Clinical Outcome After Microvascular Decompression According to the Progression Rates of Hemifacial Spasm.
The progression rate for clinical manifestations in hemifacial spasm (HFS) varies; however, little is known about the factors contributing to this. The purpose of this study was to identify independent factors affecting the rate of symptom progression and to evaluate clinical outcomes according to progression rates. The study enrolled 1335 patients who underwent microvascular decompression for HFS between July 2004 and January 2015. We assessed detailed history, clinical manifestations, and outcomes. Based on the duration and severity of symptoms, patients were classified into rapidly progressive and slowly progressive groups. We identified predisposing factors affecting the differences between the 2 groups and evaluated the clinical outcome in each group. Of 1335 patients with HFS, 825 (61.8%) were classified as rapidly progressive, and 510 (38.2%) were classified as slowly progressive. In univariable and multivariable analyses, younger age at surgery, older age at symptom onset, and absence of intraoperative facial nerve indentation were significant predisposing factors for rapid progression. The rapidly progressive group had worse outcomes than the slowly progressive group following microvascular decompression. In this study, patients with rapidly progressive HFS had worse clinical outcomes. Therefore, patients with rapidly progressive symptoms should be warned in advance that the prognosis may be worse after microvascular decompression. This study is also useful to understand the differences in symptom progression rates in HFS in order to inform patients about symptom progression.


Gender differences in febrile seizure-induced proliferation and survival in the rat dentate gyrus.
Febrile seizures are fever-associated early-life seizures that are thought play a role in the development of epilepsy. Seizure-induced proliferation of dentate granule cells has been demonstrated in several adult animal models and is thought to be an integral part of epileptogenesis. The aim of the present study was to investigate proliferation and survival of dentate gyrus (DG) cells born after early-life hyperthermia (HT)-induced seizures in male and female rats. At postnatal day (PN) 10, male and female rats were exposed to heated air to induce seizures. Littermates were used as normothermia controls. Convulsive behavior was observed by two researchers. From PN11 to PN16, rats were injected with bromodeoxyuridine (BrdU) to label dividing cells. The number of BrdU-immunoreactive cells in the DG was counted at PN17 and PN66. At PN17, male as well as female HT rats had the same amount of BrdU-positive cells compared with controls. At PN66, significantly more BrdU-positive cells were left in HT females (53%) than in controls (44%, percentage of BrdU-positive cells at PN17), whereas no difference was found between HT males and male controls. The net result of proliferation and survival at PN66 was that female HT rats had the same number of BrdU-immunoreactive cells as controls, whereas male HT rats had 25% more BrdU-immunoreactive cells than did controls (p < 0.05). Early-life seizures cause a sexually dimorphic cytogenic response that results in an increased population of newborn DG cells in young adult males, while leaving that of young adult females unaltered.


The ABCA4 2588G>C Stargardt mutation: single origin and increasing frequency from South-West to North-East Europe.
Inherited retinal dystrophies represent the most important cause of vision impairment in adolescence, affecting approximately 1 out of 3000 individuals. Mutations of the photoreceptor-specific gene ABCA4 (ABCR) are a common cause of retinal dystrophy. A number of mutations have been repeatedly reported for this gene, notably the 2588G>C mutation which is frequent in both patients and controls. Here we ascertained the frequency of the 2588G>C mutation in a total of 2343 unrelated random control individuals from 11 European countries and 241 control individuals from the US, as well as in 614 patients with STGD both from Europe and the US. We found an overall carrier frequency of 1 out of 54 in Europe, compared with 1 out of 121 in the US, confirming that the 2588G>C ABCA4 mutation is one of the most frequent autosomal recessive mutations in the European population. Carrier frequencies show an increasing gradient in Europe from South-West to North-East. The lowest carrier frequency, 0 out of 199 (0%), was found in Portugal; the highest, 11 out of 197 (5.5%), was found in Sweden. Haplotype analysis in 16 families segregating the 2588G>C mutation showed four intragenic polymorphisms invariably present in all 16 disease chromosomes and sharing of the same allele for several markers flanking the ABCA4 locus in most of the disease chromosomes. These results indicate a single origin of the 2588G>C mutation which, to our best estimate, occurred between 2400 and 3000 years ago.


Current achievements using ProteinChip Array technology.
Because of its inherent flexibility, the ProteinChip Array platform has demonstrated utility into basic research as well as clinical research. In the domain of basic research, it has been used to examine protein modifications, characterize protein-protein interactions and study signal transduction and enzymatic pathways. In clinical research, it has been used to elucidate and identify biomarkers of disease, and as a platform for predictive medicine.


