SPARC expression in desmoplastic and non desmoplastic pancreatic carcinoma and cholangiocarcinoma.
The pancreatobiliary carcinomas are characterized by presence of desmoplastic stroma. Overexpression of secreted protein acid and rich in cysteine (SPARC), a matrix producing agent has been documented in pancreatic ductal adenocarcinomas, with survival benefits. This study was targeted to see if SPARC expression in pancreatobiliary carcinomas is responsible for stromal desmoplasia and its prognostic significance. In this retrospective study 48 cases of pancreatic cancer and 27 cases of cholangiocarcinoma were analyzed. The expression pattern of SPARC and vascular endothelial growth factor (VEGF) (angiogenic factors) was evaluated by immunohistochemistry on formalin fixed paraffin embedded tissues. Immunoreactivity was scored semi quantitatively based on stain intensity and stain distribution. SPARC expression was correlated with tumor histology, stromal desmoplasia, VEGF expression, various histological parameters and overall survival in patients. Real time polymerase chain reaction was performed in few cases to validate the immunohistochemistry expression pattern. SPARC expression was high in peritumoral stroma in pancreatic carcinoma than in pancreatic controls; however, SPARC expression pattern was not grossly different in desmoplastic and non-desmoplastic pancreatobiliary carcinomas and in cholangiocarcinomas. No definite correlation was noted between SPARC expression and histological markers of severity and overall survival data. The relevance of SPARC expression in pancreato-biliary carcinomas though may still be important for therapeutic decision making, it is not responsible for peritumoral stromal desmoplasia in these tumors and it does not have any significant prognostic implication.


Peritoneal seeding of embolic beads after uterine artery embolization.
Incidental identification of peritoneal nodules during laparoscopy may present a diagnostic dilemma. The differential diagnosis includes a variety of benign and malignant entities such as peritoneal carcinomatosis. A 44-year-old G2P2 woman presented with recurrent menorrhagia and pelvic pain was found to have large uterine fibroids on imaging studies. Bilateral uterine artery embolization was performed with complete devascularization of the fibroid. Seven years later, she presented with similar symptoms. Imaging studies demonstrated a vascular uterine lesion. A total laparoscopic hysterectomy with bilateral salpingectomy was performed with no complications. During surgery, vesicular peritoneal implants were incidentally identified posterior to the uterus between the uterosacral ligaments. Biopsy and pathologic analysis of these nodules confirmed that they contained foreign material consistent with embolization beads. Pathologic analysis of the uterus demonstrated an intramural uterine fibroid, and presence of embolization beads in cervix, myometrium and bilateral peritubal regions. Non-target peritoneal implantation of embolic beads after uterine artery embolization is a rare entity that can result in vesicular appearing nodules.


Stability of periodic travelling wave solutions of a nerve conduction equation.
Nagumo's nerve conduction equation has travelling wave solutions of pulse type and periodic wave type. We consider the stability of the latter ones. We denote by L(c) the minimum spatial period of a periodic travelling wave solution whose propagation speed is c. It is shown that this travelling wave solution is unstable if L'(c) less than 0.


Inhibition of rat cervical epithelial cell growth by heparin and its reversal by EGF.
The effects of heparin on the in vitro growth of rat cervical epithelial cells were examined. Heparin was found to inhibit in a dose dependent fashion the log-phase growth of rat cervical epithelial cells (RCEC) grown in the absence of medium supplements. An inhibition of growth is observed at concentrations as low as 500 ng/ml and 50% inhibition of growth occurs at a concentration of 5 micrograms/ml. The growth inhibitory activity of heparin is independent of anticoagulant activity since three separate non-anticoagulant preparations of heparin all inhibit growth. Other glycosaminoglycans including chondroitin 4-sulfate, chondroitin 6-sulfate, dermatan sulfate, hyaluronic acid, and keratin sulfate do not inhibit the growth of rat cervical epithelial cells. The ability of heparin to inhibit the log-phase growth of rat cervical epithelial cells is dependent on the composition of the medium in which the cells are grown. The addition of greater than or equal to 7.5 ng/ml epidermal growth factor to epithelial cultures blocks the growth inhibitory activity of heparin. These results suggest that components of the extracellular matrix modulate the growth responses of epithelial cells and may be important in regulating cellular proliferation in normal and pathological states.


Adverse events during hospitalization: results of a patient survey.
A two-stage probability sample of patients recently discharged from 16 general acute care hospitals in Massachusetts were interviewed to determine the rates at which patients experience what they considered to be adverse events, to describe the kinds of events they reported, and to identify the correlates of those reports. Eligible respondents were adults, 18 years of age or older, who were medical or surgical patients overnight or longer between April 1 and October 1, 2003, and who were discharged to their homes in Massachusetts. Questions covered perceptions of adverse events during hospitalizations and possible correlates of those events. Telephone interviews were carried out an average of nine months after discharge with 2,582 patients (response rate, 53%-60%). Twenty-nine percent of respondents reported at least one unexpected "negative" event during their hospitalization. After physician review, the revised estimate was that 25% perceived that they had experienced at least one event that met our definition for an adverse event. The most common reported events were reactions to newly prescribed drugs (40%) and the effects of surgery (34%). Physician reviewers coded 57% of the adverse events as "significant" and 18% as "serious" or "life-threatening." The physician reviewers also rated 31% of the reported adverse events as likely to be preventable. The estimate that one in four hospital patients experienced an adverse event is considerably higher than the published rates based on hospital record review, indicating the potential value of surveys for studies of patient safety. Because of nonresponse among older patients, that estimate is probably an underestimate. Designs that would reduce lags between discharge and interviews and decrease hospital nonresponses would reduce two key threats to confidence in the survey results.


Association between breastfeeding and eruption of the first tooth in preschool children in Nigeria.
This study specifically examines the effect of the form and duration of breastfeeding on the timing of eruption of the first tooth in Nigerian children The study included 398 children aged 6 months to 71 months. The mothers were asked to provide information on the duration and form of breastfeeding, and the age of eruption of the first deciduous teeth. The socioeconomic status (SES) of the child was calculated using the mother's level of education and the father's occupation. Intraoral examination was conducted to assess the teeth present and dentition status of the child. A tooth was considered present in the mouth when any part of the tooth was visible. There was no association found between the duration of breastfeeding (p=0.48), form of breast feeding (p=0.61), duration of exclusive breast feeding (p=0.41) and timing of eruption of the first tooth. The duration of breast feeding does not affect the timing of eruption of the first deciduous tooth, neither does the form of breastfeeding.


The evolving metabolic landscape of chromatin biology and epigenetics.
Molecular inputs to chromatin via cellular metabolism are modifiers of the epigenome. These inputs - which include both nutrient availability as a result of diet and growth factor signalling - are implicated in linking the environment to the maintenance of cellular homeostasis and cell identity. Recent studies have demonstrated that these inputs are much broader than had previously been known, encompassing metabolism from a wide variety of sources, including alcohol and microbiotal metabolism. These factors modify DNA and histones and exert specific effects on cell biology, systemic physiology and pathology. In this Review, we discuss the nature of these molecular networks, highlight their role in mediating cellular responses and explore their modifiability through dietary and pharmacological interventions.


The arcuate nucleus as a conduit for diverse signals relevant to energy homeostasis.
Arcuate nucleus neurons are known to be responsive to a wide array of hormones and nutrients, including leptin, insulin, gonadal steroids and glucose. In addition to potential transport mechanisms, peripheral substances may access these neurons via arcuate cell bodies in and projections to the median eminence, a region considered to be a circumventricular organ. The arcuate is a potent site of leptin action, probably mediating a component of leptin's effects via arcuate neuropeptide Y/agouti-related peptide (NPY/AgRP) and pro-opiomelanocortin (POMC) neurons, and implicating this structure in the long-term control of energy stores. However, ghrelin, the endogenous ligand of the growth hormone secretagogue receptor, may also stimulate feeding and weight gain, in part through action on receptors in arcuate NPY neurons. Since ghrelin is secreted by the stomach upon content depletion, with a half-life of no more than an hour, the arcuate nucleus may also be important in sensing and responding to acute changes in nutrients. We have developed a system for recording from arcuate POMC neurons using a mouse containing a transgene in which the POMC promoter is driving expression of the green fluorescent protein (GFP). In these mice, 99% of the beta-endorphin positive neurons express GFP, making whole cell patch clamp recordings from the sparsely distributed POMC neurons facile. All of the POMC neurons appear to be activated by leptin, via two different mechanisms, while approximately 30-50% of the neurons appear to be inhibited by a gamma-melanocyte stimulating hormone (MSH) specific agonist. The latter result suggests that the melanocortin-3 receptor (MC3-R) may act as an autoinhibitory receptor on some POMC neurons. This hypothalamic slice preparation also confirms the responsiveness of arcuate POMC neurons to a wide variety of nutrients and hormones. Thus the arcuate melanocortin system is best described as a conduit of many diverse signals involved in energy homeostasis, with leptin acting tonically to regulate the responsiveness of the circuit to a wide variety of hormones and nutrients.


Assignment of the human intestinal Na+/glucose cotransporter gene (SGLT1) to the q11.2----qter region of chromosome 22.
The chromosomal location of the human intestinal Na+/glucose cotransporter gene (SGLT1) was determined using human cDNA and genomic probes for this transporter gene. Southern blot analysis of genomic DNA from 15 mouse-human somatic cell hybrids showed that the human gene for this transporter resides on chromosome 22. Analysis of hamster-human hybrids selectively retaining chromosome 22 or a portion of it allowed specific assignment of the locus to the q11.2----qter region of chromosome 22. A restriction fragment length polymorphism was identified with EcoRI.


Ecology of plant dioecy in the intermountain region of Western North America and California.
Data from 44 plant communities of the arid zone of western North America and from the entire California flora suggest that the dioecious habit (separate sexed individuals) is best developed among wind pollinated woody plants. A rationale is presented for the ways in which wind pollination and large plant size have favored the development of the dioecious habit. Based upon the patterns examined, it is concluded that inbreeding depression alone is insufficient to account for the evolution of the dioecious habit in many temperate species.


