[Theory and practice in the care of diabetic pregnancy--a timely concept].
Perinatal mortality in diabetic pregnancy has decreased markedly over the past 25 years; this reduction in fetal loss can be attributed to a variety of advances. These include technologic advances in obstetrics and pediatrics, as well as greater understanding of the metabolic aberrations occurring in pregnancy complicated by diabetes. Basically it seems convenient to consider the various disorders in cases of diabetes in pregnancy from several points of view: 1. the effect of pregnancy on the maternal diabetes and 2. the effect of maternal diabetes on the pregnancy and especially on the fetus, and from the above results we can consider 3. an actual procedure in the care of diabetic pregnancy. Regarding the necessary criteria in the care of pregnant diabetics neither pregnancy nor delivery will cause any serious problems.


Cerebral disconnectivity: an early event in schizophrenia.
Neuroimaging and electrophysiological investigations have demonstrated numerous differences in brain morphology and function of chronic schizophrenia patients compared to healthy controls. Studying patients at the beginning of their disease without the confounding effects of chronicity, medication, and institutionalization may provide a better understanding of schizophrenia. Recently, at many institutions around the world, special projects have been launched for specialized treatment and research of this interesting patient group. Using the PubMed search engine in this update, the authors summarize recent investigations between January 2002 and September 2006 that focus on whether signs of disconnectivity already exist early in the disease process. They discuss gray and white matter changes, their impact on symptomatology, electroencephalogram-based studies on connectivity, and possible influences of medication.


Bailout coronary stenting without anticoagulation or intravascular ultrasound guidance: acute and six-month angiographic results in a series of 120 consecutive patients.
The purpose of this study was to evaluate the feasibility, safety, and efficacy of bailout coronary stenting without anticoagulation or intravascular ultrasound guidance in patients with acute or unequivocal threatened closure after conventional angioplasty. One hundred twenty consecutive patients were prospectively enrolled according to the following criteria: 1) acute or threatened closure after balloon angioplasty; 2) reference vessel diameter > or = 2.5 mm. All patients after stent implantation were on antiplatelet treatment with aspirin and ticlopidine. Four types of stents were used: Palmaz-Schatz (J&J), Gianturco-Roubin (Cook), Freedom (Global Therapeutics), and Microstent (AVE). Procedural results: a total of 206 stents were implanted in 134 target lesions with a stent deployment success rate of 100%; 44 target lesions were treated with multiple stent implantation; the mean luminal diameter after stenting was 3.14 +/- 0.34 mm, and the mean final percent diameter stenosis was -2 +/- 10%; the mean balloon to vessel ratio was 1.11 +/- 0.15; the mean final pressure inflation was 13.9 +/- 2.4 atm; an optimal angiographic result was achieved in 128 lesions (96%). In-hospital results: in-hospital recurrent ischemia occurred in 4 patients (3%); recurrent ischemia resulted directly in death in 1 patient, in nonfatal Q-waves infarction in 2 patients, and in emergency coronary artery surgery in 1 patient. Six-month clinical follow-up results: event free survival rate was 77%; 1 patient had non fatal infarction; the incidence of repeat revascularization procedures was 19%; there were no cardiac deaths. Angiographic follow-up results (follow-up rate 93%): the restenosis or reocclusion rate was 28%. Bailout coronary stenting without chronic anticoagulation treatment or intravascular ultrasound guidance may be considered a highly feasible and safe treatment for acute or threatened closure after failed angioplasty.


Significant Decreasing Trend in Low Back Injuries in a Beverage Company.
Work-related injuries in the U.S. have steadily declined over the past three decades. The aim of this study was to compare trends of the most frequently injured body parts from a beverage company over an 8-year study period (2008 to 2015). Work-related injury claims with more than 3 days of missed work (N = 20,203) were classified into body part groups, including low back, knee, shoulder, and all other(s). Descriptive statistics and linear models were used to evaluate trends over time. The total number of injuries decreased from 6.57 per 100 to 3.79 per 100 employees from 2008 to 2015. Proportion of low back injuries decreased from 22.0% to 15.4% (P < 0.001) over the study period. Proportionally, knee(s), shoulder(s), and all other injuries increased, but the changes did not reach statistical significance. Low back injuries decreased at a faster rate than knee, shoulder, and all other injuries.


Structured phonetic variation facilitates talker identification.
Listeners use talker-specific phonetic structure to facilitate language comprehension. This study tests whether sensitivity to talker-specific phonetic variation also facilitates talker identification. During training, two listener groups learned to associate talkers' voices with cartoon pseudo-faces. For one group, each talker produced characteristically different voice-onset-time values; for the other group, no talker-specific phonetic structure was present. After training, listeners were tested on talker identification for trained and novel words, which was improved for those who heard structured phonetic variation compared to those who did not. These findings suggest an additive benefit of talker-specific phonetic variation for talker identification beyond traditional indexical cues.


Environmental dependence of mutational (co)variances of adaptive traits.
Standing genetic variation, and capacity to adapt to environment change, will ultimately depend on the fitness effects of mutations across the range of environments experienced by contemporary, panmictic, populations. We investigated how mild perturbations in diet and temperature affect mutational (co)variances of traits that evolve under climatic adaptation, and contribute to individual fitness in Drosophila serrata. We assessed egg-to-adult viability, development time and wing size of 64 lines that had diverged from one another via spontaneous mutation over 30 generations of brother-sister mating. Our results suggested most mutations have directionally concordant (i.e., synergistic) effects in all environments and both sexes. However, elevated mutational variance under reduced macronutrient conditions suggested environment-dependent variation in mutational effect sizes for development time. We also observed evidence for antagonistic effects under standard versus reduced macronutrient conditions, where these effects were further contingent on temperature (for development time) or sex (for size). Diet also influenced the magnitude and sign of mutational correlations between traits, although this result was largely due to a single genotype (line), which may reflect a rare, large effect mutation. Overall, our results suggest environmental heterogeneity and environment-dependency of mutational effects could contribute to the maintenance of genetic variance.


Application of the Haddon matrix to COVID-19 prevention and containment in nursing homes.
COVID-19 has exacted a disproportionate toll on the health of persons living in nursing homes. Healthcare providers and other decision-makers in those settings must refer to multiple evolving sources of guidance to coordinate care delivery in such a way as to minimize the introduction and spread of the causal virus, SARS-CoV-2. It is essential that guidance be presented in an accessible and usable format to facilitate its translation into evidence-based best practice. In this article, we propose the Haddon matrix as a tool well-suited to this task. The Haddon matrix is a conceptual model that organizes influencing factors into pre-event, event, and post-event phases, and into host, agent, and environment domains akin to the components of the epidemiologic triad. The Haddon matrix has previously been applied to topics relevant to the care of older persons, such as fall prevention, as well as to pandemic planning and response. Presented here is a novel application of the Haddon matrix to pandemic response in nursing homes, with practical applications for nursing home decision-makers in their efforts to prevent and contain COVID-19.


Relationship of parental psychological distress to consequences of chronic health conditions in children.
To assess whether parents' self-reported psychological distress was related to consequences of chronic health conditions in their children as reflected by three domains: functional limitations, reliance on compensatory mechanisms, and service use above routine care. We used telephone survey data on children's health and parents' psychiatric symptoms from an inner-city community sample (n = 380) and a population-based national sample (n =398). In the national sample, parents of children with functional limitations were more distressed than parents whose children experienced other types of condition consequences or none. In the inner-city sample, presence of a health condition was associated with greater parental distress, but there were no significant effects by consequence type. Research needs to determine if parents of children with functional limitations represent a high-risk group and to identify the factors associated with their elevated distress.


[Hepatoprotective effects of extracts and polysaccharides from seaweed].
Antioxidants of natural origin are considered as possible agents for prevention and treatment of liver diseases. Marine algae and in particular their extracts and obtained from them sulfated polysaccharides are significant sources of natural antioxidants. The recent data on the effect of the extracts and sulfated polysaccharides of seaweed on the functional activity of the liver with injuries induced by CCl4, some drugs (paracetamol, diclofenac), N-nitrosocompounds, aflatoxin are presented in the review. Particular attention is paid to the effect of sulfated polysaccharides and in particular fucoidans on the functional activity of the liver in patients with chronic viral hepatitis C. Fucoidan is highly safe and active not only as an antioxidant but also as an inhibitor of HCV replication, has antiinflammatory and immunomodulating effects. The data of the review allow to conclude that seaweed extracts and sulfated polysaccharides may be a basis for development of new generation drugs in the future for the treatment and prevention of liver diseases.


Iterative surgical resection of a recurrent gallbladder carcinoma with long-term survival: report of a case.
Gallbladder carcinoma is a rare, but often lethal disease. Unfortunately, at the time of diagnosis, patients usually have advanced disease (T3-T4) and long-term survival is dismal, ranging from 5 to 12% in the literature. However, this cancer can be successfully treated when the tumour is organ-confined (T1-T2 tumours), as happens in the case of incidental diagnosis at the time of cholecystectomy for gallstones. Here we describe a patient with recurrent gallbladder carcinoma who, treated with iterative surgical resection, is alive and disease-free at 5 years after the final surgical procedure.


Application of Regulatory Cell Death in Cancer: Based on Targeted Therapy and Immunotherapy.
The development of cancer treatment methods is constantly changing. For common cancers, our treatment methods are still based on conventional treatment methods, such as chemotherapy, radiotherapy, and targeted drug therapy. Nevertheless, the emergence of tumor resistance has a negative impact on treatment. Regulated cell death is a gene-regulated mode of programmed cell death. After receiving specific signal transduction, cells change their physical and chemical properties and the extracellular microenvironment, resulting in structural destruction and decomposition. As research accumulates, we now know that by precisely inducing specific cell death patterns, we can treat cancer with less collateral damage than other treatments. Many newly discovered types of RCD are thought to be useful for cancer treatment. However, some experimental results suggest that some RCDs are not sensitive to cancer cell death, and some may even promote cancer progression. This review summarizes the discovered types of RCDs, reviews their clinical efficacy in cancer treatment, explores their anticancer mechanisms, and discusses the feasibility of some newly discovered RCDs for cancer treatment in combination with the immune and tumor microenvironment.