Chromatographic analysis of Polygalae Radix by online hyphenating pressurized liquid extraction.
Practicing "green analytical chemistry" is of great importance when profiling the chemical composition of complex matrices. Herein, a novel hybrid analytical platform was developed for direct chemical analysis of complex matrices by online hyphenating pressurized warm water extraction followed by turbulent flow chromatography coupled with high performance liquid chromatography-tandem mass spectrometry (PWWE-TFC-LC-MS/MS). Two parallel hollow guard columns acted as extraction vessels connected to a long narrow polyether ether ketone tube, while warm water served as extraction solvent and was delivered at a flow rate of 2.5 mL/min to generate considerable back pressure at either vessel. A column oven heated both the solvent and crude materials. A TFC column, which is advantageous for the comprehensive trapping of small molecular substances from fluids under turbulent flow conditions, was employed to transfer analytes from the PWWE module to LC-MS/MS. Two electronic valves alternated each vessel between extraction and elution phases. As a proof-of-concept, a famous herbal medicine for the treatment of neurodegenerative disorders, namely Polygalae Radix, was selected for the qualitative and quantitative analyses. The results suggest that the hybrid platform is advantageous in terms of decreasing time, material, and solvent consumption and in its automation, versatility, and environmental friendliness.


Sticking together the Crumbs - an unexpected function for an old friend.
Cell polarity and cell-cell junctions have pivotal roles in organizing cells into tissues and in mediating cell-cell communication. The transmembrane protein Crumbs has a well-established role in the maintenance of epithelial polarity, and it can also regulate signalling via the Notch and Hippo pathways to influence tissue growth. The functions of Crumbs in epithelial polarity and Hippo-mediated growth depend on its short intracellular domain. Recent evidence now points to a conserved and fundamental role for the extracellular domain of Crumbs in mediating homophilic Crumbs-Crumbs interactions at cell-cell junctions.


Mapping and size estimates of female sex workers in Cameroon: Toward informed policy for design and implementation in the national HIV program.
Due to high HIV prevalence among Female Sex Workers (FSWs) in Cameroon (36.5%), this population is especially vulnerable to HIV acquisition and transmission nationwide. Though being prioritized in the national HIV response, it would be relevant to generate statistics on the number of FSWs in order to guide HIV interventions among FSWs. Our objective was to estimate the size of FSWs within hotspots of Cameroon. A cross-sectional study was conducted from September-November 2015 in selected cities in Cameroon: Bafoussam, Bamenda, Bertoua, Buea, Douala, Kribi, Limbé, and Yaoundé. A programmatic mapping was used, consisting of interviews with secondary key informants (KI) to identify hotspots of FSWs and their respective estimated numbers. Validation of size estimates was done by interviews with FSW at each hotspot. Size estimations in the councils mapped were extended to others not mapped using a Poisson regression model. A total of 2,194 hotspots were identified: Douala (760), Yaoundé (622), Bamenda (263), Bafoussam (194), Kribi (154), Bertoua (140), Limbé (35), and Buea (26). The estimated total number (range) of FSWs was 21,124 (16,079-26,170), distributed per city as follows: Douala 7,557 (5,550-9,364), Yaoundé 6,596 (4,712-8,480), Bafoussam 2,458 (1,994-2,923), Bamenda 1,975 (1,605-2,345), Kribi 1,121 (832-1,408), Bertoua 1,044 (891-1,198), Buea 225 (185-266), and Limbé 148 (110-148). The variability of estimates among cities was also observed within the councils of each city. The national predicted estimate of FSW population was 112,580 (103,436-121,723), covering all councils of Cameroon. An estimate of 1.91% (112,580/5,881,526; 0.47%-3.36%) adult female population in Cameroon could be sex workers. There are considerable numbers of FSW in major cities in Cameroon. There is a need to prioritize interventions for HIV prevention toward this population in order to limit the burden of HIV sexual transmission nationwide.


[Animal experiment research on the application of a human bone collagen substance].
The possibility of the application demineralised human cortical substance with a particle size of 315 micron was investigated on the filling of artificial defects at the tibial diaphysis in rabbit. A clear induction of the bone healing was observed histologically on the transplant side already after 4 weeks and the absence of a periosseous callus formation radiologically.


[Structural and metabolic organisation of the brain area 4 in the norm and after unilateral ocular enucleation in cats].
Comparative data on structural-metabolic organization of cat's brain area 4 in normal conditions and after unilateral ocular enucleation are presented. The investigation was performed using histochemical demonstration of cytochrome oxidase activity. The data obtained were processed by computer methods using original device of image analysis. The results of the investigations indicate an uneven cytochrome oxidase distribution along sublayer IIIb of area 4 in unilaterally enucleated animals. On the basis of literature data it is suggested that such an alternation of areas of high and low reactivity is the evidence of ordering of retinal representation of right and left eyes in the sensomotor cortex.