Induction to oxidative stress by saxitoxin investigated through lipid peroxidation in Neuro 2A cells and Chlamydomonas reinhardtii alga.
Saxitoxin (STX) is a cyanotoxin, which can cause neurotoxic effects and induce ecological changes in aquatic environments, a potential risk to public and environmental health. Many studies of cytotoxicity on animal cells and algae have been performed, although few compare the toxic effects between the two models. In this sense, we investigated the oxidative stress induced by STX (0.4-3.0 nM) in two different cellular models: Neuro-2A (N2A) cells and Chlamydomonas reinhardtii alga by quantification of malondialdehyde (MDA) levels as indicative of lipid peroxidation (LPO). Also was evaluated the antioxidant defense of these cells systems after exposure to STX by the addition of antioxidants in N2A cells culture, and by the measure of antioxidants enzymes activity in C. reinhardtii cells. The MDA levels of N2A cells increased from 15% to 113% for 0.4 and 3.0 nM of STX, respectively, as compared to control. Superoxide-dismutase and catalase did not appear to protect the cell from STX effect while, in cells treated with vitamin E, the rates of MDA production decreased significantly, except for higher concentrations of STX. No MDA productions were observed in algal cells however some effects on antioxidant enzymes activity were observed when algae were exposed to 3.0 nM STX. Our results indicate that the concentrations of STX that may induce oxidative stress through LPO are different in animal and phytoplankton communities. A combination of algal and animal bioassays should be conducted for reliable assessment of oxidative stress induced by STX.


A putative zinc-binding protein on lampbrush chromosome loops.
We used mAb A33/22, which recognizes a nuclear protein on the loops of amphibian lampbrush chromosomes, to select cDNA clone PwA33 from an expression library of the newt Pleurodeles waltl. A myc-tagged transcript of clone PwA33 was injected into Pleurodeles oocytes. The translation product localized in the germinal vesicle (GV) and was distributed on the lampbrush loops in a pattern identical to that of the endogenous protein. PwA33 encodes a 71 kDa protein with three distinct domains: a region rich in Cys/His residues that may form zinc fingers, a coiled-coil domain with potential for dimerization and a third 'rfp-like' domain that is shared by several other nuclear proteins. The putative zinc fingers and the coiled-coil domain resemble features in known nucleic acid-binding regulatory proteins. These structures, coupled with a distinctive pattern of expression in embryonic tissues, suggest that A33 may function as a regulatory protein during early development. It is unlikely that the large store of A33 in the GV is bound to DNA. Instead, its association with the nascent transcripts on the lampbrush chromosome loops suggests a role in pre-mRNA synthesis or processing.


Randomized, prospective trial comparing 0.2 percent isosorbide dinitrate ointment with sphincterotomy in treatment of chronic anal fissure: a two-year follow-up.
The aim of this trial was to compare lateral internal sphincterotomy with local 0.2 percent isosorbide dinitrate in the treatment of chronic anal fissure to minimize surgical complications such as minor fecal incontinence. Fifty-four patients with chronic anal fissure were randomized in a prospective trial to either sphincterotomy or local 0.2 percent isosorbide dinitrate. All patients had anal function tests before and 5 weeks after treatment. In the ointment group, 18 patients (67 percent) healed at 5 weeks and 24 (89 percent) healed at 10 weeks of treatment. Maximum resting anal pressure was reduced 30 percent. Eight patients (30 percent) had minor side effects. In the surgical group, 26 patients (96 percent) healed at 5 weeks and 100 percent healed at 10 weeks after treatment, with 33 percent reduction in maximum resting anal pressure. Forty-four percent of patients had minor fecal incontinence, which remained in 15 percent after 24 months follow-up. No statistical difference in maximum resting anal pressure was found between groups ( P = 0.16), but the percentage of healing at 5 weeks was greater in the surgical group ( P < 0.001). Isosorbide dinitrate ointment must be considered as the first choice of treatment in patients with chronic anal fissure. Surgery should be indicated if chemical sphincterotomy fails.


Current intimate relationship status, depression, and alcohol use among bisexual women: The mediating roles of bisexual-specific minority stressors.
Current intimate relationship characteristics, including gender and number of partner(s), may affect one's visibility as a bisexual individual and the minority stressors they experience, which may in turn influence their health. The current study tested four hypotheses: 1) minority stressors vary by current intimate relationship status; 2) higher minority stressors are associated with higher depressive symptoms and alcohol-related outcomes; 3) depressive symptoms and alcohol-related outcomes vary by current intimate relationship status; and 4) minority stressors will mediate differences in these outcomes. Participants included 470 self-identified bisexual women (65% Caucasian, mean age: 21) from a sample of sexual minority women recruited from different geographic regions in the United States through advertisements on social networking sites and Craigslist. Participants completed a 45 minute survey. Respondents with single partners were first grouped by partner gender (male partner: n=282; female partner: n=56). Second, women were grouped by partner gender/number (single female/male partner: n = 338; women with multiple female and male partners: n=132). Women with single male partners and women with multiple male and female partners exhibited elevated experienced bi-negativity and differences in outness (H1). Experienced and internalized bi-negativity were associated with health outcomes, but not outness (H2). Differences in outcomes emerged by partner number and partner number/gender (H3); these differences were mediated by experienced bi-negativity (H4). These results suggest that experiences of discrimination may underlie differences in health related to bisexual women's relationship structure and highlight the importance of evaluating women's relational context as well as sexual identification in understanding health risk behaviors.


Resection of Kommerell's diverticulum in an infant with prenatal diagnosis of right aortic arch.
A right aortic arch is a congenital vascular anomaly that is present in up to 0.1% of pregnancies. The anomaly observed by fetal ultrasonography was recently reported to indicate vascular and chromosomal abnormalities that may complicate postnatal management. We report the successful resection of a Kommerell's diverticulum with left subclavian artery transfer to the left carotid artery in a 5-month-old Japanese boy. The patient was prenatally diagnosed as having a right aortic arch, and a vascular ring was confirmed at 4 months of age with enhanced computed tomography. The pathology of the resected aortic wall revealed severe disruption and fragmentation of elastic fibers associated with a disarray of smooth muscle cells in the tunica media, and cystic medial necrosis with mucoid extracellular matrix deposition. These abnormal pathological findings supported the resection of Kommerell's diverticulum at this point of time, and division of the ligamentum arteriosus alone was not recommended. Early intervention in this condition once the diagnosis is made may thus be advocated. The fetal diagnosis of a right aortic arch may provide a clue to the possibility of a vascular ring.


[Psychological and somatic aspects of living liver donors: preoperative assessment and postoperative course].
Living donor liver transplantation (LDLT) has been gaining importance in the treatment of end-stage liver disease in adults as a partial solution to the growing organ shortage. Thus far, only few empirical studies have been published on the situation of donors who are faced with the risk of medical complications after resection of the right hepatic lobe. 87 potential donors were preoperatively assessed in the years 2000 and 2001 at the Charité Berlin. 41 potential donors were excluded, 46 donors (31 women, 15 men, mean age 41 [19 - 67] years) underwent liver surgery and were re-assessed 6 months after the operation. The frequency of postoperative complications and the course of psychosocial parameters were investigated. Donors' moods were analysed with the Berlin Mood Questionnaire, the physical complaints were assessed with the Giessen Complaint Questionnaire. The preoperative interviews of 20 potential donors were analysed according the current social qualitative research methods. In 11 % (n = 10) of potential donors transplantation was not recommended for psychosocial reasons because they showed a marked ambivalence towards the operation. After operation, 22 % (n = 12) of donors had postoperative complications. Most relevant single causes of severe impairment were temporary and reversible biliary leakages from the cutting edge. There were no long- term complications. 26 % (n = 10) of donors showed postoperative high values for anxious depression and physical complaints. The resection of the right hepatic lobe holds promise of a good psychosocial outcome for most donors, irrespective of donation-related complications. The psychosocial impairment and physical complaints of some donors after transplantation are yet not clearly understood. Further psychosocial studies will be necessary to develop criteria for an evidence based medical care of living donors.


Azacitidine vs. Decitabine in Unfit Newly Diagnosed Acute Myeloid Leukemia Patients: Results from the PETHEMA Registry.
The hypomethylating agents, decitabine (DEC) and azacitidine (AZA), allowed more elderly acute myeloid leukemia (AML) patients to be treated. However, there are little direct comparative data on AZA and DEC. This multicenter retrospective study compared the outcomes of AZA and DEC in terms of response and overall survival (OS). Potential predictors associated with response and OS were also evaluated. A total of 626 AML patients were included (487 treated with AZA and 139 with DEC). Response rates were similar in both groups: CR was 18% with AZA vs. 23% with DEC (p = 0.20), CR/CRi was 20.5% vs. 25% (p = 0.27) and ORR was 32% vs. 39.5% (p = 0.12), respectively. Patients with leukocytes < 10 × 109/L, bone marrow blasts < 50% and ECOG ≥ 2 had higher ORR with DEC than with AZA. OS was similar in both groups: 10.4 months (95% CI: 9.2−11.7) vs. 8.8 months (95% CI: 6.7−11.0, p = 0.455), for AZA and DEC, respectively. Age (≥80 years), leukocytes (≥ 10 × 109/L), platelet count (<20 × 109/L) and eGFR (≥45 mL/min/1.73 m2) were associated with higher OS with AZA compared to DEC. In conclusion, we found no differences in response and OS rates in AML patients treated with AZA or DEC.


[Flower species identification and coverage estimation based on hyperspectral remote sensing data in Hulunbeier grassland].
Monitoring grassland species and area real-timely and accurately is of great significance in species diversity research, as well as in sustainable development of ecosystem. Flowers have their own unique spectral characteristics. Compared with the nutrient stage, species are more easily identified by florescence. So, florescence is a critical period for identification. In the present paper, spectral differences among such flowers as Galium verum Linn., Hemerocallis citrina Baroni, Serratula centauroides Linn., Clematis hexapetala Pall., Lilium concolor var. pulchellum, Lilium pumilum and Artemisia frigida Willd. Sp. Pl. were found, along with identification methods, by analyzing canopies spectra and parametrizing characteristics. Verification results showed that when the coverage of flowers was greater than 10%, the accuracy of identification methods would be higher than 90%. On this basis, linear unmixing model was adopted to calculate the area of flowers in quadrates. Results showed that linear unmixing model was an effective method for estimating the coverage of flowers in grassland because the accuracy was about 4%.