Four-petal evisceration: a new technique.
To describe a new evisceration technique that allows the use of large orbital implants and closure without tension on the wound. Interventional prospective study. The technique involves quadrisectioning the sclera and placement of a large orbital implant. The sclera is sutured in 2 layers covering the implant. A total of 73 eyes underwent surgery. The implants were 22 mm in 11 eyes (15%), 20 mm in 60 eyes (82.2%), and 18 mm in 2 eyes (2.8%). Thirty-one eyes (42%) were phthisical with small scleral cavities. There was 1 case of postoperative mild superior sulcus deficiency and no cases of extrusion of the implant. The 4-petal evisceration is technically easy to perform and provides excellent results with few complications. It allows the use of orbital implants of any desired size.


[Results of spectral determination of metals in human tissues adjacent to K.M. Sivash's endoprosthesis].
The paper presents the data of semiquantitative determination of metals in the tissues surrounding the total titanium-comochromium endoprosthesis of the Sivash system. The prostheses of this design which have a point of metal-metal friction have been used in the past 30 years. It has been shown that chromium and cobalt accumulate constantly and in great quantities, molybdenum and tin do less frequently and in lower quantities. Seventy tissue specimens were obtained from 20 patients followed up for 3 weeks to 15-19 years. The fine, highly sensitive method, emission spectral analysis, used by procedure developed by the Moscow Forensic Bureau of Experts was chosen. The study was undertaken to determine the association of the severity of metallosis with the aseptic instability of prostheses. However, there was no strong evidence for this: commensurable quantities of metals were found when permanent and temporary prostheses had been used. The author considers that the patients have not survived yet to have metallic instability that could have developed in some of them in the later periods of endoprosthesis use. Based on this and early studies, it is concluded that instability in the given periods is a result of mechanical action of some parts of the prostheses on bony formations. The findings show that the severity of metallosis depends on the number of cycles of prosthesis loading, which can be calculated by the duration of prosthesis use and the number of kilometers covered by the patient every day. The ascertained number of cycles may be correlated with the severity of metallosis expressed in arbitrary units.


Reduced Risk of Inflammatory Bowel Disease-associated Colorectal Neoplasia with Use of Thiopurines: a Systematic Review and Meta-analysis.
The association between thiopurines and colorectal neoplasia risk remains controversial in inflammatory bowel disease [IBD] patients. We performed a systematic review and meta-analysis examining this association. A comprehensive search of the PubMed, EMBASE and Cochrane Library databases was performed to identify relevant literature. Random-effects models were applied to calculate the pooled odds ratio [OR] and relative risk [RR] with corresponding 95% confidence intervals [CIs] among case-control and cohort studies. Eleven cohort and 16 case-control studies involving 95397 patients were included in this study. Overall, the use of thiopurines was associated with a reduced risk of colorectal neoplasia both in case-control [OR = 0.49, 95% CI: 0.34-0.70] and cohort studies [RR = 0.96, 95% CI: 0.94-0.98]. Moreover, a protective effect of thiopurines against advanced neoplasia [high-grade dysplasia and cancer] [OR = 0.51, 95% CI: 0.31-0.84 for case-control studies; RR = 0.96, 95% CI: 0.94-0.98 for cohort studies] and colorectal cancer [CRC] [OR = 0.56, 95% CI: 0.34-0.93 for case-control studies; RR = 0.96, 95% CI: 0.94-0.98 for cohort studies] was also observed. Furthermore, when the analysis was conducted on patients at a high risk for colorectal neoplasia, the chemopreventive effect was confirmed in patients with long disease duration [> 8 years] but not in those with extensive colitis or primary sclerosing cholangitis. This study demonstrated that thiopurine use was associated with a reduced risk of colorectal neoplasia, advanced neoplasia and CRC in IBD patients, especially those with long disease duration [> 8 years].


Mesoporous calcium phosphate using casein as a template: Application to bovine serum albumin sorption.
Mesoporous hydroxyapatites were synthesized at room temperature using casein as a template, and key experimental factors, such as casein concentration, pH and extraction of casein in the final solids by washing and thermal treatment, were systematically investigated. The X-Ray Diffraction (XRD) patterns confirmed the synthesis of well-crystallized hydroxyapatite. The N2 adsorption/desorption isotherms were in agreement with the formation of mesoporous hydroxyapatite with a maximum surface area of 106m2g-1. Infrared spectroscopy and thermogravimetry analysis were performed to investigate the extraction of casein in water in the post-synthesis stage. Pure mesoporous hydroxyapatite exhibited good BSA adsorption capacity higher than the one obtained for conventional hydroxyapatite.


Predictors of outpatient kidney function recovery among patients who initiate hemodialysis in the hospital.
Recent policy clarifications by the Centers for Medicare & Medicaid Services have changed access to outpatient dialysis care at end-stage renal disease (ESRD) facilities for individuals with acute kidney injury in the United States. Tools to predict "ESRD" and "acute" status in terms of kidney function recovery among patients who previously initiated dialysis therapy in the hospital could help inform patient management decisions. Historical cohort study. Incident hemodialysis patients in the Mayo Clinic Health System who initiated in-hospital renal replacement therapy (RRT) and continued outpatient dialysis following hospital dismissal (2006 through 2009). Baseline estimated glomerular filtration rate (eGFR), acute tubular necrosis from sepsis or surgery, heart failure, intensive care unit, and dialysis access. Kidney function recovery defined as sufficient kidney function for outpatient hemodialysis therapy discontinuation. Cohort consisted of 281 patients with a mean age of 64 years, 63% men, 45% with heart failure, and baseline eGFR≥30mL/min/1.73m(2) in 46%. During a median of 8 months, 52 (19%) recovered, most (94%) within 6 months. Higher baseline eGFR (HR per 10-mL/min/1.73m(2) increase eGFR, 1.27; 95% CI, 1.16-1.39; P<0.001), acute tubular necrosis from sepsis or surgery (HR, 3.34; 95% CI, 1.83-6.24; P<0.001), and heart failure (HR, 0.40; 95% CI, 0.19-0.78, P=0.007) were independent predictors of recovery within 6 months, whereas first RRT in the intensive care unit and catheter dialysis access were not. There was a positive interaction between absence of heart failure and eGFR≥30mL/min/1.73m(2) for predicting kidney function recovery (P<0.001). Sample size. Kidney function recovery in the outpatient hemodialysis unit following in-hospital RRT initiation is not rare. As expected, higher baseline eGFR is an important determinant of recovery. However, patients with heart failure are less likely to recover even with a higher baseline eGFR. Consideration of these factors at hospital discharge informs decisions on ESRD status designation and long-term hemodialysis care.


Outcomes of Pediatric Kidney Transplantation in Recipients of a Previous Non-Renal Solid Organ Transplant.
Children who receive a non-renal solid organ transplant may develop secondary renal failure requiring kidney transplantation. We investigated outcomes of 165 pediatric kidney transplant recipients who previously received a heart, lung, or liver transplant using data from 1988 to 2012 reported to the United Network for Organ Sharing. Patient and allograft survival were compared with 330 matched primary kidney transplant (PKT) recipients. Kidney transplantation after solid organ transplant (KASOT) recipients experienced similar allograft survival: 5- and 10-year graft survival was 78% and 60% in KASOT recipients, compared to 80% and 61% in PKT recipients (p = 0.69). However, KASOT recipients demonstrated worse 10-year patient survival (75% KASOT vs. 97% PKT, p < 0.001). Competing risks analysis indicated that KASOT recipients more often experienced graft loss due to patient death (p < 0.001), whereas allograft failure per se was more common in PKT recipients (p = 0.01). To study more recent outcomes, kidney transplants performed from 2006 to 2012 were separately investigated. Since 2006, KASOT and PKT recipients had similar 5-year graft survival (82% KASOT vs. 83% PKT, p = 0.48), although 5-year patient survival of KASOT recipients remained inferior (90% KASOT vs. 98% PKT, p < 0.001). We conclude that despite decreased patient survival, kidney allograft outcomes in pediatric KASOT recipients are comparable to those of PKT recipients.


Random sample community-based health surveys: does the effort to reach participants matter?
Conducting health surveys with community-based random samples are essential to capture an otherwise unreachable population, but these surveys can be biased if the effort to reach participants is insufficient. This study determines the desirable amount of effort to minimise such bias. A household-based health survey with random sampling and face-to-face interviews. Up to 11 visits, organised by canvassing rounds, were made to obtain an interview. Single-family homes in an underserved and understudied population in North Miami-Dade County, Florida, USA. Of a probabilistic sample of 2200 household addresses, 30 corresponded to empty lots, 74 were abandoned houses, 625 households declined to participate and 265 could not be reached and interviewed within 11 attempts. Analyses were performed on the 1206 remaining households. Each household was asked if any of their members had been told by a doctor that they had high blood pressure, heart disease including heart attack, cancer, diabetes, anxiety/ depression, obesity or asthma. Responses to these questions were analysed by the number of visit attempts needed to obtain the interview. Return per visit fell below 10% after four attempts, below 5% after six attempts and below 2% after eight attempts. As the effort increased, household size decreased, while household income and the percentage of interviewees active and employed increased; proportion of the seven health conditions decreased, four of which did so significantly: heart disease 20.4-9.2%, high blood pressure 63.5-58.1%, anxiety/depression 24.4-9.2% and obesity 21.8-12.6%. Beyond the fifth attempt, however, cumulative percentages varied by less than 1% and precision varied by less than 0.1%. In spite of the early and steep drop, sustaining at least five attempts to reach participants is necessary to reduce selection bias.


Using the split-ubiquitin yeast two-hybrid system to test protein-protein interactions of transmembrane proteins.
Proteins are responsible for many biological processes within living organisms. Many proteins have the ability to specifically interact with other proteins in order to function properly. The identification of protein-protein interactions (PPIs) can provide useful information about the function of a protein of interest. Historically, the properties of transmembrane proteins have caused difficulty in analyzing PPIs among transmembrane proteins. The development of an assay that is capable of analyzing PPIs involving transmembrane proteins, the split-ubiquitin yeast two-hybrid (SU-Y2H) assay, has provided a method to probe pairwise PPIs between two proteins of interest or to screen a single protein of interest for interaction partners. The following protocol explains how to use the SU-Y2H assay, which is compatible with the use of transmembrane proteins, to investigate PPIs between two proteins of interest and also briefly describes how to adjust the system to be used as a high-throughput screen for interaction partners of a particular protein of interest.