Domain coupling in a multimodular cellobiohydrolase CbhA from Clostridium thermocellum.
Cellobiohydrolase A (CbhA) from Clostridium thermocellum is composed of an N-terminal carbohydrate-binding domain 4 (CBD4), an immunoglobulin-like domain (Ig), a glycoside hydrolase 9 (GH9), X1(1) and X1(2) domains, a CBD3, and a dockerin domain. All domains, except the Ig, bind Ca2+. The following constructs were made: X1(2), X1(1)X1(2), CBD3, X1(1)X1(2)-CBD3, Ig, GH9, Ig-GH9, Ig-GH9-X1(1)X1(2), and Ig-GH9-X1(1)X1(2)-CBD3. Interactions between domains in (1) buffer, (2) with Ca2+, or (3) ethylenediaminetetraacetic acid (EDTA) were studied by differential scanning calorimetry. Thermal unfoldings of all constructs were irreversible. Calcium increased T(d) and cooperativity of unfolding. Multi-domain constructs exhibited more cooperative unfolding in buffer and in the presence of EDTA than did individual domains. They denatured by mechanism simpler than expected from their modular architecture. The results indicate that domain coupling in thermophilic proteins constitutes a significant stabilizing factor.


The effects of tiazofurin on basal and amphetamine-induced motor activity in rats.
The effects of tiazofurin (TR; 2-beta-d-ribofuranosylthiazole-4-carboxamide), a purine nucleoside analogue on basal and amphetamine (AMPH)-induced locomotor and stereotypic activity of adult Wistar rat males were studied. The animals were injected with low (3.75, 7.5, and 15 mg/kg ip) and high (62.5, 125, and 250 mg/kg ip) TR doses. Neither low nor high TR doses influenced basal locomotor and stereotypic activity in comparison with the corresponding controls treated with saline only. However, pretreatment with TR at any dose applied, except for the lowest one, significantly decreased AMPH-induced (1.5 mg/kg ip) locomotor activity, while AMPH-induced stereotypic activity was inhibited with the two highest TR doses. In addition, TR was detected in the brain by HPLC already 15 min after the injection (125 mg/kg ip) to reach a maximum 2 h after the administration and was detectable in this tissue during the next 4 h. Our results indicate that TR modifies central regulation of the motor activity, possibly by influencing dopaminergic (DA-ergic) transmission.


Postoperative results of looped nylon suture used in injuries of the digital flexor tendons.
Primary or delayed suture was performed on 174 patients involving 234 digits with flexor tendon injury on the day of injury to a maximum of 486 days after injury during the past eight years from 1974. In the treatment a 4-0 or 5-0 looped nylon suture was used. Follow-up study was made on 121 patients involving 164 digits in whom at least six months had elapsed since the operation. The evaluation showed the results in 53.0% excellent, 15.3% good, 18.9% fair and 12.8% poor. Discussion is made of a number of factors which have effects upon the results of treatment of flexor tendon injury of the hand.


In vitro digestion of cow's milk proteins by duodenal juice from infants with various gastrointestinal disorders.
The hydrolysis of bovine alpha-lactalbumin, beta-lactoglobulin, and casein by duodenal juice from 20 infants (18 with normal exocrine pancreatic function, 2 with pancreatic insufficiency), aged 3-19 months was studied in vitro with the aid of electroimmunoassay and sodium dodecyl sulfate-poly-acrylamide gel electrophoresis. The results from the two methods were almost identical. Duodenal juice from infants with cow's milk protein intolerance (7), celiac disease (5), and unclassified gastrointestinal disorder (6) had the same capacity to hydrolyze the milk proteins. No hydrolysis occurred in the two patients with pancreatic insufficiency. The hydrolyzing capacity was not correlated with age in the actual age group. The hydrolysis of the milk proteins occurred at a considerably slower rate when the proteins were crude, as in cow's milk, adapted, or unadapted formula, than when they were in a purified form. About 1 mg of purified alpha-lactalbumin or beta-lactoglobulin, and about 30 mg of purified casein could be hydrolyzed per milliliter duodenal juice per minute. Corresponding figures for the hydrolysis of the various proteins in cow's milk were 0.03, 0.12, and 16.1 mg/ml duodenal juice/min. Preincubation (60 min) with gastric aspirate after adjusting pH to 4-5 did not change the results. In conclusion, the duodenal juice from infants with normal exocrine pancreatic function has a great ability to hydrolyze casein. Corresponding hydrolytic capacity for alpha-lactalbumin or beta-lactoglobulin is considerably lower.


