Influence of microwave heating on fluoride, chloride, nitrate and sulfate concentrations in water.
This paper describes a study about the influence of microwave radiation using closed vessels on fluoride, chloride, nitrate and sulfate concentrations in aqueous media. The experiments were processed by heating water using PFA vessels and a microwave cavity oven, determining the anions by ion chromatography. The influence of the exposure time, the atmospheric composition, the kind of heating (water bath or microwave radiation) and the possible formation of hydrogen peroxide were investigated. The limits of quantification for fluoride, chloride, nitrate and sulfate were respectively of 0.17, 0.15, 0.55 and 0.57 μg L(-1), and precision, expressed as RSD, was <4% for all considered anions. The hydrogen peroxide was quantified by spectrophotometry, and the limit of quantification and precision were 24 μg L(-1) and <5% (n=10), respectively. The results demonstrate a significant increase in the anion concentration levels (between 63 and 89%) when microwave heating was used in comparison with heating by water bath. In addition, these changes observed can be mainly attributed to the species transfers, either between gaseous (atmospheric gases) and liquid (water) phases for nitrate, or between vessels walls and water for fluoride, chloride and sulfate. Additionally, hydrogen peroxide concentration higher than 45 μg L(-1) was determined when water was exposed to microwave radiation.


Specific surface area of polydispersions as a function of size distribution sharpness.
Knowledge of particulate system properties is very important in various industrial instances and the possibility of fast predicting the behavior of such systems is an important control tool. The specific surface area of simulated particulate systems was studied as a function of the sharpness parameter of the size distribution of the Gates-Gaudin-Schumann, Gaudin-Meloy and Rosin-Rammler equations. The results showed good statistical adherence, especially the Rosin-Rammler equation, in situations where it is the best descriptor of particle size distribution.


How to use leadership to spark innovation: Good nursing leadership when practising innovation is vital to quality patient care.
Innovation, creativity and leadership in nursing are essential to meet healthcare's constantly growing demands and to improve health and well-being. However, improvement initiatives require leadership and innovation support to make a positive impact ( Knol and van Linge 2009 ).


Endoscopic thyroidectomy and parathyroidectomy by the axillary approach. A preliminary report.
The use of endoscopic procedures leads to a reduction in the size of the surgical scar, making it more inconspicuous. In this paper, we evaluated the merits and limits of endoscopic neck surgery. Between August 1999 and July 2000, 102 patients underwent neck surgery in our department for thyroid or parathyroid disease. Twenty-eight of them were treated by the axillary. A 12-mm and two 5-mm trocars were inserted through the skin of the axilla. Carbon dioxide was then insufflated up to 4 mmHg, and the endoscopic surgery was performed. Endoscopic procedures were performed successfully in 26 cases (19 thyroidectomies and seven parathyroidectomies). There were two conversions to open procedures. The mean operating times for the thyroidectomies and parathyroidectomies were 212 and 171 min, respectively. No evidence of injury to the recurrent laryngeal nerve was observed in any of the cases. The postoperative cosmetic status of the patients was excellent. We believe that endoscopic thyroidectomy and parathyroidectomy by the axillary approach will find a role in the treatment of endocrine diseases in the neck.


Skin cancer preventive behavior and sun protection recommendations.
To summarize, in tabular form, the current literature and information available for skin cancer preventive behaviors and sun protection recommendations. Peer-reviewed literature, web sites of professional and federal organizations. The link between skin cancer and ultra-violet radiation (UVR) exposure is well documented. Primary skin cancer prevention must focus on proven ways to reduce the amount of UVR that reaches the skin, including avoiding UVR, covering up, wearing a wide-brimmed hat and sunglasses and use of sunscreen. Nurses play a key role in patient education and should use evidence-based resources to provide skin cancer prevention recommendations.


Management of severe hypospadias using Glassberg's modification of the Duckett repair.
To assess the effectiveness of Glassberg's modification of Duckett's technique in the surgical correction of severe hypospadias. The case notes of 24 boys who underwent hypospadias repair using this technique were reviewed, noting the severity of the lesion, the method of repair and the clinical outcome. One operation was required in 14 (58%) of patients; complications requiring further surgery occurred in 10 boys (42%). This technique allows a single-stage procedure when otherwise a two-stage procedure would be necessary.


Localization and release of 5-hydroxytryptamine thyrotrophin releasing hormone and substance P in rat ventral spinal cord.
1. The highest spinal cord levels of 5-hydroxytryptamine (5-HT) and thyrotrophin releasing hormone (TRH) were found in the ventral lumbar cord, in contrast to substance P which was found predominantly in the dorsal cord. 2. 5,6- and 5,7-dihydroxytryptamine, administered into the lateral ventricles reduced 5-HT in the dorsal and ventral spinal cord by up to 90%. 3. There was a parallel reduction in substance P and TRH in ventral spinal cord while methionine-enkephalin and somatostatin in ventral and dorsal cord increased. 4. Reserpine and tetrabenazine depleted 5-HT and partially depleted substance P and TRH in the ventral cord, but had no effect on either methionine-enkephalin or somatostatin. 5. The rates of loss and recovery, after reserpine and tetrabenazine, of 5-HT were different from those of the two peptides. 6. Endogenous 5-HT and TRH release from slices of lumbar cord was enhanced by high potassium. 7. p-Chloroamphetamine and fenfluramine increased 5-HT release but reduced or had no effect on TRH release. The effect of p-chloroamphetamine on TRH release was not dependent on either the presence of 5-HT or 5-HT receptor activity. 8. The results are discussed in terms of the possible co-existence, co-storage and release of 5-HT, substance P and TRH in descending bulbospinal neurones.


Multi-scale modeling of the follicle selection process in the ovary.
The biological meaning of follicular development is to free fertilizable oocytes at the time of ovulation. The ovulation rate results from an FSH-dependent follicle selection process. In this paper, we designed a multi-scale model of follicular development, where selection arises from the endocrine feedback between the ovaries and pituitary gland and appeals to control theory concepts. Each ovarian follicle is described through a 2D density function giving an age and maturity-structured description of its cell population. The control intervenes in the velocity, gain and loss terms of the conservation law ruling the changes in the density. The model accounts for the changes in the total cell number, growth fraction and global maturity of both ovulatory and degenerating follicles for various intensities of the selection rate. The different selection process outputs (mono- or poly-ovulation, anovulation) predicted by the model are consistent with physiological knowledge regarding vascularization, pituitary sensitivity to ovarian feedback and treatment with exogenous FSH.


Cabbage juice protect against lead-induced liver and kidney damage in male Wistar rat.
Liver and kidney has been implicated in Lead toxicity and this has been linked to oxidative damage. On the other hand, cabbage is one of the widely consumed vegetables with a plethora of health benefits. This present study investigated the protective effect of cabbage juice on lead-induced toxicity in male Wistar rats. Twenty male Wistar rats were randomly divided into four groups (n = 5) and were treated with distilled water (1 ml/100 g b.wt), Lead acetate (25 mg/kg b.wt), cabbage juice (1 ml/100 g b.wt) and Lead acetate plus cabbage juice respectively. All treatments were administered orally for 28 days. Following euthanasia, blood was collected and serum decanted for biochemical assay and liver and kidney tissues were harvested, prepared for antioxidant activity and histological study. Cabbage juice significantly attenuated Lead-induced liver and kidney dysfunction by lowering serum concentrations of urea, creatinine, ALP, AST and ALT. Antioxidants (SOD, CAT, GSH) were also upregulated in liver and kidney tissues. Cabbage juice restored the histoarchitectural changes caused by lead intoxication. Cabbage juice consumption protected the liver and kidney against lead-induced toxicity by enhancing in vivo anti-oxidant defense system.


[Sensitivity of different strains of the causative agent of plague to disinfectants].
Various strains of the plague microbe was found to have statistically significant differences in their sensitivity to phenol, formaldehyde and chloramine. These differences did not correlate with the origin, virulence and nutritional requirements of the plague strains. The sensitivity of the plague microbe to formaldehyde and phenol was found to be related to the permeability of its cell wall.


Gene activation and deactivation related changes in the three-dimensional structure of chromatin.
Chromatin in the interphase nucleus is dynamic, decondensing where genes are activated and condensing where they are silenced. Local chromatin remodelling to a more open structure during gene activation is followed by changes in nucleosome distribution through the action of the transcriptional machinery. This leads to chromatin expansion and looping out of whole genomic regions. Such chromatin loops can extend beyond the chromosome territory. As several studies point to the location of transcription sites inside chromosome territories as well as at their periphery, extraterritorial loops cannot simply be a mechanism for making transcribed genes accessible to the transcriptional machinery and must occur for other reasons. The level of decondensation within an activated region varies greatly and probably depends on the density of activated genes and the number of engaged RNA polymerases. Genes that are silenced during development form a more closed chromatin structure. Specific histone modifications are correlated with gene activation and silencing, and silenced genes may become associated with heterochromatin protein 1 homologues or with polycomb group complexes. Several levels of chromatin packaging are found in the nucleus relating to the different functions of and performed by active genes; euchromatic and heterochromatic regions and the models explaining higher-order chromatin structure are still disputed.


Transferrin response in normal and iron-deficient mice heterozygotic for hypotransferrinemia; effects on iron and manganese accumulation.
Hypotransferrinemia is a genetic defect in mice resulting < 1% of normal plasma transferrin (Tf) concentrations; heterozygotes for this mutation (+/hpx) have low circulating Tf concentrations. These mice provide a unique opportunity to examine the developmental pattern and response of Tf to iron-deficient diets, and furthermore, to address the controversial role of Tf in Mn transport. Twenty-three weanling +/hpx mice and forty-five wild-type BALB/cJ mice were either killed at weaning or fed diets containing either 13 or 72 mg kg-1 Fe, and killed after four or eight weeks. Plasma Tf concentrations were lower in +/hpx mice, plasma Tf nearly doubled and liver Tf was only 50% of normal in response to iron deficiency. Brain iron concentration did not correlate significantly with either plasma Tf or TIBC. However, iron accumulation into brain continued with iron deficiency whereas most other organs had less iron. These results imply that either there is a selected targeting of iron to the brain by plasma Tf or there is an alternative iron delivery system to the brain. Furthermore, we observed no differences in tissue distribution of 54Mn despite the differences in circulating Tf concentrations and body iron stores; this suggests that there are non-Tf dependent mechanisms for Mn transport.


