Shape-memory and self-healing functions of DNA-based carboxymethyl cellulose hydrogels driven by chemical or light triggers.
Photoresponsive nucleic acid-based carboxymethyl cellulose (CMC) hydrogels are synthesized, and their application as shape-memory and self-healing functional matrices are discussed. One system involves the preparation of a carboxymethyl cellulose hydrogel crosslinked by self-complementary nucleic acid duplexes and by photoresponsive trans-azobenzene/β-cyclodextrin (β-CD) supramolecular complexes. Photoisomerization of the trans-azobenzene to the cis-azobenzene results in a hydrogel exhibiting lower stiffness due to the separation of the azobenzene/β-CD bridging units. The hydrogel is switched between high and low stiffness states by the cyclic and reversible light-induced isomerization of the azobenzene units between the trans and cis states. The light-controlled stiffness properties of the hydrogel are used to develop a shape-memory hydrogel, where the duplex bridging units act as permanent memory in the quasi-liquid shapeless state of the hydrogel. A second system in the study is a carboxymethyl cellulose hydrogel crosslinked by the K+-stabilized G-quadruplex bridging units and by trans-azobenzene/β-CD complexes. The resulting hydrogel includes dual-trigger functionalities, where the trans-azobenzene/β-CD complexes can be reversibly formed and dissociated through the trans and cis photoisomerization of the azobenzene units, and the K+-stabilized G-quadruplexes can be reversibly dissociated and reformed in the presence of 18-crown-6-ether/K+-ions. The signal-responsive crosslinked hydrogel reveals controlled stiffness properties, where the hydrogel crosslinked by the trans-azobenzene/β-CD and K+-ion-stabilized G-quadruplex reveals high stiffness and the hydrogel crosslinked only by the K+-ion-stabilized G-quadruplexes or only by the trans-azobenzene/β-CD complexes reveals low stiffness properties. The controlled stiffness properties of the hydrogel are used to develop shape-memory hydrogels, where the trans-azobenzene/β-CD complexes or the K+-ion-stabilized G-quadruplexes act as permanent memories in the shapeless and quasi-liquid states of the hydrogels. In addition, the hydrogel that includes two types of stimuli-responsive crosslinking units is used as a self-healing matrix, where each of the triggers guides the self-healing processes.


[Results of a Representative Survey on the Psychosocial Evaluation Before Living Donor Kidney Transplantation in Germany].
Aim Since there is no consensus about how to perform the predonation psychosocial evaluation of living kidney donor candidates, this is conducted differently in German transplant centers. Thus, the goal of the study was to learn more about how psychosocial evaluations are currently conducted in German transplant centers. Methods The psychosocial evaluators of the 38 transplant centers performing kidney transplantations in 2015 were contacted and asked to participate in an anonymous online survey. Results Psychosocial evaluators from 28 (75%) transplant centers responded. In only 30 (4%) of the evaluations contraindications for donation were reported. In most centers the psychosocial evaluation was performed after the completion of all medical tests. The evaluations were realized after only short waiting periods and were reported to be time-consuming. Financial reimbursement was mainly realized by internal cost allocation. In most centers the evaluators used semi-structured interviews. Still, there was limited consensus about structure and content of the psychosocial evaluation. Conclusion Standardization of the psychosocial evaluation process could be helpful to enable comparisons between transplant centers and to achieve equal opportunities for the potential living kidney donors and recipients.


In vitro release of tranilast from oily gels and penetration of the drug into Yucatan micropig skin.
For the transdermal delivery of tranilast (TL), a drug used for the treatment of skin diseases such as keloids and hypertrophic scars, its oily gels were prepared; its in vitro release and penetration into Yucatan micropig skin were evaluated. In the gels that consisted of hydrogenated soybean phospholipids (HSL) and octyl isononanoate (IOIN), a fatty-acid ester, the release of TL from the gels was proportional to the drug content, and the extent of TL released up to 6 h from them was approximately 70% of the amount of applied TL. On the other hand, with the gels consisting of HSL and isocetyl isostearate (ICIS), the release of TL from the gels was about half of that from IOIN gels, even at the same drug concentration. When oily gels were used, the TL skin concentration was rapidly increased compared with the level obtained with suspensions. With 0.1% IOIN gel, a high concentration of TL (ca. 160 microg/g) in the dermis was obtained and continued until at least 48 h. These results suggest that oily gels may be useful for the topical application of TL.


Effects of Vitamin D-Deficient Diet on Intestinal Epithelial Integrity and Zonulin Expression in a C57BL/6 Mouse Model.
Background and Aims: Vitamin D (VD) plays an important role not only in mineral balance and skeletal maintenance but also in immune modulation. VD status was found correlated with the pathophysiology and severity of inflammatory bowel diseases and other autoimmune disorders. Epithelial barrier function is primarily regulated by the tight-junction (TJ) proteins. In this study, we try to establish an animal model by raising mice fed VD-deficient diet and to investigate the effects of VD-deficient diet on gut integrity and zonulin expression. Methods: Male C57BL/6 mice were administered either VD-deficient [VDD group, 25(OH)2D3 0 IU/per mouse] or VD-sufficient [VDS group, 25(OH)2D3 37.8 IU/per mouse] special diets for 7 weeks. Body weight and diet intake were recorded weekly. Serum VD levels were detected. After sacrifice, jejunum and colon specimens were collected. The villus length and crypt depth of the jejunum as well as mucosa thickness of the colon were measured. Various serum pro-inflammatory cytokines and intestinal TJ proteins were assessed. The serum level of zonulin and the mRNA expression of jejunum zonulin were also investigated. Results: We found that mice fed a VDD diet had a lower serum level of VD after 7 weeks (p < 0.001). VDD mice gained significant less weight (p = 0.022) and took a similar amount of diet (p = 0.398) when compared to mice raised on a VDS diet. Significantly decreased colon mucosa thickness was found in VDD mice compared with the VDS group (p = 0.022). A marked increase in serum pro-inflammatory cytokine levels was demonstrated in VDD mice. All relative levels of claudin (CLD)-1 (p = 0.007), CLD-3 (p < 0.001), CLD-7 (p < 0.001), and zonulin-1 (ZO-1, p = 0.038) protein expressions were significantly decreased in the VDD group when compared to the VDS group. A significant upregulation of mRNA expression of jejunum zonulin (p = 0.043) and elevated serum zonulin (p = 0.001) were found in the VDD group. Conclusions: We successfully demonstrated that VDD could lead to impaired barrier properties. We assume that sufficient VD could maintain intestinal epithelial integrity and prevent mucosal barrier dysfunction. VD supplementation may serve as part of a therapeutic strategy for human autoimmune and infectious diseases with intestinal barrier dysfunction (leaky gut) in the future. To our knowledge, this is the first study to demonstrate that VDD could lead to a significant upregulation in mRNA expression of the jejunum zonulin level and also a marked elevation of serum zonulin in a mouse model.


The isolation of strand-specific nicking endonucleases from a randomized SapI expression library.
The Type IIS restriction endonuclease SapI recognizes the DNA sequence 5'-GCTCTTC-3' (top strand by convention) and cleaves downstream (N1/N4) indicating top- and bottom-strand spacing, respectively. The asymmetric nature of DNA recognition presented the possibility that one, if not two, nicking variants might be created from SapI. To explore this possibility, two parallel selection procedures were designed to isolate either top-strand nicking or bottom-strand nicking variants from a randomly mutated SapI expression library. These procedures take advantage of a SapI substrate site designed into the expression plasmid, which allows for in vitro selection of plasmid clones possessing a site-specific and strand-specific nick. A procedure designed to isolate bottom-strand nicking enzymes yielded Nb.SapI-1 containing a critical R420I substitution near the end of the protein. The top-strand procedure yielded several SapI variants with a distinct preference for top-strand cleavage. Mutations present within the selected clones were segregated to confirm a top-strand nicking phenotype for single variants Q240R, E250K, G271R or K273R. The nature of the amino acid substitutions found in the selected variants provides evidence that SapI may possess two active sites per monomer. This work presents a framework for establishing the mechanism of SapI DNA cleavage.


A comprehensive study of reaction parameters in the enzymatic production of novel biofuels integrating glycerol into their composition.
A comprehensive study of critical parameters in the pig pancreatic lipase (PPL) catalysed transesterification of sunflower oil to novel biofuels integrating glycerol into their composition is reported. The influence of oil/alcohol ratio, temperature, quantity of enzyme and water added and pH have been investigated. The enzymatic activity of PPL was found to be greatly influenced by the pH, reaching notable activities at high pH values (10-12), in contrast to other lipases. The addition of small quantities of NaOH (up to 0.1 mL) as coadjuvant in the transesterification reaction enhances the activity of the enzymes. This remarkable behaviour, reported for the first time, may pave the way for the utilisation of these relatively cheap enzymes in large scale commercial biodiesel production. Besides, a novel biofuels containing glycerol into their composition as mono- and diglycerides using PPL as biocatalyst has been developed.


Serum Calprotectin Is a Valid Biomarker in Distinction of Bacterial Urinary Tract Infection From Viral Respiratory Illness in Children Under 3 Years of Age.
Febrile illnesses in young children can be a major diagnostic challenge, despite the routine use of various laboratory markers. Recent advancements in the understanding of inflammatory processes have highlighted the role of calprotectin, a heterodimer consisting of S100A8 and S100A9 proteins, with many studies suggesting its clinical value as a biomarker of inflammation. This research aimed to evaluate the usefulness of serum calprotectin (sCal) as a biomarker of urinary tract infection (UTI), which was due to its high pooled prevalence and feasibility of urine culture as a diagnostic reference standard selected for a model of bacterial infection in children. Febrile children aged 0-36 months with suspected UTI based on positive urinalysis or viral respiratory tract infection were included. Children with significant bacteriuria in urine culture were labeled as cases (n = 58), while those with confirmed viral infection (n = 51), as well as those with suspected UTI but sterile urine culture who went on to develop symptoms consistent with viral respiratory infection (n = 7), were labeled as controls. sCal levels were determined by a commercial immunoassay. Conventional inflammation markers (C-reactive protein, procalcitonin, white blood cell count, absolute neutrophil count, and neutrophil percentage) were measured on the day of the clinical examination. Differences in measured inflammatory markers between cases and controls were analyzed with Mann-Whitney U-test. ROC analysis reported cut-off values with the best sensitivity and specificity to distinguish bacterial UTI from viral respiratory infection. All analyzed inflammatory biomarkers, including sCal, were significantly higher in cases than in controls. Median concentration of sCal was 4.97 μg/mL (IQR 3.43-6.42) and 2.45 μg/mL (IQR 1.63-3.85) for cases and controls, respectively (p < 0.001). For identifying bacterial UTI, sensitivity and specificity of sCal were 77.6 and 69.0%, respectively, at an adjusted cut-off point of >3.24 μg/mL (AUC 80.2%). sCal could have substantial added value in the management of a child with fever and positive urinalysis and is a promising biomarker in distinction between bacterial UTI and viral respiratory causes of febrile illness in children under the age of 3 years.


