aspects of neuronal development. With the help of the models presented here, identification of these factors and their specific biological activity can now be initiated.


Tert-butylhydroquinone preserve testicular steroidogenesis and spermatogenesis in cisplatin-intoxicated rats by targeting oxidative stress, inflammation and apoptosis.
Cisplatin (Cis) is an effective chemotherapeutic intervention against many cancer types. However, the oxidative stress-related toxicities associated with cancer cell resistance-induced dose scaling has limited its long-term use. In the present study, we explored the benefits of the antioxidant, tert-butylhydroquinone (tBHQ; 50 mg/kg b.w./day, for 14 days) against Cis single dose injection (7 mg/kg b.w., i.p on Day 8), on testicular toxicity of male Wistar rats. Cis triggered testicular and epididymal oxidative stress, testicular inflammation (upregulated NF-κB, TNF-α and IL-1β mRNA levels, and downregulated IL-10 mRNA level), increased testicular apoptosis (increased Bax/Bcl2 and caspase-3 mRNA levels) and decreased testicular germ cells proliferation. Further, Cis decreased testicular steroidogenesis (decreased expression of StAR, CYP11A1, 3β-HSD and 17β-HSD mRNA and proteins) and decreased follicle stimulating hormone, luteinizing hormone and testosterone levels. Cis also decreased sperm count, motility, viability, normal morphology and Johnsen score. However, intervention with tBHQ significantly decreased oxidative stress by upregulating Nrf2 gene, suppressed inflammation, apoptosis and increased testicular germ cells proliferation. tBHQ also increased steroidogenesis and improved sperm parameters. Taken together, tBHQ improves steroidogenesis and spermatogenesis in Cis-intoxicated rats by improving antioxidant status, dampening inflammation and apoptosis, thus improving the proliferative capacity of spermatogenic cells.


On neighborhood Zagreb index of product graphs.
The properties and activities of chemicals are strongly related to their molecular structures. Topological indices defined on these molecular structures are capable to predict those properties and activities. In this article, a new topological index named as neighborhood Zagreb index (MN ) is presented. Here the chemical importance of the MN index is investigated and it is shown that the newly introduced index is useful in predicting physico-chemical properties with high accuracy compared to some well-established and often used indices. The isomer-discrimination ability of MN is also examined. To demonstrate how the computational formula of the novel index for chemical compounds is simple and convenient, the chemical structures of favipiravir and hydroxychloroquine are used. In addition, some explicit results for this index of different product graphs such as Cartesian, tensor and wreath product are derived. Some of these results are applied to obtain the MN index of some special structures.


Spontaneous resolution of lumbar pseudomeningocoele.
A case report of spontaneous resolution of a lumbar postdiscectomy pseudomeningocoele. To suggest the role of nonoperative treatment even in symptomatic pseudomeningocoeles. Withybush General Hospital, Haverfordwest, Pembrokeshire, South Wales, UK. A 65-year-old lady underwent L4/L5 discectomy for lumbar disc prolapse in 1998. As the patient did not have relief of symptoms, an MRI was taken at 1 month following the operation, which showed a residual disc at L4/L5 and a pseudomeningocoele communicating with the subarachnoid space. The patient could not undergo further treatment because of the untimely demise of the surgeon. Over the next 3 months, the symptoms began to improve and the patient was totally asymptomatic and remained so for 3 years. In 2001, she was seen for a recurring leg pain and back pain and an MRI was done, which showed complete disappearance of the pseudomeningocoele but with recurrent disc lesion. Although the current medical literature favours re-exploration and repair of the dural defect in symptomatic pseudomeningocoele, the authors are of the opinion that conservative treatment may have a role in the treatment of the above condition as illustrated by the above example.