Eye drop instillation technique in patients with glaucoma.
To evaluate the technique of eye drop instillation in patients with glaucoma and assess factors associated with a good technique. A cross-sectional observational study of 85 participants using self-administered topical medication for glaucoma or ocular hypertension. Patients were asked to demonstrate how they normally instil eye drops using a 5-ml bottle of sterile artificial tear solution. The procedure was recorded and assessed by two masked graders. Whether the patient had been previously shown how to instil drops, the number of eye medications used, and self-perceived difficulty of using drops were also recorded. Univariable logistic regression was performed to relate each variable to drop technique and variables with P<0.2 were included in a multivariable logistic regression analysis. 54.1% (46/85) of patients had a poor drop technique, 11.8% (10/85) missed the eye, 15.3% (13/85) touched the tip of the bottle to the bulbar conjunctiva or cornea, and 27.1% (23/85) touched the eyelid or lashes with the bottle tip. 81.2% (69/85) could not recall being shown how to instil eye drops. In the multivariable model, previous instruction regarding drop instillation technique was significantly associated with good technique (adjusted OR=8.17, 95% CI 2.02-33.05, P=0.003) and increasing age was associated with poor technique (adjusted OR=0.95, 95% CI 0.91-0.99, P=0.017). Education relating to eye drop instillation technique is significantly associated with a patient's ability to instil drops correctly. The assessment of a patient's ability to instil eye drops correctly should be a routine part of the glaucoma examination.


Early-life carbamate exposure and intelligence quotient of seven-year-old children.
Early-life carbamate exposure during developmental period has been linked with adverse health effects and attracted attention. Three hundred and three children at age of seven were included in the current study. Urinary carbofuranphenol concentrations were measured using gas chromatography-tandem mass spectrometry. Verbal, performance and full-scale intelligence quotients (IQV, IQP, and IQFS) were assessed using Wechsler Intelligence Scale for Children-Chinese Revised. Generalized linear models were used to explore the associations between carbofuranphenol levels and IQs. Generalized estimating equations were used to explore long-term health effect and sensitive time window. Carbofuranphenol was detected in 96.6% of the seven-year-old urinary samples, the geometric mean, median, and inter quartile range of the carbofuranphenol concentrations were 0.67 μg/L, 0.30 μg/L, and 0.09-3.72 μg/L, respectively, which were similar with the level of three-year-old children from the SMBCS cohort. Seven-year-old carbofuranphenol level was negatively associated with IQP [β = -0.044; 95% confidence interval (CI): -0.087, -0.001; p = 0.045]. Three-year-old carbofuranphenol level was negatively associated with IQP (β = -0.100; 95% CI: -0.186, -0.014; p = 0.022) and IQFS (β = -0.087; 95% CI: -0.173, -0.001; p = 0.047). Carbamate exposure of maternal and children at both three and seven years old had negative associations with IQP (β = -0.089; 95% CI: -0.171, -0.007; p = 0.034), and IQFS (β = -0.064; 95% CI: -0.127, -0.000; p = 0.049) of children at age of seven. Results of the present study verify that children in an agricultural region of China were widely exposed to carbamate pesticides. Carbamate exposure in utero and at three and seven years may adversely impact children's neurodevelopment.


Guidelines for Potassium Channel Blocker Use.
This article summarizes recommendations for the clinical use of antiarrhythmic drugs for the treatment and prevention of atrial and ventricular arrhythmias based on current guideline and consensus documents. The choice of antiarrhythmic drug is based on the efficacy and safety profile and influenced by the presence or absence of structural heart disease. Because of its adverse side-effect profile, amiodarone is recommended for the management of atrial fibrillation only when other agents have failed or are contraindicated. For treatment of symptomatic ventricular arrhythmias in the setting of structural heart disease, amiodarone is generally the preferred agent.


Inhibition of β-ARK1 Ameliorates Morphine-induced Tolerance and Hyperalgesia Via Modulating the Activity of Spinal NMDA Receptors.
Our previous study has proposed that increased presynaptic NMDARs activities play pivotal roles in the development of opioid tolerance and hyperalgesia, and blocking spinal NMDARs attenuates chronic morphine-induced synaptic plasticity and behavior. However, the cellular signaling mechanisms remain to be investigated. The aim of this research was to address the role of β-ARK1 in opioid analgesia. Opioid tolerance and hyperalgesia was induced by daily systemic morphine injections in rats for eight consecutive days. Whole-cell voltage-clamp was employed to record spontaneous EPSCs and evoked-AMPA-EPSCs in dorsal lamina II neurons. Strikingly, brief application of 1 μM morphine decreased the percentage of inhibition and was followed by a large LTP in the amplitude of monosynaptic evoked-AMPA-EPSCs in opioid-tolerant rats. There was no effect on these responses by postsynaptic dialysis of the G-protein inhibitor. Incubation with the NMDAR blocker AP5 potentiated morphine-induced inhibition and attenuated washout potentiation after cessation of morphine in the amplitude of AMPA-EPSCs. Incubation with β-ARK1 inhibitor had the same effect on these responses. Incubation with β-ARK1 inhibitor diminished NMDAR hyperfunction-increased glutamatergic synaptic transmission and enhanced the analgesic effect of morphine. Intrathecal injections of β-ARK1 inhibitor significantly attenuated opioid-induced hyperalgesia and tolerance. β-ARK1 plays a pivotal role in the development and maintenance of opioid tolerance and hyperalgesia. Blockade of β-ARK1 activation ameliorates morphine tolerance and hyperalgesia via regulating the activity of spinal NMDARs. These findings provide electrophysiological evidence and useful insights regarding the mechanistic action of β-ARK1 inhibitor as a potential anti-hyperalgesic agent to improve the efficacy of opioid therapies.


Health system resource use among populations with complex social and behavioral needs in an urban, safety-net health system.
Costs incurred by health systems when caring for populations with social or behavioral complexity are poorly understood. We compared the frequency and costs of unreimbursed care among individuals with complexity factors (homelessness, a history of county jail incarceration, and/or substance use disorder or mental illness [SUD/MI]). We conducted a cross-sectional analysis using electronic health record data for adults aged 18 and older between January 1, 2016 and December 31, 2017 from a Midwestern safety-net health system. Zero-inflated negative binomial regression models were used to assess risk-adjusted associations between complexity factors and care coordination encounters, missed appointments, and excess inpatient days. Our sample included 154,719 unique patients; 6.8% were identified as homeless, 7.8% had a history of county jail incarceration, and 20.6% had SUD/MI. Individuals with complexity factors were more likely to be African-American, Native American, or covered by Medicaid. In adjusted models, homelessness and SUD/MI were significantly associated with care coordination encounters (RR 1.8 [95% CI,1.7-2.0]; RR 1.9 [95% CI,1.8-2.0]), missed appointments (RR 1.5 [95% CI,1.4-1.6]; RR 1.7 [95% CI,1.7-1.8]), and excess inpatient days (RR 1.5 [95% CI,1.3-1.8]; RR 2.8 [95% CI,2.5-3.1]). County jail incarceration was associated with a significant increase in missed appointments. In 2017, SUD/MI accounted for 81.8% ($7,773,000/$9,502,000) of excess costs among those with social or behavioral complexity. Social and behavioral complexity are independently associated with high levels of unreimbursed health system resource use. Future payment models should account for the health system resources required to care for populations with complex social and behavioral needs. IV.


Robotic-assisted laparoscopic prostatectomy: An update on functional and oncologic outcomes, techniques, and advancements in technology.
The robotic platform has revolutionized the management of prostate cancer over the last 15 years. Several techniques have been developed to improve functional and oncologic outcomes, including meticulous apical and posterior dissection, nerve sparing techniques, bladder neck and urethral length sparing, and anastomotic reconstruction. Future developments involving novel single-site, robotic technology will undoubtedly further the field of minimally invasive urology. These topics are reviewed within this article.


Diabetes in transgenic mice resulting from over-expression of class I histocompatibility molecules in pancreatic beta cells.
A class I histocompatibility gene, H-2Kb, linked to the rat insulin promoter, is overexpressed in the pancreatic beta cells of transgenic mice. The mice, whether syngeneic or allogeneic to the transgene, develop insulin dependent diabetes without detectable T cell infiltration, suggesting a direct, non-immune role for the transgenic class I molecules in the disease process.


Coerced coordination, not cooperation.
Norenzayan et al. propose that Big God (BG) religions are large-group cooperative enterprises that promote internal harmony and higher fertility, resulting in "mutually beneficial exchanges" for those involved. We examine the possible distributions of costs and benefits within BG religions and propose that they are, instead, successful coordinating mechanisms that rely on intragroup competition and exploitation between the classes and sexes.


Separate induction of the two isozymes of cytochrome P-450(11) beta in rat adrenal zona glomerulosa cells.
In the rat adrenal cortex, two isozymes of cytochrome P-450(11) beta (CYP11B1 and CYP11B2) have been identified. They are encoded by two different genes with a homology much higher in their coding than in their 5'-flanking regions. CYP11B1 is found in all the zones of the gland and catalyzes a single hydroxylation of deoxycorticosterone (DOC) in the 11 beta- or the 18-position. CYP11B2 is produced exclusively in the zona glomerulosa and catalyzes all three reactions involved in the conversion of DOC to aldosterone. In vivo and in vitro, the expression of the genes encoding CYP11B1 and CYP11B2 is regulated by two separate control systems which appear to operate both independently and interdependently. In vivo zona glomerulosa expression of CYP11B1 was enhanced by ACTH treatment or potassium depletion and was lowered by potassium repletion. CYP11B2 expression disappeared upon potassium depletion or ACTH treatment, but reappeared during potassium repletion. In vitro, only CYP11B1 activity was detectable and responsive to ACTH treatment in zona glomerulosa cells cultured at a potassium concentration of 6.4 mmol/l. Aldosterone biosynthetic activity and mRNA encoding CYP11B2 could be detected only after at least 1 day of exposure to a high extracellular potassium concentration (> or = 12 mmol/l).


The influence of somatic cells of milk on the growth of staphylococci and streptococci in whey and serum.
Staphylococci differ from streptococci in susceptibility to somatic cells of milk which inhibit the growth of bacteria.