Effects of age-associated regional changes in aortic stiffness on human hemodynamics revealed by computational modeling.
Although considered by many as the gold standard clinical measure of arterial stiffness, carotid-to-femoral pulse wave velocity (cf-PWV) averages material and geometric properties over a large portion of the central arterial tree. Given that such properties may evolve differentially as a function of region in cases of hypertension and aging, among other conditions, there is a need to evaluate the potential utility of cf-PWV as an early diagnostic of progressive vascular stiffening. In this paper, we introduce a data-driven fluid-solid-interaction computational model of the human aorta to simulate effects of aging-related changes in regional wall properties (e.g., biaxial material stiffness and wall thickness) and conduit geometry (e.g., vessel caliber, length, and tortuosity) on several metrics of arterial stiffness, including distensibility, augmented pulse pressure, and cyclic changes in stored elastic energy. Using the best available biomechanical data, our results for PWV compare well to findings reported for large population studies while rendering a higher resolution description of evolving local and global metrics of aortic stiffening. Our results reveal similar spatio-temporal trends between stiffness and its surrogate metrics, except PWV, thus indicating a complex dependency of the latter on geometry. Lastly, our analysis highlights the importance of the tethering exerted by external tissues, which was iteratively estimated until hemodynamic simulations recovered typical values of tissue properties, pulse pressure, and PWV for each age group.


Relationship between entero-hepatic bile acid circulation and interdigestive migrating myoelectrical activity in rats.
To investigate the effects of entero-hepatic bile acid circulation on the inter-digestive migrating myoelectrical complex (MMC) in rats. Thirty-two rats were divided into four groups. Three pairs of bipolar silver electrodes were chronically implanted in the antrum, duodenum and jejunum. Three groups of them were ligated around the upper part of common bile duct (CBD). The experiments were performed in conscious and fasting state. The gastrointestinal myoelectrical activity was recorded. Ursodeoxycholic acid (UDCA) and saline were then perfused into stomachs of two groups with CBD obstruction and the effects of them on the MMC were observed. A typical pattern of MMC was observed in normal fasting rats. MMC of antral and duodenal origin disappeared temporarily in earlier stage of CBD obstruction. While MMC of jejunum origin appeared. increased MMC cycle duration was seen after 4 d in rats with CBD obstruction. The MMC after CBD obstruction was characterized by an increased duration of phase II-like activity and decreased duration of phase I and III activity. Perfusion into stomachs with UDCA resulted in a shorter MMC cycle duration and a longer duration of phase III of duodenal origin compared to the normal group. Entero-hepatic bile acid circulation initiates inter-digestive MMC of duodenal origin.


Safety and efficacy of varenicline to reduce positive subjective effects produced by methamphetamine in methamphetamine-dependent volunteers.
Methamphetamine use is increasing in the US. Although there are no Food and Drug Administration (FDA)-approved medications for methamphetamine dependence, preclinical and clinical studies suggest that methamphetamine users may benefit from treatments that enhance cholinergic neurotransmission. Consequently, we determined the safety and the efficacy of varenicline treatment, a partial agonist at α4β2 and a full agonist at α7 nicotinic acetylcholine receptors, to reduce positive subjective effects produced by smoked methamphetamine. Additionally, the effects of treatment with varenicline on the cardiovascular and reinforcing effects of methamphetamine were determined. We conducted a double-blind, placebo-controlled, within-subjects trial of varenicline vs. placebo in methamphetamine-dependent volunteers who were not seeking treatment. Participants were randomly assigned to receive one dose of varenicline (0, 1, or 2 mg) po BID, titrated up to the target dose over days 1-7, during each of three separate inpatient phases. Safety measures included the frequency, duration, severity, and relatedness of adverse events reported. Positive subjective effects included 'Any drug effect', 'High', 'Good effects', 'Stimulated', and 'Drug liking', which were rated by participants before and for 1 h after smoking methamphetamine (0, 10, and 30 mg). There were no serious adverse events and no differences in adverse events reported during the three phases. Varenicline (2 mg) significantly reduced ratings of 'Any drug effect' and 'Stimulated', as well as attenuated ratings of 'High', 'Drug liking', and 'Good effects', produced by methamphetamine (30 mg). The ability of varenicline to attenuate the positive subjective effects of methamphetamine in the laboratory suggests that varenicline should continue to be explored as a treatment for methamphetamine dependence.


Systems analysis of ethanol production in the genetically engineered cyanobacterium Synechococcus sp. PCC 7002.
Future sustainable energy production can be achieved using mass cultures of photoautotrophic microorganisms, which are engineered to synthesize valuable products directly from CO2 and sunlight. As cyanobacteria can be cultivated in large scale on non-arable land, these phototrophic bacteria have become attractive organisms for production of biofuels. Synechococcus sp. PCC 7002, one of the cyanobacterial model organisms, provides many attractive properties for biofuel production such as tolerance of seawater and high light intensities. Here, we performed a systems analysis of an engineered ethanol-producing strain of the cyanobacterium Synechococcus sp. PCC 7002, which was grown in artificial seawater medium over 30 days applying a 12:12 h day-night cycle. Biosynthesis of ethanol resulted in a final accumulation of 0.25% (v/v) ethanol, including ethanol lost due to evaporation. The cultivation experiment revealed three production phases. The highest production rate was observed in the initial phase when cells were actively growing. In phase II growth of the producer strain stopped, but ethanol production rate was still high. Phase III was characterized by a decrease of both ethanol production and optical density of the culture. Metabolomics revealed that the carbon drain due to ethanol diffusion from the cell resulted in the expected reduction of pyruvate-based intermediates. Carbon-saving strategies successfully compensated the decrease of central intermediates of carbon metabolism during the first phase of fermentation. However, during long-term ethanol production the producer strain showed clear indications of intracellular carbon limitation. Despite the decreased levels of glycolytic and tricarboxylic acid cycle intermediates, soluble sugars and even glycogen accumulated in the producer strain. The changes in carbon assimilation patterns are partly supported by proteome analysis, which detected decreased levels of many enzymes and also revealed the stress phenotype of ethanol-producing cells. Strategies towards improved ethanol production are discussed. Systems analysis of ethanol production in Synechococcus sp. PCC 7002 revealed initial compensation followed by increasing metabolic limitation due to excessive carbon drain from primary metabolism.


Area moments of inertia as a measure of the mandible stiffness of the implant patient.
It was hypothesized that the bending stiffness of the mandible is an important biomechanical parameter in implant dentistry. It was shown how this bending stiffness can be estimated by means of the principal area moments of inertia of the cortical and cancellous cross-sections as obtained by computed tomography, some image processing and subsequent calculation. It was found that the contribution of the cancellous bone to the bending stiffness is normally insignificant and that the principal area moments of inertia of the cortical cross-section show large variations, depending on the degree of resorption. It was furthermore found that the variations in the principal area moments of inertia of the cortical cross-section in one and the same potential implant patient were minor. Finally, in a three-dimensional finite element study, it was found that the peak bone stresses adjacent to implants, resulting from a standardized load at the distal end of an implant-supported bridge, were inversely related to the magnitude of the principal area moment of inertia about the horizontal axis of the cortical cross-section. It was concluded that the principal area moments of inertia of the cortical cross-section and the angulation of the principal axes of inertia might be useful as a quantitative characterization of the mandible stiffness in clinical research and perhaps also in clinical practice.


Transitioning to an EMR system without pain.
Nearly every medical practice in the United States is going to be confronted with the decision to transition from a paper record to an electronic medical record (EMR). Horror stories abound about practices attempting to make the changeover and losing productivity, creating obstacles andproblems that are insolvable, and even abandoning the project to return to paper charts and wasting thousands of dollars. This article will review the path to implementation of an EMR system that will reduce the tension, anxiety, and disruption that often accompanies any practice that wants to make the paperless leap.


Radiotherapy in thyroid eye disease: the effect on the field of binocular single vision.
Thyroid eye disease (TED) can be a functionally disabling condition if ocular muscle involvement causes diplopia. The extraocular muscle restriction creates a reduced or eccentric field of binocular single vision (BSV). Orbital radiotherapy is now widely used in the treatment of TED, and although it has been reported as improving ocular motility, there have been few quantitative studies of the effect of treatment on ocular motor function. Retrospective case note review of patients undergoing orbital radiotherapy for TED between 1992-1998 identified 79 case records. A total of 27 patients had diplopia in primary position or a significantly reduced binocular field before undergoing radiotherapy. The fields of BSV were analyzed pretreatment and at 3, 12, and 24 months after therapy to assess any improvement in function. We used the field of BSV as an outcome measure because it can be quantified and is a good indicator of functional ability. None of the 12 patients with double vision in primary position pretreatment regained a central binocular field with radiotherapy alone. Of the 15 patients with a central but reduced binocular field, 8 (53%) remained unchanged with treatment. In 4 patients (26.6%), there was an improvement in the field, while in 3 (20%) the field deteriorated. In all, 12 patients (44%) went on to require strabismus surgery. Orbital radiotherapy alone is ineffective in treating restrictive thyroid myopathy and improving binocular function.


Intravenous thrombolytic therapy for acute ischemic stroke. Weighing the risks and benefits of tissue plasminogen activator.
The use of intravenous tPA within 3 hours after acute ischemic stroke has been proved to increase the number of good outcomes. However, tPA is a toxic therapy that carries a substantial risk of intracerebral hemorrhage. To decrease the risk, tPA use must be restricted to a carefully selected patient population. Treatment must be administered in an intensive care setting and directed by physicians with expertise in diagnosing and managing stroke.