Detecting multineuronal temporal patterns in parallel spike trains.
We present a non-parametric and computationally efficient method that detects spatiotemporal firing patterns and pattern sequences in parallel spike trains and tests whether the observed numbers of repeating patterns and sequences on a given timescale are significantly different from those expected by chance. The method is generally applicable and uncovers coordinated activity with arbitrary precision by comparing it to appropriate surrogate data. The analysis of coherent patterns of spatially and temporally distributed spiking activity on various timescales enables the immediate tracking of diverse qualities of coordinated firing related to neuronal state changes and information processing. We apply the method to simulated data and multineuronal recordings from rat visual cortex and show that it reliably discriminates between data sets with random pattern occurrences and with additional exactly repeating spatiotemporal patterns and pattern sequences. Multineuronal cortical spiking activity appears to be precisely coordinated and exhibits a sequential organization beyond the cell assembly concept.


Measurement of informal care time in a study of patients with dementia.
Previous assessments of informal care time have tended to consider only the amount of time spent with the patient by the primary informal caregiver; however, in many cases, more than one person is providing care for the patient. We assess total informal care time of people caring for patients with dementia, and estimate the bias that can arise if consideration is not made of the time spent by all participating informal caregivers. We used an extended version of the questions on informal care time from the Resource Utilization in Dementia (RUD) instrument. Caregivers were asked to state the number of days and the number of hours on a typical day they had assisted the patient in activities of daily living (ADL), instrumental ADL (IADL), and supervision during the last four weeks. Multivariate regression analyses were conducted to identify factors that could account for the amount of informal care time. 357 informal caregivers took part. Values were missing from only 4.5% of all interviews. On average, the primary informal caregiver cared for the patient 1.5, 2.1 and 1.9 hours per day in ADL, IADL and supervision respectively. Fifty-seven percent of all patients had more than one informal caregiver. Total informal care time was underestimated by about 14% if the time of caregivers other than the primary caregiver was not taken into account. The informal care time was significantly higher if the caregiver was the patient's partner and the patient's health status was lower. Our results show that most previous studies probably underestimated costs of informal care because the time of informal caregivers other than the primary caregiver was not considered.


Kynurenine formamidase: determination of primary structure and modeling-based prediction of tertiary structure and catalytic triad.
Kynurenine formamidase (KFase) (EC 22.214.171.124) hydrolyzes N-formyl-L-kynurenine, an obligatory step in the conversion of tryptophan to nicotinic acid. Low KFase activity in chicken embryos, from inhibition by organophosphorus insecticides and their metabolites such as diazoxon, leads to marked developmental abnormalities. While KFase was purportedly isolated previously, the structure and residues important for catalysis and inhibition were not established. KFase was isolated here from mouse liver cytosol by (NH4)2SO4 precipitation and three FPLC steps (resulting in 221-fold increase in specific activity for N-formyl-L-kynurenine hydrolysis) followed by conversion to [3H]diethylphosphoryl-KFase and finally isolation by C4 reverse-phase high-performance liquid chromatography. Determination of tryptic fragment amino acid sequences and cDNA cloning produced a new 305-amino-acid protein sequence. Although an amidase by function, the primary structure of KFase lacks the amidase signature sequence and is more similar to esterases and lipases. Sequence profile analysis indicates KFase is related to the esterase/lipase/thioesterase family containing the conserved active-site serine sequence GXSXG. The alpha/beta-hydrolase fold is suggested for KFase by its primary sequence and predicted secondary conformation. A three-dimensional model based on the structures of homologous carboxylesterase EST2 and brefeldin A esterase implicates Ser162, Asp247 and His279 as the active site triad.


Gene silencing and a novel monoallelic expression pattern in distinct CD177 neutrophil subsets.
CD177 presents antigens in allo- and autoimmune diseases on the neutrophil surface. Individuals can be either CD177-deficient or harbor distinct CD177neg and CD177pos neutrophil subsets. We studied mechanisms controlling subset-restricted CD177 expression in bimodal individuals. CD177pos, but not CD177neg neutrophils, produced CD177 protein and mRNA. Haplotype analysis indicated a unique monoallelic CD177 expression pattern, where the offspring stably transcribed either the maternal or paternal allele. Hematopoietic stem cells expressed both CD177 alleles and silenced one copy during neutrophil differentiation. ChIP and reporter assays in HeLa cells with monoallelic CD177 expression showed that methylation reduced reporter activity, whereas demethylation caused biallelic CD177 expression. HeLa cell transfection with c-Jun and c-Fos increased CD177 mRNA. Importantly, CD177pos human neutrophils, but not CD177neg neutrophils, showed a euchromatic CD177 promoter, unmethylated CpGs, and c-Jun and c-Fos binding. We describe epigenetic mechanisms explaining the two distinct CD177 neutrophil subsets and a novel monoallelic CD177 expression pattern that does not follow classical random monoallelic expression or imprinting.


Alterations in the suppressor gene PPP2R1B in parathyroid hyperplasias and adenomas.
Deletion of chromosome 11q23 is a common alteration in parathyroid adenomas and hyperplasias. A new potential suppressor gene PPP2R1B encoding the beta isoform of the A subunit of the serine/threorine protein phosphatase 2A was recently identified and localized to chromosome 11q23. We performed polymerase chain reaction-based single-strand conformation polymorphism and direct sequencing on six parathyroid hyperplasias and 12 adenomas to evaluate the role of PPP2R1B in the pathogenesis of parathyroid lesions. A previously identified germline G-A transition (GGC-GAC) in codon 90, changing glycine (Gly) to aspartic acid (Asp), was detected in one adenoma. Both the common Gly allele and the variant Asp allele were detected by direct sequencing in the patient's somatic cells. We conclude mutations of PPP2R1B are not frequent in parathyroid lesions, and that other genes located at 11q23 may be more closely associated with pathogenesis of parathyroid hyperplasia and adenoma.


Self-regulation of phosphate intake in the rat: the influence of age, vitamin D and parathyroid hormone.
Growing rats offered a choice of four pairs of diets, one low in P (0.1%) and the others containing 0.3, 0.6, 1.2 or 1.8% P, selected food mixtures in each case with nearly identical P contents (0.23-0.24%) (Ca:P = 2.2:1). Mature rats offered the same dietary choices exhibited less rigid diet selection but clearly preferred a diet higher in P (0.64-0.69%) (Ca:P = 0.9:1). Vitamin D-deficient animals selected less P than controls and parathyroidectomized rats severely limited their P intake. The increase in self-determined P consumption relative to Ca in mature rats is consonant with the greater decrease in the requirement for Ca associated with maturation and cessation of bone growth. Susceptibility to hypocalcemia in vitamin D deficiency and parathyroidectomy is a probable factor in the increased sensitivity to excess dietary P, which further depresses plasma Ca. These experiments confirm the existence of a feedback mechanism that regulates the voluntary consumption of P in accordance with physiological needs.


Primary Blast Causes Delayed Effects without Cell Death in Shell-Encased Brain Cell Aggregates.
Previous work in this laboratory used underwater explosive exposures to isolate the effects of shock-induced principle stress without shear on rat brain aggregate cultures. The current study has utilized simulated air blast to expose aggregates in suspension and enclosed within a spherical shell, enabling the examination of a much more complex biomechanical insult. Culture medium-filled spheres were exposed to single pulse overpressures of 15-30 psi (∼6-7 msec duration) and measurements within the sphere at defined sites showed complex and spatially dependent pressure changes. When brain aggregates were exposed to similar conditions, no cell death was observed and no changes in several commonly used biomarkers of traumatic brain injury (TBI) were noted. However, similarly to underwater blast, immediate and transient increases in the protein kinase B signaling pathway were observed at early time-points (3 days). In contrast, the oligodendrocyte marker 2',3'-cyclic nucleotide 3'-phosphodiesterase, as well as vascular endothelial growth factor, both displayed markedly delayed (14-28 days) and pressure-dependent responses. The imposition of a spherical shell between the single pulse shock wave and the target brain tissue introduces greatly increased complexity to the insult. This work shows that brain tissue can not only discriminate the nature of the pressure changes it experiences, but that a portion of its response is significantly delayed. These results have mechanistic implications for the study of primary blast-induced TBI and also highlight the importance of rigorously characterizing the actual pressure variations experienced by target tissue in primary blast studies.


Gastropleural Fistula with Aortic Intramural Involvement.
Gastropleural fistula is a relatively rare complication that can be seen as a result of traumatic, nontraumatic, benign, and neoplastic etiologies. Most commonly, these are found in patients with diaphragmatic herniation or prior thoracic surgery. Aortoenteric fistulas are rare communications typically between the abdominal aorta and bowel. We present a rare case of an 88-year-old male who developed a gastropleural fistula with erosions into the wall of the descending thoracic aorta. Computed tomography (CT) is a leading modality in evaluation of suspected gastropleural or aortoenteric fistulas given the quick scan time and widespread availability. Prompt diagnosis is essential and requires an understanding of appropriate CT protocols and CT imaging appearance.