Site-specific Chemotherapy Based on Predicted Primary Site by Pathological Profile for Carcinoma of Unknown Primary Site.
Although platinum-based combination chemotherapies are commonly used for unfavourable subsets of cancer of unknown primary (CUP), the prognosis remains poor. Several studies have suggested that gene expression profiling or immunohistochemistry was useful for the prediction of primary sites in CUP, and site-specific therapy based on predicted primary sites might improve overall outcomes. In Japan, to identify primary sites, immunohistochemical tests were commonly used for CUP in clinical practice. However, it is unclear whether site-specific therapy based on predicted primary sites by pathological examination contributes survival benefit for unfavourable CUP subsets. In this study, 122 patients with unfavourable subsets of CUP were retrospectively reviewed. Ninety patients assigned to cohort A after July 2012 had received chemotherapy according to predicted primary sites; 32 patients assigned to cohort B before June 2012 had received platinum-based empiric chemotherapy. In cohort A, 56 patients (62.2%) with predicted primary sites by pathological examination received site-specific therapy; 34 patients (37.8%) with unpredictable primary sites received platinum-based empiric chemotherapy, the same as cohort B. The median overall survival was 20.3 months in patients with predictable primary sites in cohort A and 10.7 months in those of cohort B, with a significant difference between these cohorts (P = 0.03, adjusted hazard ratio = 0.57, 95% confidence interval 0.34-0.94). Site-specific therapy based on predicted primary sites by pathological examination could improve prognosis in patients with an unfavourable subset of CUP.


Purification of follitropin receptor from bovine calf testes.
Follitropin (FSH) receptors were solubilized from pure light membranes of bovine calf testis, using an optimum detergent to protein ratio of 0.01. The soluble FSH receptor fraction was gel filtered through Sepharose 6B to isolate an active fraction (6B-Fr-1) which behaved as a complex of FSH receptor and Gs protein. The 6B-Fr-1 was concentrated by ultrafiltration and further purified by sequential Sepharose 4B gel filtration, DEAE-cellulose chromatography (to separate the receptor from Gs protein), and wheat germ lectin affinity chromatography. The purified receptor had an FSH-binding capacity of approximately 3.47 nmol/mg of protein with a Kd of 1.9 X 10(-10) M. Yield was 526 micrograms/11.5 kg tested. Radioiodinated, as well as unlabeled purified FSH receptor, migrated on sodium dodecyl sulfate-polyacrylamide gels as a single major band of Mr approximately 240,000. This band was not affected by 8 M urea treatment prior to analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, but treatment with dithiothreitol induced the loss of the 240-kDa band, with appearance of an Mr approximately 60,000 band. The availability of highly purified, stable FSH receptor should allow direct studies on its structure-function relationships.


Successful hydraulic strategies to start up OLAND sequencing batch reactors at lab scale.
Oxygen-limited autotrophic nitrification/denitrification (OLAND) is a one-stage combination of partial nitritation and anammox, which can have a challenging process start-up. In this study, start-up strategies were tested for sequencing batch reactors (SBR), varying hydraulic parameters, i.e. volumetric exchange ratio (VER) and feeding regime, and salinity. Two sequential tests with two parallel SBR were performed, and stable removal rates > 0.4 g N l(-1) day(-1) with minimal nitrite and nitrate accumulation were considered a successful start-up. SBR A and B were operated at 50% VER with 3 g NaCl l(-1) in the influent, and the influent was fed over 8% and 82% of the cycle time respectively. SBR B started up in 24 days, but SBR A achieved no start-up in 39 days. SBR C and D were fed over 65% of the cycle time at 25% VER, and salt was added only to the influent of SBR D (5 g NaCl l(-1)). Start-up of both SBR C and D was successful in 9 and 32 days respectively. Reactor D developed a higher proportion of small aggregates (0.10-0.25 mm), with a high nitritation to anammox rate ratio, likely the cause of the observed nitrite accumulation. The latter was overcome by temporarily including an anoxic period at the end of the reaction phase. All systems achieved granulation and similar biomass-specific nitrogen removal rates (141-220 mg N g(-1) VSS day(-1)). FISH revealed a close juxtapositioning of aerobic and anoxic ammonium-oxidizing bacteria (AerAOB and AnAOB), also in small aggregates. DGGE showed that AerAOB communities had a lower evenness than Planctomycetes communities. A higher richness of the latter seemed to be correlated with better reactor performance. Overall, the fast start-up of SBR B, C and D suggests that stable hydraulic conditions are beneficial for OLAND while increased salinity at the tested levels is not needed for good reactor performance.


Vegetation change in large clearings: Patterns in the Chilean matorral.
Previous studies have shown that in Chile the so called mature matorral can have the form of either a continuous matrix of shrubs (wet sites) or of multispecific clumps of shrubs (dry sites). After clearing, sites are known to be initially covered by annuals and then byBaccharis spp. orAcacia caven shrubs. Further vegetation changes are still not documented. In the first part of this contribution we show evidence indicating that the "seed rain" of plants dispersed by birds is important only around bird perches and that in general "seed shadows" of mature matorral shrubs are small. These results suggest that late recolonization of cleared areas occurs by a slow diffusion process in which the presence of perching sites for birds plays a significant role. Then we exhibit results regarding the importance of seasonal droughts and European rabbits in explaining transitions between the various types of plant cover. Here we conclude that nursing by older shrubs and not by rocks or fallen branches, is a requirement to insure the survival of seedlings belonging to mature matorral shrubs. Nurses are important regarding both summer desiccation and herbivory. These nurse effects seem to be more important at dry sites where rabbits are also more numerous, than at wet sites where conditions seem somewhat milder and vegetation change could be faster. In the last part we discuss a scheme of vegetation change that incorporates these processes and explains the relation between them, the vegetation types and the recolonization of wet and dry areas. Finally, a brief mention is made to the difference between these processes and the comparable ones in the California chaparral.


Inhibition of insulin release in vitro mediated by mononuclear cells from diabetic patients treated with cyclosporin A or placebo.
Anti-beta-cell-specific cell-mediated immunity was studied over a 12-mo period in 65 recently diagnosed diabetic patients randomly receiving either cyclosporin or placebo. Anti-beta-cell cellular immunity was assessed by an in vitro test based on the inhibition of insulin release from cultured rat islet cells by patients' mononuclear cells. This beta-cell-suppressive effect disappeared in cyclosporin A-treated patients within 1 mo and did not reappear during 12 mo of follow-up. Conversely, the suppressive effect persisted unchanged in placebo-treated patients during 12 mo of follow-up. These changes were predictive neither of cyclosporin A-induced remission nor of relapses. Results of the insulin-release inhibition test were not correlated to islet cell autoantibodies or HLA phenotype.


Restructuring of Hydration Shell Water due to Solvent-Shared Ion Pairing (SSIP): A Case Study of Aqueous MgCl2 and LaCl3 Solutions.
Hydration of ions plays a crucial role in interionic interactions and associated processes in aqueous media, but selective probing of the hydration shell water is nontrivial. Here, we introduce Raman difference with simultaneous curve fitting (RD-SCF) analysis to extract the OH-stretch spectrum of hydration shell water, not only for the fully hydrated ions (Mg2+, La3+, and Cl-) but also for the ion pairs. RD-SCF analyses of diluted MgCl2 (0.18 M) and LaCl3 (0.12 M) solutions relative to aqueous NaCl of equivalent Cl- concentrations provide the OH-stretch spectra of water in the hydration shells of fully hydrated Mg2+ and La3+ cations relative to that of Na+. Integrated intensities of the hydration shell spectra of Mg2+ and La3+ ions increase linearly with the salt concentration (up to 2.0 M MgCl2 and 1.3 M LaCl3), which suggests no contact ion pair (CIP) formation in the MgCl2 and LaCl3 solutions. Nevertheless, the band shapes of the cation hydration shell spectra show a growing signature of Cl--associated water with the rising salt concentration, which is a manifestation of the formation of a solvent-shared ion pair (SSIP). The OH-stretch spectrum of the shared/intervening water in the SSIP, retrieved by second-round RD-SCF analysis (2RD-SCF), shows that the average H-bonding of the shared water is weaker than that of the hydration water of the fully hydrated cation (Mg2+ or La3+) but stronger than that of the anion (Cl-). The shared water displays an overall second-order dependence on the concentration of the interacting ions, unveiling 1:1 stoichiometry of the SSIP formed between Mg2+ and Cl- as well as La3+ and Cl-.


Development of retinal bullae in dogs with progressive retinal atrophy.
To report the development of focal bullous retinal detachments (bullae) in dogs with different forms of progressive retinal atrophy (PRA). Dogs with three distinct forms of PRA (PRA-affected Whippets, German Spitzes and CNGB1-mutant Papillon crosses) were examined by indirect ophthalmoscopy and spectral domain optical coherence tomography (SD-OCT). Retinal bullae were monitored over time. One CNGB1-mutant dog was treated with gene augmentation therapy. The canine BEST1 gene coding region and flanking intronic sequence was sequenced in at least one affected dog of each breed. Multiple focal bullous retinal detachments (bullae) were identified in PRA-affected dogs of all three types. They developed in 4 of 5 PRA-affected Whippets, 3 of 8 PRA-affected Germans Spitzes and 15 of 20 CNGB1-mutant dogs. The bullae appeared prior to marked retinal degeneration and became less apparent as retinal degeneration progressed. Bullae were not seen in any heterozygous animals of any of the types of PRA. Screening of the coding region and flanking intronic regions of the canine BEST1 gene failed to reveal any associated pathogenic variants. Retinal gene augmentation therapy in one of the CNGB1-mutant dogs appeared to prevent formation of bullae. Retinal bullae were identified in dogs with three distinct forms of progressive retinal atrophy. The lesions develop prior to retinal thinning. This clinical change should be monitored for in dogs with PRA.


Effects of light on the circadian rhythm of diabetic rats under restricted feeding.
The aim of this study was to investigate whether the entrainment of light cue is affected or not in diabetic animals. We found that the individual light/dark (LD) reversal showed a tissue- and gene-specific effect on the circadian phases of peripheral clock genes, which was generally similar between the control and diabetic rats. In the liver and heart, the peak phases of examined clock genes (Bmal1, Rev-erbα, Per1, and Per2) were slightly shifted by 0∼4 h in the liver and heart of control and diabetic rats. However, we found that the peak phases of these clock genes were greatly shifted by 8∼12 h after the LD reversal for 7 days in the pineal gland of both control and diabetic rats. However, the activity rhythm was greatly different between two groups. After the individual LD reversal, the activity rhythm was completely shifted in the control rats but retained in the diabetic rats. These observations suggested that the behavioral rhythm of diabetic rats may be uncoupled from the master clock after the individual LD reversal. Moreover, we also found that the serum glucose levels of diabetic rats kept equally high throughout the whole day without any shift of peak phase after the individual reversal of LD cycle. While the serum glucose levels of control rats were tightly controlled during the normal and LD reversal conditions. Thus, the impaired insulin secretion induced uncontrollable serum glucose level may result in uncoupled activity rhythm in the diabetic rats after the individual LD reversal.