Chemotherapy-induced diarrhea is associated with changes in the luminal environment in the DA rat.
The microflora of the gastrointestinal tract (GIT) are a complex ecosystem, performing a number of beneficial functions. Irinotecan causes both early and late diarrhea, the latter possibly caused, in part, by changes in the microflora of the GIT. Female DA rats were given atropine subcutaneously, prior to a single 200 mg/kg intraperitoneal dose of irinotecan. Animals were monitored for diarrhea and killed at 30 and 60 mins, 2, 6, 12, 24, 48, and 72 hrs after chemotherapy administration. Control rats received no treatment. Fecal samples and stomach, jejunum, and colon samples were collected and stored at -70 degrees C until required. Standard microbiological culture techniques were used to grow and isolate the flora. Biochemical tests were used to identify the bacteria. The level of growth was noted for relative comparison between time points and graded accordingly. Early diarrhea was observed in the rats from 2-6 hrs after treatment, after which time the diarrhea resolved. Late onset diarrhea was apparent 72 hrs after treatment. Changes were seen in the flora of the stomach, jejunum, colon and feces. The majority of microflora changes were seen 6, 12, and 24 hrs after treatment, with a relative increase or decrease in the presence of bacteria in comparison with control rats. In some rats bacteria were not observed at all time points, and different bacteria not seen in control animals were identified in rats treated with irinotecan. These changes were observed up to 72 hrs after treatment. In conclusion, irinotecan treatment causes changes in the flora of the stomach, jejunum, colon, and feces of rats and is associated with the development of diarrhea. These changes in flora may have systemic effects and in particular may contribute to the development of chemotherapy-induced mucositis.


Electroencephalography complexity in resting and task states in adults with attention-deficit/hyperactivity disorder.
Analysing EEG complexity could provide insight into neural connectivity underlying attention-deficit/hyperactivity disorder symptoms. EEG complexity was calculated through multiscale entropy and compared between adults with attention-deficit/hyperactivity disorder and their peers during resting and go/nogo task states. Multiscale entropy change from the resting state to the task state was also examined as an index of the brain's ability to change from a resting to an active state. Thirty unmedicated adults with attention-deficit/hyperactivity disorder were compared with 30 match-paired healthy peers on the multiscale entropy in the resting and task states as well as their multiscale entropy change. Results showed differences in multiscale entropy between individuals with attention-deficit/hyperactivity disorder and their peers during the resting state as well as the task state. The multiscale entropy measured from the comparison group was larger than that from the attention-deficit/hyperactivity disorder group in the resting state, whereas the reverse pattern was found during the task state. Our most robust finding showed that the multiscale entropy change from individuals with attention-deficit/hyperactivity disorder was smaller than that from their peers, specifically at frontal sites. Interestingly, individuals without attention-deficit/hyperactivity disorder performed better with decreasing multiscale entropy changes, demonstrating higher accuracy, faster reaction time and less variability in their reaction times. These data suggest that multiscale entropy could not only provide insight into neural connectivity differences between adults with attention-deficit/hyperactivity disorder and their peers but also into their behavioural performance.


Persistent beneficial effects of breast milk ingested in the neonatal intensive care unit on outcomes of extremely low birth weight infants at 30 months of age.
We previously reported beneficial effects of breast milk ingestion by infants with extremely low birth weight in the NICU on developmental outcomes at 18 months' corrected age. The objective of this study was to determine whether these effects of breast milk in infants with extremely low birth weight persisted at 30 months' corrected age. Nutrition data, including enteral and parenteral feeds, were prospectively collected, and 30 months' corrected age follow-up assessments were completed on 773 infants with extremely low birth weight who participated in the National Institute of Child Health and Human Development Neonatal Research Network Glutamine Trial. A total of 593 ingested some breast milk during the neonatal hospitalization, and 180 ingested none. Neonatal feeding characteristics and morbidities and 30-month interim history, neurodevelopmental outcomes, and growth parameters were analyzed. Children were divided into quintiles of breast milk volume to evaluate the effects of volume of human milk ingested during the NICU hospitalization. At 30 months, increased ingestion of breast milk was associated with higher Bayley Mental Developmental Index scores, higher Bayley behavior score percentiles for emotional regulation, and fewer rehospitalizations between discharge and 30 months. There were no differences in growth parameters or cerebral palsy. For every 10 mL/kg per day increase in breast milk, the Mental Developmental Index increased by 0.59 points, the Psychomotor Developmental Index by 0.56 points, and the total behavior percentile score by 0.99 points, and the risk of rehospitalization between discharge and 30 months decreased by 5%. Beneficial effects of ingestion of breast milk in the NICU persist at 30 months' corrected age in this vulnerable extremely low birth weight population. Continued efforts must be made to offer breast milk to all extremely low birth weight infants both in the NICU and after discharge.


Clinical profile and inheritance pattern of CYP21A2 gene mutations in patients with classical congenital adrenal hyperplasia from 10 families.
Congenital adrenal hyperplasia (CAH) is an autosomal recessive metabolic disorder caused by mutations in the CYP21A2 gene. Genetic diagnosis of 21-OH deficiency causing CAH is more complicated than any other monogenic disorder due to high variability of the locus. The disease has a wide spectrum of clinical variants making it difficult to establish a genotyp-phenotype correlation. Therefore, family studies are necessary to ascertain parental genotype and segregation of the mutant allele among the offspring. The present study aimed to identify CYP21A2 gene mutations and analyze the segregation pattern in CAH trios (patients and their parents). A total of ten families having at least one CAH child were recruited. Out of 31 children from ten families, 15 were affected with CAH and 13 of/them (12 females and 1 male) were available for genetic testing. One family had all the children affected with CAH. Compound heterozygous mutations were identified in seven patients (53.8%) whereas p.P30L, In2 and Δ8 bp mutations were present in homozygous state in three (23.1%), two (15.3 %) and one (7.6%) patient respectively. In majority of the families, mutant alleles observed in the patients were inherited from the parents whereas three families showed sporadic mutations without any paternal or maternal origin. This indicated their novel occurrence due to misalignment of the parental genes and/or large deletion of the gene. Female preponderance was noted in the CAH families and also among the patients raising the possibility of survival advantage among females.


Analysis of non-derivatised bacteriohopanepolyols by ultrahigh-performance liquid chromatography/tandem mass spectrometry.
Traditional investigation of bacteriohopanepolyols (BHPs) has relied on derivatisation by acetylation prior to gas chromatography/mass spectrometry (GC/MS) or liquid chromatography/MS (LC/MS) analysis. Here, modern chromatographic techniques (ultrahigh-performance liquid chromatography (UPLC)) and new column chemistries were tested to develop a method for BHP analysis without the need for derivatisation. Bacterial culture and sedimentary lipid extracts were analysed using a Waters Acquity Xevo TQ-S triple quadrupole mass spectrometer in positive ion atmospheric pressure chemical ionisation (APCI) mode. Waters BEH C18 and ACE Excel C18 were the central columns evaluated using a binary solvent gradient with 0.1% formic acid in the polar solvent phase in order to optimise performance and selectivity. Non-amine BHPs and adenosylhopane showed similar performance on each C18 column; however, BHP-containing terminal amines were only identified eluting from the ultra-inert ACE Excel C18 column. APCI-MS/MS product ion scans revealed significant differences in fragmentation pathways from previous methods for acetylated compounds. The product ions used for targeted multiple reaction monitoring (MRM) are summarised. UPLC/MS/MS analysis using an ACE Excel C18 column produced superior separation for amine-containing BHPs and reduced run times from 60 to 9 min compared with previous methods. Unexpected variations in fragmentation pathways between structural subgroups must be taken into account when optimising MRM transitions for future quantitative studies. Copyright © 2016 John Wiley & Sons, Ltd.


Glucagon-like peptide 2 improves intestinal wound healing through induction of epithelial cell migration in vitro-evidence for a TGF--beta-mediated effect.
In vitro studies suggest that glucagon-like peptide 2 (GLP-2), secreted from enteroendocrine cells in the gastrointestinal tract after food intake, is able to ameliorate mucosal injury in settings of human disease characterized by injury and dysfunction of the intestinal mucosal epithelium. We evaluated this potential of GLP-2 after epithelial trauma by using two in vitro models measuring intestinal epithelial cell proliferation and cell migration. Injuries were induced in confluent monolayers of the small intestinal cells lines IEC-6 and IEC-18, as well as in the colonic cell lines Caco-2 and Colo 320. GLP-2 (50-500 nM) or other peptides were added to the media. Wound healing was investigated after 24 h by quantification of the number of cells migrating across the wound edge. Proliferation of cells was assessed by using photometric mitochondrial incorporation measurement of MTT (3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide). Monoclonal TGF-beta antibodies were added to wounded monolayers to examine whether the GLP-2-induced wound healing was TGF-beta-mediated. Migration assessments revealed a significant stimulation of GLP-2-induced migration in IEC-6 and IEC-18 monolayers compared to the placebo group. No effect was observed in the colon cancer cell lines Caco-2 and Colo 320. Results of the proliferation assays show a significant inhibition of proliferation by GLP-2 in small intestinal cell lines whereas a dose-dependent stimulation of proliferation in colonic epithelial cells was observed. Addition of neutralizing TGF-beta1 antibodies to wounded IEC-6 and IEC-18 monolayers incubated with GLP-2 significantly reduced the number of migrating cells to the level of the placebo group. In our in vitro model, it was shown that the GLP-2-induced improvement of intestinal wound healing is TGF-beta-mediated. These effects were predominant in the epithelium of the small intestine compared to colonic epithelium. Our findings provide further insight into mechanisms leading to GLP-2-induced mucosal wound healing. These results suggest that GLP-2 or analogues of this peptide may potentially be useful for the treatment of intestinal disorders characterized by injury and ineffective repair of the intestinal mucosa.


Synthesis and anticonvulsant activity of novel 1-substituted-1,2-dihydro-pyridazine-3,6-diones.
The synthesis and pharmacological evaluation of novel 1-substituted-1,2-dihydro-pyridazine-3,6-diones (4a--l, 5a--j) as potential anticonvulsant agents are described. The compounds were tested in vivo for the anticonvulsant activity. The compound which have maximum protection against MES induced seizures is 1-[3-(2-aminophenylamino)-2-hydroxypropyl)-1,2-dihydro-pyridazine-3,6-dione 4h (ED(50)=44.7 mg x kg(-1) i.p.) 1-[2-hydroxy-3-piperazin1-yl-propyl)-1,2-dihydro-pyridazine-3,6-dione 4c (ED(50)=72 mg x kg(-1) i.p.) and 1-[2-hydroxy-3-imidazol-1-yl-propyl)-1,2-dihydro-pyridazine-3,6-dione 4d (ED(50)=79 mg x kg(-1) i.p.) were also found to have maximum protection against MES induced seizures. Whereas all these compounds failed to protect the animals from subcutaneous pentylenetetrazole (Metrozol) seizure threshold test (sc-Met).