Branch blight of Juglans regia caused by Palmiascoma qujingense in China.
Juglans regia L. is one of the major cultivated walnut species in China for nuts and wood (Pollegioni et al. 2012). In June 2020, branches with blight symptoms were observed in an orchard at Chongzhou City (30°33'34″N, 103°38'35″E). In an orchard of 30 hectares, disease incidence was around 50%. A total of 15 plants were sampled and 40% of their branches were affected by this disease. Firstly, brown and irregular spots appeared, then the spots gradually expanded and encircled the branch, which eventually killed the branch. Five samples of diseased branches from different trees were collected and a single fungal isolate was obtained from each of the five samples using the single ascospore isolation (Chomnunti et al. 2014). Colonies of the five isolates on potato dextrose agar (PDA) were identical that initially appeared white on the top, becoming light to dark brown with age. On the host, ascostroma were black, globose to subglobose, short-papillate, ostiolate, 260 - 410 × 210 - 320 µm (x = 335 × 265 µm, n = 20). Asci were 8-spored, bitunicate, cylindrical, short pedicellate, 55 - 78 × 8 - 12 µm (x = 67.5 × 10 µm, n = 40). Ascospores were 1-septate, fusiform to ellipsoidal, slightly curved, guttulate, 12 - 17 × 3 - 5 µm (x = 14.5 × 4 µm, n = 40). These sexual morphological characteristics are consistent with the Palmiascoma qujingense Phook. & K.D. Hyde (Monkai et al. 2021). Asexual morphs were formed on PDA in incubator after 17 days (25℃, 90% relative humidity, 12-h photoperiod). Conidiomata were black, globose to subglobose, 220 - 300 × 240 - 380 µm (x = 270 × 310 µm, n = 20). Conidia were oblong to ellipsoidal, aseptate and smooth-walled, 3 - 7 × 2 - 4 μm (x = 4.9 × 3 μm, n = 50). The genomic DNA of a representative isolate SICAUCC 21-0013 was extracted, and the internal transcribed spacers (ITS) region, large subunit rDNA (LSU) region, small subunit rDNA (SSU) region, and the largest subunit of RNA polymerase II (rpb2) gene were amplified and sequenced with primers ITS5/ITS4 (White et al. 1990), LR0R/LR5 (Rehner et al. 1994), NS1/NS4 (White et al. 1990), and fRPB2-5F/fRPB2-7cR (Liu et al. 1999), respectively. The sequences were deposited in NCBI with accession numbers MZ983549, MZ959419, MZ951112, and MZ818772, respectively, which showed 100%, 100%, 99.14%, and 99.59% identities with P. qujingense KUMCC 19-0201 (holotype) (accession numbers MT477185, MT477186, MT477183, MT495782respectively). Phylogenetic analysis (maximum likelihood) based on a concatenated dataset showed 93% bootstrap support values with P. qujingense. To verify Koch's postulates, 9 healthy branches from three 1-year-old seedlings were inoculated with conidial suspension (106 conidia/ml) from 4-week-old cultures via pin-prick inoculation (Desai et al. 2019), and the same number of seedlings and branches were inoculated with sterile water as controls. Plants were placed in a greenhouse at 25℃ and 90% RH on a 12-h fluorescent light/dark regime. After 28 days, brown spots were formed on P. qujingense-inoculated branches and similar to those observed in the field, while the controls remained asymptomatic. The pathogen was re-isolated from the lesions and identified by morphology and phylogeny. To our knowledge, this is the first report of P. qujingense causing branch blight on J. regia in the world. This disease potentially impacts the growth and yield of J. regia, and control measures should be made.


Nicotinic acid: a review of its clinical use in the treatment of lipid disorders.
Nicotinic acid (niacin) is a water-soluble vitamin widely used for the treatment of lipid disorders. In pharmacologic doses (1 g or more/day), alone or in combination with other lipid-lowering drugs, nicotinic acid lowers very low-density (VLDL) and low-density lipoprotein (LDL) levels, while concurrently increasing high-density lipoprotein (HDL) levels. It may reduce long-term mortality in patients with known coronary artery disease and may slow or reverse the progression of atherosclerosis. A major consideration against using nicotinic acid is the occurrence of frequent, bothersome, adverse reactions such as cutaneous flushing, skin rash, and gastric upset. Careful dosing titration may, however, minimize these effects. The beneficial effects, taken together with the low cost of nicotinic acid therapy and the relative freedom from serious side effects, have made nicotinic acid the agent of choice for the treatment of many patients with hyperlipidemia.


Developmental variation in floral volatiles composition of a fragrant orchid Zygopetalum maculatum (Kunth) Garay.
Emitted scent volatile profile of an orchid species Zygopetalum maculatum was studied using dynamic headspace sampling technique with four different adsorbent matrices, namely Porapak Type Q polymer (mesh size: 80/100), Tenax (mesh size: 60/80), activated charcoal and graphite. In addition, developmental variations in scent emissions and endogenous volatile levels were also investigated. Gas chromatography-mass spectrometry analysis revealed the presence of 21 volatile compounds in the headspace, which was predominantly enriched with benzenoid compounds. Among these benzenoids, o-diethylbenzene and p-diethylbenzene were the major compounds followed by benzyl acetate and methyl salicylate. Among the phenylpropanoid compounds, 2-phenylethyl acetate was the major volatile. However, as compared to benzenoids, the quantity was much lesser, indicating the inclination of phenylalanine flux towards benzenoid pathway. The outcome of this study has the implications in enhancing fragrance and vase life of orchids of the Sikkim Himalaya region and thus may further help to meet the growing market demand.


The state of ADP or ATP fixed to the mitochondria by bongkrekate.
The reported studies are intended to clarify the binding state of ADP fixed to mitochondria under the influence of bongkrekate, and thus to discern between the affinity increase and reorientation mechanism proposed for the bongkrekate effect. (a) The composition of the intramitochondrial adenine nucleotide pool is not changed under the influence of bongkrekate with and without added nucleotides. (b) The added ADP and ATP fixed by bongkrekate can be identified as AMP, ADP and ATP in the same proportions as in the endogenous pool. (c) The bound nucleotides respond to oxidative phosphorylation or uncoupler stimulated dephosphorylation similar as endogenous nucleotides. It can be concluded that the ADP or ATP fixed under the influence of bongkrekate to the mitochondria are equilibrated with the intramitochondrial adenine nucleotide pool and are active in intramitochondrial phosphate transfer reactions. The results disagree with the affinity increase mechanism but support the reorientation mechanism which postulates that ADP and ATP are trapped in the mitochondria under the influence of bongkrekate in the same amount as there are carrier sites available outside before bongkrekate addition.


Myelin basic protein-primed T cells induce neurotrophins in glial cells via alphavbeta3 [corrected] integrin.
Increasing the level of neurotrophins within the central nervous system may have therapeutic efficacy in patients with various neurological diseases. Earlier we have demonstrated that myelin basic protein (MBP)-primed T cells induce the expression of various proinflammatory molecules in glial cells via cell-to-cell contact. Here we describe that after Th2 polarization by gemfibrozil or other drugs, MBP-primed T cells induced the expression of neurotrophic molecules such as brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3), but not proinflammatory molecules in microglia and astroglia via cell-to-cell contact. MBP-primed Th2 cells expressed alpha5 and beta3 integrins and functional blocking antibodies against both alpha5 and beta3 integrins inhibited the ability of MBP-primed Th2 cells to induce glial neurotrophins. On the other hand, glial cells expressed PDGF-Rbeta and neutralization of this glial receptor abrogated the ability of Th2 cells to induce neurotrophins in glia. Activation of glial cAMP response element-binding protein (CREB) by MBP-primed Th2 cell contact and inhibition of contact-mediated expression of neurotrophins by antisense knockdown of glial CREB suggest that MBP-primed Th2 cell-glia contact induces the expression of neurotrophins through glial activation of CREB. Accordingly, blocking of either alpha5beta3 integrins on T cells or PDGF-Rbeta on glial cells impaired the ability of MBP-primed Th2 cells to induce glial activation of CREB. Furthermore, we demonstrate that these MBP-primed Th2 cells entered into the central nervous system and increased the expression of neurotrophins in vivo in the brain. This study illuminates the importance of alpha5beta3 and PDGF-Rbeta in guiding the novel neurotrophic property of neuroantigen-primed T cells via activation of CREB that may be of therapeutic importance in various neurological disorders.


Bioethical Dimensions of International Cooperation for Health: still a controversial issue?
This essay stresses the importance of undertaking a critical analysis of international cooperation for health based upon reflections on diplomacy, acknowledging the ethical limits and possibilities of cooperation within this context. It emphasizes the importance of adopting an historical perspective, highlighting the circumstances surrounding the consolidation of the current international system, whereby, after two world wars, the victorious countries created the United Nations Organization, which today brings together all the world's nations, notwithstanding the fact that the majority of countries are in favor of significant changes to its institutional framework. It also stresses the importance of the bioethics dimension, despite the systematic disregard of principles adopted in relevant UN documents, especially in view of inequalities pari passu with asymmetries of knowledge and enjoyment of innovations that separate nations. This reflection also suggests that South-South cooperation is fundamental to the analysis of the inequality and dependence that demarcate North-South and East-West bipolarity. These reflections are, in short, important guiding elements for deepening analysis and resolutions in the arena of international cooperation for health, leaving aside catastrophic visions and idealistic illusions.


The temporal relationship in arterial and venous prostacyclin and thromboxane activity during 24 hours of intraaortic balloon counterpulsation in dogs.
We studied the effects of intraaortic balloon counterpulsation (IABCP) on prostacyclin (PGI2) and thromboxane (TXB2) levels in dogs during 24 hours of 1:1 IABCP or a sham procedure in which the balloon was positioned but left deflated. The arterial PGI2 levels in the IABCP group increased from control values of 95 +/- 20 pg/ml to 268 +/- 95 pg/ml at 1 hour, 429 +/- 95 pg/ml at 4 hours, and 1,884 +/- 532 pg/ml at 24 hours. The arterial PGI2 levels were consistently higher in the IABCP group. Although the TXB2 measurements revealed no significant differences between groups, the IABCP group consistently had a higher level than the sham group. The platelet count in the control group decreased to 45% of baseline levels versus 55% for the IABCP group. We conclude that prolonged IABCP results in either net production of PGI2 or decreased degradation. The correlation between TXB2 and platelet counts is unclear and remains to be defined.