Deficient hippocampal neuron expression of proteasome, ubiquitin, and mitochondrial genes in multiple schizophrenia cohorts.
Hippocampal dentate granule neurons are altered in schizophrenia, but it is unknown if their gene expressions change in schizophrenia or other psychiatric diseases. Laser-captured dentate granule neurons from two groups of schizophrenia and control cases and from major depression and bipolar disease cases were examined for alterations in gene expression using complementary DNA (cDNA) microarrays and reverse transcription polymerase chain reaction (RT-PCR). Compared with 24 control cases, the 22 schizophrenia patients in both groups revealed decreases in clusters of genes that encode for protein turnover (proteasome subunits and ubiquitin), mitochondrial oxidative energy metabolism (isocitrate, lactate, malate, nicotinamide adenine dinucleotide [NADH], and succinate dehydrogenases; cytochrome C oxidase; adenosine triphosphate [ATP] synthase), and genes associated with neurite outgrowth, cytoskeletal proteins, and synapse plasticity. These changes were not obtained in 9 bipolar cases or 10 major depression cases and were not associated with age, sex, brain weight, body weight, postmortem interval, or drug history. Brain pH contributed to the variance of some genes but was mostly independent of the disease effect. Decreases in hippocampal neuron gene expression are consistent with brain imaging and microarray studies of the frontal cortex in schizophrenia. A mitochondrial and ubiquitin-proteasome hypofunctioning of dentate granule neurons may contribute to the deficits of schizophrenia.


Detailed analysis of the essential oil from Cistus albidus L. by combination of GC/RI, GC/MS and 13C-NMR spectroscopy.
The composition of the essential oil of Cistus albidus (L.) obtained from plants growing wild in Provence (France) has been investigated using GC-RI (RI = retention indices), GC/MS and (13)C-NMR. Eighty-eight components were reported accounting for 81.8% of the essential oil. This essential oil was characterized by a high content of sesquiterpenes with alpha-zingiberene (12.8%), alpha-curcumene (7.7%), (E)-beta-caryophyllene (5.9%), alpha-cadinol (5.4%), alpha-bisabolol (4.1%), caryophyllene oxide (3.8%), allo-aromadendrene (3.4%), delta-cadinene (3.4%), and germacrene D (3.1%) being the main components.


Reduced 30-Day Mortality After Laparoscopic Colorectal Cancer Surgery: A Population Based Study From the Dutch Surgical Colorectal Audit (DSCA).
To evaluate the impact of a laparoscopic resection on postoperative mortality after colorectal cancer surgery. The question whether laparoscopic resection (LR) compared with open surgery [open resection (OR)] for colorectal cancer influences the risk of postoperative mortality remains unresolved. Several meta-analyses showed a trend but failed to reach statistical significance. The exclusion of high-risk patients and insufficient power might be responsible for that. We analyzed the influence of LR on postoperative mortality in a risk-stratified comparison and secondly, we studied the effect of LR on postoperative morbidity. Data from the Dutch Surgical Colorectal Audit (2010-2013) were used. Homogenous subgroups of patients were defined on the basis of factors influencing the choice of surgical approach and risk factors for postoperative mortality. Crude mortality rates were compared between LR and OR. The influence of LR on postoperative complications was evaluated using both univariable and multivariable analyses. In patients undergoing elective surgery for nonlocally advanced, nonmetastasized colon cancer, LR was associated with a significant lower risk of postoperative mortality than OR in 20/22 subgroups. LR was independently associated with a lower risk of cardiac (odds ratio: 0.73, 95% confidence interval: 0.66-0.82) and respiratory (odds ratio: 0.73, 95% confidence interval: 0.64-0.84) complications. LR reduces the risk of postoperative mortality compared with OR in elective setting in patients with nonlocally advanced, nonmetastasized colorectal cancer. Especially elderly frail patients seem to benefit because of reduced cardiopulmonary complications. These findings support widespread implementation of LR for colorectal cancer also in patients at high operative risk.


Metabolites downstream of predicted loss-of-function variants inform relationship to disease.
A small minority (< 3%) of protein-coding genetic variants are predicted to lead to loss of protein function. However, these predicted loss-of-function (pLOF) variants can provide insight into mode of transcriptional effect. To examine how these changes are propagated to phenotype, we determined associations with downstream metabolites. We performed association analyses of 37 pLOF variants - previously reported to be significantly associated with disease in >400,000 subjects in UK Biobank - with metabolites. We conducted these analyses in three community-based cohorts: the Framingham Heart Study (FHS) Offspring Cohort, FHS Generation 3, and the KORA F4 cohort. We identified 19 new low-frequency or rare (minor allele frequency (MAF) <5%) pLOF variant-metabolite associations, and 12 new common (MAF > 5%) pLOF variant-metabolite associations. Rare pLOF variants in the genes BTN3A2, ENPEP, and GEM that have been associated with blood pressure in UK Biobank, were associated with vasoactive metabolites indoxyl sulfate, asymmetric dimethylarginine (ADMA), and with niacinamide, respectively. A common pLOF variant in gene CCHCR1, associated with asthma in UK Biobank, was associated with histamine and niacinamide in FHS Generation 3, both reported to play a role in this disease. Common variants in olfactory receptor gene OX4C11 that associated with blood pressure in UK Biobank were associated with the nicotine metabolite cotinine, suggesting an interaction between altered olfaction, smoking behaviour, and blood pressure. These findings provide biological validity for pLOF variant-disease associations, and point to the effector roles of common metabolites. Such an approach may provide novel disease markers and therapeutic targets.


Kimura disease in a patient with renal allograft failure secondary to chronic rejection.
Recent studies suggest that CD4(+ )T helper 2 (Th2) cell proliferation and overexpression of Th2 cytokines may play an important role in the development of Kimura disease. Chronic rejection of a renal allograft by the indirect allo recognition pathway is also induced by Th2 cytokines. We report a 12-year-old boy who had presented with nephrotic syndrome 10 years previously. He was found to have focal segmental glomerulosclerosis, which was attributed to vesicoureteral reflux, and he underwent renal transplantation at the age of 5 years. Allograft dysfunction secondary to chronic rejection was noted by 2 years post transplant, after which continuous ambulatory peritoneal dialysis was instituted. After discontinuation of immunosuppressive therapy, he progressively developed peripheral eosinophilia and eczema, followed by cervical lymphadenopathy and then epitrochlear lymphadenopathy. Kimura disease was diagnosed on lymph node biopsy. Our patient demonstrated that Kimura disease can occur after renal allograft failure secondary to chronic rejection. Both disorders involve the Th2-dominant immune response, according to previous observations.


Lower limb inter-joint coordination in individuals with osteoarthritis before and after a total knee arthroplasty.
Total knee arthroplasty is the most common treatment for severe knee osteoarthritis. Coordination and variability analyses are effective measures of the injury stage or rehabilitation process. This study compared the inter-joint coordination before and after arthroplasty, compared to controls. Twenty-seven patients were evaluated before and 12 months after surgery, compared to 27 controls. Coordination and variability in the sagittal plane between the hip-knee and knee-ankle were calculated using vector coding and circular statistics. Coordination was categorized as in-phase, anti-phase, or distal or proximal joint-phase. The gait cycle was divided into sub-phases for the coordination, variability, and range of motion results. Coordination and range of motion differed significantly between the patient groups and controls, while small differences between pre- and post-operative groups were also detected. The hip-knee showed a reduced in-phase frequency in the patient group compared to control during stance, particularly mid-stance: pre-operative 24.3% ± 33.9, post-operative 29.5 ± 29.7, and controls 70.7 ± 17.0. This difference was compensated for by increasing proximal-phase (hip) frequency in the patient groups. For knee-ankle coordination, the patient groups showed higher distal-phase (ankle) frequency during the early and mid-stance. Coordination variability was higher post-operatively during swing and terminal swing phases, compared to controls. The results indicated reduced degrees of freedom for the knee during stance phase with a reduced capacity to move the knee and hip in opposing directions before and one year after surgery. The patient group after the surgery increased knee range of motion and coordination compared to pre-operative during swing phase.


Imaging-Guided Therapies for Pericardial Diseases.
Frequently, multimodality imaging is indispensable in the care of patients with pericardial disease. With cardiac magnetic resonance imaging, pericardial inflammation can be characterized as acute, subacute, or chronic. This spectrum of inflammation is variably associated with reduced compliance of the pericardium, which may result in constrictive pathophysiology, typically well-defined with echocardiography. This interplay between inflammation and hemodynamics is often optimally characterized with multimodality imaging and has redefined the approach of pericardiologists to diagnose, prognosticate, and tailor individual therapies.


Syntheses of D- and L-myo-inositol 1,2,4,5-tetrakisphosphate and stereoselectivity of the I(1,4,5)P3 receptor binding.
D- and L-myo-Inositol 1,2,4,5-tetrakisphosphate [D- & L-I(1,2,4,5)P4], which are analogues of D-myo-Inositol 1,4,5-trisphosphate [D-I(1,4,5)P3], a calcium mobilizing second messenger, were synthesized via resolution of the camphanate ester of a myo-inositol derivative, and the binding affinities to I(1,4,5)P3 receptor were measured.


Subarachnoid haemorrhage of unknown aetiology.
One hundred and forty consecutive subarachnoid haemorrhages (SAH) which presented either an intracranial vascular malformation (102 cases: aneurysm 80 cases, AVH 22 cases) or remained of "unknown aetiology" (38 cases) were studied. SAH caused by other factors (neoplasms, thrombo-embolisms, systemic diseases etc.) were excluded. The 38 cases with bleeding of "unknown aetiology" have been studied by complete cerebral angiography, pneumoencephalogram or CT scan, and have been followed for two years. The most important clinical factors in the three groups have been compared by a statistical method to verify the hypothesis that SAH of "unknown aetiology" is caused by vascular micromalformations which are angiographically not evident either because of their small size or because of their "spontaneous" recovery after bleeding due to thrombosis and disappearance of the malformation. From the data collected it may be concluded that SAH of "unknown aetiology" is a benign lesion, typically occurring in middle age, but with no clear characteristics that enable identification of the anatomical substratum from it originates.