Tonal split and laryngeal contrast of onset consonant in Lili Wu Chinese.
This study examines the acoustic properties concerning tonal split and stop onsets in an under-documented Wu Chinese variety, Lili Wu, using speech production data collected from field research. Lili Wu Chinese has been reported to demonstrate an unusual tonal split phenomenon known as "aspiration-induced tonal split" (ATS). ATS refers to the distinct lowering of f0 of a lexical tone over syllables beginning with a voiceless aspirated obstruent, compared to that of syllables beginning with an unaspirated obstruent. Two debates lingering in the existing literature are discussed: (i) is ATS an on-going change or a completed change? and (ii) is it onset aspiration or vowel breathiness that directly triggers ATS? Results suggest that ATS is a completed change, which, however, is conditioned by tonal contexts. Regarding the second debate, results suggest that neither aspiration nor breathiness serves as the direct trigger for tonal split. Moreover, one unexpected on-going sound change was observed: The breathiness of vowels after voiced onsets seems to be disappearing among the younger generation. These findings extend the understanding of the acoustic properties of tonal development in a complex system and highlight the importance of experimental methods in understanding the sound structure and changes of under-documented languages.


Structure-activity relationship of acetylenes from galls of Hedera rhombea as plant growth inhibitors.
The structure-activity relationship of 12 isolated acetylenes from galls of Hedera rhombea (Araliaceae) induced by Asphondylia sp. (Cecidomyiidae) and their derivatives has been studied for the inhibition of the shoot and root growth of rice, perennial ryegrass, cockscomb, lettuce, and cress. Almost all acetylenes generally showed growth inhibitory activity. The diacetylenes exhibited higher activity than the monoacetylenes, suggesting that a conjugated diyne segment is essential for the activity. On the other hand, the acetylenes with a nonoxidated methylene group at C-8 showed stronger activity comparing with those possessing hydroxy and acetoxy groups at C-8. Furthermore, it has been demonstrated that the acetylenes bearing a terminal olefinic group at C-16, C-17 enhanced the activity. It is thus clarified that important sites for the activity of the acetylenes from galls of H. rhombea are a conjugated diyne and a terminal olefinic group connecting to the aliphatic chain and that less oxidated compounds show more activity.


Glycosaminoglycan glycomics using mass spectrometry.
The fact that sulfated glycosaminoglycans (GAGs) are necessary for the functioning of all animal physiological systems drives the need to understand their biology. This understanding is limited, however, by the heterogeneous nature of GAG chains and their dynamic spatial and temporal expression patterns. GAGs have a regulated structure overlaid by heterogeneity but lack the detail necessary to build structure/function relationships. In order to provide this information, we need glycomics platforms that are sensitive, robust, high throughput, and information rich. This review summarizes progress on mass-spectrometry-based GAG glycomics methods. The areas covered include disaccharide analysis, oligosaccharide profiling, and tandem mass spectrometric sequencing.


Cavitatory mesenteric lymph node syndrome: A rare entity.
Celiac disease is a gluten sensitive enteropathy that involves an abnormal immunological response to glutens in wheat, rye etc. It predominantly involves the small intestinal mucosa, though, extra luminal manifestations can also occur. One rare extraluminal manifestation is cavitatory mesenteric lymph node syndrome. It occurs in refractory celiac disease and is associated with poor prognosis due to various complications. The diagnosis is often made on imaging when cystic mesenteric lymph nodes with fat-fluid levels are seen and this can then be confirmed by histopathological examination. We recently had a typical case where we were able to make this diagnosis.


The first case of a littoral spleen-preserving resection: a case report.
Littoral cell angiomas are uncommon primary splenic haemangiomas with rare malignant potential. We report a case of a 76-year-old male with an incidental solitary littoral cell angioma found within an accessory spleen. We provide an overview of the literature of littoral cell angiomas and highlight the diagnostic challenge and treatment of this important differential for general surgeons caring for patients with splenic masses. This is the first case to describe primary resection of a littoral cell angioma with splenic preservation.


Impact of ondansetron and granisetron on chemotherapy-induced emesis in adults: the need for comparative pharmacoeconomic data.
The introduction of the 5-hydroxytryptamine 3 (5-HT3) antagonists has made a significant contribution to the control of chemotherapy-induced nausea and vomiting and to improving patient quality of life. The clinical impact of two of these compounds, ondansetron and granisetron, was reviewed. It was concluded that, given the existing body of data on ondansetron and granisetron, it is difficult to determine whether any major differences can be identified between these two drugs, but that in most instances both are significantly superior to conventional antiemetics. To ensure efficient use of scarce health care resources, a decision to select one or the other should be based on economic (cost-effectiveness) data from appropriately designed randomized trials that include all aspects of antiemetic therapy (including iatrogenic complications) and that also consider relevant alternatives (eg, a conventional regimen vs two or more regimens based on 5-HT3 antagonists). Prospective studies designed to generate comparative clinical and economic data are needed in which outcomes are assessed by a common scale and in which previously established optimal doses and dosing schedules of each compound (either alone or in combination therapy) are used.


The hospital ethics committee and the nurse.
This article discusses all aspects of the hospital ethics committee. The nurse's use of the committee and participation on the committee are delineated. Neonatal examples are given.


2-Azaallyl Anions, 2-Azaallyl Cations, 2-Azaallyl Radicals, and Azomethine Ylides.
This review covers the use of 2-azaallyl anions, 2-azaallyl cations, and 2-azaallyl radicals in organic synthesis up through June 2018. Particular attention is paid to both foundational studies and recent advances over the past decade involving semistabilized and nonstabilized 2-azaallyl anions as key intermediates in various carbon-carbon and carbon-heteroatom bond-forming processes. Both transition-metal-catalyzed and transition-metal-free transformations are covered. Azomethine ylides, which have received significant attention elsewhere, are discussed briefly with the primary focus on critical comparisons with 2-azaallyl anions in regard to generation and use.


Mapping lipid alterations in traumatically injured rat spinal cord by desorption electrospray ionization imaging mass spectrometry.
Desorption electrospray ionization (DESI) mass spectrometry (MS) is used in an imaging mode to interrogate the lipid profiles of 15 μm thin tissue cross sections of injured rat spinal cord and normal healthy tissue. Increased relative intensities of fatty acids, diacylglycerols, and lysolipids (between +120% and +240%) as well as a small decrease in intensities of lipids (-30%) were visualized in the lesion epicenter and adjacent areas after spinal cord injury. This indicates the hydrolysis of lipids during the demyelination process due to activation of phospholipase A(2) enzyme. In addition, signals corresponding to oxidative degradation products, such as prostaglandin and hydroxyeicosatetraenoic acid, exhibited increased signal intensity by a factor of 2 in the negative ion mode in lesions relative to the normal healthy tissue. Analysis of malondialdehyde, a product of lipid peroxidation and marker of oxidative stress, was accomplished in the ambient environment using reactive DESI mass spectrometry imaging. This was achieved by electrospraying reagent solution containing dinitrophenylhydrazine as high-velocity charged droplets onto the tissue section. The hydrazine reacts selectively and rapidly with the carbonyl groups of malondialdehyde, and signal intensity of twice the intensity was detected in the lesions compared to healthy spinal cord. With a small amount of tissue sample, DESI-MS imaging provides information on the composition and distribution of specific compounds (limited by the occurrence of isomeric lipids with very similar fragmentation patterns) in lesions after spinal cord injury in comparison with normal healthy tissue allowing identification of the extent of the lesion and its repair.


Chemical modification of L-asparaginase from Cladosporium sp. for improved activity and thermal stability.
L-Asparaginase (ASNase), an antileukemia enzyme, is facing problems with antigenicity in the blood. Modification of L-asparaginase from Cladosporium sp. was tried to obtain improved stability and improved functionality. In our experiment, modification of the enzyme was tried with bovine serum albumin, ovalbumin by crosslinking using glutaraldehyde, N-bromosuccinimide, and mono-methoxy polyethylene glycol. Modified enzymes were studied for activity, temperature stability, rate constants (kd), and protection to proteolytic digestion. Modification with ovalbumin resulted in improved enzyme activity that was 10-fold higher compared to native enzyme, while modification with bovine serum albumin through glutaraldehyde cross-linking resulted in high stability of L-asparaginase that was 8.5- and 7.62-fold more compared to native enzyme at 28°C and 37°C by the end of 24 hr. These effects were dependent on the quantity of conjugate formed. Modification also markedly prolonged L-asparaginase half-life and serum stability. N-Bromosuccinimide-modified ASNase presented greater stability with prolonged in vitro half-life of 144 hr to proteolytic digestion relative to unmodified enzyme (93 h). The present work could be seen as producing a modified L-asparaginase with improved activity and stability and can be a potential source for developing therapeutic agents for cancer treatment.


High Leptin Level Attenuates Embryo Development in Overweight/Obese Infertile Women by Inhibiting Proliferation and Promotes Apoptosis in Granule Cell.
Obesity appears to be associated with female reproductive dysfunction and infertility. Women with obesity undergoing in vitro fertilization (IVF) had poor oocyte quality, decreased embryo development, and poor pregnancy outcome. However, the mechanism linking obesity to poor reproductive outcomes is still unclear. Obesity is frequently accompanied with elevated leptin levels. Here we aimed to evaluate the effect of high leptin level in follicular fluid (FF) on the proliferation and apoptosis in granule cells and correlate these findings with poor reproductive outcomes in infertile women with overweight or obesity who underwent IVF treatment. We investigated clinical and ongoing pregnancy rates in 189 infertile women who underwent IVF. Leptin levels were quantified in peripheral blood and FF as well. In vitro cell model was used to explore the potential effect of high leptin on the proliferation and apoptosis in granulosa cells. Results showed reduced clinical and ongoing pregnancy rates in overweight/obesity women who underwent IVF compared to control with normal BMI. On the other hand, leptin levels presented significant increase in peripheral blood and FF in overweight/obese women. Leptin level in FF was negatively correlated to good quality embryo rate. Importantly, in vitro study showed that leptin inhibited cells proliferation and promoted apoptosis by upregulation of caspase-3 and downregulation of Bcl-2 in granulosa cells in a dose dependent manner. These observations suggest that leptin may acts as a local mediator to attenuate embryo development and reduce fertility in obese patients.