Role of thrombolysis and thrombin in patients with acute coronary occlusion during percutaneous transluminal coronary angioplasty.
In a series of 447 patients with single vessel angioplasty, 27 (6.0%) had acute thrombotic occlusion early after the procedure. They were treated with combined intracoronary (20 mg)/intravenous (50 mg) thrombolysis with recombinant tissue-type plasminogen activator (rt-PA) and repeat mild balloon inflations. Reopening of the vessel was achieved in 22 patients (81.5%). Follow-up coronary angiography 24 to 36 h later revealed reocclusion in 12 patients (54.5%). Thrombin levels measured as thrombin-antithrombin-III complex in patients with successful thrombolysis and persistent patency decreased from 8.5 +/- 11.4 micrograms/liter at baseline to 3.5 +/- 1.4 micrograms/liter 120 min after the start of thrombolysis; these levels increased from 9.4 +/- 15.0 micrograms/liter at baseline to 15.7 +/- 13.5 micrograms/liter 120 min after the start of thrombolysis in the patients with unsuccessful thrombolysis or early reocclusion (p less than 0.05). When a borderline value for thrombin-antithrombin-III complex level of 6 micrograms/liter was selected to separate the two groups of patients, patients with an unfavorable clinical course were identified 120 min after the start of thrombolysis by levels greater than 6 micrograms/liter (sensitivity 100%, specificity 92.8%). Thus, after abrupt thrombotic vessel closure during coronary angioplasty, the short-term results of thrombolysis seem to be governed by the release of thrombin. In two thirds of patients, however, the thrombin release cannot be suppressed by concomitant aspirin and heparin therapy. Even after successful reopening of the vessel these patients should therefore undergo immediate aortocoronary bypass grafting.


Comparison of bone marrow component removal from processed femoral head bone from living and deceased donors: presence of geodes in living donor bone can prevent maximum removal of marrow components.
NHS Blood and Transplant Tissue and Eye Services banks and issues, cut, shaped and washed bone from deceased donors. The bone is cut/shaped prior to washing and then processed to remove up to 99.9% of blood, bone marrow and associated cells. The processed bone is then sterilised by gamma irradiation with or without a freeze-drying step. Removal of donor blood and bone marrow has been reported to aid incorporation of allograft bone without affecting the biomechanical properties of the bone. However, cut and shaped bone is not suitable for some orthopaedic procedures and some orthopaedic surgeons do not wish to use irradiated bone. Therefore, Tissue and Eye Services have also developed a method for washing intact femoral head bone, from living and deceased donors. We have observed that processing of intact femoral head bone does not always result in removal of 99% (or above) of marrow components and can be as low as 93% removal. We have examined washed femoral head bone and found the presence of internal fluid-filled cysts within subchondral cancellous bone in bone from living donors. The cysts have been identified as geodes and we suggest that these geodes may be responsible for the reduction in bone marrow component removal in living donor bone during processing.


Treatment experience, burden, and unmet needs (TRIBUNE) in multiple sclerosis: the costs and utilities of MS patients in Canada.
Multiple sclerosis (MS) is the most common neurological disease among young adults in Canada, but few studies to date have measured the burden imposed by MS on Canadian society. To estimate the costs and quality of life of MS patients in Canada, while focusing on the burden of relapses and increasing disease severity. MS patients in Canada (N=241) completed a web-based questionnaire which captured information on demographics, disease characteristics, severity (Expanded Disability Status Scale [EDSS]), comorbidities, relapses, as well as resource consumption and quality of life associated with MS. Most patients (74%) reported treatment with disease modifying therapies (DMTs). 54% of patients with the relapsing-remitting form of the disease with an EDSS score ≤ 5 had experienced at least one relapse in the past year. The mean cost per patient per year increased with worsening disability, and was estimated at Can $30,836 for patients with mild disability (EDSS score 0-3), Can $46,622 for patients with moderate disability (EDSS 4-6.5), and Can $77,981 for patients with severe disability due to MS (EDSS score 7-9). The excess costs of relapsing-remitting MS patients with EDSS score ≤ 5 that could be attributable to relapse(s) were estimated at Can $10,512. More severe disease and experiencing a relapse were also associated with poorer quality of life of MS patients. Costs of MS patients are higher today than shown in previous studies. Disease progression and relapses are associated with increased economic and quality of life burden. Effective treatment that reduces relapse frequency and prevents progression could impact both costs and quality of life and may help to reduce the societal burden of MS.


A review of transgenic animal techniques and their applications.
Nowadays, breakthroughs in molecular biology are happening at an unprecedented rate. One of them is the ability to engineer transgenic animals. A transgenic animal is one whose genome has been changed to carry genes from another species or to use techniques for animal genome editing for specific traits. Animal features can be changed by purposefully altering the gene (or genes). A mouse was the first successful transgenic animal. Then pigs, sheep, cattle, and rabbits came a few years later. The foreign-interested genes that will be used in animal transgenic techniques are prepared using a variety of methods. The produced gene of interest is placed into a variety of vectors, including yeast artificial chromosomes, bacterial plasmids, and cosmids. Several techniques, including heat shock, electroporation, viruses, the gene gun, microinjection, and liposomes, are used to deliver the created vector, which includes the interesting gene, into the host cell. Transgenesis can be carried out in the gonads, sperm, fertilized eggs, and embryos through DNA microinjection, retroviruses, stem cells, and cloning. The most effective transgenic marker at the moment is fluorescent protein. Although transgenesis raises a number of ethical concerns, this review concentrates on the fundamentals of animal transgenesis and its usage in industry, medicine, and agriculture. Transgenesis success is confirmed by the integration of an antibiotic resistance gene, western and southern blots, PCR, and ELISA. If technology solves social and ethical problems, it will be the most promising in the future.


A possible maternal-effect mutant of Xenopus laevis I. Cytological and biochemical analyses of the unfertilized eggs and embryos.
In an effort to define the cause of the developmental arrest of offspring from a certain Xenopus female (designated as No. 65), we have examined eggs and embryos from the female both cytologically and biochemically. Light and electron microscopic observations revealed that all of the blastomeres from embryos of female No. 65 had multiple small spherical nuclei, while wild-type counterparts had a single lobulated nucleus. Two-dimensional gel electrophoretic analyses demonstrated that a major acidic protein, whose molecular weight was 38 kDa, was always found in samples from wild-type unfertilized eggs and embryos, but was not recognizable in those from female No. 65. These facts, coupled with the death of the offspring at gastrulation, suggest the possibility that female No. 65 carries a mutation of the ova-deficient type.


Reticulated platelets predict platelet count recovery following chemotherapy.
A laboratory measure that predicted the timing of platelet recovery after chemotherapy could guide prophylactic platelet transfusion. Reticulated platelets (RPs) are the youngest circulating platelets; an increased percentage of RPs is diagnostic of increased marrow platelet production, such as seen with idiopathic thrombocytopenic purpura, whereas a low percentage of RPs with thrombocytopenia indicates marrow suppression. This study examined whether the percentage of RPs, in combination with a newly devised measurement of "stress thrombopoiesis," the RP maturation index (RP-MI), could predict platelet count recovery following chemotherapy-induced thrombocytopenia. Platelet count nadirs were retrospectively determined in 35 chemotherapy-induced thrombocytopenia patients; percentage of RPs and RP-MI values were assayed at the early nadir (no imminent platelet recovery) and the late nadir (imminent platelet recovery). The latter was defined by a platelet count increase of 20 x 10(9) per L or more in the subsequent 48 hours without platelet transfusion. Early in the nadir (when platelet recovery did not occur in the subsequent 48 h after sampling), a low RP-MI and a low percentage of RPs were found in 29 of 35 patients. Late in the nadir, when recovery was imminent, 27 of 30 evaluable patients had elevated percentages of RPs or RP-MI values; the mean time from sampling to an increase of 20 x 10(9) per L or more was 42 hours. The positive and negative predictive values of this assay were 82 and 91 percent, respectively. Furthermore, when thrombocytopenia was severe (platelet count < or = 20 x 10(9)/L), an elevated RP-MI and/or percentage of RPs correctly predicted imminent platelet count recovery in five of five patients. This noninvasive, rapid, whole-blood assay of stress thrombopoiesis provides reproducible indices for timing platelet recovery following chemotherapy and the potential to optimize the use of prophylactic platelet transfusions in chemotherapy patients.


Brief Report: Autism Spectrum Disorder and Substance Use Disorder: A Review and Case Study.
There is limited literature available on the comorbidity between autism spectrum disorder (ASD) and substance use disorder (SUD). This paper reviews existing literature and exemplifies the challenges of treating this population with a case report of an adult male with ASD and DSM-5 alcohol use disorder. This review and case study seeks to illustrate risk factors which predispose individuals with ASD to developing SUD and discuss the obstacles to and modifications of evidence-based treatments for SUD. A review of the therapeutic interventions implemented in the treatment of this young male are described to highlight potential recommendations for the general management of SUD in those with ASD.


Electrical characteristics of the mammalian distal tubule: Comparison of Ling-Gerard and macroelectrodes.
Studies were performed to 1) systematically compare Ling-Gerard microelectrodes and electrodes with large tips (3 to 5 mu O.D.) in the measurement of the transepithelial potential difference (PD) in the mammalian distal tubule and 2) to examine the sign and magnitude of the transepithelial PD along the length of the distal tubule. Recordings made with the tips of both types of electrodes placed together in the same tubule segment demonstrated no difference in transepithelial PD. Rapid influx of tubular fluid into the macroelectrode, however, was found to depolarize the tubular membrane, as recorded by both types of electrodes simultaneously. Technical critera were therefore established to prevent rapid influx of fluid and efflux of potassium chloride, filling the electrode, in the use of exploring electrodes with large tips. The sign of the transepithelial PD in early distal tubule was found to be negative and averaged -17.7 +/- 9.4 (mean +/- SEM) in Sprague-Dawley rats and approximately -12 mV in Wistar-Munich rats. The site of puncture was identified by dye transit time rate, microdissection, and cell morphology. The transepithelial PD increased along the length of the distal tubule and averaged -41.9 +/- 8.5 in the last portion accessible to examination.


Photodynamic ion sensor systems with spiropyran: photoactivated acidity changes in plasticized poly(vinyl chloride).
We aim to introduce photoactivated optical ion sensors based on a triggered ion exchange process as novel dynamic tools. The quantification of the acidity change upon photoactivation of spiropyran within an organic membrane phase during photoexcitation is described here for the first time, suggesting a large pK(a) change of more than 6 orders of magnitude.