Biotin deficiency affects both synthesis and degradation of pyruvate carboxylase in rat primary hepatocyte cultures.
Pyruvate carboxylase (PC) is a biotin-dependent enzyme that plays a crucial role in gluconeogenesis, lipogenesis, Krebs cycle anaplerosis and amino acid catabolism. Biotin deficiency reduces its mass besides its activity. Enzyme mass is the result of its cellular turnover, i.e., its rates of synthesis and degradation. We have now investigated, by a pulse and chase approach in cultured primary hepatocytes, the effects of biotin deficiency on these rates. Wistar rats were fed a biotin-deficient diet and the controls were fed the same diet supplemented with biotin; their biotin status was monitored measuring lymphocytes propionyl-CoA carboxylase activity and urinary 3-hydroxyisovaleric acid. After 6-7 weeks primary hepatocytes were cultured in biotin-deficient or complete DMEM. PC activity was determined by measuring the incorporation of (14)C-bicarbonate into acid-non-volatile products, and its mass by streptavidin Western blots. Its synthesis rate was estimated from [(35)S] methionine incorporation into anti-PC antibody immunoprecipitate. Its degradation rate was calculated from the loss of radioactivity from previously labeled hepatocytes, in a medium containing an excess of non-radioactive methionine. PC synthesis rate in biotin-deficient hepatocytes was approximately 4.5-fold lower than in the controls, and its degradation rate was 5.1-fold higher. Therefore, the decrement of PC mass during biotin deficiency results both from a decrease in its synthesis and an increase in its degradation rates. To our knowledge, this is the first instance where a mammalian enzyme cofactor is necessary to sustain both processes.


[Skin manifestations of new targeted treatments].
Many cutaneous adverse events have been identified with recently developed targeted treatments. Some of them are common and specific, like paradoxical psoriasiform eruptions with anti-TNFα, papulopustular eruptions and paronychias with EGFR inhibitors and peculiar hand-foot skin reactions with multitargeted kinase inhibitors sorefenib and sunitinib. Patients treated with these recently available biologics need a careful monitoring.


Interactions between nectar robbers and seed predators mediated by a shared host plant, Ipomopsis aggregata.
Animals that consume plant parts or rewards but provide no services in return are likely to have significant impacts on the reproductive success of their host plants. The effects of multiple antagonists to plant reproduction may not be predictable from studying their individual effects in isolation. If consumer behaviors are contingent on each other, such interactions may limit the ability of the host to evolve in response to any one enemy. Here, we asked whether nectar robbing by a bumblebee (Bombus occidentalis) altered the likelihood of pre-dispersal seed predation by a fly (Hylemya sp.) on a shared host plant, Ipomopsis aggregata (Polemoniaceae). We estimated the fitness consequences of the combined interactions using experimental manipulations of nectar robbing within and among sites. Within sites, nectar robbing reduced the percentage of fruits destroyed by Hylemya. However, the negative effects of robbing on seed production outweighed any advantages associated with decreased seed predation in robbed plants. We found similar trends among sites when we manipulated robbing to all plants within a local population, although the results were not statistically significant. Taken together, our results suggest that seed predation is not independent of nectar robbing. Thus, accounting for the interactions among species is crucial to predicting their ecological effects and plant evolutionary response.


Slowly progressive L-DOPA nonresponsive pure akinesia due to nigropallidal degeneration: a clinicopathological case study.
We report an autopsy case of a 51-year old man who showed slowly progressive pure akinesia: freezing phenomenon and festination during 21 years of illness without tremor, rigidity, upward gaze palsy, bradykinesia and dementia, which were not responded to L-DOPA clinically. Neuropathological findings revealed the circumscribed regions in the substantia nigra and middle portion of the internal globus pallidus (GPi), without neurofibrillary tangles, neuropil threads, and glial fibrillary tangles. So this case was clearly distinguished with progressive nuclear palsy and pallidonigroluisian atrophy. It was first reported to describe that L-DOPA nonresponsive pure akinesia can arise from nigopallidal atrophy.


Subcortical neurofibrillary tangles and argyrophilic grains in a case of familial frontotemporal dementia with parkinsonism.
A case of familial frontotemporal dementia with parkinsonism (FTDP) similar to progressive supranuclear palsy (PSP) was reported. A 58-year-old man developed personality change followed by parkinsonism and dementia. Three family members showed similar symptoms. Cerebral atrophy was marked on the anterior frontotemporal lobes. The substantia nigra, hippocampus, peri-aqueductal gray matter and pontine nucleus were affected with globose neurofibrillary tangles (NFT) and glial tangles. Argyrophilic grains were distributed in the CA1-CA2. NFT, glial tangles and argyrophilic grains expressed four-repeat microtubule-associated protein tau (MAPT). MAPT gene had no mutation. Familial occurrence of FTDP with PSP-like tauopathy is rare.