Effects of sialidase NEU1 siRNA on proliferation, apoptosis, and invasion in human ovarian cancer.
Ovarian cancer is one of the most common malignancies encountered in the world. In ovarian cancer tissues of patients, NEU1 was expressed in a higher level than that in adjacent normal tissues. In this research, we aimed to elucidate the role of NEU1 siRNA on proliferation, apoptosis, and invasion of OVCAR3 and SKOV3 cells which expressed NEU1 notably. By cell viability assay and flow cytometry method, we found that NEU1 siRNA effectively inhibited the cancer proliferation, arrested cells cycle at G0/G1 phase, and induced apoptosis when compared to the Mock group. Result of transwell assay showed that invasion of cells in OVCAR3 and SKOV3 treated with NEU1 siRNA were suppressed significantly. Gene set enrichment analysis showed that lysosome and oxidative phosphorylation related signal pathway were associated with the NEU1 expression. In addition, Western blot revealed that expressions of Cln3 and Cln5 were depressed, and ATP5B and ATP5J expressions were also reduced. In conclusion, NEU1 siRNA can effectively inhibit proliferation, apoptosis, and invasion of human ovarian cancer cells by targeting lysosome and oxidative phosphorylation signaling, which can serve as a new target ovarian cancer treatment.


A modified statistical approach for the detection of outlying values in external quality control: comparison with other techniques.
Laboratory results submitted to External Quality Assessment Schemes (EQAS) are evaluated against the arithmetic mean (m) and standard deviation (SD) of the result from other participants assuming a normal distribution of individual results. The sample statistics m and SD can only be reliable estimates of the theoretical mean (mu) and standard deviation (sigma), if they are not distorted by outlying values. Outliers are commonly detected by defining a confidence interval m +/- k SD, typically with k-values fixed at 3.0 or 3.2. The objective of our study was to prove the deficiency of the use of these fixed limits in large-scale EQAS, because it results in an unacceptable increase of outlier rate and hence in a serious distortion of the estimate of sigma. We have proposed a modified approach using a variable k-value which is dependent upon sample size and keeping the significance level constant at 5%. The influence of different decision limits on the number of outliers and on the sample statistics m and SD was compared using data from the Belgian National EQAS obtained in 6 consecutive surveys.


GM2/GD2 and GM3 gangliosides have no effect on cellular cholesterol pools or turnover in normal or NPC1 mice.
These studies investigated the role of gangliosides in governing the steady-state concentration and turnover of unesterified cholesterol in normal tissues and in those of mice carrying the NPC1 mutation. In animals lacking either GM2/GD2 or GM3 synthase, tissue cholesterol concentrations and synthesis rates were normal in nearly all organs, and whole-animal sterol pools and turnover also were not different from control animals. Mice lacking both synthases, however, had small elevations in cholesterol concentrations in several organs, and the whole-animal cholesterol pool was marginally elevated. None of these three groups, however, had changes in any parameter of cholesterol homeostasis in the major regions of the central nervous system. When either the GM2/GD2 or GM3 synthase activity was deleted in mice lacking NPC1 function, the clinical phenotype was not changed, but lifespan was shortened. However, the abnormal cholesterol accumulation seen in the tissues of the NPC1 mouse was unaffected by loss of either synthase, and clinical and molecular markers of hepatic and cerebellar disease also were unchanged. These studies demonstrate that hydrophobic interactions between cholesterol and various gangliosides do not play an important role in determining cellular cholesterol concentrations in the normal animal or in the mouse with the NPC1 mutation.


Erratum to "Blood calcium as a prognostic indicator of success after surgical correction of left displaced abomasum" (JDS Commun. 2:207-211).
[This corrects the article DOI: 10.3168/jdsc.2021-0079.].


The Association Between Autism Spectrum Traits and the Successful Transition to Mainstream Secondary School in an Australian School-Based Sample.
The transition to secondary school is an important educational milestone impacting wellbeing and academic achievement. Students with Autism Spectrum Disorder may be vulnerable during transition however little is known about how Autism Spectrum (AS) traits influence transition outcomes. Generalised estimating equations were used to examine how AS traits were associated with four indicators of successful transition in a school-based sample of 51 students. Higher AS traits were associated with lower quality of life, school belonging and mental health, however the hypothesised decline after school transition was not supported. Characteristics of both the primary and secondary school appeared to be contributing to the wellbeing of students with high AS traits which could be clarified by further investigation with a larger sample.


Barrier inhomogeneities limited current and 1/f noise transport in GaN based nanoscale Schottky barrier diodes.
The electrical behaviour of Schottky barrier diodes realized on vertically standing individual GaN nanorods and array of nanorods is investigated. The Schottky diodes on individual nanorod show highest barrier height in comparison with large area diodes on nanorods array and epitaxial film which is in contrast with previously published work. The discrepancy between the electrical behaviour of nanoscale Schottky diodes and large area diodes is explained using cathodoluminescence measurements, surface potential analysis using Kelvin probe force microscopy and 1ow frequency noise measurements. The noise measurements on large area diodes on nanorods array and epitaxial film suggest the presence of barrier inhomogeneities at the metal/semiconductor interface which deviate the noise spectra from Lorentzian to 1/f type. These barrier inhomogeneities in large area diodes resulted in reduced barrier height whereas due to the limited role of barrier inhomogeneities in individual nanorod based Schottky diode, a higher barrier height is obtained.


Imaging hepatic angiomyolipomas: key features and avoiding errors.
Hepatic angiomyolipomas (HAMLs) are rare mesenchymal neoplasms, which have highly variable imaging appearances, often leading to misdiagnosis. They belong to the family of perivascular epithelioid cell neoplasms (PEComas). HAMLs have a wide spectrum of imaging appearances due to variable amounts of smooth muscle cells, adipose tissue, and blood vessels in their makeup. Although typically sporadic, they are also associated with tuberous sclerosis. Sporadic lesions tend to be solitary whilst patients with tuberous sclerosis often have multiple HAMLs invariably accompanied by renal AMLs. Having been originally considered benign hamartomas, increasing reports of complications, including malignant behaviour, has also resulted in uncertainty in regard to their optimal management. Typically described imaging characteristics are of a hypervascular fat-containing lesion with prominent intratumoural vessels and an early draining vein; however HAMLs commonly demonstrate a paucity of fat or wash-out on contrast-enhanced imaging, and not all HAML lesions are hypervascular. HAMLs can therefore easily be misdiagnosed as other hepatic lesions, in particular hepatocellular carcinoma. This review describes the imaging characteristics of HAMLs, illustrating the wide variety of potential appearances across ultrasound, contrast-enhanced ultrasound, computed tomography, and magnetic resonance imaging, and highlights the challenges and potential errors that can be made. This review will aid radiologists in avoiding potentially major pitfalls when faced with this rare but important liver pathology.


The Stark law, from inception to COVID-19 blanket waivers: a review.
The concept of physicians referring patients to their own healthcare entities is considered a "self-referral". A discerning factor of a self-referral is when the physician has a financial interest in the entity of patient referral. Prospects of healthcare overutilization and costs, thereby, rise. Self-referral laws, therefore, are important to regulate overutilization and contain costs. In the 1980s, Congressman Fortney Stark initiated an act that was one of the precursors to one such self-referral law, known as the Stark Law. The Stark Law, in its initial phase, known as Stark I, addressed self-referrals selectively from laboratory services. Stark I, thereafter, in a series of subsequent amendments and enactments, burgeoned to include multiple services, referred as Designated Health Services (DHS), for self-referrals. The expanded law, inclusive of those DHS, is now known as Stark II. The passage of the 2010 Affordable Care Act as well as the prevailing 2019 Coronavirus Disease (COVID-19) pandemic further modified the Stark Law. Given the legislative history of the said law, the present review curates the legal initiatives of this law from its nascent formative stages to the present form. The purpose of the above curation is to present a bird's eye view of its evolution and present analysts of any future research segments. This review, furthermore, describes the waivers of this law specific to COVID-19, or COVID-19 blanket waivers, which are instruments to assuage any barriers and further placate any hurdles arising from this law prevalent in this pandemic.


Ethnicity, race, and baseline retinopathy correlates in the veterans affairs diabetes trial.
The Veterans Affairs Diabetes Trial (VADT) cohort is enriched with approximately 20% Hispanics and 20% African Americans, affording a unique opportunity to study ethnic differences in retinopathy. Cross-sectional analyses on the baseline seven-field stereo fundus photos of 1,283 patients are reported here. Diabetic retinopathy scores are grouped into four classes of increasing severity: none (10-14), minimal nonproliferative diabetic retinopathy (NPDR) (15-39), moderate to severe NPDR (40-59), and proliferative diabetic retinopathy (60+). These four groups have also been dichotomized to none or minimal (10-39) and moderate to severe diabetic retinopathy (40+). The prevalence of diabetic retinopathy scores >40 was higher for Hispanics (36%) and African Americans (29%) than for non-Hispanic whites (22%). The difference between Hispanics and non-Hispanic whites was significant (P < 0.05). Similarly, the prevalence of diabetic retinopathy scores >40 was significantly higher in African Americans than in non-Hispanic whites (P < 0.05). These differences could not be accounted for by an imbalance in traditional risk factors such as age, duration of diagnosed diabetes, HbA(1c) (A1C), and blood pressure. Diabetic retinopathy severity scores were also significantly associated with increasing years of disease duration, A1C, systolic and diastolic blood pressure, the degree of microalbuminuria, fibrinogen, and the percentage of patients with amputations. There was no relationship between retinopathy severity and the percentage of people who had strokes or cardiac revascularization procedures. There was an inverse relationship between retinopathy severity and total cholesterol, triglycerides, and plasminogen activator inhibitor-1 as well as with smoking history. Diabetic retinopathy scores were not associated with age. In addition to many well-known associations with retinopathy, a higher frequency of severe diabetic retinopathy was found in the Hispanic and African-American patients at entry into the VADT that is not accounted for by traditional risk factors for diabetic retinopathy, and these substantial ethnic differences remain to be explained.


Removal of phosphate from phosphohistidine in proteins.
Kinetic constants of KM = 0.8 microM, 3 microM and 1.6 microM, and kcat = 9 s-1, 7 s-1 or 9 s-1 were determined for histidine dephosphorylation by protein phosphatases 1, 2A and 2C respectively. IC50 values were determined for the inhibition of protein phosphatase 1 by inhibitor 1 (IC50 = 1 nM), inhibitor-2 (IC50 = 3 nM) and okadaic acid (IC50 = 30 nM) and for the inhibition of protein phosphatase 2A by okadaic acid (IC50 = 0.02 nM) and microcystin-LR (IC50 = 1 nM). Inhibitor-1 (Ki = 0.7 nM) and okadaic acid (Ki = 32 nM) are noncompetitive with protein phosphatase 1. Some of the IC50 values were low enough to violate the assumptions of the usual inhibition equations and a more general approach to the analysis of the data was used. On the basis of these kinetic parameters and the presence of phosphohistidine, the major cellular protein serine/threonine phosphatases are likely to act as protein histidine phosphatases in the cell.