Genetic diversity of bottlenose dolphin (Tursiops sp.) populations in the western North Pacific and the conservation implications.
The evolutionary processes that shape patterns of diversity in highly mobile marine species are poorly understood, but important towards transferable inference on their effective conservation. In this study, bottlenose dolphins (Tursiops sp.) are studied to address this broader question. They exhibit remarkable geographical variation for morphology, life history, and genetic diversity, and this high level of variation has made the taxonomy of the genus controversial. A significant population structure has been reported for the most widely distributed species, the common bottlenose dolphin (T. truncatus), in almost all ocean basins, though no data have been available for the western North Pacific Ocean (WNP). The genetic diversity of bottlenose dolphins in the WNP was investigated based on 20 microsatellite and one mitochondrial DNA markers for samples collected from Taiwanese, Japanese, and Philippine waters (9°-39°N, 120°-140°E) during 1986-2012. The results indicated that there are at least four genetically differentiated populations of common bottlenose dolphins in the western and central North Pacific Ocean. The pattern of differentiation appears to correspond to habitat types, resembling results seen in other populations of the same species. Our analyses also showed that there was no evident gene flow between the two "sister species", the common bottlenose dolphins, and the Indo-Pacific bottlenose dolphins (T. aduncus) occurring sympatrically in our study region.


Energy metabolism in the brain, adaptation towards starvation.
It is hypothesized that the brain's incapacity to utilize energy sources other than glucose and ketone bodies, constitutes a mechanism of protecting it from self degradation, at the expense of the rest of the body, during periods of starvation. This protection is based upon the brain's inability to catabolize substances of which it is built, for energy production.


Carbamazepine-induced hypersensitivity syndrome associated with transient hypogammaglobulinaemia and reactivation of human herpesvirus 6 infection demonstrated by real-time quantitative polymerase chain reaction.
Drug-induced hypersensitivity syndrome (HS) is a rare but severe disease with multiorgan failure. Many different precipitating factors have been reported, but the pathophysiology of HS remains unknown. However, the association of the human herpesvirus (HHV) family, particularly of HHV-6, has recently been reported in patients with HS. We report a 14-year-old boy who was diagnosed as having carbamazepine-induced HS based on the clinical course, laboratory data and results of drug-induced lymphocyte stimulation tests. In addition, the reactivation of HHV-6 was demonstrated by real-time quantitative polymerase chain reaction and by significantly increased levels of the specific antibody in his paired sera. Furthermore, transient hypogammaglobulinaemia was detected in the early stage of the disease. In addition, serum levels of interferon-gamma, interleukin (IL)-6, IL-5 and eosinophil cationic protein, which were increased on admission, decreased dramatically after steroid therapy. This is the first report of carbamazepine-induced HS associated with reactivation of HHV-6, transient hypogammaglobulinaemia, increased serum levels of inflammatory cytokines and activated eosinophils. This case might contribute to the understanding of the pathophysiology of HS.


Long-term outcomes of catheter ablation of atrial fibrillation in dilated cardiomyopathy.
The long-term outcomes, efficacy and safety of catheter ablation in atrial fibrillation (AF) patients with dilated cardiomyopathy (DCM) have not been reported previously. Forty nine patients with AF (59% longstanding persistent AF, LSP-AF) and DCM were enrolled. Circumferential pulmonary vein ablation (CPVA, paroxysmal AF), bidirectional block of lines and disappearance of complex fractionated atrial electrograms (CFAEs, persistent and LSP-AF) were the endpoints of the index and repeat procedures. Cumulative success rate reached 49% (mean, 1.4 procedures) during the first year, and dropped to 38% at median follow-up of 45 months (range, 36-64 months) for multiple procedures (mean, 1.9 ± 0.8 [1-4]). Incidence of procedural complications was similar to that of conventional procedures. In multivariate analysis, LSP-AF (OR, 7.40 [95% CI, 1.42-38.34]; P = 0.017) and larger left ventricular end-diastolic diameter (OR, 1.24 [95% CI, 1.01-1.52]; P = 0.034) were significant independent predictors of recurrent atrial tachyarrhythmia (ATa). Compared with patients with ATa recurrence, those free from ATa had better New York Heart Association functional class, 6-minute walk distance and left ventricular ejection fraction during long-term follow-up compared with pre-ablation, but this improvement was not sustained beyond 3 years. In patients with DCM, current commonly used ablation strategies including CPVA, linear ablation and CFAE ablation are not associated with long-term AF treatment success up to five years. Freedom from ATa is associated with improved heart failure during but not beyond 3 years post ablation.


Finding and evaluating randomised controlled trials in nursing conducted by Spanish research teams: A scoping review.
To identify and assess the main characteristics and the potential risk of bias of randomised controlled trials (RCTs) in nursing conducted by Spanish research teams. Scoping review of an electronic search in three major databases (date of search: October 2021). For the eligible studies, both descriptive data, and data to assess the potential risk of bias, were collected and analysed. Of 3391 references retrieved, 199 were eligible. These RCTs were published in 122 journals, most of them in English (101, 82.1%) and were included in the Journal Citation Report (JCR) (107, 87.7%). Moreover, 32 (26.2%) of those included in the JCR were classified under nursing. Two thirds (81, 66.4%) of the journals followed the CONSORT guidelines. A total of 65 RCTs (33.7%) had a high overall risk of bias. Most of the identified RCTs were published in journals not specific to nursing and in English language. Also, shortcomings in RCT design and reporting were observed despite recommendations to adhere the CONSORT guidelines. Comprehensive identification of RCTs in nursing may require searching in journals other than nursing-related. RCTs from Spanish research teams are more likely to be published in international journals published in English. CONSORT should be strongly advised to encourage proper design and reporting of RCTs.


Scanning electron microscopic studies of the nasal blood vessels.
Current histological and transmission electron microscopic techniques are insufficient for studying all different aspects of vascular morphology. As a result, we have used scanning electron microscopy (SEM) to examine nasal blood vessels. In our present studies the nasal septa of 15 rabbits were fixed by vascular perfusion, dried by the critical point method and coated with gold for SEM studies. Lower magnifications of specimens using this method show the tissue arrangement in the nasal septum. In higher magnifications the different vessels can be distinguished by their morphological features. The course of the vascular structures can be observed as well as the junctions between the different vessels. Our results indicate that different morphological techniques must be combined to understand the endonasal vasculature.


Reversal of p-glycoprotein-mediated multidrug resistance by macrocyclic bisbibenzyl derivatives in adriamycin-resistant human myelogenous leukemia (K562/A02) cells.
Macrocyclic bisbibenzyls, a class of characteristic natural molecules derived from liverworts, have diverse biological significances. Dihydroptychantol A (DHA) was identified to be an antifungal active macrocyclic bisbibenzyl from liverwort Asterella angusta. In an attempt to understand other biological activities of this compound, the chemical synthesized DHA and its analogues (compounds 1-3) were employed to test this possibility by using adriamycin-resistant K562/A02 cells. Among the tested compounds (1-4), DHA showed the strongest potency to increase adriamycin cytotoxicity toward K562/A02 cells by MTT assays and its reversal fold is 8.18 (20 microM). Mechanisms of DHA on p-glycoprotein (P-gp)-mediated multidrug resistance (MDR) were further investigated. Based on the flow cytometry, we detected the significant increase of adriamycin and rhodamine123 accumulation in K562/A02 cells exposed to various concentrations of DHA, meanwhile, notable decrease of rhodamine123 efflux was also observed, which revealed DHA caused a decline of P-gp activity. Furthermore, P-gp expression was analyzed by the flow cytometry and RT-PCR. Dose-dependent reduction of P-gp expression was measured in K562/A02 cells pretreated with DHA for 24h. No such results were found in parental K562 cells. These results demonstrated DHA reversed effectively MDR by blocking the drugs to be pumped out via inhibiting P-gp function and expression pathway.


Decline in Cognition from Mid-Life Improves Specificity of Mini-Mental State Examination: Diagnostic Test Accuracy in Caerphilly Prospective Study (CaPs).
The merit of using baseline cognitive assessments in mid-life to help interpret cross-sectional cognitive tests scores in later life is uncertain. Evaluate how accuracy for diagnosing dementia is enhanced by comparing cross-sectional results to a midlife measure. Cohort study of 2,512 men with repeated measures of Mini-Mental State Examination (MMSE) over approximately 10 years. Index test MMSE at threshold of 24 indicating normal, as a cross-sectional measure and in combination with decline in MMSE score from mid-life. Reference standard consensus clinical diagnosis of dementia by two clinicians according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). 1,150 men participated at phase 4 of whom 75 had dementia. A cross-sectional MMSE alone produced a sensitivity of 60% (50% to 70%) and specificity 95% (94% to 97%) with a threshold of≥24 points indicating normal. For lower-scoring men in late life, with cross sectional scores of < 22, combining cross-sectional AND a three-point or more decline over time had a sensitivity of 52% (39% to 64%) and specificity 99% (99% to 100%). For higher-scoring men in later life, with cross sectional scores < 26 combining cross-sectional OR decline of at least three points had a sensitivity of 98% (92% to 100%) and specificity 38% (32% to 44%). It may be helpful in practice to formally evaluate cognition in mid-life as a baseline to compare with if problems develop in future, as this may enhance diagnostic accuracy and classification of people in later life.


Dietary glycemic index, glycemic load and all-cause and cause-specific mortality: A meta-analysis of prospective cohort studies.
The findings of previous studies investigating the association between dietary glycemic index, glycemic load, and the risk of mortality have been inconsistent. We performed a meta-analysis to evaluate this association. A systematic search in PubMed and Web of Science databases was conducted to identify prospective cohort studies on dietary glycemic index and load with risk of mortality through January 2023. Study-specific relative risks (RR) were combined by using random effects models. Fifteen prospective cohort studies with a total of 527,650 participants and 48,598 all-cause and cause-specific deaths were included in the current meta-analysis. Pooled analyses indicated a higher risk of all-cause mortality (RR = 1.10, 95% CI: 1.00-1.20) and stroke mortality (RR = 1.30, 95% CI: 1.04-1.62) for the highest versus lowest levels of glycemic index. A significant non-linear association was found between glycemic index and mortality of all-causes (P for non-linearity = 0.02) and CVD (P for non-linearity <0.001), indicating increased risk at high levels of glycemic index (≥63.1 for all-cause mortality; ≥72.8 for CVD mortality). Glycemic load was positively associated with risk of CVD mortality (RR = 1.18, 95% CI: 1.09-1.27) and stroke mortality (RR = 1.30, 95% CI: 1.05-1.60) in the highest versus lowest meta-analysis. For cancer mortality, there was no significant association with glycemic index, but the association with glycemic load differed by sex. Our results indicated that high glycemic index and glycemic load was associated with an increased risk of mortality from CVD and stroke. Further large prospective studies are warranted to provide definitive evidence in subgroups.