Antiarrhythmic effects of selective prolongation of refractoriness. Electrophysiologic actions of sematilide HCl in humans.
Recent data have suggested that antiarrhythmic agents that act largely by delaying conduction may not be as effective in controlling ventricular arrhythmias as those that prolong repolarization. Recently, numerous "pure" class III agents have been developed. The antiarrhythmic and electrophysiologic profiles of sematilide, a "pure" class III agent, were determined in 27 patients with clinical ventricular arrhythmias and inducible sustained ventricular tachycardia during electrophysiologic study. After treatment with oral sematilide (mean dose, 133 +/- 29 mg every 8 hours), the patients underwent repeat 24-hour ambulatory ECG monitoring and electrophysiologic study. The baseline sinus cycle length and QT, QTc, JT, and JTc intervals were significantly increased 8 to 17% by sematilide (P = .001 to .029). There were no changes in the PR or QRS intervals. Sematilide (at a paced cycle length of 600 ms) significantly increased the atrial effective refractory period (238 +/- 32 to 264 +/- 32 ms; 11 +/- 16% increase from baseline; P = .013), atrioventricular nodal effective refractory period (296 +/- 74 to 354 +/- 71 ms; 20 +/- 19%; P = .029), and right ventricular effective refractory period (252 +/- 25 to 281 +/- 30 ms; 12 +/- 8%; P < .001) but did not significantly change the PA or HV intervals, the corrected sinus node recovery time, or the Wenckebach cycle length. Determination of the frequency-dependent effects of sematilide (n = 10) on the right ventricular monophasic action potential duration (APD90) during ventricular pacing at cycle lengths of 600 to 300 ms revealed that the APD90 was significantly prolonged by sematilide during ventricular pacing at 600 to 350 ms (APD90 increase of 40 +/- 17, 27 +/- 21, 18 +/- 18, and 14 +/- 15 ms, respectively) but not at 300 ms (APD increase of 13 +/- 19 ms). Sematilide significantly prolonged the APD90 to a greater degree at longer than at shorter cycle lengths (P = .02). The ventricular effective refractory period had a similar reverse frequency-dependent relation as the APD90. Sematilide had no effect on the ventricular effective refractory period-to-APD90 ratio or on ventricular conduction. Sematilide suppressed the induction of sustained ventricular tachycardia in 41% of all patients exposed to sematilide. Prolongation of ventricular refractoriness was correlated with ventricular tachycardia suppression. The right ventricular effective refractory period (at 600 ms) increased by 38 +/- 14 ms in patients whose sustained ventricular tachycardia was suppressed by sematilide and by 19 +/- 18 ms in patients not suppressed (P = .015). One patient developed short runs of pause-dependent nonsustained ventricular tachycardia. Eight patients were placed on long-term sematilide therapy, and during a mean follow-up period of 7.0 +/- 7.5 months, two patients developed sudden cardiac death, and one additional patient had recurrent sustained ventricular tachycardia. The electrophysiologic profile of sematilide is consistent with selective block of outward potassium currents and associated isolated lengthening of the ventricular effective refractory period and APD; sematilide demonstrates a significant degree of reverse frequency-dependence of the ventricular APD and effective refractory period; and suppression of ventricular tachycardia inducibility by sematilide appears to be correlated with increases in the right ventricular effective refractory period.


Learning curves and procedural times in Senhance®-robotic assisted fundoplication: results from 237 consecutive patients undergoing robotic fundoplication in a single center as part of the European TRUST Robotic Surgery Registry Study.
Gastroesophageal reflux disease requiring an operative solution is common. Minimally invasive surgery to generate an anti-reflux barrier at the distal esophagus following the principle of the "floppy Nissen" technique has become the gold standard. Advanced robotic-assisted systems may deliver more consisted outcomes. This registry study analyzed safety and efficacy of the Senhance® surgical system in the surgical treatment of reflux disease and procedural proficiency. Data from 237 consecutive patients operated in a single center were evaluated. Historic standard laparoscopies from the same center were analyzed to compare robotic surgery learning curve effects. Using the Senhance® Surgical System, during the first 50 patients there was a significant decrease in surgery time which was maintained over the duration of study, pointing to the surgical staff's system-specific learning. After this phase, procedural times were comparable between the robotic-assisted and traditional laparoscopic surgery. The effect of learning was greater than for standard laparoscopy. For 237 patients, there were four conversions to laparoscopic surgery. Two serious adverse events were recorded, both cardiac in nature and not related to the use of the robot. Robotic fundoplication was swiftly implemented in a non-university hospital with 65 surgical beds. The operating time was no longer than in standard laparoscopy, the procedure was more standardized than open or laparoscopic surgery and hospitalization times may have been sustainably shortened. The autonomy at the system's digital platform (cockpit) to conduct robotic fundoplications is a big step forward in surgery.


[An attempt to treat esophageal cancer by intraoperative local administration of oil bleomycin].
Intraoperative local chemotherapy was performed on patients with esophageal cancer, using oil bleomycin (oil BLM). Oil BLM was injected into the muscular layer of the thoracic esophagus to be resected, 2 ml (30 mg of BLM base) each near the anal and oral stumps of the esophagus. BLM concentrations in the regional lymph nodes which were determined were elevated, and the tumor tissue of the esophagus also showed high levels. The evidence has been recognized in this study that oil BLM which features lymphogenous transport and tissue accumulation spreads fast in the entire esophageal wall and is transported to and retained in the regional lymph nodes. Side effects from local administration of oil BLM or recurrence of cancer has not so far been observed. Judging from the results of this study, intraoperative local administration of oil BLM seems to be effective for adjuvant chemotherapy.


Draft Genome Sequence of Limisphaera ngatamarikiensis NGM72.4T, a Moderately Alkaliphilic Thermophile Belonging to the Class Verrucomicrobiae.
Limisphaera ngatamarikiensis NGM72.4T is a thermophilic representative of the class Verrucomicrobiae Isolated from geothermally heated subaqueous clay sediments from a Ngatamariki hotspring in Aotearoa New Zealand, the 3,908,748-bp genome was sequenced using the Illumina HiSeq 2500 platform. Annotation revealed 3,083 coding sequences, including 3,031 proteins, 3 rRNA genes, and 46 tRNA genes.


Initial Results of Hypofractionated Carbon Ion Radiotherapy for Cholangiocarcinoma.
To report initial results of hypofractionated carbon ion radiotherapy (C-ion RT) for cholangiocarcinoma. Data regarding seven patients with cholangiocarcinoma treated by C-ion RT were analyzed. Prescribed doses were 52.8 Gy [relative biological effectiveness (RBE)] or 60.0 Gy (RBE) in four fractions for intrahepatic cases and 12 fractions for hilar hepatic/close to gastro-intestinal tract cases. Local control and overall survival were evaluated and toxicity was graded using Common Terminology Criteria for Adverse Events, version 4.0. The median follow-up period was 16 months. There were two patients with stage I cancer, one with stage II, one with stage III, and three with stage IVA. Local control was achieved in five out of seven patients (71%) and survival was maintained in six out of seven patients (86%). There were no occurrences of acute or late toxicity of grade 3 or higher. Initial results show that hypofractionated C-ion RT appears to be tolerated and effective for cholangiocarcinoma.


Genome-Wide Association Mapping for Yield and Related Traits Under Drought Stressed and Non-stressed Environments in Wheat.
Understanding the genetics of drought tolerance in hard red spring wheat (HRSW) in northern USA is a prerequisite for developing drought-tolerant cultivars for this region. An association mapping (AM) study for drought tolerance in spring wheat in northern USA was undertaken using 361 wheat genotypes and Infinium 90K single-nucleotide polymorphism (SNP) assay. The genotypes were evaluated in nine different locations of North Dakota (ND) for plant height (PH), days to heading (DH), yield (YLD), test weight (TW), and thousand kernel weight (TKW) under rain-fed conditions. Rainfall data and soil type of the locations were used to assess drought conditions. A mixed linear model (MLM), which accounts for population structure and kinship (PC+K), was used for marker-trait association. A total of 69 consistent QTL involved with drought tolerance-related traits were identified, with p ≤ 0.001. Chromosomes 1A, 3A, 3B, 4B, 4D, 5B, 6A, and 6B were identified to harbor major QTL for drought tolerance. Six potential novel QTL were identified on chromosomes 3D, 4A, 5B, 7A, and 7B. The novel QTL were identified for DH, PH, and TKW. The findings of this study can be used in marker-assisted selection (MAS) for drought-tolerance breeding in spring wheat.


Proteomics: a biotechnology tool for crop improvement.
A sharp decline in the availability of arable land and sufficient supply of irrigation water along with a continuous steep increase in food demands have exerted a pressure on farmers to produce more with fewer resources. A viable solution to release this pressure is to speed up the plant breeding process by employing biotechnology in breeding programs. The majority of biotechnological applications rely on information generated from various -omic technologies. The latest outstanding improvements in proteomic platforms and many other but related advances in plant biotechnology techniques offer various new ways to encourage the usage of these technologies by plant scientists for crop improvement programs. A combinatorial approach of accelerated gene discovery through genomics, proteomics, and other associated -omic branches of biotechnology, as an applied approach, is proving to be an effective way to speed up the crop improvement programs worldwide. In the near future, swift improvements in -omic databases are becoming critical and demand immediate attention for the effective utilization of these techniques to produce next-generation crops for the progressive farmers. Here, we have reviewed the recent advances in proteomics, as tools of biotechnology, which are offering great promise and leading the path toward crop improvement for sustainable agriculture.


Extracellular and protease-released pullulanases.
The extracellular form of pullulanase (EC 188.8.131.52) from Klebsiella aerogenes has been purified to homogeneity by successive chromatography through diethylaminoethyl-cellulose, Sephadex G-200, and 1,6-diaminohexane-Sepharose. In addition, the cell-bound form of pullulanase has been released by the action of a serine endopeptidase obtained from Pronase and purified to apparent homogeneity. Protease-released pullulanase has a slightly larger molecular weight and a specific activity over twice that of the extracellular protein. The properties of each of these forms of pullulanase have been compared with those reported for the detergent-released form. Each form has different features as examined by amino acid composition, specific activity, molecular weight, or inhibition pattern, which distinguish it from the other pullulanases. It is hypothesized that a single gene product consisting of a single polypeptide chain generates these different enzyme forms after selective cleavages by endogenous or applied proteases.


Primary umbilical endometriosis.
A case of primary solitary umbilical endometriosis is presented. The presentation, differential diagnosis and work-up is discussed and the literature is reviewed.


Effect of whitening toothpastes on wear and roughness of ormocer and methacrylate-based composites.
To investigate the effects of whitening toothpastes over the wear and surface roughness of ormocer and methacrylate composites. Cylindrical specimens (n=120) were prepared using methacrylate-based composites (Filtek Z350 XT, TPH3 and GrandioSO) and a pure-ormocer composite (Admira Fusion). Brushing abrasion (100,000 strokes) was performed using whitening toothpastes containing different abrasives: alumina (Colgate Ultrawhite), perlite (CloseUp Whitening) and sodium bicarbonate (Kin Progressive Whitening). Wear and roughness alteration were evaluated. Additional analyses of microhardness, degree of conversion and scanning electron microscopy were also performed. Data were separately analyzed with Kruskal-Wallis and ANOVA tests. Statistically significant differences were found for the composites and whitening toothpastes (P<0.05). For all toothpastes, GrandioSO showed lower wear than Z350 XT and Admira Fusion, although non-significant differences in relation to TPH3 were observed. For perlite and bicarbonate-based toothpastes, Z350 XT, Admira Fusion and TPH3 did not present significant differences among them for wear. For alumina-based toothpaste, Z350 XT showed higher wear than TPH3, while Admira Fusion showed intermediate values. Higher wear and roughness alteration were observed after using alumina-containing toothpaste. All composites tested showed increased roughness after brushing. Z350 XT presented the lowest roughness alteration, while Admira Fusion the highest. The alumina-containing whitening toothpaste significantly increased the wear and roughness of composites in relation to the other abrasives tested. However, using the ADA standards, the wear promoted by all whitening toothpastes tested would be considered clinically acceptable for all materials. The type of organic matrix in a composite is not the main factor that determines the wear rate, but also its interaction with the inorganic fillers and the filler content. The composite GrandioSO showed the lowest overall wear values, while Z350 XT resulted in the smoothest surfaces.