Underreporting characteristics of osteoporotic vertebral fracture in back pain clinic patients of a tertiary hospital in China.
Osteoporotic vertebral compressive fractures (VCFs) are known to be commonly missed in X-rays indicated for pulmonary or heart diseases. In this study, we investigated the underreporting status of VCF in back pain clinic patients when the spine was the focus of interest. This is a retrospective analysis of 105 female cases (mean: 72 years, range: 55-93 years) from a tertiary hospital in China (facility A, FA). The patients with back and/or leg pain were referred for a spine X-ray. The images were retrieved and transferred to a central reading facility (facility B, FB), where images were double-read by two readers experienced in evaluating osteoporotic vertebral compressive deformity (VCD)/VCF. A qualitative VCD with <20%, 20-25%, 25-40%, and >40% vertebral body height loss was recorded as minimal, mild, moderate, and severe grades, respectively. A VCD coexisted with endplate/cortex fracture (ECF) was VCF. FB readings were considered as the reference. There were 34 true negative cases where FA and FB had a consensus. In 7 cases with minimal VCD, 3 cases with ECF, and 7 cases with minimal or mild VCFs, the FA readings were false negative. No standalone singular moderate or severe VCD/VCF in a patient was missed in FA's reports. In 25 FA reading positive cases with multiple VCFs, one VCF was missed in 8 cases, more than one VCF was missed in 15 cases, and one additional ECF was missed in 2 cases. In 14 cases, FA and FB had VCF number agreement, with the term 'vertebral fracture' was used appropriately in FA reports. In 15 cases, FA and FB had agreement in VCF number; however, the appropriate term 'vertebral fracture' was not used in FA reports; instead the terms of 'compressive change' or 'wedging change' were used. In most VCFs, severity grading was not given in FA. In 13 VCFs where grading was reported, all were marked as 'mild', including seven mild VCFs, five moderate VCFs, and even one severe VCF. Among the patients with VCD/VCF, the false negative rate among was 23.9% (17/71), but the missed cases were all minimal or mild grades. One or more VCFs were missed in 32.4% (23/71) of the cases with multiple VCFs. Appropriate severity grading was not reported for most cases. The underreporting rate of osteoporotic vertebral compressive fracture in back pain clinic patients in a typical tertiary hospital setting in China compared favorably with literature reports. However, there is a general lack of awareness of vertebral endplate/cortex fracture sign and vertebral fracture severity grading, while minimal and mild VCD with endplate/cortex fracture may have clinical significance. Moreover, after one VCF is spotted in a patient, it is highly advisable to carefully check the whole spine so that multiple VCFs will not be missed.


Increased fibronectin expression in developing embryos is associated with abnormal notochord in the Adriamycin rat model.
The VACTERL association is a spectrum of clinical conditions, including esophageal atresia (EA) and tracheoesophageal fistula (TEF), which affects approximately 1 in 5,000 live human births. The administration of intraperitoneal Adriamycin to pregnant rats reliably induces anomalies, such as EA and TEF, in their offspring, in what is known as the Adriamycin rat model (ARM). In affected embryos the presence of gross notochord abnormalities is commonly found, with typical features being ectopic ventral branches and adherence of the notochord to the foregut. Fibronectin (FN) is an extracellular matrix (ECM) glycoprotein present on most cell surfaces, in extracellular fluids and in plasma. FN is involved in various functions, including cell adhesion, cell motility and wound healing. Previous studies in rats have shown that a single dose of Adriamycin can produce an appreciable rise in FN levels in various organs such as kidney and heart. We hypothesised that Adriamycin administration could promote upregulation of FN expression contributing to increased gut-notochord adherence and the development of abnormal ventral notochordal branching in the ARM. This study was designed to investigate FN expression in ARM embryos. Adriamycin (1.75 mg/kg) was administered intraperitoneally to pregnant rats on days 7,8 and 9 of gestation (E7, E8 and E9 respectively). Control animals were given saline. Embryos recovered on E10-E14 were fixed, embedded in paraffin and sectioned. Immunohistochemistry using an anti-FN rabbit polyclonal antibody was performed. FN expression in both Adriamycin and control embryos on E10, E11 and E12 was comparable. However, the levels of FN expression in Adriamycin embryos on E13 and E14 were significantly greater in embryos with abnormal notochords than in equivalent control embryos. Adriamycin-induced increased expression of FN, in the ARM, may contribute to abnormal notochord development leading to the VACTERL association.


Changed times at Hematological Oncology.
This editorial describes the changes to Hematological Oncology over the past 12 months and redefines the scope and the goals of the journal. As well as changes in format, an electronic manuscript submission system and a stringent peer-review policy (outlined here) have been implemented. The journal is a vehicle for high-quality articles in the broad field of experimental and clinical hematological oncology, and a medium for the publication of translational research. As well as submitted material, the journal solicits and publishes high-quality reviews from leading experts.


Prophylaxis for hemophilia A without inhibitors: treatment options and considerations.
Hemophilia A is a bleeding disorder traditionally managed with standard half-life (SHL) factor (F) VIII concentrates. Extended half-life (EHL) FVIII products and emicizumab-kywh, a nonfactor therapy, are newer treatment options. Additional nonfactor agents and gene therapy are expected to reach the market in the near future. A PubMed (MEDLINE) search from 1962 to April 2020 related to hemophilia A, its management, and the products currently available for prophylaxis was performed to comprehensively review these topics and analyze the benefits and drawbacks of each therapeutic. Prophylaxis with SHL FVIII concentrates remains the standard of care for patients with severe hemophilia A and may also be considered for selected individuals with moderate disease. Several years of real-world experience with EHL FVIII, emicizumab-kywh, and other agents in development will be necessary to determine their ultimate roles in the prevention of bleeding and its complications. Gene therapy may not provide a permanent cure for hemophilia A.


MRI-Guided Online Adaptive Stereotactic Body Radiation Therapy of Liver and Pancreas Tumors on an MR-Linac System.
To describe a comprehensive workflow for MRI-guided online adaptive stereotactic body radiation therapy (SBRT) specific to upper gastrointestinal cancer patients with abdominal compression on a 1.5T MR-Linac system. Additionally, we discuss the workflow's clinical feasibility and early experience in the case of 16 liver and pancreas patients. Eleven patients with liver cancer and five patients with pancreas cancer were treated with online adaptive MRI-guidance under abdominal compression. Two liver patients received single-fraction treatments; the remainder plus all pancreas cancer patients received five fractions. A total of 65 treatment sessions were investigated to provide analytics relevant to the online adaptive processes. The quantification of target and organ motion as well as definition and validation of internal target volume (ITV) margins were performed via multi-contrast imaging provided by three different 2D cine sequences. The plan generation was driven by full re-optimization strategies and using T2-weighted 3D image series acquired by means of a respiratory-triggered exhale phase or a time-averaged imaging protocol. As a pre-requisite for the clinical development of the procedure, the image quality was thoroughly investigated via phantom measurements and numerical simulations specific to upper abdominal sites. The delivery of the online adaptive treatments was facilitated by real-time monitoring with 2D cine imaging. Liver 1-fraction and 5-fraction online adaptive session time were on average 80 and 67.5 min, respectively. The total session length varied between 70-90 min for a single fraction and 55-90 min for five fractions. The pancreas sessions were 54-85 min long with an average session time of 68.2 min. Target visualization on the 2D cine image data varied per patient, with at least one of the 2D cine sequences providing sufficient contrast to confidently identify its location and confirm reproducibility of ITV margins. The mean/range of absolute and relative dose values for all treatment sessions evaluated with ArcCheck were 90.6/80.9-96.1% and 99/95.4-100%, respectively. MR-guidance is feasible for liver and pancreas tumors when abdominal compression is used to reduce organ motion, improve imaging quality, and achieve a robust intra- and inter-fraction patient setup. However, the treatment length is significantly longer than for the conventional linac, and patient compliance is paramount for the successful completion of the treatment. Opportunities for reducing the online adaptive session time should be explored. As the next steps, dose-of-the-day and dose accumulation analysis and tools are needed to enhance the workflow and to help further refine the online re-planning processes.


Thyroid suppression and stimulation testing: The place of scanning in the evaluation of nodular thyroid disease.
In the past, T3 suppression testing was often required to confirm the presence of autonomous thyroid function in patients with borderline clinical and laboratory findings suggestive of hyperthyroidism or in euthyroid patients with the stigmata of Graves' disease. Similarly, TSH stimulation testing was used to document the presence of "low thyroid reserve" in patients with borderline clinical and laboratory findings suggestive of hypothyroidism. The current availability of radioimmunoassays for triiodothyronine (T3) and thyrotorpin (TSH) plus the ability to evalate pituitary responsiveness by performing a TRH stimulation test permits a definitive diagnosis to be made in the majority of borderline situations without recourse to the more cumbersome suppression and stimulation tests. Suppression and stimulation thyroid scanning retain a unique position in the evaluation of localized areas in increased uptake of radionuclide (hot nodules), especially in patients who are euthyroid. Proof that such nodules are autonomously functioning thyroid adenomas (AFTN) greatly decreases the possibility that they represent malignant thyroid tumors. Suppression and stimulation scanning have a more limited role in the evaluation of patients with hyperthyroidism arising in a multinodular goiter, where TSH stimulation scanning may help to differentiate between toxic multinodular goiter and Graves' disease arising in a preexisting goiter.


Nutritional recommendations in the prevention and treatment of atherogenic dyslipidemia.
The incorporation of a healthy diet, regular physical exercise and smoking cessation are the initial measures to reduce cardiovascular risk in patients with atherogenic dyslipidemia. In these patients, the nutritional quality of their diet should be improved, replacing foods with a greater atherogenic effect for others with a healthier effect. There is strong evidence that plant-based dietary patterns, low in saturated fatty acids, cholesterol and sodium, with a high content of fiber, potassium and unsaturated fatty acids, are beneficial and reduce the expression of cardiovascular risk factors. This document focuses on the role of nutrition in the prevention and treatment of atherogenic dyslipidemia, providing current evidence to serve as a tool for health professionals in its clinical management. To facilitate the reading of these recommendations, they are presented in a user-friendly table format, with a hierarchy of different levels of evidence.