A novel technique of pancreaticojejunostomy for laparoscopic pancreaticoduodenectomy.
Pancreaticojejunostomy (PJ) reconstruction is the Achilles' heel of laparoscopic pancreaticoduodenectomy (LPD). However, only a few studies have focused on the performance of this difficult procedure laparoscopically. We present a safe and feasible technique of duct-to-mucosa pancreaticojejunostomy for LPD, named Bing's anastomosis. Our study included 238 cases of LPDs that underwent Bing's anastomosis. Data on the demographic characteristics, operative outcomes (total operative time, PJ duration, and estimated blood loss), and postoperative results (length of hospital stay, recovery of bowel function, and rates of postoperative morbidity and mortality) of the cases were prospectively collected and retrospectively analyzed. Only one patient (0.4%) in our series required conversion to open surgery as a result of uncontrolled bleeding from the superior mesenteric artery. The average operative time was 358 min (220 min to 495 min). The mean duration for PJ was 23 min (19 min to 33 min). The mean estimated blood loss was 112 ml (50 ml to 800 ml). The overall incidence of pancreatic fistula was 21.4% and included 42 cases (17.6%) of biochemical leak, eight cases (3.4%) of Grade B, and one case (0.4%) of Grade C pancreatic fistulas. The 90-day mortality was 0.4%. Bing's anastomosis is a safe, reliable, and rapid PJ technique for LPD that is associated with favorable outcomes and a low risk of pancreatic fistula. However, its safety and feasibility should be verified by performing prospective randomized controlled trials at different institutions.


Pleiotropic melatonin-mediated responses on growth and cadmium phytoextraction of Brassica napus: A bioecological trial for enhancing phytoremediation of soil cadmium.
Melatonin (MT) has recently gained significant scientific interest, though its mechanism of action in enhancing plant vigor, cadmium (Cd) tolerance, and Cd phytoremediation processes are poorly understood. Therefore, here we investigated the beneficial role of MT in improving growth and Cd remediation potential of rapeseed (Brassica napus). Plants, with or without MT (200 µM L-1), were subjected to Cd stress (30 mg kg1). Without MT, higher Cd accumulation (up to 99%) negatively affected plant growth and developmental feature as well as altered expression of several key genes (DEGs) involved in different molecular pathways of B. napus. As compared to only Cd-stressed counterparts, MT-treated plants exhibited better physiological performance as indicated by improved leaf photosynthetic and gaseous exchange processes (3-48%) followed by plant growth (up to 50%), fresh plant biomass (up to 45%), dry plant biomass (up to 32%), and growth tolerance indices (up to 50%) under Cd exposure. MT application enhanced Cd tolerance and phytoremediation capacity of B. napus by augmenting (1) Cd accumulation in plant tissues and its translocation to above-ground parts (by up to 45.0%), (2) Cd distribution in the leaf cell wall (by up to 42%), and (3) Cd detoxification by elevating phytochelatins (by up to 8%) and metallothioneins (by upto 14%) biosynthesis, in comparison to Cd-treated plants. MT played a protective role in stabilizing hydrogen peroxide and malondialdehyde levels in the tissue of the Cd-treated plants by enhancing the content of osmolytes (proline and total soluble protein) and activities of antioxidant enzymes (SOD, CAT, APX and GR). Transcriptomic analysis revealed that MT regulated 1809 differentially expressed genes (828 up and 981 down) together with 297 commonly expressed DEGs (CK vs Cd and Cd vs CdMT groups) involved in plant-pathogen interaction pathway, protein processing in the endoplasmic reticulum pathway, mitogen-activated protein kinase signaling pathway, and plant hormone signal transduction pathway which ultimately promoted plant growth and Cd remediation potential in the Cd-stressed plants. These results provide insights into the unexplored pleiotropic beneficial action of MT in enhancing in the growth and Cd phytoextraction potential of B. napus, paving the way for developing Cd-tolerant oilseed crops with higher remediation capacity as a bioecological trial for enhancing phytoremediation of hazardous toxic metals in the environment.


Physical mapping of 60 DNA markers in the p21.1----q21.3 region of the human X chromosome.
Using a panel of human/rodent somatic cell hybrids and human lymphoblast lines segregating 18 different human X-chromosome rearrangements and deletions, we have assigned 60 DNA markers to the physical map of the X chromosome from Xp21.1 to Xq21.3. Data from Southern blot hybridization and polymerase chain reaction (PCR) amplification assign these markers to 15 primary map intervals. This provides a basis for further long-range cloning and mapping of the pericentromeric region of the X chromosome.


Diversity of two-pore channels and the accessory NAADP receptors in intracellular Ca2+ signaling.
Intracellular Ca2+ signaling via changes or oscillation in cytosolic Ca2+ concentration controls almost every aspect of cellular function and physiological processes, such as gene transcription, cell motility and proliferation, muscle contraction, and learning and memory. Two-pore channels (TPCs) are a class of eukaryotic cation channels involved in intracellular Ca2+ signaling, likely present in a multitude of organisms from unicellular organisms to mammals. Accumulated evidence indicates that TPCs play a critical role in Ca2+ mobilization from intracellular stores mediated by the second messenger molecule, nicotinic acid adenine dinucleotide phosphate (NAADP). In recent years, significant progress has been made regarding our understanding of the structures and function of TPCs, including Cryo-EM structure determination of mammalian TPCs and characterization of a plastid TPC in a single-celled parasite.. The recent identification of Lsm12 and JPT2 as NAADP-binding proteins provides a new molecular basis for understanding NAADP-evoked Ca2+ signaling. In this review, we summarize basic structural and functional aspects of TPCs and highlight the most recent studies on the newly discovered TPC in a parasitic protozoan and the NAADP-binding proteins LSM12 and JPT2 as new key players in NAADP signaling.


Enhanced catalase synthesis by a novel combined system of photocatalytic reactor and fermentor.
A novel combined system of a photocatalytic reactor, with UV and titanium dioxide as photocatalyst, and a fermentor with Bacillus sp. F26 as catalase producer was developed. Production of catalase was enhanced by 14% to 18.5 U ml-1 without affecting cell growth.


Annual production of two Nova Scotian populations of Nucella lapillus (L.).
One population of Nucella lapillus, under conditions of food shortage, decreased in biomass with an annual production of 5.5 kcal per m2. The second population, with plenty of food, gained biomass and the annual production was 16.7 kcal per m2.Individuals grew faster, while attaining sexual maturity and terminating growth at a larger size in the second population. In both populations, energy produced as gametes exceeded the energy produced due to growth. A 2.56 cm female was estimated to produce 46.6 egg capsules (about 1 kcal) a year but the output of males was unknown and assumed to be half that of females. The sex ratio was equal.


Clinical characteristics and image features of pulmonary cryptococcosis: a retrospective analysis of 50 cases in a Chinese hospital.
To investigate the clinical manifestations and imaging characteristics of pulmonary cryptococcosis, and discuss its guidance in diagnosing. The clinical data of patients diagnosed with cryptococcosis in our hospital from January 2014 to May 2020 were collected and retrospectively analyzed. Patients were divided into the immunocompromised group and the immunocompetent group. The symptomatic features, laboratory examination, imaging manifestations, and curative effect were analyzed. The most common symptoms of patients were cough and sputum production, followed by fever. The immunocompetent group has a significantly higher accident rate of cough and fever than the immunocompromised group, while the immunocompromised group has a significantly higher accident rate of headache and dizziness (P < 0.05). The positive rate of serum cryptococcal capsular antigen (CrAg) test of the two groups were 83.33% and 86.96%, respectively. While the positive rate of CrAg test in cerebrospinal fluid of the immunocompromised group was significantly higher than that of the immunocompetent group (P < 0.05). The lesions of pulmonary cryptococcosis were predominantly present in the lower part of the lung periphery and significantly distributed in the right lung (P < 0.05). The most common imaging finding of pulmonary cryptococcosis was halo sign (64.58%), followed by multiple nodules, and trachea sign was significantly more common in the immunocompetent group. Cryptococcosis has an insidious onset, which can infect healthy people as well. Conducting a CrAg test is good for screening and diagnosing cryptococcosis. We should be alert for the high risk of cryptococcal meningoencephalitis in patients with compromised immune function.


Care provider perspectives on medical travel: A three-country study of destination hospitals.
Despite growing interest in the current and potential role of medical travel in U.S. patient care, very little research has been conducted on clinician and other provider organizations' perspectives on providing international patient care. The present study sought to gain formative insights about medical travel from the providers' perspectives, by conducting structured interviews and focus groups in six hospitals from three countries catering to patients traveling from the United States. Findings highlighted the surprising role of international events and policies in the evolution of medical travel, as well as both the desire and need for more transparent quality standards.


Liver factors involved in drug metabolism in experimentally infected rats: deleterious effect of ornithine alpha-ketoisocaproate.
This study was designed to determine the effect of ornithine alpha-ketoisocaproate (O-KIC), a compound reducing muscle protein breakdown in physiological conditions, on liver factors involved in drug metabolism in rats with acute retrograde pyelonephritis. 91 rats were assigned to 7 groups differing in the level of food intake, induced infection, and the treatment by O-KIC (168 mg/kg bw/day). Rats were killed on the third day. O-KIC increased nitrogen balance and weight gain in controls, but not in malnourished infected or non-infected rats. Liver glutathione was significantly reduced by O-KIC in malnourished infected and non-infected rats. Though O-KIC induced a rise in liver microsomal proteins in control and infected animals, it decreased cytochrome P-450 in controls, and aminopyrine demethylase in both control and infected groups.


Expression and function of atrial myosin light chain 1 in the porcine right ventricle of normal and pulmonary hypertensive animals.
We investigated the expression of atrial myosin light chain 1 (ALC-1) and myosin cycling kinetics in the normal and hypertrophied right ventricle of the neonatal porcine heart. Right ventricular hypertrophy was induced by exposing piglets immediately after birth to hypobaric hypoxia for 3 days. Control piglets were kept under normal conditions for the same time. ALC-1 expression in the hypertrophied right ventricle was 16.9%. No ALC-1 expression could be observed in the right ventricle of control pigs. Force-velocity of chemically skinned right ventricular fibers was analyzed in order to examine the functional role of ALC-1 expression on myosin cross-bridge kinetics. Force generation per cross-section at maximal Ca2+ activation (pCa 4.5) was significantly higher in the hypertrophied group. Maximal shortening velocity (Vmax) of skinned fibers increased statistically significant from 0.69 muscle length per second (ML/s) in the control to 1.2 ML/s in the hypertrophied right ventricle. We conclude that the expression of ALC-1 in the hypertrophied ventricle of neonatal pigs increased cross-bridge cycling kinetics and contractility.