Parotid-sparing intensity-modulated radiotherapy (IMRT) for nasopharyngeal carcinoma: preserved parotid function after IMRT on quantitative salivary scintigraphy, and comparison with historical data after conventional radiotherapy.
To evaluate the parotid function after parotid-sparing intensity-modulated radiotherapy (IMRT) in patients with nasopharyngeal carcinoma (NPC). From March 2003 to May 2004, 16 patients with nonmetastatic NPC underwent parotid-sparing IMRT. Eight of these patients had Stage III or IV NPC based on the 1997 American Joint Committee on Cancer staging system. The post-IMRT parotid function was evaluated by quantitative salivary scintigraphy and represented by the maximal excretion ratio (MER) of the parotid gland after sialogogue stimulation. The parotid function of 16 NPC patients who were previously treated with conventional radiotherapy was reviewed as the historical control. In the parotid-sparing IMRT group, all 16 patients were alive and without cancer at the end of follow-up period (median, 24.2 months). The mean parotid MER was 53.5% before radiotherapy, 10.7% at 1 month post-IMRT, and 23.3% at 9 months post-IMRT. In the conventional radiotherapy group, the mean parotid MER was 0.6% at 6 to 12 months postradiotherapy. The difference was statistically significant (23.3% vs. 0.6%, p<0.001, Mann-Whitney test). In the IMRT group, the mean parotid doses ranged from 33.2 Gy to 58.8 Gy (average, 43.9 Gy). The correlation between the mean parotid dose and the percentage decrease of parotid MER at 9 months post-IMRT (dMER) was statically significant (p=0.008, Pearson correlation). Although the mean parotid doses are relatively high, the significant preservation of parotid function is achieved with IMRT for NPC patients. The significant correlation between mean parotid dose and parotid dMER demonstrates the dose-function relationship of the parotid gland.


Daily hassles, major and minor life events, and their interaction with sociotropy and autonomy.
A cross-sectional study investigated whether Beck's (1983; 1987) (Treatment of depression: Old controversies and new approaches. New York: Raven Press; Journal of Cognitive Psychotherapy, 1, 2-27) cognitive-personality traits of sociotropy and autonomy had a specific interaction with daily minor life events (hassles) or major life experiences within the interpersonal and autonomous domains. Ninety-four undergraduates were administered the revised Sociotropy-Autonomy Scale (SAS), Beck Depression Inventory (BDI), Negative Experiences Inventory--Student Version (NEI), List of Threatening Events and the Hassles and Uplifts Scale. Hierarchical multiple regression analysis, with the BDI as the dependent variable, revealed a specific congruent interaction between Solitude, one of the two dimensions of autonomy, and NEI negative autonomous events. Sociotropy and the other dimension of autonomy, Independence, did not interact significantly with any of the life event scales. The findings suggest that more severe life events rather than daily hassles or strains may be more relevant when investigating cognitive diathesis-stress interactions in dysphoria.


How Do Clinicians Prefer Cultural Competence Training? Findings from the DSM-5 Cultural Formulation Interview Field Trial.
This study's objective is to analyze training methods clinicians reported as most and least helpful during the DSM-5 Cultural Formulation Interview field trial, reasons why, and associations between demographic characteristics and method preferences. The authors used mixed methods to analyze interviews from 75 clinicians in five continents on their training preferences after a standardized training session and clinicians' first administration of the Cultural Formulation Interview. Content analysis identified most and least helpful educational methods by reason. Bivariate and logistic regression analysis compared clinician characteristics to method preferences. Most frequently, clinicians named case-based behavioral simulations as "most helpful" and video as "least helpful" training methods. Bivariate and logistic regression models, first unadjusted and then clustered by country, found that each additional year of a clinician's age was associated with a preference for behavioral simulations: OR = 1.05 (95 % CI: 1.01-1.10; p = 0.025). Most clinicians preferred active behavioral simulations in cultural competence training, and this effect was most pronounced among older clinicians. Effective training may be best accomplished through a combination of reviewing written guidelines, video demonstration, and behavioral simulations. Future work can examine the impact of clinician training satisfaction on patient symptoms and quality of life.


Etiology of hemolysis in two patients with hepatitis A infection: glucose-6-phosphate dehydrogenase deficiency or autoimmune hemolytic anemia.
We report two children with hemolytic anemia during the course of hepatitis A infection. On admission, the patients had high blood urea nitrogen, creatinine, and uric acid levels, as well as anemia, leucocytosis, and direct and indirect hyperbilirubinemia. Both patients had a glucose-6-phosphate dehydrogenase deficiency (G6PD) and autoimmune antibodies. They were given vitamin K on admission. Inadvertent administration of vitamin K could have been related to an acute reduction in hemoglobin concentration. To prevent renal damage, plasmapheresis with fresh frozen plasma was done to clear bilirubin and plasma hemoglobin. The hyperbilirubinemia responded to plasmapheresis. However, acute tubular necrosis complicated the clinical course in one patient, and several sessions of hemodialysis were required. In conclusion, intravascular hemolysis should be considered in patients with hepatitis A infection, marked hyperbilirubinemia, and anemia. Although hepatitis A vaccination is not yet recommended for routine administration, high-risk patients, including those with a G6PD deficiency, should be vaccinated against hepatitis A.