Early discrimination of fungal species responsible of ochratoxin A contamination of wine and other grape products using an electronic nose.
An electronic nose (e-nose) system using an array of metal oxide sensors (Fox 3000, Alpha MOS) was used to detect and discriminate two ochratoxigenic fungal species, Aspergillus carbonarius (Bain.) Thom and A. niger Van Tieghem, that are responsible for the contamination of wine and other wine grape products, using their volatile production patterns. Two well-known ochratoxigenic strains were used in this study: A. carbonarius A941 and A. niger A75. These strains were grown on three culture media, Czapek Dox modified (CDm) agar, yeast extract sucrose (YES) agar and white grape juice (WGJ) agar, and the volatile organic compounds produced in the headspace by these species were evaluated over periods of 48-120 h. The e-nose system was able to differentiate between the two species within 48 h of growth on YES and WGJ agar using principal component analysis (PCA), which accounted for 99.9% and 97.2% of the data respectively, in principal components 1 and 2, based on the qualitative volatile profiles. This differentiation was confirmed by cluster analysis of data. However, it was not possible to separate these species on CDm agar. Our results show that the two closely related ochratoxigenic species responsible for the contamination of wine and other wine grape products can be discriminated by the use of qualitative volatile fingerprints. This approach could have potential for rapid identification of A. carbonarius and A. niger on wine grape samples, thereby significantly reducing the time of detection of these ochratoxin A producing species.


Estimation of kinetic parameters of neutrophilic, eosinophilic, and basophilic granulocytes in human blood.
Two hematologically normal patients with glioblastoma and six patients with chronic lymphocytic leukemia received continuous 3H-thymidine infusions for 3--10 days. In autoradiographs of blood cell smears taken for 25 days or more after the beginning of 3H-thymidine administration the labeling index and the labeling intensity of granulocytes were determined. A sufficiently high labeling intensity, i.e. a sufficiently long autoradiographic exposure time was found to be critical for obtaining valid and reproducible results. On the basis of certain assumptions discussed in detail, complete labeling of cells with 3H-thymidine followed by autoradiographic evaluation and mathematical analysis of the labeling patterns seems to be a suitable method for estimation of kinetic parameters of postmitotic granulocytes in vivo. The mean intramedullary maturation and storage time was observed to be 115 +/- 7 h or neutrophils, 103 +/- 4 h for eosinophils and 103 +/- 11 h for basophils. The mean relative inflow rate into the blood (or relative turnover rate in the blood) was found to be 4.2 +/- 0.4/h for neutrophils, 4.0 +/- 0.4%/h for eosinophils and 1.2 +/- 0.3%/h for basophils. The mean blood transit time (or blood sojourn time) was estimated to be 25 +/- 2 h or neutrophils, 26 +/- 3 h for eosinophils and 89 +/- 21 h for basophils. Accordingly the half lifes (T 1/2) of granulocytes in the blood were 17.3 +/- 1.4 h for neutrophils, 18.0 +/- 2.1 for eosinophils and 62 +/- 15 h for basophils. Under the quasi steady state conditions of this study the kinetics of granulocytes in the present CLL patients appeared to be normal, despite a marked lymphocytic infiltration of the bone marrow. The apparent discrepancy between these findings and the data obtained with autotransfusion of DFP-labeled granulocytes is discussed.


Cervical intradiskal injection of aprotinin. Technical note and preliminary report.
Chemonucleolysis is widely used in the treatment of disease of the lumbar intervertebral disk. From a series of 28 patients, the authors report their experience using this technique at the cervical level using aprotinin instead of chymopapain.


Effect of Eu(3+) on characterization of photosystem II particles from spinach by spectroscopy.
Photosystem II (PSII) particles were purified from Eu(3+)-treated spinach and studied by spectroscopy. The results showed that electron transport rate of PS II was accelerated by Eu3+ treating, that violet shift of the PSII Soret band or Q-band was 6 nm or 2 nm for the ultraviolet-visible (UV-Vis) spectrum, that the violet shift of the PSII fluorescence emission peak was 9 nm for fluorescence emission spectrum, that the PSII Signal II's of low-temperature electron paramagnetic resonance (EPR) spectrum was intensified under light, and that the PSII CD spectrum was similar to that of control. It is suggested that Eu(3+) might bind to the PSII reaction center complex and enhance the electron transport rate of PSII CD; however, Eu(3+) treatment does not change the configuration of the PSII reaction center complex.


Pd-Catalyzed Difluoromethylations of Aryl Boronic Acids, Halides, and Pseudohalides with ICF2 H Generated ex Situ.
An expedient ex-situ generation of difluoroiodomethane (DFIM) and its immediate use in a Pd-catalyzed difluoromethylation of aryl boronic acids and ester derivatives in a two-chamber reactor is reported. Heating a solution of bromodifluoroacetic acid with sodium iodide in sulfolane proved to be effective for the generation of near stoichiometric amounts of DFIM for the ensuing catalytic coupling step. A two-step difluoromethylation of aryl (pseudo)halides with tetrahydroxydiboron as a low-cost reducing agent, both promoted by Pd catalysis, proved effective to install this fluorine-containing C1 group onto several pharmaceutically relevant molecules. Finally, the method proved adaptable to deuterium incorporation by simply adding D2 O to the DFIM-generating chamber.


The meaning of non-culprit stenosis in hyperacute stroke with large vessel occlusion.
To diagnose atherosclerotic occlusion mechanism in acute ischemic stroke patients with large vessel occlusion prior to revascularization therapy is challenging. The aim was to verify the relationship between atherosclerotic occlusion and non-culprit stenosis detected in urgent neuroimaging prior to interventional procedure. This study collected hyperacute stroke with large vessel occlusion, who underwent revascularization therapy (intravenous thrombolysis, thrombectomy, or both). An atherosclerotic occlusion was defined as an occlusion that did not recanalize or had residual stenosis at the initially occluded lesion, ensured in the second angiographic imaging performed after 1 week. The remaining patients who did not fulfill the definition of atherosclerotic occlusion was classified as embolic occlusion. A non-culprit stenosis was defined as a ≥ 50%-99% stenosis located other than the culprit occluded artery. Logistic regression analyses were performed to determine the factors independently associated with atherosclerotic occlusion. A total of 162 patients (104 men, median age 76 years old) were enrolled in our study. Forty one patients (25%) was atherosclerotic occlusion. Non-culprit stenosis was frequently observed in the atherosclerotic occlusion group than the embolic occlusion group (68% vs. 26%, P < 0.001). The presence of non-culprit stenosis was independently associated with atherosclerotic occlusion (OR, 11.00; 95% CI, 3.96-30.52; P < 0.001). In hyperacute stroke receiving endovascular therapy, non-culprit stenosis identification may be needed in order to perform an adequate revascularization, especially for atherosclerotic occlusion.


Oral clonidine advances spermatogenesis in oligozoospermic patients with spermatogenetic maturation arrest.
Growth hormone (GH) plays an important role in the pubertal development of males and females, and influences the male reproductive function after puberty. The purpose of this study was to investigate the cause of GH deficiency in infertile men with spermatogenetic maturation arrest using the clonidine loading test (GH stimulation test). Based on the results of the loading test, we tried to con fi rm whether clonidine might be usable as a male infertility remedy. We studied 75 infertile men (55 oligozoospermic and 20 azoospermic men) and 25 normal fertile volunteers. We used the oral clonidine (0.15 mg/m2) loading test to evaluate the GH secretory reserve. Histological diagnoses were performed using testicular biopsy and testicular sperm extraction specimens. The most important finding was that the clonidine loading test caused a good response in 41 out of 55 (74.6%) patients with oligozoospermia. We treated these 41 good-response patients with oral clonidine, and the sperm count improved in 34 (82.9%) cases, increasing to 12-79 million/mL. Spontaneous pregnancy was subsequently achieved by 10 (24.4%) couples. These findings also suggest that GH is necessary for spermatogenesis, at least for the process of spermatozoa maturation. Oral clonidine therapy improved the sperm count in patients who showed an excessive response to the clonidine loading test.


Coagulation defects in trauma patients: etiology, recognition, and therapy.
Trauma patients have many reasons to have defects in coagulation. These can be caused by the trauma or because of pre-existing disorders. Trauma patients who are at risk for coagulation defects should be screened with the basic tests (aPTT, INR/PT, platelet counts, hematocrit, and fibrinogen), with therapy based on the results. Attention also should be paid to any other correctable factors such as hypothermia. Finally, pre-existing disorders can influence the patient's hemostasis greatly and may require specific therapies.


Gastrointestinal aspects of Peutz-Jeghers syndrome.
There are two main problems in the clinical management of the gastrointestinal (GI) tract in patients with Peutz-Jeghers syndrome (PJS), namely long-term cancer risk and managing polyp related complications (of which the most important clinically is intussusception). Given the rarity of this condition, the evidence base upon which to make recommendations is small. Furthermore, controversies persist regarding the relationship between PJ polyps, cancer development and cancer risk. In this article we will explore some of these controversies, to put into context the recommendations for clinical management of these patients. We will provide an overview, particularly focusing on clinical data, and on the recommendations for clinical management and surveillance of the GI tract in PJS. We highlight knowledge gaps which need to be addressed by further research.


Molecular cloning, expression, purification, and functional characterization of palustrin-2CE, an antimicrobial peptide of Rana chensinensis.
Antimicrobial peptides are effector molecules of the innate immunity of amphibians. Here, one antimicrobial peptide cDNA precursor, prepropalustrin-2CE3, from the tadpole of the Chinese brown frog Rana chensinensis was cloned. The coding sequence corresponding to the mature palustrin-2CE peptide was subcloned into pGEX-6p-1. The soluble GST-palustrin-2CE fusion protein was successfully expressed in the BL21(DE3)pLysS strain at 16 °C, and the proportion of the fusion protein reached 35%-39% of the total cellular protein. After removal of the GST-fusion tag, the purity of the palustrin-2CE obtained by Sephadex G50 chromatography was about 97%. Moreover, the purified palustrin-2CE displayed obviously inhibitory activities against the sensitive bacteria Staphylococcus aureus, Bacillus subtilis, Pseudomonas aeruginosa, and Escherichia coli, and multi-drug resistant S. aureus and E. coli. These findings suggest that the tadpole of the Chinese brown frog is a unique source of antimicrobial peptides and indicates the therapeutic potential of the palustrin-2CE peptide.