Management of high cows-share-contribution of SCC to the bulk milk tank by acoustic pulse technology (APT).
A cow with mastitis has a high somatic cell count (SCC) in its milk. Cow-share-contribution of somatic cells to the bulk milk tank (BMTSCC) refers to the relative addition made by each cow's milk to the bulk tank's SCC. Since bulk milk is graded and priced according to the BMTSCC, high-yielding cows with mastitis are the main contributors to penalizations in milk price. The benefits of acoustic pulse technology (APT) application to tissues are well documented, including its anti-inflammatory effect and restoration of tissue function by triggering natural healing processes. An APT-based device was developed specifically for treating mastitis in dairy cows. It enables rapid and deep penetration of the acoustic pulses over a large area of the udder in a single session. A study was performed on six farms with a total of 3,900 cows. One unit of cow-share-contribution equaled the addition of 1,000 cells to each mL of the bulk milk volume above the mean BMTSCC. A total of 206 cows were selected: 103 were treated with APT and 103 served as controls. All of the cows contributed over 1.5 units to the BMTSCC at the time of treatment. Seventy-five days after APT treatment, 2 of the 103 treated cows (1.9%) were culled, compared to 19 (18.5%) of the 103 control cows, as well as infected quarter dry-off in 5 others (4.85%). Overall success was defined as a decrease of >75% in cow-share-contribution from treatment time in two of the three monthly milk recordings following treatment. Results indicated 57.3% success for the APT-treated cows vs. 14.6% for the untreated control groups. Highest share-contribution provide an additional tool for the farmer's decision of how to control BMTSCC. Because the cow-share-contribution value is relative to herd size and BMTSCC, this study included a similar number of cows, with similar SCC and milk yield from each of the six herds.


Sex Education on TikTok: A Content Analysis of Themes.
Leading medical and public health societies endorse comprehensive sex education, but only 20 states and Washington, D.C., currently require information about contraception when sex education is taught, and even fewer require the inclusion of topics such as gender diversity or consent. At the same time, social media use, especially the video-sharing app TikTok, is increasing among teens. TikTok, therefore, offers a novel opportunity to make up for shortcomings in sex education and convey sexual health information to adolescents. To describe the availability and content of sexual education on TikTok, we conducted a content analysis of themes for 100 sex education-focused videos. We found that female anatomy was the most frequently addressed topic. Sexual pleasure was the second most common theme, within which discussions of the female orgasm and arousal constituted the most common subtheme. Other common themes include contraception and sexual health. These sought-after topics may be incongruent with those presented in standard school- or home-based sex education or interactions with health care providers, and this disconnect suggests opportunities for health care providers and educators to initiate conversations or offer resources on these themes as part of routine interaction. We conclude with recommendations for future research to consider the factual accuracy of sex education on TikTok and determine how exposure to this content affects adolescents' understanding of the risks and benefits of intercourse, sexual practices, age- and gender-based sexual norms, and other health behaviors.


A meaningful exploration of ofatumumab in refractory NMOSD: a case report.
To report the case of a patient with refractory neuromyelitis optica spectrum disorder (NMOSD), who, despite showing poor response or intolerance to multiple immunosuppressants, was successfully treated with Ofatumumab. A 42-year-old female was diagnosed with NMOSD in the first episode of the disease. Despite treatment with intravenous methylprednisolone, immunoglobulin, rituximab and immunoadsorption, together with oral steroids, azathioprine, mycophenolate mofetil and tacrolimus, she underwent various adverse events, such as abnormal liver function, repeated infections, fever, rashes, hemorrhagic shock, etc., and experienced five relapses over the ensuing four years. Finally, clinicians decided to initiate Ofatumumab to control the disease. The patient received 9 doses of Ofatumumab over the next 10 months at customized intervals. Her symptoms were stable and there was no recurrence or any adverse events. Ofatumumab might serve as an effective and safe alternative for NMOSD patients who are resistant to other current immunotherapies.


Association between continuous renal replacement therapy and 28-day mortality of critically ill patients with COVID-19 receiving mechanical ventilation.
Continuous renal replacement therapy (CRRT) has become an important multiple organ support therapy and it is widely used in the intensive care unit (ICU). The aim of this study was to clarify the association between CRRT and 28-day mortality in critically ill coronavirus disease 2019 (-COVID-19) patients receiving mechanical ventilation. 112 respiratory decompensated critically ill adult patients with COVID-19 admitted to a COVID-19-designated ICU were included in this retrospective cohort study. Data on demographic information, comorbidities, laboratory findings upon ICU admission, and clinical outcomes were collected. The Kaplan-Meier method and Cox proportional hazard model were applied to determine the potential risk factors associated with 28-day mortality. The median age was 65.7 years, 67.8% were males, and 58.9% patients had at least one comorbidity. The median scores of the Charlson Comorbidity Index and Sequential Organ Failure Assessment (SOFA) were 3 and 7, respectively. Acute kidney injury (AKI) occurred in 57 critically ill patients upon ICU admission; 43 patients were classified as stage 2 - 3 AKI, and 36 patients were treated with CRRT. Age > 65 years, high SOFA score, damaged cardiac function, poor nutrition, and severe infection were significantly associated with increased 28-day mortality. AKI patients receiving CRRT had lower 28-day mortality compared with those not receiving CRRT (HR = 0.35, 95% CI: 0.21 - 0.58, p < 0.001). Initiating CRRT within 72 hours after mechanical ventilation did not improve survival after CRRT initiation. AKI prevalence and 28-day mortality are high in critically ill patients with COVID-19 receiving mechanical ventilation. CRRT plays a part in decreasing the mortality of critically ill COVID-19 patients with AKI receiving mechanical ventilation.


Molecular basis of aflatoxin-induced mutagenesis-role of the aflatoxin B1-formamidopyrimidine adduct.
Aflatoxin B1 (AFB1) is a known carcinogen associated with early-onset hepatocellular carcinoma (HCC) and is thought to contribute to over half a million new HCCs per year. Although some of the fundamental risk factors are established, the molecular basis of AFB1-induced mutagenesis in primate cells has not been rigorously investigated. To gain insights into genome instability that is produced as a result of replicating DNAs containing AFB1 adducts, site-specific mutagenesis assays were used to establish the mutagenic potential of the persistent ring-opened AFB1 adduct, AFB1-formamidopyrimidine (AFB1-FAPY). This lesion was highly mutagenic, yielding replication error frequencies of 97%, with the predominant base substitution being a G to T transversion. This transversion is consistent with previous mutational data derived from aflatoxin-associated HCCs. In vitro translesion synthesis assays demonstrated that polymerase (pol) ζ was the most likely candidate polymerase that is responsible for the G to T mutations induced by this adduct.


Topographic Findings of the Porcine Cornea.
The porcine eye is often used as an ex vivo animal model in ophthalmological research. It is well suited for investigations concerning refractive surgery; however, corneal topography data are scarce. This study investigated the corneal topography and pachymetry of the porcine eye to provide further reproducible data. We evaluated freshly enucleated porcine eyes (n = 16) by performing computerized corneal topographies (Orbscan® IIz, Bausch and Lomb, Rochester, NY, USA). We assessed the steepest and flattest keratometric powers (K1 and K2, units in diopters (D)), astigmatism (D), white-to-white (WTW) diameter (mm), thinnest point pachymetry (µm), anterior and posterior best-fit sphere (BFS) (D), refractive power of the anterior and posterior curvatures, and total refractive power of the cornea (D). The mean keratometric powers were 39.6 ± 0.89 D (K1) and 38.5 ± 0.92 D (K2), and the mean astigmatism was 1.1 ± 0.78 D. The mean WTW diameter was 13.81 ± 0.83 mm, and the mean corneal thickness was 832.6 ± 40.18 µm. The BFSs were 38.14 ± 0.73 D (anterior) and 42.56 ± 1.15 D (posterior), and the mean refractive powers were 43.27 ± 1.08 D (anterior) and -5.15 ± 0.20 D (posterior); therefore, the mean of the total refractive power was 38.16 ± 1.00 D. The topography and pachymetry of the porcine cornea showed a specific configuration differing from the human cornea. When using animal ex vivo models such as porcine corneas for experimental corneal surgery, findings such as these should be considered.


On-target action of anti-tropomyosin drugs regulates glucose metabolism.
The development of novel small molecule inhibitors of the cancer-associated tropomyosin 3.1 (Tpm3.1) provides the ability to examine the metabolic function of specific actin filament populations. We have determined the ability of these anti-Tpm (ATM) compounds to regulate glucose metabolism in mice. Acute treatment (1 h) of wild-type (WT) mice with the compounds (TR100 and ATM1001) led to a decrease in glucose clearance due mainly to suppression of glucose-stimulated insulin secretion (GSIS) from the pancreatic islets. The impact of the drugs on GSIS was significantly less in Tpm3.1 knock out (KO) mice indicating that the drug action is on-target. Experiments in MIN6 β-cells indicated that the inhibition of GSIS by the drugs was due to disruption to the cortical actin cytoskeleton. The impact of the drugs on insulin-stimulated glucose uptake (ISGU) was also examined in skeletal muscle ex vivo. In the absence of drug, ISGU was decreased in KO compared to WT muscle, confirming a role of Tpm3.1 in glucose uptake. Both compounds suppressed ISGU in WT muscle, but in the KO muscle there was little impact of the drugs. Collectively, this data indicates that the ATM drugs affect glucose metabolism in vivo by inhibiting Tpm3.1's function with few off-target effects.


Dietary zinc intake and brain cancer in adults: a case-control study.
Little is known about the aetiology of brain tumours. One putative factor suggested from animal models is a protective effect of dietary Zn. We tested the hypothesis that increased compared with low dietary Zn intake is protective against brain tumour development. We conducted a population-based case-control study in the UK, of adults aged 18-69 years, between 2001 and 2004 aiming to identify possible risk factors. Dietary information was collected from 637 cases diagnosed with a glioma or meningioma, and 876 controls. Data were obtained from a self-completed FFQ. Multivariate logistic regression analysis was conducted, adjusting for socio-demographic factors, season of questionnaire return, multivitamin supplementation and energy intake. Although a weak protective effect was observed for the third quartile of intake (normal compared with low intake) in the meningioma group, this was limited to the specific brain tumour subtype and quartile, and was not significant after also adjusting for intake of other elements. Overall there was no significant effect of Zn intake. No association or dose-response relationship was observed between increased compared with low Zn intake and risk of glioma or meningioma.