Limb salvage after vascular reconstruction followed by tissue transfer during the Global War on Terror.
Combat extremity wounds are complex and frequently require an immediate vascular reconstruction in the operational environment followed by delayed tissue coverage at a stateside medical treatment facility. The purpose of this study was to evaluate limb salvage outcomes after combat-related vascular reconstruction that subsequently required delayed soft tissue coverage during the Global War on Terror. Patients who incurred a war-related extremity injury necessitating an immediate vascular intervention followed by definitive limb reconstruction requiring flap coverage from combat injuries were reviewed. Patient demographics, types of vascular and extremity injuries, and surgical interventions were examined. Outcomes included limb salvage, primary and secondary graft patency, flap outcomes, and complications. Differences between upper extremities (UEs) and lower extremities (LEs) were compared. From 2003 to 2012, 27 patients were treated for combat-related extremity injuries with an immediate vascular reconstruction followed by delayed tissue coverage. Fifteen LEs and 12 UEs were treated. The mean age was 24 years. An explosion was the cause in 77% of patients, with a mean Injury Severity Score (ISS) of 19. An autogenous vein bypass was the most common reconstruction performed in 20 patients (74%). Other vascular repairs included a primary repair, a patch angioplasty with bovine pericardium, and a bypass with use of a prosthetic graft. Eight patients (30%) had a concomitant venous injury, and 23 (85%) had a bone fracture. Thirty flaps were performed at a mean of 33 days from the original injury. Pedicle flaps were used in 24 limbs and free tissue flaps in six limbs. Muscle, fasciocutaneous, bone, and composite flaps were used for tissue coverage. At a mean follow-up of 16 months, primary patency rates of all arterial reconstructions were 66% in the UE and 53% in the LE (P = .69). Secondary patency rates were 100% in the UE and 86% in the LE (P = .48). The overall limb salvage rate was 81%. Limb salvage rates were 66% in the LE and 100% in the UE (P = .04). Three amputated lower limbs (60%) had inline flow to the foot. The flap success rate was 96%. Reasons for amputation included arterial thrombosis, flap failure, persistent soft tissue infection, osteomyelitis, and debilitating peripheral nerve injuries with associated chronic pain. Immediate vascular repair followed by delayed tissue coverage can be performed with a high (>80%) limb salvage rate after combat trauma. Limb salvage rates were higher in the UE despite equivocally high arterial patency rates. Wounded warriors can expect limb salvage by use of this international algorithm.


A retrospective analysis of early and immediately loaded osseotite implants in cross-arch rehabilitations in edentulous maxillas and mandibles up to 7 years.
Immediate loading of full-arch restorations yields good results in selected cases, but long-term follow-up and the outcome in compromised bone are scarcely evaluated. To evaluate immediately loaded Osseotite implants (Biomet 3i, Palm Beach, FL, USA) installed in healed or grafted bone, with regard to implant survival and peri-implant bone loss up to 7 years in function. Information was retrospectively retrieved from 83 patients' records with 749 Osseotite implants supporting immediately loaded semipermanent full-arch acrylic restorations. Five hundred sixty-eight (75.8%) implants were placed in healed bone and 181 (24.2%) in augmented bone, regenerated with sinus lifting and/or onlay/inlay grafts with/without biomaterials and membranes. Implant survival and success based on radiological peri-implant bone loss were registered. Wilcoxon rank sum tests evaluated peri-implant bone loss in compromised versus healed bone or between jaws or time intervals with p<.05 as statistically significant. Sixteen of 749 implants failed (2.1%), 11/343 in maxilla (3.2%) and 5/406 (1.2%) in mandible. After 7 years, the cumulative failure rate was 9%. Mean peri-implant bone loss increased to 1.2 mm (SD 1.0) during the first 2 years but remained unchanged thereafter. Around implants in grafted bone, on average, 0.3 mm more bone loss was found. The Osseotite implants offer a predictable long-term outcome in terms of implant survival and stable peri-implant bone under immediate loading even in grafted bone. However, the high incidence of technical repair because of fractures of the semipermanent provisionals requires attention because it may be negative from a cost-benefit perspective. Implants in grafted bone show a tendency to a more pronounced initial bone remodeling without clinical consequence in the long term.


Evaluation of serum-free culture conditions for primary human nasal epithelial cells.
Defined culture conditions are essential for the interpretation of effects caused by volatile substances on human nasal epithelial cells (HUNEC) cultured in vitro. Conventionally, serum-containing media are used. However, the results of these experiments are of restricted value as serum contains many unknown and undefined substances. Not all serum-free media on the market are suitable for culturing primary HUNEC. Therefore, serum-free defined cell culture media were compared to evaluate optimal conditions for HUNEC and their cell lines. HUNEC were generated by trypsin digestion of mucosal tissue of the inferior turbinate. Cells were cultured on uncoated polystyrene dishes adding pre-warmed medium. Viability was controlled by trypan blue dye exclusion; colony forming units and cell morphology were controlled microscopically. The expression of different cytokeratins was studied immunocytochemically. Dulbecco's modified Eagle's medium was not suitable to grow HUNEC and passage them. HUNEC cultured in bronchial epithelial growth medium presented a more homogeneous cell morphology compared to other media and had a doubling time of 1.2 days. The maximum number of cell passages was 11 with bronchial epithelial growth medium.


Determination of beta 2-microglobulin in human urine and serum by latex immunoassay.
This highly sensitive method for determination of beta 2-microglobulin (beta 2-m) in human urine or serum is based on direct agglutination by beta 2-m of latex particles on which an antibody against beta 2-m is adsorbed. The agglutination is quantified by counting the remaining unagglutinated particles, or by turbidimetry. A novel aspect of this method is the capability to prevent nonspecific agglutination of the antibody-coated particles by diluting them with an albumin solution of well-defined characteristics (pH, freshness, concentration) just before the assay. The assayable concentration range is 1--32 micrograms/L, the detection limit 0.5 micrograms/L. Within-assay CV, based on 10 determinations of beta 2-m in urine and serum at two different dilutions, ranged from 4.6 to 8.7%. Between-assay CV, calculated from 10 determinations of beta 2-m in urine and serum, was 10 and 8.4%, respectively. Analytical recovery of beta 2-m in urine averaged 97% and in serum 104% (n = 10). No component of urine or serum interfered. Coefficients of correlation for beta 2-m in urine or serum as measured by radioimmunoassay and latex immunoassay were 0.97 and 0.93, respectively. Concentrations of beta 2-m in serum and urine from 33 healthy men (ages 20 to 67 years) averaged 1.5 mg/l and 54 micrograms/g of creatine, respectively.


Life shocks and homelessness.
We exploited an exogenous health shock-namely, the birth of a child with a severe health condition-to investigate the effect of a life shock on homelessness in large cities in the United States as well as the interactive effects of the shock with housing market characteristics. We considered a traditional measure of homelessness, two measures of housing instability thought to be precursors to homelessness, and a combined measure that approximates the broadened conceptualization of homelessness under the 2009 Homeless Emergency Assistance and Rapid Transition to Housing Act (2010). We found that the shock substantially increases the likelihood of family homelessness, particularly in cities with high housing costs. The findings are consistent with the economic theory of homelessness, which posits that homelessness results from a conjunction of adverse circumstances in which housing markets and individual characteristics collide.


Planar cell polarization: an emerging model points in the right direction.
Polarization is a feature common to many cell types. Epithelial cells, for example, exhibit a characteristic apical-basolateral polarity that is critical for their function. In addition to this ubiquitous form of polarity, whole fields of cells are often polarized in a plane perpendicular to the apical-basal axis. This form of polarity, referred to as planar cell polarity (PCP), exists in all adult Drosophila cuticular tissues, as well as in numerous vertebrate tissues, including the mammalian skin and inner ear epithelia. Recent advances in the study of PCP establishment are beginning to unravel the molecular mechanisms underlying this cellular process. This review discusses new developments in the molecular understanding of PCP in Drosophila and vertebrates and integrates the current data in a model to illustrate how interactions between PCP factors might function to generate planar polarity.


Experiences in the management of anastomotic leakages and analysis of the factors affecting leakage healing in patients with esophagogastric junction cancer.
It was reported in the literatures that the incidence of anastomotic leakage in patients with esophagogastric junction cancer decreased due to application of staplers and closure devices as well as gastric conduit technique in recent years, however, it increased slightly at our center since widely using the above devices and gastric conduit techniques from 2009. The objective of this study was to summarize our experiences in the management of anastomotic leakages and analyze the factors affecting leakage healing in the patients with esophagogastric junction cancer after surgical resection in recent 6 years. All patients who received surgical resections for esophagogastric junction cancer and diagnosed anastomotic leak at our center between January 2009 and December 2014 were retrospectively analyzed, we also enrolled the patients who had a longer hospital stay (>30 days) as they may develop anastomotic leak. The binary logistic regression in SPSS 16.0 was applied to analyze the factors that may affect leakage healing. Of the 1,815 surgically treated esophagogastric junction cancer patients, 91 cases were diagnosed anastomotic leakage postoperatively. The patients were divided into two groups based on the median leakage healing time (40 days) in this series: fast healing group (37 cases) and slowly healing group (54 cases). All factors that may affect the leakage healing were put into analysis by using binary logistic regression. The results of the analysis showed that leakage size (OR =1.073, P=0.004), thoracic drainage (OR =12.937, P=0.037) and smoking index ≤400 (OR =1.001, P=0.04) significantly affected the healing time, while drinking history (P=0.177), duration of fever after anastomotic leak developed (P=0.084), and hypoproteinemia after leak (P=0.169) also apparently but not significantly affect the healing time. Though many factors may affect leakage healing in the esophagogastric junction carcinoma patients, leakage size, thoracic drainage and smoking index (≤400) are the most important factors affecting the leakage healing. Placement of a chest tube beside the anastomosis area during operation for early identification and control of an anastomotic leak to minimize contamination of the mediastinum is the most important way to promote leakage healing. A chest tube placing into the purulent cavities after the patients experienced leaks is also important for the cure of leakage. More attention should be paid perioperatively to the patients who had a smoking index (≥400) and the patients who suffered fever or hypoproteinemia.