Effect of tibolone on turnover of cholesterol to bile acids in ovariectomized rats.
Tibolone is used in breast cancer therapy in women. The most important aspect of this therapy concerns its influence on bone and lipid metabolism. Several studies have reported the effect of tibolone on plasma lipids. Approximately 40% of total cholesterol removal occurs by its conversion to bile acids, a process that takes place in the liver. The aim of the study was to evaluate the influence of tibolone on the conversion of cholesterol to bile acids in estrogen-deficient rats. Thirty female Wistar rats were divided into three groups: sham-operated controls, ovariectomized controls, and ovariectomized rats treated with tibolone. After 42 days of drug administration, bile was collected under anesthesia after administration of radioactive 4-C cholesterol. Bile was assayed for total C radioactivity; C bile acids were determined after thin-layer chromatography separation by using the isotopic technique. The ovariectomy decreased the concentrations of C-radioactive bile, taurocholic acid, and cholic acid. The administration of tibolone significantly increased the excretion of C-radioactive bile and C-radioactive bile acids as compared with ovariectomized controls. Moreover, the therapy with tibolone significantly increased the concentrations of C taurocholic acid, C glycocholic acid, cholic acid, and taurochenodeoxycholic plus taurodeoxycholic acids. The results of the present study suggest that tibolone may increase the concentrations of cholesterol and trihydroxy bile acids in bile. These changes may be associated with an increased risk of gallstone generation.


Protective Effect of RIVA Against Sunitinib-Induced Cardiotoxicity by Inhibiting Oxidative Stress-Mediated Inflammation: Probable Role of TGF-β and Smad Signaling.
Sunitinib (SUN) is an oral tyrosine kinase inhibitor approved in 2006 as a first-line treatment for metastatic renal cell cancer. However, weak selectivity to kinase receptors and cardiotoxicity have limited the use of sunitinib. Rivaroxaban (RIVA) is a Factor Xa inhibitor with cardioprotective action. It inhibits atherosclerosis and numerous inflammatory cascades. The present study was designed to investigate the cardioprotective effects of RIVA in sunitinib-induced cardiotoxicity. Thirty male Wistar rats were divided into five groups. Group 1 was the normal control (control). Group 2 was administered i.p. SUN 25 mg kg-1 thrice weekly for 3 weeks. Groups 3 and 4 received the same treatment as Group 2 followed by the administration of RIVA 5 mg kg-1 day-1 and 10 mg kg-1 day-1, respectively, for 3 weeks. Group 5 received only 10 mg kg-1 day-1 RIVA for 3 weeks. Serum levels of Ca2+, Mg2+, Fe3+/Fe2+, lipid profiles, and cardiac enzymes were measured. Cardiac tissues were isolated for the measurements of oxidant/antioxidant balance gene and protein expressions. Relative to the controls, the administration of SUN significantly altered serum levels of (Ca2+, Mg2+, Fe3+/Fe2+, lipid profiles, and cardiac enzymes), intracellular antioxidant enzymes, and the expression levels of the genes encoding certain proteins. RIVA treatment significantly restored these parameters to near-normal levels. RIVA treatment significantly mitigated SUN-induced cardiac injuries by restoring antioxidant enzyme levels and attenuating the proinflammatory cascades resulting from SUN-induced cardiac injuries.


The use of recombinant protein and RNA interference approaches to study the reproductive functions of a gonad-stimulating hormone from the shrimp Metapenaeus ensis.
Although the crustacean crustacean hyperglycemic hormone/molt-inhibiting hormone/gonad-inhibiting hormone neuropeptides have been studied extensively in the last two decades and several neuropeptides from the shrimp Metapenaeus ensis have been cloned, the functions of most of these neuropeptides remained putative. In this article, we describe the use of recombinant protein and an RNA interference approach to study the reproductive function of the previously reported molt-inhibiting hormone (MeMIH-B) in M. ensis. When hepatopancreas and ovary explants were cultured in medium containing recombinant MeMIH-B, the vitellogenin gene (MeVg1) expression level was upregulated in a dose-dependent manner, reaching a maximum in explants treated with 0.3 nm recombinant MeMIH-B. Shrimp injected with recombinant MeMIH-B showed an increase in vitellogenin gene expression in the hepatopancreas. Moreover, a corresponding increase in the vitellogenin-like immunoreactive protein was detected in the hemolymph and ovary of these females. Injection of MeMIH-B dsRNA into the female shrimp caused a decrease in MeMIH-B transcript level in thoracic ganglion and eyestalk. These shrimp also showed reduction of vitellogenin gene expression in the hepatopancreas and ovary. Furthermore, the hemolymph vitellogenin level was also reduced in these animals. In summary, the results from recombinant protein and RNA interference experiments have demonstrated the gonad-stimulatory function of MeMIH-B in shrimp.


Cellular and synaptic alterations in the aging brain.
The morphological and functional impairments observed in the aging brain are discussed in the framework of theoretical concepts, such as the existence of different modalities of intercellular communication and of specific trophic features in the central nervous system. The relevance of changes at the cellular level (disappearance of neuronal cell bodies and proliferation of astroglial cells) and at the synaptic level (alterations in neurotransmitter and receptor levels) is discussed. Two, non-mutually exclusive hypotheses are advanced to explain the frequent absence of correlation between neuropathological findings and functional deficits in aged patients. According to the first, the physiological reshaping of brain circuits during aging may lead to "wrong" readjustments of neural networks (e.g. due to less effective endogenous and exogenous orienting signals) causing minor morphological alterations but marked functional deficits. The second hypothesis maintains that the absence of correlation between neuropathological and functional deficits is due to the impairment of restricted neuronal populations ("pacemaker and command neurons") which play a special role in the hierarchical organization of neuronal networks. These neurons (inter alia, peptidergic neurons) may also be involved in volume transmission (diffusion of electrical and chemical signals in the extracellular fluid to reach distant targets). Moreover, the relevance of glial cells, not only as regulators of the extracellular medium but also on the basis of their trophic links with neurons, is considered. Finally, the interplay between trophic factors and therapeutical experience for the maintenance and/or recovery of an impaired function in elderly patients is discussed.


Does the prevalence of otolaryngological diseases in deaf children differ from children without hearing impairment?
There is no enough data about the prevalence of otorhinolaryngological (ORL) diseases in deaf children. In this study, we aimed to determine the prevalence of ORL diseases among deaf children and compare children from a school for the deaf with those attending regular primary schools for the presence of ear, nose and throat (ENT) problems. The subjects were 1,282 children attending three primary schools in the province of Duzce and 572 hearing-impaired children from eight schools for the deaf. Following ENT examinations, ORL findings were statistically compared between two groups using a Chi-square test and P values less than 0.05 were considered significant. Upper airway pathologies including chronic tonsillitis, rhinitis, septal deviation and tubal dysfunction, and chronic otitis media (COM) were found to be statistically higher in deaf children than in children without hearing impairment. Although the incidence of middle ear effusion was found to be higher in deaf children, it was not statistically significant. On the other hand, the incidence of impacted wax was lower in deaf children than others. In conclusion, we should have enough data on the prevalence of ORL diseases in deaf children to give a clue to help prevent ORL diseases and if we can detect them early, we can solve the problems before they become more complicated and we can rehabilitate these children better.


Characterization of clinafloxacin photodegradation products by LC-MS/MS and NMR.
Exposure of clinafloxacin to light results in photochemical degradation. The polar and nonpolar photodegradation products were profiled by HPLC using two sets of conditions. Clinafloxacin was subjected to severe light exposure conditions to obtain elevated levels of the photodegradation products for characterization. The structures of eight new degradation products were elucidated based on information from LC-MS/MS fragmentation and NMR spectra following isolation by preparative HPLC. Two photodegradation routes were identified: (1) dechlorination, followed by further reactions involving the quinolone ring, to yield polar photodegradation products; and (2) degradation of the pyrrolidine side-chain, yielding the nonpolar photodegradation products.


Comparison of the spectroscopic speciation and chemical fractionation of chromium in contaminated paddy soils.
Sequential extraction has been widely used to classify metal species in soils and sediments; however, the lack of selectivity in extraction reagents may lead to the misinterpretation of metal speciation. In this study, we used X-ray absorption near edge structure (XANES) spectroscopy to classify Cr species based on its molecular form. These results complement the conventional Cr fractionation derived from the Tessier extraction method. The linear combination fitting (LCF) for the Cr-XANES spectra indicated that the Cr species in the soils could generally be described as Cr(III) sorbed on ferrihydrite (Cr-FH), Cr(III) complexed with humic acid (Cr-HA), and precipitated Cr. While the sum of the adsorbed Cr(III) and Cr(III)/Fe coprecipitates showed a nearly 1:1 relationship with reducible Cr, the total of Cr precipitates and organic Cr also followed the same trend with oxidizable Cr. This result indicated that there might be a underestimation in the reducible fraction as pure Cr(III) precipitates associated with surfaces of Fe minerals would not be extracted in the reducible process. Instead, such pure Cr(III) precipitates were dissolved during the oxidizable process, resulting in a overestimation in the fractionation of organic-related Cr.


Patterns of drought response in leaf-succulent shrubs of the coastal Atacama Desert in Northern Chile.
Despite the extrame aridity of the coastal Atacama Desert in northern Chile, sparse communities of leaf succulent shrubs and small cacti are regularly present. While most shrub species have small succulent leaves and accumulate high concentrations of salts in their tissues, the variable rooting patterns and mixed dominance of CAM and C3 species indicates a significant divergence in adaptive strategies. All dominant shrubs are readily surviving extended drought, but some species are much better able than others to maintain active growth and flowering. Regular flowering may not be a prerequisite for shrub population maintenance since large piles of viable seeds are present under the canopies of many species.


Berberine protects 6-hydroxydopamine-induced human dopaminergic neuronal cell death through the induction of heme oxygenase-1.
Berberine (BBR) is one of the major alkaloids and has been reported to have a variety of pharmacologic effects, including inhibition of cell cycle progression. Here, we investigated the mechanisms of BBR protection of neuronal cells from cell death induced by the Parkinson's disease-related neurotoxin 6-hydroxydopamine (6-OHDA). Pretreatment of SH-SY5Y cells with BBR significantly reduced 6-OHDAinduced generation of reactive oxygen species (ROS), caspase-3 activation, and subsequent cell death. BBR also upregulated heme oxygenase-1 (HO-1) expression, which conferred protection against 6-OHDA-induced dopaminergic neuron injury and besides, effect of BBR on HO-1 was reversed by siRNA-Nrf2. Furthermore, BBR induced PI3K/Akt and p38 activation, which are involved in the induction of Nrf2 expression and neuroprotection. These results suggest that BBR may be useful as a therapeutic agent for the treatment of dopaminergic neuronal diseases.