[Follicle dynamics and characteristics of ovulation in heifers after Ovsynch treatment in the last third of the estrous cycle].
The objective of the experiment was to study follicular dynamics and characteristics of ovulations in dairy heifers after application of the Ovsynch protocol in the last third of estrous cycle. Therefore, altogether 27 regular cycling Holstein heifers were given an injection of GnRH on day 14, 16 or 18 (9 heifers each in group 1 to 3) of the estrous cycle. All heifers were administered PGF2alpha seven days later. Blood was collected for progesterone determination, just before, 24 hours and 48 hours after the PGF2alpha injection. A second injection of GnRH was administered 48 hours after the PGF2alpha injection. Ovarian follicular dynamics were monitored by frequent ultrasound scanning of the ovaries after first and second GnRH injection. Altogether 22 of 27 heifers (81.5%) ovulated 27 to 33 h after first GnRH injection. In 4 heifers ovulations were recorded 45 to 51 h after first GnRH application. Mean intervals between GnRH application and ovulation were 33.0, 33.6 and 28.3 h, respectively. At the time of PGF2alpha injection mean progesterone concentrations were similar in groups 1 and 2, but significantly lower than in group 3. After the second GnRH treatment 5,6 and 8 heifers had ovulations. The average intervals from the second GnRH treatment to ovulation were 24.8, 24.0 and 24.4 h respectively. The results show that Ovsynch is not sufficient to ensure synchronisation of oestrous and ovulation in each animal treated.


Unusual Cause of Back Pain in a Multiple Myeloma Patient: Infectious Discitis.
A 58 year old patient, followed up for diabetes mellitus and multiple myeloma for ten years and six months, respectively, presented with persistent back pain, weakness at his lower extremity and intermittent fever. Activation markers of myeloma were in normal limits except high erythrocyte sedimentation rate and elevated C-reactive protein. Magnetic resonance imaging revealed increased T1 spinal intensity at the suspected disc level. Discitis was suspected on the basis of MRl and high fever. An intraoperative examination of specimens revealed Staphylococcus aureus. Detailed laboratory and radiological investigations should be performed to diagnose unusual causes of persistent back pain, such as discitis in patients with myeloma.


[Oropharyngeal dysphagia in neuromuscular diseases--differential diagnosis, examination procedure and therapy].
After a synopsis of brain stem structures participating in swallowing, the main neurologic diseases are presented as a part of which swallowing disorders may occur: central and peripheral nervous system, motor end-plates and muscles can be involved. The sequence of clinical examination is described with special reference to findings in mouth, pharynx and larynx as well as to findings in high-frequency cinematography. After description of normal swallowing pre-, intra- and postdeglutitive mechanisms of aspiration are shown. This distinction has proved useful for practical reasons. Finally we give a survey of therapeutic possibilities reported in recent years in literature and developed in our hospital, divided into indirect (facilitation of orofacial and laryngeal voluntary muscles) and direct therapeutic strategies (strategy of compensation during feeding). In connection with this therapeutic possibilities applied during pre-, intra- and postdeglutitive phase, depending on neuromuscular disturbances, are also described.


Extrinsic and Intrinsic Predictors of Variation in Infection by Posthodiplostomum minimum MacCallum, 1921 (Trematoda) in Sunfishes ( Lepomis Rafinesque, 1819) from Eastern Ohio.
The trematode Posthodiplostomum minimum MacCallum, 1921 (white grub) is a common parasite of centrarchid fishes, frequently reaching high prevalence and intensity in local populations. However, significant variation in infection has been observed across Lepomis Rafinesque, 1819 sunfish species, which are common and abundant hosts for this parasite. Previous observations suggest both extrinsic factors (e.g., habitat-specific characteristics and environmental parameters) and intrinsic factors (e.g., host size, behavior, and susceptibility) as important predictors of infection in this parasite-host system. In the present study, we evaluated the prevalence and intensity of P. minimum in 6 sympatric species of Lepomis sunfish (total of 563 individuals) across 9 lakes in eastern Ohio, U.S.A., that range in surface area from 5.6 to 1,448.7 hectares, and assessed the importance of both extrinsic and intrinsic factors as predictors of infection. We found that collection site (extrinsic factor) and host body mass and species identity (intrinsic factors) were the strongest predictors of infection intensity. Specifically, infection intensity was negatively associated with lake surface area and positively associated host body mass. Lepomis macrochirus (bluegill sunfish) and hybrid sunfish displayed the highest infection intensities, whereas Lepomis cyanellus (green sunfish) and Lepomis gulosus (warmouth sunfish) were significantly less burdened. We were unable to conclude if the observed variation among host species was due to host ecology or susceptibility. These general findings were supported by classification and regression tree (CART) analysis, which optimally partitioned variation in individual host infection intensities by using lake size and host body mass (but not host species identity). Although infection intensity was negatively associated with lake surface area (even among host individuals of the same size and species), the causal mechanisms involved remain unresolved and should be the impetus of future work on this parasite-host system.


Genetic Susceptibility to Rotavirus Gastroenteritis and Vaccine Effectiveness in Taiwanese Children.
The genetic susceptibility to and vaccine effectiveness against rotavirus gastroenteritis were different in distinct ethnic groups. The case-control study was aimed to evaluate the effectiveness of rotavirus vaccines and associations between the histo-blood group antigens and susceptibility to rotavirus infections in a Taiwanese population. Cases were children <18 years old who were hospitalized because of laboratory-confirmed rotavirus infection. Controls were healthy children matched to cases by age and gender. The secretor status and Lewis antigen and ABO types were determined by molecular methods. A total of 68 cases and 133 controls were included. Rotavirus immunization was recorded in 8 (12%) cases and 77 (58%) controls, indicating a vaccine effectiveness of 90.3% (95% confidence interval [CI], 78.1% - 95.7%). The secretor and Lewis-positive genotypes were independently associated with increased risk of rotavirus infections (matched odds ratio [mOR] 28.5, 95% CI 2.94-277, P = 0.003 and mOR 16.8, 95% CI 1.08-2601, P = 0.04, respectively). The distribution of ABO blood types did not differ significantly between cases and controls (P = 0.47). In conclusion, Taiwanese children with the secretor genotype and Lewis-positive genotype were at increased risk of moderate-to-severe rotavirus infections. The illness can be effectively prevented by immunization in this population.


Universal rate constants for reactive collisions of ultracold molecules.
A simple quantum-defect model gives analytic expressions for the complex scattering length and threshold collision rates of ultracold molecules. If the probability of reaction in the short-range part of the collision is high, the model gives universal rate constants for s- and p-wave collisions that are independent of short-range dynamics. This model explains the magnitudes of the recently measured rate constants for collisions of two ultracold 40K87Rb molecules, or an ultracold 40K atom with the 40K87Rb molecule [S. Ospelkaus et al., Science 327, 853 (2010).


CholecTriplet2022: Show me a tool and tell me the triplet - An endoscopic vision challenge for surgical action triplet detection.
Formalizing surgical activities as triplets of the used instruments, actions performed, and target anatomies is becoming a gold standard approach for surgical activity modeling. The benefit is that this formalization helps to obtain a more detailed understanding of tool-tissue interaction which can be used to develop better Artificial Intelligence assistance for image-guided surgery. Earlier efforts and the CholecTriplet challenge introduced in 2021 have put together techniques aimed at recognizing these triplets from surgical footage. Estimating also the spatial locations of the triplets would offer a more precise intraoperative context-aware decision support for computer-assisted intervention. This paper presents the CholecTriplet2022 challenge, which extends surgical action triplet modeling from recognition to detection. It includes weakly-supervised bounding box localization of every visible surgical instrument (or tool), as the key actors, and the modeling of each tool-activity in the form of ‹instrument, verb, target› triplet. The paper describes a baseline method and 10 new deep learning algorithms presented at the challenge to solve the task. It also provides thorough methodological comparisons of the methods, an in-depth analysis of the obtained results across multiple metrics, visual and procedural challenges; their significance, and useful insights for future research directions and applications in surgery.


Vertebral artery compression as an adjunct to transcutaneous Doppler ultrasound examination.
Transcranial Doppler (TCD) evaluation is dependent on the accurate identification of intracranial vessels. Manual extracranial vertebral artery compression was used to modulate blood flow in vessels of the vertebrobasilar system in 118 patients examined by TCD. Two examples of its utility are presented in detail. Complete examination by TCD should include evaluation of the posterior cerebral circulation and its collaterals; vertebral artery compression is a new and important adjunct to the complete evaluation of intracranial vascular anatomy and cerebral collateralization.


An insect brain peptide as a member of insulin family.
Amino acid sequencing of bombyxin (previously called 4K-PTTH) isolated from the heads of the silkmoth Bombyx mori has disclosed sequence homology of this insect neuropeptide with insulin. Immunohistochemistry using an antibody against a synthetic bombyxin fragment detected 4 pairs of immunoreactive neurosecretory cells in the dorso-medial region of the Bombyx brain. The same cells were reactive to bovine insulin antibody.


The Spectrum of Sleep Disorders Among Children: A Cross-sectional Study at a South Indian Tertiary Care Hospital.
Introduction Sleep problems during infancy and early childhood are fairly common and rarely recognized in pediatric practice. These are mostly related to the initiation and maintenance of night-time sleep. Understanding sleep patterns and disorders associated with sleep is challenging, especially in the pediatric age group. This study was done to estimate the magnitude of sleep disorders in children and to evaluate the associated risk factors. Methods This cross-sectional study was carried out among 450 children visiting the pediatric outpatient department of Sri Ramachandra Institute of Higher Education and Research, Chennai, India between November 2018 and June 2019. Children with chronic illnesses and a history of physical or mental trauma in the past six months were excluded. The Sleep Disturbance Scale for Children (SDSC) was used to gather information regarding sleep disorders. Results It was observed that a majority of the participants (72.2%) slept 9-11 hours per day. Among 46.2% of the participants, the time lag between bedtime and sleep time was less than 15 minutes. Overall, sleep problems were present in 34% of the participants. History of sleep problems in infancy, absence of siblings, and parental presence while sleeping emerged as statistically significant risk factors for childhood sleep disorders (p: <0.05). Conclusion We believe our study provides a basis for exploring the pattern and problems associated with sleep behavior among children. There is a need for setting up routine screening measures in pediatric outpatient departments to facilitate early detection of sleep disorders in order to avoid complications.