Evaluation of mobile health applications for cervical cancer in the digital marketplace.
To assess the quality of mobile health (mHealth) applications (apps) for cervical cancer using the mobile app rating scale (MARS), APPLICATIONS scoring system, and app rating using specific statements. We searched for cervical cancer apps on two major mobile operating systems (Google Play Store and Apple iTunes Store) in March 2021. Eligible apps were downloaded and assessed for quality by two independent reviewers using multimodal assessment tools. The overall quality of the MARS score was 2.61±0.795. The highest scoring app was "The American Society for Colposcopy and Cervical Pathology (ASCCP) Management Guidelines" (3.98). Overall, apps scored highest in the functionality domain, followed by information, engagement, and aesthetics domains. The mean±standard deviation of the APPLICATIONS scoring system was 8.50±1.712. The highest-rated apps were "ASCCP Management Guidelines," "The British Society for Colposcopy and Cervical Pathology (BSCCP)," and "Cervical Cancer Guide." Apps scored the highest in the paid subscription and price domains. By contrast, apps scored poorly in the text search, literature, and subjective presentation domains. Concerning app content, many apps infrequently provided misconceptions regarding cervical cancer. The apps' rating using specific statements was 7.81±4.562. Overall, the apps analyzed using the MARS and APPLICATIONS scoring systems demonstrated above-average quality. However, there is a need to improve the essential information conveyed by these applications. Moreover, the assessment tools have influenced different app quality rating results, confirming the lack of standardized quality assessment tools for mHealth apps.


Clostridium difficile carbohydrates: glucan in spores, PSII common antigen in cells, immunogenicity of PSII in swine and synthesis of a dual C. difficile-ETEC conjugate vaccine.
Clostridium difficile is responsible for severe diarrhea in humans that may cause death. Spores are the infectious form of C. difficile, which germinate into toxin-producing vegetative cells in response to bile acids. Recently, we discovered that C. difficile cells possess three complex polysaccharides (PSs), named PSI, PSII, and PSIII, in which PSI was only associated with a hypervirulent ribotype 027 strain, PSII was hypothesized to be a common antigen, and PSIII was a water-insoluble polymer. Here, we show that (i) C. difficile spores contain, at least in part, a D-glucan, (ii) PSI is not a ribotype 027-unique antigen, (iii) common antigen PSII may in part be present as a low molecular weight lipoteichoic acid, (iv) selective hydrolysis of PSII yields single PSII repeat units, (v) the glycosyl diester-phosphate linkage affords high flexibility to PSII, and (vi) that PSII is immunogenic in sows. Also, with the intent of creating a dual anti-diarrheal vaccine against C. difficile and enterotoxin Escherichia coli (ETEC) infections in humans, we describe the conjugation of PSII to the ETEC-associated LTB enterotoxin.


Determination of clozapine and its metabolite, norclozapine in various biological matrices using high-performance liquid chromatography.
To develop and validate an HPLC method for the quantitation of clozapine and its metabolite, norclozapine in human plasma, rat plasma, and the various human plasma lipoprotein fractions. Using liquid-liquid extraction, clozapine, and norclozapine are extracted from the biological matrix with MTBE. After concentration, the residue was reconstituted in 1mM HCl and injected on to a C6 Phenyl column (3 microm, 2.0 x 150 mm). Mobile phase was 10 mM ammonium acetate, pH 5--acetonitrile--methanol (5:3:2, v/v/v). Loxapine served as the internal standard. Absorbance was measured at 254 nm. Quantitation limits for clozapine and norclozapine was 100 ng/mL and 50 ng/mL, respectively. Recovery for both clozapine and norclozapine was near 100%. Percent accuracy for intraday variability in human plasma, rat plasma, and human TRL, HDL, LDL, and LPDP lipoprotein fraction was between 92 to 113% for both analytes. Intraday precision for the same matrices was less than 9% CV for both analytes. Percent accuracy and precision for interday variability in human plasma was 97 to 103% and less than 10% CV, respectively. Samples were stabile in the autosampler for 80 h at 10 degrees C and on the benchtop for 2 h. It should be noted, Clozapine-N-oxide, which is a known metabolite of Clozapine, was not determined since it is not clinically active. This method is a simple, fast and robust HPLC assay for the determination of clozapine and norclozapine in various matrices and lipoprotein fractions.


Direct atomic-resolution observation of two phases in the Li(1.2)Mn(0.567)Ni(0.166)Co(0.067)O2 cathode material for lithium-ion batteries.
About phase: The coexistence of rhombohedral LiTMO2 (TM=Ni, Co, or Mn) and monoclinic Li2MnO3-like structures inside Li1.2Mn0.567Ni0.166Co0.067O2 is revealed directly at atomic resolution. The hetero-interface along the [001]rh/[103]mon zone axis direction is demonstrated, indicating the two-phase nature of these lithium-rich cathode materials (green Li, blue Mn, red O, cyan TM).


Rapid detection of multiple SARS-CoV-2 variants of concern by PAM-targeting mutations.
SARS-CoV-2 variants of concern (VOCs) that increase transmission or disease severity or reduce diagnostic or vaccine efficacy continue to emerge across the world. Current methods available to rapidly detect these can be resource intensive and thus sub-optimal for large-scale deployment needed during a pandemic response. Here, we describe a CRISPR-based assay that detects mutations in spike gene CRISPR PAM motif or seed regions to identify a pan-specific VOC single-nucleotide polymorphism (SNP)) ((D614G) and Alpha- and Delta-specific (S982A and D950N) SNPs. This assay exhibits good diagnostic sensitivity and strain specificity with nasal swabs and is designed for use in laboratory and point-of-care settings. This should enable rapid, high-throughput VOC identification required for surveillance and characterization efforts to inform clinical and public health decisions. Furthermore, the assay can be adapted to target similar SNPs associated with emerging SARS-CoV-2 VOCs, or other rapidly evolving viruses.


Relationships between essential fatty acid levels, pulmonary function and fat absorption in pre-adolescent cystic fibrosis children with good clinical scores.
Twenty-one pre-adolescent cystic fibrosis (CF) children with good clinical scores had significant (P less than 0.001) deficiencies of arachidonic (mean 3.8% of total plasma fatty acids +/- SD 1.4) and linoleic (18.1 +/- 6.3) acids compared with controls (6.0 +/- 1.0, and 27.6 +/- 3.9, respectively). Despite the presence of pulmonary involvement of varying severity in all the CF children, neither arachidonic nor linoleic acid levels correlated significantly with pulmonary function measured by spirometry. All children had adequate caloric and fat intakes, and the coefficient of fat absorption correlated with none of the deficient fatty acid levels. These findings suggest that deficiencies of arachidonic and linoleic acids are of minor importance in the early development of pulmonary involvement in CF, and that factors other than fat malabsorption and decreased dietary intake probably contribute to fatty acid deficiency.


Eurasian beavers in Central Italy: perceptions in the local community.
According to the IUCN guidelines, wildlife reintroduction should consider any impacts on humans within feasibility assessments. Eurasian beavers Castor fiber are recovering across their native range, due to protection laws and reintroductions. In Central Italy, a self-sustaining, naturalised population of Eurasian beavers has been identified in the last five years. A questionnaire to measure whether and how citizens in the local area perceive the presence of the beaver was administered to 1114 respondents. We observed a comprehensive awareness of the presence of the beaver in Italy and a high ability to distinguish it from non-native coypus Myocastor coypus (92.3%). We also recorded a general high knowledge of issues related to the presence of the beaver (i.e., potential effects on indigenous biodiversity). The majority (65.5%) of the surveyed population was in favour of reintroducing the beaver in Central Italy, and only 1.2% was firmly against it. The majority of interviewed people was against the removal of beavers from Central Italy (65.8%), whereas only 3.7% was in favor, citing fears of perceived impacts on the river, crops, and fish populations.


Interferon modifies morphine withdrawal phenomena in rodents.
Interferon injection in morphine dependent rats prior to naloxone treatment eliminates 7 behavioral sings of the abstinence (withdrawal) phenomenon. When a single injection of interferon was given prior to chronic morphine treatment it reduces opiate addiction liability.


Factor structure of the Jefferson Scale for Empathy among medical undergraduates from South India.
Empathy is a multidimensional construct and is considered an essential attribute among healthcare professionals. The Jefferson Scale for Empathy (JSE) is a commonly used tool to measure physician empathy and has been used in medical students as well; however, the psychometric properties have not been well studied in India. We aimed to study the factor structure of JSE among medical undergraduates. This was a secondary analysis of baseline data obtained from the Stigma, Empathy and Attitude module study among medical undergraduates (N = 157). The scores obtained on the 20-item JSE Medical Student Version were subjected to principal component analysis with varimax rotation. Eigenvalues greater than unity, scree plot, and Horn's parallel analysis were used for identifying the factors. Items with loading more than 0.4 were included based on Steven's recommendation. The sample was adequate for factor analysis (Kaiser-Meyer-Olkin (KMO) measure 0.832). Five factors were extracted using principal component analysis, which explained 60% of the variance. The first three appeared as stable factors, and the last two factors had two items each. The first factor was the strongest (explained 18.8% of variance) with loadings from nine items. The second factor (explained 15.6% of variance) had loadings from six items, and two of the items showed correlation with the first factor. JSE has a multidimensional structure with five factors in our sample of medical undergraduates.


Propofol-associated hypertriglyceridemia and pancreatitis in the intensive care unit: an analysis of frequency and risk factors.
To characterize the frequency, severity, risk factors, and clinician response to propofol-associated hypertriglyceridemia and hypertriglyceridemia-associated pancreatitis. Retrospective analysis. Medical and surgical intensive care units. One hundred fifty-nine adult intensive care patients administered propofol for 24 hours or longer and who had at least one serum triglyceride concentration. Patient records were reviewed to identify the frequency of hypertriglyceridemia (serum triglyceride concentration > or = 400 mg/dl) and pancreatitis (amylase concentration > or = 125 IU/L, lipase concentration > or = 60 IU/L, and abdominal computed tomography scan or clinical examination findings consistent with pancreatitis). Of the 159 patients, 29 (18%) developed hypertriglyceridemia; six (21%) of the 29 had a serum triglyceride concentration of 1000 mg/dl or greater. The median maximum serum triglyceride concentration was 696 mg/dl (range 403-1737 mg/dl). At the time when hypertriglyceridemia was detected, the median infusion rate of propofol was 50 microg/kg/minute (range 5-110 microg/kg/min). The median time from the start of propofol therapy to identification of hypertriglyceridemia was 54 hours (range 14-319 hrs). Propofol was discontinued within 24 hours of detecting the hypertriglyceridemia 84% of the time. Compared with those who did not develop hypertriglyceridemia, patients who developed hypertriglyceridemia were older, had a longer intensive care unit stay, and received propofol for a longer duration; they were also more likely to be admitted to the medical versus the surgical intensive care unit. Pancreatitis developed in three (10%) of the 29 patients with hypertriglyceridemia. Hypertriglyceridemia and hypertriglyceridemia-associated pancreatitis are often seen in intensive care patients receiving propofol. Serum triglyceride concentrations should be routinely monitored in these patients. In addition, alternative sedation strategies should be considered when hypertriglyceridemia is detected.