Facilitatory effect of oxytocin on oxytocin cell background activity in the rat is suckling-dependent.
The injection of oxytocin into the third ventricle during suckling in lactating rats not only enhances neurosecretory bursts but also the background activity of oxytocin cells. However, removing the young rats 10 min after the oxytocin injection is immediately followed by a decrease in background activity, while injecting oxytocin alone (i.e. without suckling) or suckling alone (i.e. without oxytocin injection) has no effect. These results, which show that the facilitatory effect of oxytocin on oxytocin cell background activity is suckling-dependent, suggest that oxytocin could act either on the afferent pathways for milk ejection or on oxytocin cells themselves, but only if they received inputs from mammary glands. Various hypotheses on the site and mode of action of oxytocin are discussed.


Fatal cardiac air embolism after CT-guided percutaneous needle lung biopsy: medical complication or medical malpractice?
Computed tomography (CT)-guided percutaneous needle biopsy of the lung is a well-recognized and relatively safe diagnostic procedure for suspicious lung masses. Systemic air embolism (SAE) is a rare complication of transthoracic percutaneous lung biopsies. Herein, we present a case of an 81-year-old man who underwent CT-guided percutaneous needle biopsy of a suspicious nodule in the lower lobe of the right lung. Shortly after the procedure, the patient coughed up blood which prompted repeat CT imaging. He was found to have a massive cardiac air embolism. The patient became unresponsive and, despite resuscitation efforts, was pronounced dead. The pathophysiology, risk factors, clinical features, radiological evidence, and autopsy findings associated with SAE are discussed, which may, in light of the current literature, assist with the dilemma between assessing procedural complications and medical liability. Given the instances of SAE in the setting of long operative procedures despite careful technical execution, providing accurate and in-depth information, including procedure-related risks, even the rarest but potentially fatal ones, is recommended for informed consent to reduce medicolegal litigation issues.


Morbidity Due to Disparity in Pediatric Electroconvulsive Therapy.
Dr. Miller and colleagues recently submitted a Letter to the Editor discussing current state laws that result in disparity of electroconvulsive therapy (ECT) availability.1 In this current letter, we present a case of treatment-resistant childhood-onset schizophrenia (COS), with morbidity due to limited access to ECT. The patient and his family presented from Kentucky to Tennessee, despite less legislative regulation in the former. The patient's family provided informed consent for this report to be published.


Degradation of cresols by phenol-acclimated aerobic granules.
High-strength cresol isomers were treated with phenol-acclimated granules in batch experiments. The aerobic granules effectively metabolized cresol isomers at concentrations up to 1,500 mg l(-1). The modified Haldane kinetic model, used to assess the kinetic behavior during cresol degradation by granule cells, yielded a high maximum specific growth rate (1.13-1.45 h(-1)) and inhibition constant (617-952 mg l(-1)). The microbial community structure, which was stable under cresol stress, was principally composed of genera Bacillus, Acinetobacter, Corynebacterium, and Nocardioides. Enzyme assay results suggest simultaneous expression of ortho- and meta-cleavage pathways during cresol degradation. Under high cresol concentrations, however, cresol isomers were largely degraded via the meta-cleavage pathway, likely attributable to the activity of Bacillus. The aerobic granular sludge system is a promising biotechnology for degrading wastewater containing high-strength cresols.


Staff skills in patient/family relations grow.
Short but cogent course on communication, attitudes, and behaviors helps staff members from many departments relate more effectively with patients, their families, and visitors.


The Emerging Resistance in Nosocomial Urinary Tract Infections: From the Pediatrics Perspective.
Healthcare-associated infections results in increased health care costs and mortality. There are limited studies concerning the distribution of the etiologic agents and the resistance patterns of the microorganisms causing healthcare-associated urinary tract infections (HA-UTI) in pediatric settings. The aim of this study was to evaluate the distribution and antibiotic susceptibility patterns of pathogens causing HA-UTI in children. Isolates from 138 children with UTI who were hospitalized in pediatric, neonatal and pediatric surgery intensive care units were reviewed. Most common isolated organism was Klebsiella pneumoniae (34.1%) and Escherichia coli (26.8%). Among the Pseudomonas aeruginosa, Meropenem and imipenem resistance rates were 46.2% and 38.5%. Extended-spectrum beta-lactamase (ESBL) production was present in 48 Klebsiella species (82.8%). Among ESBL positive Klebsiella species, the rate of meropenem and imipenem resistance was 18.8%, and ertapenem resistance was 45.9%. Extended spectrum beta-lactamase production was present in 27 (72.9%) Escherichia coli species. Among ESBL positive E. coli, the rate of meropenem and imipenem resistance was 7.4%, and ertapenem resistance was 14.8. Emerging meropenem resistance in P. aeruginosa, higher rates of ertapenem resistance in ESBL positive ones in E. coli and Klebsiella species in pediatric nosocomial UTI are important notifying signs for superbug infections.