Photonic Characterisation of Indium Tin Oxide as a Function of Deposition Conditions.
Indium tin oxide (ITO) has recently gained prominence as a photonic nanomaterial, for example, in modulators, tuneable metasurfaces and for epsilon-near-zero (ENZ) photonics. The optical properties of ITO are typically described by the Drude model and are strongly dependent on the deposition conditions. In the current literature, studies often make several assumptions to connect the optically measured material parameters to the electrical properties of ITO, which are not always clear, nor do they necessarily apply. Here, we present a comprehensive study of the structural, electrical, and optical properties of ITO and showed how they relate to the deposition conditions. We use guided mode resonances to determine the dispersion curves of the deposited material and relate these to structural and electrical measurements to extract all relevant material parameters. We demonstrate how the carrier density, mobility, plasma frequency, electron effective mass, and collision frequency vary as a function of deposition conditions, and that the high-frequency permittivity (ϵ∞) can vary significantly from the value of ϵ∞ = 3.9 that many papers simply assume to be a constant. The depth of analysis we demonstrate allows the findings to be easily extrapolated to the photonic characterisation of other transparent conducting oxides (TCOs), whilst providing a much-needed reference for the research area.


The effect of acetaminophen ingestion on cortico-spinal excitability.
Acetaminophen (ACT) facilitates the inhibition of voltage-gated calcium and sodium currents, which may effect cortico-spinal excitability. Twelve subjects ingested acetaminophen or a placebo and underwent transcranial magnetic stimulation to assess the motor evoked potential (MEP), and cortical silent period (CSP). ACT significantly increased MEP response (P > 0.05) but had no effect on CSP (P > 0.05). This indicates that ACT increases MEP and should be controlled for in studies where these measures are of interest.


Temporal Trends in Dietary Macronutrient Intakes among Adults in Rural China from 1991 to 2011: Findings from the CHNS.
Few studies have examined nutrition transitions among the rural population of China, even though half of the Chinese population (about 700 million) is living in rural China. To fill this research gap, we examined temporal trends in dietary macronutrient intakes in members of the Chinese rural population aged 18-60 years. The analysis used data from consecutive three-day dietary recalls, collected from the China Health and Nutrition Surveys (CHNS). Mixed-effect models were constructed to obtain adjusted means and to examine temporal trends after adjusting for intra-class correlation within clusters and covariates, including age, sex, geographical region, urbanicity, and income. From 1991 to 2011, a downward trend in daily energy, protein, and carbohydrate intakes was seen in all categories, with a significant reduction among all rural people (p < 0.0001). In contrast, a significant increment in daily fat intake, the proportion of energy from fat, and the proportion of rural people consuming a diet with more than 30% of energy from fat, were observed in the present study (p < 0.0001). These results suggest that adults in rural China have been undergoing a rapid nutrition transition towards a high-fat diet. Therefore, more emphasis should be placed on the quality of fat and maintaining a balanced diet during the process of nutritional education.


Discrimination of breast cancer by anti-malignin antibody serum test in women undergoing biopsy.
The anti-malignin antibody serum (AMAS) test (Oncolab, Boston, MA) has been reported as 97% sensitive and 95% specific for malignancies. To objectively assess accuracy of this test for discrimination of breast cancer, we studied a series of women undergoing core breast biopsy. Seventy-one core-needle breast biopsies were classified as malignant, suspicious, or benign by two independent pathologists blinded to AMAS results. Corresponding sera were read as AMAS positive, negative, or borderline by criteria used by Oncolab and also using criteria derived from receiver-operator curves based on values for slow (S-tag), fast (F-tag), and their difference (Net-tag) antibody reported by Oncolab. We calculated sensitivity and specificity and analyzed distributions by Fisher's exact test. Biopsies were read as 42 (59%) benign, 12 (17%) suspicious, and 17 (24%) malignant. By Oncolab criteria, sensitivity (59%) and specificity (62%) were maximized by pooling suspicious with malignant and AMAS borderline with positive (P = 0.098). Receiver-operator curves showed best sensitivity (62%) and specificity (69%) for the criterion AMAS positive if Net-Tag > 135 microg/mL or S-Tag > 220 microg/mL (P = 0.015). The AMAS test discriminates suspicious and malignant from benign lesions, but sensitivity is insufficient to identify patients to be spared biopsy and false-positive rates are too high for population screening.


[The integrated management software of primary care,a tool for analysing indicators of use].
To analyse the indicators of use in the Gran Canaria Health Area. To characterise over-users so that the primary care team can take corrective measures. To design a computer tool giving appropriate useful information to the management, that can be directly put into practice in primary care. Retrospective descriptive study. SATTING: Gran Canaria Health Area. Hierarchical descent in the analysis of data in the base health area and family care unit, in the year 2000. Users of the Canaries Health Service registered on the individual health card data base. The activity generated by 636 270 users with 2 876 394 appointments was studied. Mean frequency of attendance in the Gran Canaria Health Area was 4.52, with a 67.3% use rate. The user causing 11 or more visits per year was defined as an over-user. 13.4% of users were over-users and caused among them 52.3% of visits. 32.7% of users registered made no visit. A small section of the population causes over half the consultations. The characteristics of these users need to be analysed so that programmes can be worked out to decrease their frequency of use. The integrated management software for primary care enables this information to be analysed and serves as a support for the primary care teams. Special attention needs to be paid to the population that does not use the health centres.


Agonist and antagonist effects of prototype opiate drugs in rats discriminating fentanyl from saline: characteristics of partial generalization.
The experiments reported here characterized the partial generalizations that prototype opiate drugs may produce in rats that are trained to discriminate 0.04 mg/kg of fentanyl from saline. Cyclazocine, nalorphine, ketocyclazocine and N-allylnormetazocine produced partial generalization with fentanyl; the same compounds also partially antagonized fentanyl. The fentanyl-like and the fentanyl-antagonist effects of these compounds occurred within similar ranges of dose. An orderly incompatibility was apparent between the agonist and antagonist effects produced by each drug; cyclazocine, for example, was unlikely to antagonize fentanyl in animals in which it produced generalization, whereas it did antagonize fentanyl in animals in which it produced no generalization. Cyclazocine, nalorphine, N-allylnormetazocine and naloxone produced either fentanyl-like or fentanyl-antagonist effects in all animals tested. A reliable relationship was apparent among the agonist and antagonist effects of different opiate drugs; rats that generalized cyclazocine also were likely to generalize nalorphine and ketocyclazocine and were relatively less responsive to cyclazocine, nalorphine, N-allylnormetazocine and naloxone as antagonists of fentanyl. The results point to the importance of a number of new methods in the analysis of drug discrimination data. Among these are the analysis of individual generalization data and the examination of agonist and antagonist effects of test drugs in the same animals. A parsimonious molecular interpretation of the data can be offered by assuming that morphine, ketocyclazocine, cyclazocine, nalorphine, N-allylnormetazocine and naloxone have affinity for, but differ in activity at, an opiate receptor where fentanyl acts to produce discriminative effects.


Fusobacterium necrophorum--beyond Lemierres syndrome.
Fusobacterium necrophorum is a non-sporulating anaerobic gram negative bacillus and has traditionally been associated with Lemierre's syndrome. The authors report a 34-year-old male who presented to the emergency department with a week's history of dull epigastirc pain. Significant medical history included chronic pancreatitis secondary to alcohol use. The patient had radiological evidence of acute on chronic pancreatitis with thrombosis of the portal vein and multiple intrahepatic abscesses. CT-guided drainage of left upper quadrant revealed fluid collection in the pancreatic bed. The fluid culture grew F necrophorum and the patient was treated with tigecycline for 4 weeks. The patient improved symptomatically and his follow-up computerised axial tomography scan 2 months later showed resolving liver abscess, cavernous transformation of the portal vein and stable findings of chronic pancreatitis. This could represent an infection of the peripancreatic tissue with F necrophorum further leading to pylephlebitis.


Cytokines in infection.
Cytokines are central to the development of effective immunity against microbial pathogens and their beneficial effects in the control of a variety of infections of man and animals are well-documented. However, it appears that cytokines may also have detrimental effects in infections by actually enhancing microbial growth. These observations emphasise the fact that many successful pathogens possess mechanisms enabling them to evade the immune response and that caution needs to be exercised in using cytokines as therapeutic agents to control infections in various human diseases.


[Interepidemic surveillance of a cutaneous leishmaniasis focus in Senegal].
The cutaneous leishmaniasis is rampant in an endemo -epidemic way in the region of Thiès, Senegal. At the occasion of an epidemic observed between 1975 and 1978, the ecological study of the focus of Keur Moussa , led by Dedet and al., permitted to discover, for the first time in West Africa, the structure of a cutaneous leishmaniasis focus. The most important part of the present laboratory work consists in the observation of that wild anthropozoonosis due to Leishmania tropica major, having as vector Phlebotomus duboscqi and the rodents Mastomys erythroleucus , Tatera gambiana and Arvicanthis niloticus as reservoir. The close study of the reservoir populations and of the vectors should enable us to avoid a new epidemic outburst.


Interpersonal vs. Non-Interpersonal Cumulative Traumas and Psychiatric Symptoms in Treatment-Seeking Incarcerated Women.
Incarcerated women are at elevated risk of lifetime trauma exposure. Prevalence rates of trauma exposure and how these events relate to specific domains of psychiatric symptomology among this group are lacking. This study hypothesized a greater range of diverse cumulative trauma experiences (CTEs) would be positively associated with psychiatric symptoms in general (depression, PTSD, distress tolerance), but that interpersonal CTEs in particular would be uniquely associated with greater symptoms of guilt and shame. A total of 112 women (87% White, Mage = 34 years) seeking treatment for a history of sexual violence victimization participated in the study. Women incarcerated for nonviolent offenses at two minimum-security prisons completed self-report measures of exposure to diverse traumatic events and internalizing symptoms. On average, participants reported a history of experiencing 5.46 traumatic event types. Total CTEs was significantly associated with all psychiatric variables in the expected direction. While both interpersonal and non-interpersonal CTEs were positively associated with levels of PTSD, depression, and distress intolerance, only interpersonal CTEs were significantly associated with guilt and shame. Traumatic experiences that are interpersonal in nature may confer specific risk for psychiatric symptoms in victims.