Immune-enhancement effects of Angelica gigas Nakai extracts via MAPK/NF-ƙB signaling pathways in cyclophosphamide-induced immunosuppressed mice.
This study investigated the immune-enhancement effects of Angelica gigas Nakai extract (ANE) and its yeast-fermented extract (FAN) in cyclophosphamide (CPP)-induced immunosuppressed mice. Angelica gigas Nakai (AGN) increased the protein level of inducible nitric oxide synthase (iNOS) and the production of nitric oxide (NO) and immune-related cytokines in mouse splenocytes. AGN also restored CPP-induced suppression of NK cell activity and splenocyte proliferation. Furthermore, AGN activated the ERK and p38 MAPK/NF-κB signaling pathways in mouse splenocytes via phosphorylation of signaling molecules. These findings indicate that upregulation of cytokines and enzymes may be closely associated with the MAPK/NF-κB signaling pathways. In conclusion, AGN can restore CPP-induced immunosuppression in mice, although there was no significant difference in the immune-enhancing effect between ANE and FAN. It is suggested that AGN might have the potential to enhance immunity as an immunostimulant under immunosuppressed conditions. Therefore, it could be used as an effective agent or a dietary supplement for improving immunity. The online version contains supplementary material available at 10.1007/s10068-023-01281-6.


Periprosthetic femoral re-fractures pathogenesis, classification, and surgical implications.
Periprosthetic femoral re-fractures (PFRFs) represent an emerging challenge for orthopaedic surgeons, since their incidence is growing in the last years, but very few experiences about their management have been currently published. The present study aims to (1) introduce, for the first time, an etiologic classification for PRFRs and (2) to provide surgical and pharmacological tips for the correct management of these injuries. Periprosthetic femoral re-fractures (PFRFs) could be classified into traumatic-PFRFs (T-PFRFs) and pathological-PFRFs (P-PFRFs). T-PFRFs, i.e. the "true" periprosthetic re-fractures, present as new fracture lines occurring proximally or distally to a previous periprosthetic fracture, that has correctly healed. They are generally unpredictable injuries but, in selected cases, it is possible to predict them by analyzing the construct used in the treatment of the previous periprosthetic fracture. P-PFRFs, on the other hand, define re-fractures occurring on a previous periprosthetic non-union or delayed union: the new fracture line appears in the same district of the old one. According to the etiologic factors influencing the P-PFRFs pathogenesis, it is possible to define re-fractures caused by mechanical failures, biological failures, septic failures and multifactorial failures, i.e., a combination of the previously mentioned concerns. A successful postoperative outcome, following the surgical management of PFRFs, requires the correct identification of all the underlying causes, which should be promptly and appropriately managed.


Activation of complement mediates antiphospholipid antibody-induced pregnancy loss.
Although it is clear that the specific antigenic reactivity of antiphospholipid (aPL) antibodies is critical to their effect, the pathogenic mechanisms that result in injury in vivo are incompletely understood. We hyphothesized that aPL antibodies targeted to the placenta activate complement locally, generating split products that mediate placental injury and lead to foetal loss and growth retardation. To test this hypothesis, we used a murine model of APS in which pregnant mice are injected with human IgG containing aPL antibodies. Mice treated with inhibitors of complement activation and mice deficient in complement components were protected from aPL antibody-induced foetal damage. Although the cause of tissue injury in this disease is probably multifactoral, we have shown that complement activation is an absolute requirement for foetal loss and growth restriction and, therefore, thatthis pathway acts upstream of other important effector mechanisms. Identification of complement activation as a mechanism that is necessary for aPL-induced tissue damage and definition ofthe complement components necessary to trigger such injury is likely to lead to a better understanding of the pathogenesis of vascular and tissue injury in SLE and to new and improved treatments.


Truncation of the TPR domain of OGT alters substrate and glycosite selection.
O-GlcNAc transferase (OGT) is an essential enzyme that installs O-linked N-acetylglucosamine (O-GlcNAc) to thousands of protein substrates. OGT and its isoforms select from these substrates through the tetratricopeptide repeat (TPR) domain, yet the impact of truncations to the TPR domain on substrate and glycosite selection is unresolved. Here, we report the effects of iterative truncations to the TPR domain of OGT on substrate and glycosite selection with the model protein GFP-JunB and the surrounding O-GlcNAc proteome in U2OS cells. Iterative truncation of the TPR domain of OGT maintains glycosyltransferase activity but alters subcellular localization of OGT in cells. The glycoproteome and glycosites modified by four OGT TPR isoforms were examined on the whole proteome and a single target protein, GFP-JunB. We found the greatest changes in O-GlcNAc on proteins associated with mRNA splicing processes and that the first four TPRs of the canonical nucleocytoplasmic OGT had the broadest substrate scope. Subsequent glycosite analysis revealed that alteration to the last four TPRs corresponded to the greatest shift in the resulting O-GlcNAc consensus sequence. This dataset provides a foundation to analyze how perturbations to the TPR domain and expression of OGT isoforms affect the glycosylation of substrates, which will be critical for future efforts in protein engineering of OGT, the biology of OGT isoforms, and diseases associated with the TPR domain of OGT.


Biostatistics pitfalls: Lessons learned from analysis of medical data.
In several recent issues of The Lancet, we identified a few common pitfalls in the analysis of clinical trial and medical data in the published articles (Mok et al., 2019; Herrlinger et al., 2019; Reindl-Schwaighofer et al., 2019; He et al., 2019). Without careful validation of model assumptions, even the primary endpoint of the trial might be analyzed using improper statistical methods. We carried out an in-depth analysis of the statistical issues in four real clinical trials, which highlights the importance of statistics in the medical field. With every effort, biostatisticians need to work with clinicians closely to take the most appropriate statistical approaches to data analysis; otherwise the conclusions drawn from the data might be problematic or misleading.


Risk scoring for preterm labor: where do we go from here?
Risk scoring systems based on traditional demographic, social, and medical factors have limited use, especially in certain populations. Newer approaches, including frequent cervical examinations, periodic outpatient monitoring for contractions, extensive daily monitoring at home for contractions in very high-risk persons, and identification and reduction of modifiable behavioral risks, offer promise.


Avermectins, new family of potent anthelmintic agents: isolation and chromatographic properties.
The avermectins, a family of new anthelmintic agents, were isolated from the mycelia of Streptomyces avermitilis. Four closely related major components and four homologous minor components were separated from the complex. Solvent extraction, solvent partition, and adsorption methods were used to isolate and purify the complex; novel partition chromatography systems using Sephadex LH-20 were used to separate the components. A reverse-phase high-pressure liquid chromatography assay for the quantitative determination of all components was used extensively to monitor the purification methods.


Treatment of keratosis pilaris rubra with 577-nm pro-yellow laser.
Keratosis pilaris rubra (KPR) is a rare group of idiopathic hereditary disorders of keratinization, and it is considered as variants of keratosis pilaris. It is characterized by a well-defined erythema and small, keratotic follicular papules that are seen on the cheeks and preauricular area. Keratosis pilaris rubra is an aesthetically distressed situation, and especially vascular erythema is the most common complaint. In recent years, pro-yellow (577 nm) laser, laser system with yellow light wavelength, has been used as an alternative for seeking more effective treatment especially in vascular lesions. However, in the literature, pro-yellow laser therapy has never been used before in keratosis pilaris rubra. Therefore, we wanted to evaluate the effectiveness of the pro-yellow laser in keratosis pilaris rubra patients. In our study, four patients with keratosis pilaris rubra treated with pro-yellow laser in our Cosmetology Unit between December 2017 and March 2019 were evaluated. The first session was started with 20 j/cm2 and the dose increased 2 j/cm2 at each session. The dose was increased up to 26 j/cm2 , a total of four sessions (20-22-24-26 j/cm2 ) was applied in treatment. All the sessions were used in treatment scanner mode. Objectifying a clearance of erythema >75% was clinically evident in three patients, in the fourth patient, erythema regressed approximately 50%. There has been no recurrence of the lesions after a minimum three months follow-up. There was no permanent side effect in any patient. Pro-yellow laser is a well option for the treatment of keratosis pilaris rubra, and we think that it could be a safety choice therapy. In addition, a well tolerance to treatment and a low incidence of serious side effects make it a very reliable therapy. Further clinical studies are needed to improve our findings.


Conjugation of 5-azido-3-oxapentyl glycosides with thiolated proteins through the use of thiophilic derivatives.
5-Azido-3-oxa-pentyl beta-D-galactopyranoside was prepared from diethylene glycol monochlorohydrin and used as a model of oligosaccharide hapten. After deprotection, a series of amides bearing thiophilic groups had been obtained through the terminal amino function and essayed in coupling reactions with thiolated BSA. Also several Lewis human blood group oligosaccharides had been conjugated with thiolated BSA demonstrating the usefulness of the methodology.


Adult circumcision outcomes study: effect on erectile function, penile sensitivity, sexual activity and satisfaction.
Evidence concerning the effect of circumcision on sexual function is lacking. Men circumcised as adults are potentially in a unique position to comment on the effect of a prepuce on sexual intercourse. We examine sexual function outcomes in men who have experienced sexual intercourse in the uncircumcised and circumcised states. Men 18 years old or older when circumcised were identified by billing records during a 5-year period at an academic medical center. Medical charts were reviewed for confirmation of the procedure and to identify the indication(s). These men were surveyed to assess erectile function, penile sensitivity, sexual activity and overall satisfaction. Data were analyzed using paired t tests to compare category scores before and after circumcision. A total of 123 men were circumcised as adults. Indications for circumcision included phimosis in 64% of cases, balanitis in 17%, condyloma in 10%, redundant foreskin in 9% and elective in 7%. The response rate was 44% among potential responders. Mean age of responders was 42 years at circumcision and 46 years at survey. Adult circumcision appears to result in worsened erectile function (p = 0.01), decreased penile sensitivity (p = 0.08), no change in sexual activity (p = 0.22) and improved satisfaction (p = 0.04). Of the men 50% reported benefits and 38% reported harm. Overall, 62% of men were satisfied with having been circumcised. Our findings may help urologists better counsel men undergoing circumcision as adults. Prospective studies are needed to better understand the relationship between circumcision and sexual function.