Proteasomes control caspase-1 activation in anthrax lethal toxin-mediated cell killing.
Activation of caspase-1 through the inflammasome protein Nalp1b controls anthrax lethal toxin (LT)-induced necrosis in murine macrophages. In this study we analyzed physiological changes controlled by caspase-1 in LT-treated murine macrophages. The caspase-1 inhibitor Boc-D-cmk blocked caspase-1 activity and membrane impairment in LT-treated cells. To determine the relationship between caspase-1 activation and membrane integrity, we added Boc-D-cmk to J774A.1 macrophages at different time points following LT exposure. Remarkably, Boc-D-cmk rescued LT-treated macrophages, even when added at the peak of caspase-1 activation. Late addition of the caspase-1 inhibitor reversed the losses of plasma membrane integrity and metabolic activity in these cells. Similar results were obtained with the proteasome inhibitor MG132, one of the most potent inhibitors of LT toxicity. LT-treated macrophages displaying evidence of membrane impairment recovered upon the addition of MG132, mirroring the Boc-D-cmk response. Strikingly, late addition of proteasome inhibitors also abrogated caspase-1 activity in LT-treated macrophages. Proteasomal control of caspase-1 activity and membrane impairment, however, was restricted to LT-induced cytolysis, because proteasome inhibitors did not block caspase-1 activation and cell death triggered by lipopolysaccharide and nigericin. Our findings indicate that proteasome inhibitors do not target caspase-1 directly but instead control an upstream event in LT-treated macrophages leading to caspase-1 activation. Taken together, caspase-1-mediated necrosis appears to be tightly controlled and differentially regulated by proteasomes depending on the source of caspase-1 induction.


Subcellular localization of hexokinase in pea leaves. Evidence for the predominance of a mitochondrially bound form.
Hexokinase (ATP: D-hexose-6-phosphotransferase, EC 22.214.171.124) activity was determined in subcellular fractions prepared from pea (Pisum sativum) leaf homogenates. About 60% of the total detectable activity of hexokinase was found associated with a particulate fraction consisting essentially of mitochondria and chloroplasts and free of cytosol contamination. The hexokinase specific activity of the particulate fraction was 2-fold higher than that of the homogenate and about 4-fold higher than that of the cytosol. Using a specially designed isokinetic-isopycnic sucrose density gradient centrifugation method, the distribution of hexokinase activity correlated with that of the mitochondrial marker (cytochrome oxidase) and not with that of the chloroplast membrane marker ( chlorophyll ) or that of the cytosol marker (phosphoenolpyruvate carboxylase). Thus, the hexokinase/mitochondria ratio was close to 1.0 along the entire gradient, while the hexokinase/chloroplast ratio varied over a 10-fold range. The results strongly suggest that hexokinase is predominantly bound to mitochondria of pea leaves, and that pea leaf chloroplasts are essentially devoid of any specifically associated hexokinase activity. This work provides the first demonstration of a specific association of hexokinase with mitochondria from photosynthetic tissues of higher plants.


[Psoriasis comorbidities].
Psoriasis is a chronic inflammatory skin disease affecting 2-4 % of Central European population. Nowadays, we know that psoriasis is not limited to the skin but is connected with several comorbidities like, psoriatic arthritis (around 25 %), Crohn's disease, ulcerative colitis, Bechterev, non-alcoholic liver steatosis, psychiatric disorders and mainly diseases of the so called metabolic syndrome, like diabetes mellitus type 2, arterial hypertension or dyslipidemia. In the last years, new information is arising which connect psoriasis with sleep apnoe and chronic obstructive pulmonary disease.


Systemic Immune Response and Cancer Risk: Filling the Missing Piece of Immuno-Oncology.
While immuno-oncology has made significant advances in activating local tumor immune responses, leading to improved outcomes, the role of systemic immunity in cancer incidence remains poorly understood. Le Cornet and colleagues prospectively studied circulating immune cells quantified by DNA methylation markers in relation to incidence of breast, colorectal, lung, and prostate cancer among initially healthy individuals. A positive association with cancer risk was observed for higher FOXP3+ T-cell-mediated immune tolerance and lower CD8+ T-cell-mediated cytotoxicity. Further studies of systemic immunity in cancer development are crucial to identify novel prediction markers and interventional targets for cancer immunoprevention.See related article by Le Cornet et al., p. 1885.


Cushing's disease presenting as pubertal arrest.
The clinical features of Cushing's disease in childhood are usually abnormal fat distribution, moon face, growth failure and hirsutism. Laboratory studies include evidence of cortisol and ACTH hypersecretion. This report concerns a boy who presented only with arrested puberty and growth failure as physical evidence of Cushing's syndrome and showed rapid progression of puberty once pituitary adenomas were removed.


The Role of PEDF in Pancreatic Cancer.
Pigment epithelium-derived factor (PEDF) is an important antiangiogenic and antitumorigenic factor in a variety of cancer forms, including pancreatic cancer. PEDF is mainly secreted as a soluble monomeric glycoprotein. In human pancreatic cancer PEDF levels are decreased, both in the tissue and serum. The decrease is associated with increased tumor angiogenesis, fibrosis, inflammation, autophagy, occurrence of liver metastasis and worse prognosis. In murine models, loss of PEDF is sufficient to induce invasive carcinoma and this phenotype is associated with large lesions characterized by poor differentiation. Lentiviral gene transfer of PEDF has resulted in decreased microvessel density and has inhibited tumor growth. Herein we review the multifunctional role of PEDF in pancreatic cancer and its therapeutic potential.


Differential mutation profiles and similar intronic TP53 polymorphisms in asbestos-related lung cancer and pleural mesothelioma.
Given the interest in defining biomarkers of asbestos exposure and to provide insights into asbestos-related and cell-specific mechanisms of neoplasia, the identification of gene alterations in asbestos-related cancers can help to a better understanding of exposure risk. To understand the aetiology of asbestos-induced malignancies and to increase our knowledge of mesothelial carcinogenesis, we compared genetic alterations in relevant cancer genes between lung cancer, induced by asbestos and tobacco smoke, and malignant pleural mesothelioma (MPM), a cancer related to asbestos, but not to tobacco smoke. TP53, KRAS, EGFR and NF2 gene alteration analyses were performed in 100 non-small cell lung cancer (NSCLC) patients, 50 asbestos-exposed and 50 unexposed patients, matched for age, gender, histology and smoking habits. Detailed assessment of asbestos exposure was based on both specific questionnaires and asbestos body quantification in lung tissue. Genetic analyses were also performed in 34 MPM patients. TP53, EGFR and KRAS mutations were found in NSCLC with no link with asbestos exposure. NF2 was only altered in MPM. Significant enhancement of TP53 G:C to T:A transversions was found in NSCLC from asbestos-exposed patients when compared with unexposed patients (P = 0.037). Interestingly, TP53 polymorphisms in intron 7 (rs12947788 and rs12951053) were more frequently identified in asbestos-exposed NSCLC (P = 0.046) and MPM patients than in unexposed patients (P < 0.001 and P = 0.012, respectively). These results emphasise distinct genetic alterations between asbestos-related thoracic tumours, but identify common potential susceptibility factors, i.e. single nucleotide polymorphisms in intron 7 of TP53. While genetic changes in NSCLC are dominated by the effects of tobacco smoke, the increase of transversions in TP53 gene is consistent with a synergistic effect of asbestos. These results may help to define cell-dependent mechanisms of action of asbestos and identify susceptibility factors to asbestos.


Bioinformatics resources for pollen.
Bioinformatics for Pollen. Pollen plays a key role in crop production, and its development is the most delicate phase in reproduction. Different metabolic pathways are involved in pollen development, and changes in the level of some metabolites, as well as responses to stress, are correlated with the reduction in pollen viability, leading consequently to a decrease in the fruit production. However, studies on pollen may be hard because gamete development and fertilization are complex processes that occur during a short window of time. The rise of the so-called -omics sciences provided key strategies to promote molecular research in pollen tissues, starting from model organisms and moving to increasing number of species. An integrated multi-level approach based on investigations from genomics, transcriptomics, proteomics and metabolomics appears now feasible to clarify key molecular processes in pollen development and viability. To this aim, bioinformatics has a fundamental role for data production and analysis, contributing varied and ad hoc methodologies, endowed with different sensitivity and specificity, necessary for extracting added-value information from the large amount of molecular data achievable. Bioinformatics is also essential for data management, organization, distribution and integration in suitable resources. This is necessary to catch the biological features of the pollen tissues and to design effective approaches to identifying structural or functional properties, enabling the modeling of the major involved processes in normal or in stress conditions. In this review, we provide an overview of the available bioinformatics resources for pollen, ranging from raw data collections to complete databases or platforms, when available, which include data and/or results from -omics efforts on the male gametophyte. Perspectives in the fields will also be described.


Aqueous extract of Codium fragile suppressed inflammatory responses in lipopolysaccharide-stimulated RAW264.7 cells and carrageenan-induced rats.
Codium fragile (Suringar) Hariot has been used in Oriental medicine for the treatment of enterobiasis, dropsy, and dysuria and has been shown to have various biological effects. In this study, we evaluated the anti-inflammatory effects of aqueous extract of C. fragile (AECF) using in vitro and in vivo models. Nitric oxide (NO), prostaglandin E2 (PGE2), inflammatory-related mRNAs, and proteins were determined using the Griess assay, enzyme-linked immunosorbent assay (ELISA), reverse transcription-polymerase chain reaction (RT-PCR), and western blotting, respectively. Our results indicate that pretreatment of cells with AECF (50, 100 and 200μg/mL) significantly inhibited LPS-induced secretion of NO and PGE2 in RAW264.7 cells without cytotoxicity. We also found that AECF (100 and 200μg/mL) inhibited LPS-induced inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 expression in a dose-dependent manner. Additionally, pretreatment of cells with AECF (100 and 200μg/mL) inhibited LPS-induced production of inflammatory cytokines including tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6. It also prevented the nuclear translocation of nuclear factor (NF)-κB by suppressing the phosphorylation and degradation of inhibitor of NF-κB (IκB)-α. Furthermore, AECF (100 and 200μg/mL) inhibited the phosphorylation of the mitogen-activated protein kinases (MAPKs) extracellular signal-regulated kinase (ERK) 1/2, c-Jun N-terminal kinase (JNK), and p38. In addition, orally administered 50, 100, and 200mg/kg body weight of AECF dose-dependently suppressed carrageenan-induced rat paw edema thickness by 6%, 31%, and 50% respectively, after 4h. Furthermore, the anti-inflammatory effect was comparable to that observed in animals treated with the standard drug diclofenac sodium (56%) in vivo. Collectively, our results suggest that AECF exerts potential anti-inflammatory effects by suppressing NF-κB activation and MAPKs pathways in vitro, as well as inhibiting carrageenan-induced rat paw edema thickness in vivo. These findings indicate that AECF could be further developed as an anti-inflammatory drug.