The binding of 7,12-dimethylbenz[a]anthracene to mammary gland macromolecules in the hamster:effects of Enovid feeding or transplacental exposure to diethylstilboestrol.
The covalent binding of 7,12-[3H]dimethylbenz[a]anthracene ([3H--DMBA) to mammary gland macromolecules was studied in hamsters fed a contraceptive mixture, Enovid, those exposed transplacentally to diethylstilboestrol (DES), and controls. Compared with rats, hamsters are relatively resistant to DMBA mammary carcinogenesis, but susceptibility is increased by either of the above treatments with Enovid or DES. The amount of DMBA bound to DNA and protein ws 4-5 times greater than to RNA, but only DNA binding was persistent. Fifty-three percent of the DNA-bound DMBA was still present after 8 days. The amount of DMBA bound to hamster mammary DNA and its persistence was similar to that found in rats. Neither Enovid nor DES treatment altered the levels of binding to mammary macromolecules, nor their persistence. These results indicate that the species differences in the susceptibility to DMBA-induced mammary carcinogenesis in hamsters and rats, and modification of the former by hormones, is not due to differences in the activation of carcinogens. The role of hormones such as prolactin in the promotion phase of mammary gland carcinogenesis may explain these differences.


Solvent-regulated assemblies of 1D lanthanide coordination polymers with the tricarboxylate ligand.
Solvothermal reactions of the tricarboxylic acid ligand, biphenyl-3,3',5-tricarboxylic acid (H3bpta), and rare earth nitrate (Ln(NO3)3·6H2O) in the presence of KOH or DMF produced eight 1D linear coordination polymers, namely, [La(bpta)(H2O)5·(H2O)3]n (), [Pr(bpta)(H2O)5·(H2O)2.5]n (), [Nd(bpta)(H2O)5·(H2O)1.75]n (), [Sm(bpta)(H2O)5·(H2O)0.5]n () and [Ln(bpta)(DMF)(H2O)3·(H2O)]n [Ln = Eu (), Gd (), Tb (), Dy ()]. The 1D chain further assembles into a 3D supramolecular network structure through hydrogen bonds and π-π stacking among chains. Complexes and display the typical emission spectra for lanthanide-centred luminescence. The optical properties of were analysed in detail and coincide well with the structural properties. The influence of temperature on the luminescence lifetime of has been studied and different non-radiative decay paths have been discussed. The magnetic properties show that and exhibit strong spin-orbit coupling, while weak antiferromagnetic coupling exists in .


The architect and the bee: some reflections on postmortem pregnancy.
Do physicians have a duty to sustain the pregnancies of women who die during the first or second trimester? Physicians cannot simply assume that the woman would have wished the pregnancy to continue, nor (in the U.S., at any rate) is it clear that the state has any interest in fetal life before viability. The conditions for beneficence-based duties of fetal rescue will often be unmet, both because sustaining the pregnancy is not always a clear gain to the born child and because it may impose a substantial burden on the benefactor. And duties of special relationship cannot readily be applied in these cases, as it is difficult to see how the relationship between someone who no longer exists and someone who does not yet exist can breed special duties. Further, to draw on Marx's distinction between the architect, who builds purposefully, and the bee, who cannot help what she is doing, I argue that human pregnancy is in a number of respects purposeful, creative, and deliberate, and that postmortem pregnancy, which follows the model of the bee, is a destructive icon that undercuts women's agency.


The clinical measurement of endothelial permeability.
The endothelium maintains corneal deturgescence in part by serving as a barrier to fluid movement into the cornea. This barrier function is estimated by measuring the permeability of the endothelium to small, nontoxic, fluorescent molecules such as fluorescein and carboxy-fluorescein. After topical or systemic application of the dye, its concentration in the cornea and the anterior chamber is measured noninvasively at intervals over several hours with a fluorophotometer. Endothelial permeability to the fluorescent dye is calculated from the changes in its concentration in the cornea and anterior chamber over time. The permeability of the endothelium to the small fluorescent molecules is assumed to be proportional to its permeability to water, and thus provides an estimate of the barrier function of the endothelium. This paper reviews the theory and technique of clinical fluorophotometry and discusses published data concerning the effects on endothelial permeability of aging, contact lens wear, medication, and surgery.


Antioxidants in the prevention of renal disease.
Reactive oxygen species (ROS) play a key role in the pathophysiological processes of renal diseases. The cellular damage is mediated by an alteration in the antioxidant status, which increases the concentration of ROS in the stationary state (oxidative stress). Oxidative stress mediates a wide range of renal impairments, from acute renal failure, rhabdomyolysis, obstructive nephropathy, hyperlipidemia, and glomerular damage to chronic renal failure and hemodialysis. Therefore, interventions favoring the scavenging and/or depuration of ROS (dietary and pharmacological antioxidants) should attenuate or prevent the oxidative stress, thereby mitigating against the subsequent renal damage.


False-positive mammography and its association with health service use.
A false-positive mammogram can result in anxiety, distress, and increased perceptions of breast cancer risk, potentially changing how women utilize healthcare. This study examined whether having an abnormal mammogram, considered a proxy for elevated risk perception, was associated with greater future health service use (outpatient visits and referrals). A retrospective cohort study using electronic health record data, spanning 2008 to 2012, from Boston Medical Center, a safety-net hospital. We grouped 3920 women aged 40 to 75 years receiving primary care and who had a mammogram between 2010 and 2011 into 3 categories: false-positive mammogram at index date; previous false positive, but normal index mammogram; and no history of false-positive mammograms. We contrasted the longitudinal changes in outpatient visits and provider referrals, before versus after the index mammogram, between women with false-positive mammogram and those without using Poisson regression models with a difference-in-differences specification. Clinical, visit, and demographic data were obtained from the institutional clinical data warehouse. Adjusting for baseline differences in sociodemographic characteristics across risk groups and for secular changes between pre- and postindex periods, a current false-positive mammogram was associated with an 18% increase in overall outpatient visits (incidence rate ratio [IRR], 1.18; 95% CI, 1.07-1.51), but no corresponding increase in provider referrals (IRR, 1.15; 95% CI, 0.99‑1.34), relative to never having a false positive. A previous false-positive mammogram had no associated change in outpatient utilization (IRR, 0.99; 95% CI, 0.91-1.07). Providers should discuss the implications of mammography findings at the time of screening to help mitigate potential detrimental effects and promote appropriate engagement in health services.


Rapid, fully automated radioimmunoassay of prostatic acid phosphatase in serum.
Prostatic acid phosphatase was purified from human semen and its purity established by biochemical and immunological criteria. Rabbits were injected with the purified isoenzyme to raise specific antisera. The prostatic acid phosphatase was radiolabeled with 125I by the Chloramine T method. We developed a fully automated double-antibody radiommunosassay for measuring prostatic acid phosphatase in serum from patients with carcinoma of the prostate and from several control groups. The lower detection limit of the radioimmunoassay was 2.0 microgram of prostatic acid phosphatase per litre of serum. Values for most members of the control group was <2.0 microgram/L; patients with metastatic carcinoma of the prostate had values ranging from <2.0 to 300 microgram/L of serum.


Increased apoptosis occurring during the first wave of spermatogenesis is stage-specific and primarily affects midpachytene spermatocytes in the rat testis.
The physiological apoptosis that occurs in immature testis appears to be necessary for the maturation of this tissue. Thus, inhibition of the early apoptotic wave associated with the first round of spermatogenesis is followed by accumulation of spermatogonia and infertility later in life. To identify the cell types undergoing apoptosis in immature rat testis and to characterize the relationship between this apoptosis and progression of the first wave of spermatogenesis, sequential viable segments of seminiferous tubules from 8-, 18-, and 26-day-old rats were examined under a phase-contrast microscope. One novel observation was the existence of pronounced stage-specificity during the peak of apoptosis at the very early postnatal ages of 18 and 26 days. Increased apoptosis of pachytene spermatocytes in stages VII-VIII was the major feature that distinguished immature spermatogenesis from the corresponding adult process. The frequency of apoptosis among type A spermatogonia in immature stages IX-I was also elevated in comparison to the corresponding mature stages. The age-related peak of apoptosis was mediated by caspase 3; furthermore, stage-dependent expression of Bax in midpachytene spermatocytes was observed in the 18- and 26-day-old testis. These observations suggest that this Bax-regulated, caspase 3-mediated, increased apoptosis of midpachytene spermatocytes during the first wave of immature spermatogenesis represents a major difference in comparison to apoptosis occurring in the mature testis, and it may play an important regulatory role in establishing spermatogenesis in the rat testis.


Transfusion results of cytapheresis platelet concentrates stored in two different polyolefin containers for five days.
Two different types of polyolefin storage containers were compared in order to estimate their ability to preserve apheresis platelet concentrates for 5 days. Ten pairs each consisting of one patient with thrombocytopenia following chemotherapy and one healthy platelet apheresis donor were examined. The platelet concentrates stored in the LE-2 bag were collected with a Fresenius AS 104 cell separator and those stored in the PL 732 with a Fenwal CS 3000. The separation efficiency of both cell separators was similar; the mean yields were 3.37 +/- 0.83 x 10(11) platelets in 274 +/- 26 ml for the AS 104 and 3.87 +/- 1.31 x 10(11) platelets in 318 +/- 22 ml for the CS 3000 (mean +/- SD). Storage for 5 days did not influence the platelet count significantly. The platelet loss due to filtration was 16 and 13%, respectively. The mean platelet volume obtained with both systems was reduced from a mean of 8.4 fl immediately after harvesting to 7.6 fl after storage (p < 0.0001) and to 7.3 fl after filtration (p = 0.001). The established corrected count increments (CCI) and the pre- and posttransfusion platelet counts were satisfactory and comparable for the 2 systems tested. The mean CCI of the AS 104-LE-2 system was 14.5 1 h and 7.4 x 10(9) platelets 24 h after transfusion, the mean CCI of the CS 3000-PL 732 system was 12.5 and 5.2 x 10(9) platelets, respectively. Single-donor apheresis concentrates with a large platelet content may be stored in the new LE-2 polyolefin container for up to 5 days and used in clinical transfusion.


Examining the quality of IEPs for young children with autism.
The purpose of this study was to develop an Individual Education Program (IEP) evaluation tool based on Individuals with Disabilities Education Act (IDEA) requirements and National Research Council recommendations for children with autism; determine the tool's reliability; test the tool on a pilot sample of IEPs of young children; and examine associations between IEP quality and school, teacher, and child characteristics. IEPs for 35 students with autism (Mage = 6.1 years; SD = 1.6) from 35 different classrooms were examined. The IEP tool had adequate interrater reliability (ICC = .70). Results identified no statistically significant association between demographics and IEP quality, and IEPs contained relatively clear descriptions of present levels of performance. Weaknesses of IEPs were described and recommendations provided.