Community Dermatology in Argentina.
All around the globe the population has limited access to dermatologic care, and there are too few dermatologists to accommodate the high demand for skin care. Education of the community and frontline health workers is key to obtaining long-term impact in the skin health of a population. Reaching a community as a whole is challenging for dermatologists coming from distant cities, because cross-cultural obstacles often arise. This article describes some simple and positive ways of addressing the community directly while training health care workers in the recognition of prevalent skin diseases and effective pathways of management of these conditions.


Cora Du Bois' Brief Stint With the World Health Organization (1950-1951): Right Time, Wrong Place.
Brock Chisholm, director-general of the World Health Organization (WHO) in the early 1950s, was heard to say that "one cultural anthropologist [Cora Du Bois] was worth one hundred malaria teams." Paul Russell, the leading malariologist at the time, responded (privately in his diary) that Chisholm's remark was the sort that "one might expect from a psychiatrist planning a world health program." George Foster reported that Du Bois "was completely disgusted with" her stay at WHO. "They never asked her to do anything. She never followed up." Chisholm was not the only one who appreciated her contribution to the work of WHO; other WHO programs and offices would have welcomed her contribution. However, by operating out of WHO's South-East Asia Regional Office (SEARO), she found herself isolated with little chance of her work being reviewed favorably, i.e., the "wrong place."


Inhibition of the epidermal growth factor receptor tyrosine kinase by PD153035 in human A431 tumors in athymic nude mice.
PD153035 is a potent (Ki = 6 pm) and specific inhibitor of the epidermal growth factor (EGF) receptor tyrosine kinase that suppresses tyrosine phosphorylation of the EGF receptor in A431 cells at nanomolar concentrations in cell culture. We have examined the pharmacokinetics of this compound and its ability to rapidly suppress phosphorylation of the EGF receptor in A431 human epidermoid tumors grown as xenografts in immunodeficient nude mice. Following a single i.p. dose of 80 mg/kg, the drug levels in the plasma and tumor rose to 50 and 22 microM within 15 minutes. While the plasma levels of PD153035 fell below 1 microM by 3 hours, in the tumors it remained at micromolar concentrations for at least 12 hours. The tyrosine phosphorylation of the EGF receptor was rapidly suppressed by 80-90% in the tumors. However receptor phosphorylation returned to control levels after 3 hours despite the continued presence of the drug at concentrations which, based on previous in vitro results, were predicted to maintain inhibition. EGF-stimulated tyrosine kinase activity in tumor extracts was decreased and recovered in parallel with the effects of PD153035 on receptor phosphorylation though the activity had reached only about half of the control activity after three hours. These results demonstrate the potential for using small molecule inhibitors to inhibit the EGF receptor tyrosine kinase in vivo, though a fair evaluation of their potential anti-cancer activity will have to wait for solutions to problems with sustained delivery which may allow us to maintain suppression of EGF receptor phosphorylation.


Gallbladder kinetics in obese patients. Effect of a regular meal and low-calorie meal.
Gallbladder contractility has been studied in 21 obese patients (greater than 130% ideal weight) and 30 nonobese subjects before and at regular intervals after the administration of a regular solid-liquid meal, and after a low-calorie, low-fat meal used conventionally for weight-loss purposes (Modifast). Gallbladder volume was determined by means of real-time ultrasonography, using a linear array scanner with a 3.5 MHZ probe. In seven of the obese patients, gallbladder contractility was also evaluated after a 10-day regimen with Modifast. The obese group showed a statistically significant greater gallbladder fasting volume and blunted contractility than controls both after the ordinary and the low-calorie meal. The 10-day low-calorie regimen was associated with a statistically significant increment in fasting gallbladder volume, while the percent volume reduction after Modifast did not change. It is suggested that, in addition to metabolic factors, gallbladder hypocontractility in the obese may contribute to the high incidence of cholesterol gallstones noted in these patients. A low-calorie, low-fat diet augmenting gallbladder volume may favor bile stasis and therefore the likelihood of developing gallstones.