Is there unity within the discipline?
This paper will examine a claim that nursing is united by its moral stance. The claim is that there are moral constraints on nurses' actions as people practising nursing (nurses qua nurses) and that they are in some way different from both what for now can be called standard morality and also different from the person's own moral views who also happens to be a nurse, hence the defining and unifying factor for nursing. I will begin by situating the claim within the broader area about the need for a definition to state features that are essential to all and only members of its class. This will highlight the fact that there are two distinct types of definition used by authors seeking to find a unity for nursing. One type of definition has to do with goals or purposes given to nursing and the other with ends discovered as nursing. But even if there are ends waiting to be discovered a particular practical concern is how we can have knowledge of them. I will suggest that knowledge by intuition is plausible but that as things currently stand in moral epistemology it will not provide the unifying ground for nursing. Then I will argue that in the latter approach to definition a certain account of human nature has been advanced in order to provide features that are there to be discovered and so not dependent on human beings for the definition or classification. However, such an attempt to define nursing cannot do what is wanted. Rather than the account of human nature grounding morality and doing so for nursing, the account of human nature itself relies upon a prior account of morality. Because of this it loses its supposed ground of unity for the profession. Nursing is not united by its moral stance especially if this is understood in a strong sense as unique moral stance, but as things currently stand in moral epistemology this is not necessarily a bad thing for practitioners or patients.


Crop Management Impacts the Soybean (Glycine max) Microbiome.
Soybean (Glycine max) is an important leguminous crop that is grown throughout the United States and around the world. In 2016, soybean was valued at $41 billion USD in the United States alone. Increasingly, soybean farmers are adopting alternative management strategies to improve the sustainability and profitability of their crop. Various benefits have been demonstrated for alternative management systems, but their effects on soybean-associated microbial communities are not well-understood. In order to better understand the impact of crop management systems on the soybean-associated microbiome, we employed DNA amplicon sequencing of the Internal Transcribed Spacer (ITS) region and 16S rRNA genes to analyze fungal and prokaryotic communities associated with soil, roots, stems, and leaves. Soybean plants were sampled from replicated fields under long-term conventional, no-till, and organic management systems at three time points throughout the growing season. Results indicated that sample origin was the main driver of beta diversity in soybean-associated microbial communities, but management regime and plant growth stage were also significant factors. Similarly, differences in alpha diversity are driven by compartment and sample origin. Overall, the organic management system had lower fungal and bacterial Shannon diversity. In prokaryotic communities, aboveground tissues were dominated by Sphingomonas and Methylobacterium while belowground samples were dominated by Bradyrhizobium and Sphingomonas. Aboveground fungal communities were dominated by Davidiella across all management systems, while belowground samples were dominated by Fusarium and Mortierella. Specific taxa including potential plant beneficials such as Mortierella were indicator species of the conventional and organic management systems. No-till management increased the abundance of groups known to contain plant beneficial organisms such as Bradyrhizobium and Glomeromycotina. Network analyses show different highly connected hub taxa were present in each management system. Overall, this research demonstrates how specific long-term cropping management systems alter microbial communities and how those communities change throughout the growth of soybean.


Mitochondrial DNA sequence variation in Iranian native dogs.
The dog mtDNA diversity picture from wide geographical sampling but from a small number of individuals per region or breed, displayed little geographical correlation and high degree of haplotype sharing between very distant breeds. For a clear picture, we extensively surveyed Iranian native dogs (n = 305) in comparison with published European (n = 443) and Southwest Asian (n = 195) dogs. Twelve haplotypes related to haplogroups A, B and C were shared by Iranian, European, Southwest Asian and East Asian dogs. In Iran, haplotype and nucleotide diversities were highest in east, southeast and northwest populations while western population had the least. Sarabi and Saluki dog populations can be assigned into haplogroups A, B, C and D; Qahderijani and Kurdi to haplogroups A, B and C, Torkaman to haplogroups A, B and D while Sangsari and Fendo into haplogroups A and B, respectively. Evaluation of population differentiation using pairwise FST generally revealed no clear population structure in most Iranian dog populations. The genetic signal of a recent demographic expansion was detected in East and Southeast populations. Further, in accordance with previous studies on dog-wolf hybridization for haplogroup d2 origin, the highest number of d2 haplotypes in Iranian dog as compared to other areas of Mediterranean basin suggests Iran as the probable center of its origin. Historical evidence showed that Silk Road linked Iran to countries in South East Asia and other parts of the world, which might have probably influenced effective gene flow within Iran and these regions. The medium nucleotide diversity observed in Iranian dog calls for utilization of appropriate management techniques in increasing effective population size.


Delayed contrast dynamics as marker of regional impairment in pulmonary fibrosis using 5D MRI - a pilot study.
To analyse delayed contrast dynamics of fibrotic lesions in interstitial lung disease (ILD) using five dimensional (5D) MRI and to correlate contrast dynamics with disease severity. 20 patients (mean age: 71 years; M:F, 13:7), with chronic fibrosing ILD: n = 12 idiopathic pulmonary fibrosis (IPF) and n = 8 non-IPF, underwent thin-section multislice CT as part of the standard diagnostic workup and additionally MRI of the lung. 2 min after contrast injection, a radial gradient echo sequence with golden-angle spacing was acquired during 5 min of free-breathing, followed by 5D image reconstruction. Disease was categorized as severe or non-severe according to CT morphological regional severity. For each patient, 10 lesions were analysed. IPF lesions showed later peak enhancement compared to non-IPF (severe: p = 0.01, non-severe: p = 0.003). Severe lesions showed later peak enhancement compared to non-severe lesions, in non-IPF (p = 0.04), but not in IPF (p = 0.35). There was a tendency towards higher accumulation and washout rates in IPF compared to non-IPF in non-severe disease. Severe lesions had lower washout rate than non-severe ones in both IPF (p = 0.003) and non-IPF (p = 0.005). Continuous contrast agent accumulation, without washout, was found only in IPF lesions. Contrast agent dynamics are influenced by type and severity of pulmonary fibrosis, which might enable a more thorough characterisation of disease burden. The regional impairment is of particular interest in the context of antifibrotic treatments and was characterised using a non-invasive, non-irradiating, free-breathing method. Delayed contrast enhancement patterns allow the assessment of regional lung impairment which could represent different disease stages or phenotypes in ILD.


Cdk5-Mediated Brain Unfolded Protein Response Upregulation Associated with Cognitive Impairments in Type 2 Diabetes and Ameliorative Action of NAC.
The role of cyclin-dependent kinase 5 (Cdk5) in the normal functioning of the central nervous system and synaptic plasticity is well established. However, dysregulated kinase activity can have a significant impact on neurodegeneration and cognitive impairment. Cdk5 hyperactivation is linked to diabetes-associated neurodegeneration, but the underlying mechanism is not fully understood. Our study reveals that oxidative stress can lead to Cdk5 hyperactivity, which in turn is linked to neurodegeneration and cognitive impairment. Specifically, our experiments with N2A cells overexpressing Cdk5 and its activators p35 and p25 show ER stress, resulting in activation of the unfolded protein response (UPR) pathway. We identified Cdk5 as the epicenter of this regulatory process, leading to the activation of the CDK5-IRE1-XBP1 arm of UPR. Moreover, our study demonstrated that Cdk5 hyperactivation can lead to ER stress and activation of the UPR pathway, which may contribute to cognitive impairments associated with diabetes. Our findings also suggest that antioxidants such as NAC and GSH can decrease deregulated Cdk5 kinase activity and rescue cells from UPR-mediated ER stress. The accumulation of phosphorylated Tau protein in AD brain protein has been widely described earlier. Notably, we observed that oral treatment with NAC decreased Cdk5 kinase activity in the hippocampus, attenuated high levels of phospho-tau (ser396), and ameliorated memory and learning impairments in a type 2 diabetic (T2D) mouse model. Additionally, the high-fat-induced T2D model exhibits elevated phospho-tau levels, which are rescued by the NAC treatment. Taken together, these results suggest that targeting Cdk5 may be a promising therapeutic strategy for treating diabetes-associated cognitive impairments.


Automatic detection and segmentation of postoperative cerebellar damage based on normalization.
Surgical resection is the gold standard in the treatment of pediatric posterior fossa tumors. However, surgical damage is often unavoidable and its association with postoperative complications is not well understood. A reliable localization and measure of cerebellar damage is fundamental to study the relationship between the damaged cerebellar regions and postoperative neurological outcomes. Existing cerebellum normalization methods are likely to fail on postoperative scans, therefore current approaches to measure postoperative damage rely on manual labelling. In this work, we develop a robust algorithm to automatically detect and measure cerebellum damage in postoperative 3D T1 magnetic resonance imaging (MRI). In our approach, normal brain tissues are first segmented using a Bayesian algorithm customized for postoperative scans. Next, the cerebellum is isolated by nonlinear registration of a whole-brain template to the native space. The isolated cerebellum is then normalized into the spatially unbiased atlas (SUIT) space using anatomical information derived from the previous step. Finally, the damage is detected in the atlas space by comparing the normalized cerebellum and the SUIT template. We evaluated our damage detection tool on postoperative scans of 153 patients with medulloblastoma based on inspection by human experts. We also designed a simulation to evaluate performance without human intervention and with an explicitly controlled and defined ground truth. Our results show that the approach performs adequately under various realistic conditions. We develop an accurate, robust, and fully automatic localization and measurement of cerebellar damage in the atlas space using postoperative MRI.