Electron microscopic studies on the development of the chorion of the viviparous teleost Dermogenys pusillus (Hemirhamphidae).
Eight stages in the oogenesis of Dermogenys pusillus were selected in order to demonstrate the formation of the egg membrane. In young oocytes (stages 1 and 2) the contact between oocyte and follicular cells is rather close. During stage 3 microvilli arise from the oocyte, and the follicular cells protrude lobopodia-like cell processes. When the microvilli have become arranged more regularly, the homogeneous material of the zona radiata externa is deposited between them (stage 4). During the subsequent stage (5) the inhomogeneous zona radiata interna appears. It attains its greatest thickness and its characteristic fine structure during stage 6. It then consists of cross-banded fibrillae and lamellae. Later on (stage 7) the egg membrane flattens, and finally it is a compact chorion consisting perhaps of very fine fibrils. Because of this development and of its comlex fine structure the egg membrane of Dermogenys like that of Zoarces resembles that of oviparous teleosts but remains consideribly thinner. The eight stages of oogenesis in Dermogenys are compared with those described by Arndt (1956) in several limnetic teleosts.


The limits of newborn's grasping to detect texture in a cross-modal transfer task.
Three experiments were conducted to investigate human newborns' ability to perceive texture property tactually, either in a cross-modal transfer task or in an intra-modal tactual discrimination task. In Experiment 1, newborns failed to tactually recognize the texture (smooth vs. granular) of flat objects that they had previously seen, when they held flat objects. This failure was mainly due to a lack of intra-modal tactual discrimination between the two objects (Experiment 2). In contrast, Experiment 3 showed that newborns were able to tactually recognize the texture of previously seen surfaces when they held volumetric objects. Taken together, the results suggest that cross-modal transfer of texture from vision to touch stem from a peripheral mechanism, not a central mechanism. Grasping only allows newborns to perceive the texture of volumetric but not flat objects. As a consequence, this study reveals the limits of newborns' grasping to detect and process information about texture. The results also suggest that more mature exploratory procedures, such as the "lateral motion" procedure exhibited by adults [Lederman, S. J., & Klatzky, R. (1987). Hand movements: A window into haptic object recognition. Cognitive Psychology, 19, 342-368], might be necessary for detecting the texture of flat objects in newborn infants.


Sustainability approaches for agrowaste solution: Biodegradable packaging and microbial polysaccharides bio-production.
Global growth impacts on the increased use and demand for natural resources, requiring solutions for the high volume of industrial waste and by-products generated from the most diverse commercial areas, mainly the food sector. Among the main residues with a large volume generated, those from fruit processing, grain cleaning in processing units, vegetables, and discards from the animal production industry stood out. Approximately 1.3 billion all food produced worldwide is lost or wasted per year being fruits, vegetables, roots, and tubers responsible for about half of the total amount. Many of these by-products have interesting nutrients in their composition such as fibers, proteins, and bioactive compounds. An interesting example is the sugarcane bagasse. Fibrous residue, derived from sugarcane extraction, the bagasse represents about 30-34 % of the total sugarcane mass. This is one of the most abundant cellulosic residues and contains approximately 39 % of cellulose, 28 % of hemicellulose, and 18 % of lignin. Therefore, as well as the bagasse, several residues from agroindustrial can be considered promising alternative substrates, being valuable sources for the development of high-value-added products, such as biopolymers, bioenergy, and chemical products. In addition, the reuse of agroindustrial wastes may be considered an attractive option for reducing the environmental impact caused by their generation. In the case of biopolymers, the energy savings of bio-based polymers is around 20-50 GJ/t of polymer. In this review, we have selected two commercially promising approaches to the application and use of agroindustrial residues, aiming their use for biodegradable packaging and microbial polysaccharides bio-production, improving overall sustainability and economic aspects of the scientific research, technology and modern industry.


Neurologic-developmental sequelae of chronic renal failure in infancy.
Twelve children who have had chronic renal failure since infancy and underwent early dialysis (mean age 18 months) and early transplantation (mean age 28 months) were studied. Although head circumference in all was within the normal range at birth, by 1 year it was greater than 2 SD below the mean in nine, including six in whom it was greater than 3 SD below the mean. Developmentally, eight children were functioning in the subnormal range; four of these were moderately and one severely mentally retarded. It was not possible to determine whether the unfavorable neurologic-developmental outcome was the result of the toxic effects of uremia, malnutrition, or the associated psychosocial and experiential deprivation related to chronic, severe illness. Even minor insults at this vulnerable stage of brain development may produce permanent damage, and institution of therapy as early as possible may be crucial in obtaining a more favorable outcome.


Interplay between Oxidative Stress, Inflammation, and Amyloidosis in the Anterior Segment of the Eye; Its Pathological Implications.
There are different pathologies associated with amyloidogenic processes caused by the increase of reactive oxygen species (ROS) and the overactivation of inflammatory responses. These alterations are present in different regions of the anterior segment of the eye, and they have been associated with the development and progression of ocular pathologies, such as glaucoma, dry eye syndrome, keratitis, and cataracts among other pathologies. Aim. To discuss briefly the anatomical characteristics of the anterior segment of the eye and describe the interaction between oxidative stress (OS) and inflammatory responses, emphasizing the misfolding of several proteins leading to amyloidogenic processes occurring in the anterior segment and their implications in the development of ocular diseases. We performed a search on PubMed, CINAHL, and Embase using the MeSH terms "eye," "anterior segment", "inflammation", "oxidative stress", and "amyloidosis". The search encompassed manuscripts published up to April 2019. A hundred forty-four published studies met the inclusion criteria. We present the current knowledge regarding the interaction between OS and the activation of inflammatory processes and how both can cause conformational changes in several peptides and proteins in each compartment of the anterior segment. However, we found that there is no consensus about which factor is the first to cause amyloidosis. Our conclusions suggest that there is an interplay among these factors forming a vicious cycle that leads to the loss of protein structure in ocular pathologies, and multifactorial therapies should be developed to avoid protein misfolding and to stop the progression of ocular pathologies.


Oncomodulin. 1H NMR and optical stopped-flow spectroscopic studies of its solution conformation and metal-binding properties.
As deduced from its 1H NMR spectrum, oncomodulin's solution conformation is very similar to the tertiary structure of other single domain 2-site calcium-binding proteins of the troponin C class. Despite its extensive amino acid sequence homology with parvalbumins, however, oncomodulin differs significantly from these proteins in its Ca(II)----Ln(III) exchange characteristics. Although the relative affinity of Lu(III) for the EF site of Ca2-oncomodulin was normal, beta Lu:EF/beta Ca:EF being 175 +/- 15, displacement of Ca(II) from the CD site was not favored, beta Lu:CD/beta Ca:CD being 1.2 +/- 0.1. Lineshape analyses of several 1H NMR resonances generated by the Lu(III) titration of Ca2-oncomodulin indicated that Ca(II)----Ln(III) exchange at the CD site was 15-20 s-1, approximately 100 times faster than exchange at the CD site of parvalbumins. Analyses of the distribution of metal-bound oncomodulin species showed that Ca(II)----Lu(III) exchange was cooperative, the coefficient of cooperativity being estimated as 5 +/- 1. The kinetics of the release of Yb(III) from oncomodulin as measured by optical stopped-flow techniques corroborated the observed cooperativity in metal binding; the off-rate constant of Yb(III) from the EF site of Yb2-oncomodulin was 0.0036 s-1, approximately 19 times slower than the release of Yb(III) from the EF site of Ca1Yb1-oncomodulin. We attribute part of the reduced preference of small Ln(III)s for the CD site of oncomodulin to a combination of this site's inherent incompressibility (Williams, T.C., Corson, D.C. & Sykes, B.D. (1984) J. Am. Chem. Soc. 106, 5698-5702) and the Glu----Asp substitution at sequence position 59, the residue which chelates metal at the -X coordination position. Like the CD site in oncomodulin, site III in troponin C has not only a lower affinity for calcium relative to the CD site of parvalbumins but also aspartic acid at its -X position; a water molecule bridges the gap between bound metal and the carboxyl group of the relatively short side chain of Asp-114 (Herzberg, O. & James, M. N. G. (1985) Biochemistry 24, 5298-5302). Hence, we suggest that Asp-59 in oncomodulin binds metal only indirectly through an intervening water molecule, a proposal which is consistent with the CD site's reduced affinity for ions the size of Ca(II) or smaller.


Association between chronic pain and risk of incident dementia: findings from a prospective cohort.
Chronic musculoskeletal pain has been linked to dementia; however, chronic pain typically occurs in multiple sites; therefore, this study was to investigate whether greater number of chronic pain sites is associated with a higher risk of dementia and its subtypes. Participants (N = 356,383) in the UK Biobank who were dementia-free at baseline were included. Pain in the hip, knee, back, and neck/shoulder or 'all over the body' and its duration were assessed. Participants were categorised into six groups: no chronic pain; chronic pain in 1, 2, 3, and 4 sites, and 'all over the body'. All-cause dementia and its subtypes were ascertained using hospital inpatient and death registry records. Cox regression was used to investigate the associations between the number of chronic pain sites and the incidence of all-cause dementia and its subtypes. Over a median follow-up of 13 years, 4959 participants developed dementia. After adjustment for sociodemographic, lifestyle, comorbidities, pain medications, psychological problems, and sleep factors, greater number of chronic pain sites was associated with an increased risk of incident all-cause dementia (hazard ratio [HR] = 1.08 per 1 site increase, 95% CI 1.05-1.11) and Alzheimer's disease (AD) (HR = 1.09 per 1-site increase, 95% CI 1.04-1.13) in a dose-response manner but not vascular and frontotemporal dementia. No significant association was found between the number of chronic pain sites and the risk of incident all-cause dementia among a subsample that underwent a fluid intelligence test. Greater number of chronic pain sites was associated with an increased risk of incident all-cause dementia and AD, suggesting that chronic pain in multiple sites may contribute to individuals' dementia risk and is an underestimated risk factor for dementia.