Autologous stem cell transplantation in follicular non-Hodgkin's lymphoma.
The failure of conventional chemotherapy to improve overall survival rates in follicular non-Hodgkin's lymphoma (NHL) has led to the development of alternative treatment regimens. One such regimen is high-dose chemotherapy (HDT) with autologous stem cell transplantation (ASCT). In ASCT stem cells, harvested predominantly from peripheral blood, are used to repopulate the haemopoietic system after high-dose chemotherapy. Comparison of failure-free survival rates following ASCT, with those previously obtained with conventional chemotherapy, suggests a benefit for ASCT in patients who have previously responded to chemotherapy. Other factors that adversely influence the outcome of ASCT include large tumour burden and bcl-2 overexpression. Although ASCT in follicular NHL can prolong the period of remission, relapse is still common and can be caused either by contamination of the stem cell harvest with tumour cells, or regrowth of residual malignant cells not eradicated by the high-dose chemotherapy. Several strategies have been developed to reduce the rate of relapse, including in vitro purging of the stem cell product to remove tumour cells and using allogenic stem cells from HLA-matched donors with no history of malignant disease. While both these methods may have some benefit, they also have limitations. In vitro purging is labour intensive, costly and, as yet, the effect on relapse is unclear. Allogenic stem cell transplants have been associated with a reduced risk of relapse, but this is offset by increased transplant-related mortality. The most promising strategy to reduce the rate of relapse following ASCT is in vivo purging using rituximab, a monoclonal antibody to CD20. Rituximab mobilises mechanisms to kill lymphoma cells, and causes a rapid depletion of B cells from peripheral blood. Rituximab has demonstrated good efficacy as monotherapy in patients with both aggressive and indolent lymphoma and has shown very high response rates (>95%) when used in combination with HDT.


Ethnic Variations in Pterygium in a Rural Population in Southwestern China: The Yunnan Minority Eye Studies.
To determine the prevalence and associations of pterygium in a multiethnic adult population in rural China and to examine potential ethnic differences Methods: A total of 6418 adults (2133 ethnic Bai, 2130 ethnic Yi, and 2155 ethnic Han) aged 50 years or older participated in the study. Anterior segment examination was performed without pupil dilation using a slit lamp. Pterygium was defined as a raised fleshy triangular fibrovascular tissue growth of the conjunctiva encroaching onto a clear cornea. Pterygium was least prevalent among adults of Yi ethnicity (29.5%) compared with Bai (39.0%, p < 0.001) or Han (39.5%, p < 0.001) ethnicities. Those of Bai ethnicity were most likely to be affected by severe pterygium (7.5%), while Yi were least likely to be affected (3.8%). Multivariate analysis revealed that increasing age (odds ratio, OR, 1.017), female sex (OR 1.53), lower educational level (OR 1.25), higher blood pressure levels (OR 1.002), and greater time spent outdoors per day (OR 1.09) were significantly associated with a higher prevalence of pterygium, while Yi ethnicity (OR 0.65, comparing Yi with Han) and wearing brimmed hats outdoors (OR 0.82) were protective factors. Ethnicity was significantly associated with prevalence of pterygium. Our findings may be applicable to many other countries located within the "pterygium belt" for health resource allocation among different ethnic groups.


Arachidonic acid metabolism in gerbil cerebra: effects of ischemia and pentobarbital.
Pentobarbital pretreatment may be used to predict biochemical events involved in ischemic brain damage following bilateral carotid artery ligations in the gerbil, since it reduces the subsequent edema and mortality. The effects of this anesthetic on the ischemia-induced modifications of cerebral arachidonic acid metabolism were investigated, in order to correlate observed alterations with tissue damage. Cerebral lipids were radiolabeled in vivo with [3H]arachidonic acid prior to 10 min of cerebral ischemia and 0-120 min of perfusion. Ischemia stimulated a 97.3% increase in unesterified [3H]arachidonate, which was due to the loss of label from choline, inositol, and ethanolamine glycerophospholipids. Tissue reperfusion stimulated further reductions in [3H]choline and [3H]inositol glycerophospholipids, while ethanolamine glycerophospholipid and triglyceride labeling increased. Inositol glycerophospholipid, but not choline glycerophospholipid, labeling returned to control level by 60 min of reperfusion. Pentobarbital pretreatment reduced the accumulation of [3H]arachidonate by 56.2% during ischemia. It increased the recovery of [3H]ethanolamine glycerophospholipids during the ischemic period and [3H]choline glycerophospholipids during the first 5 min of reperfusion. These effects accounted for the reduction of unesterified [3H]arachidonate observed during ischemia and reperfusion.


Plasma fibronectin concentrations in healthy and septic infants.
The concentration of plasma fibronectin was determined by Laurell's electroimmunoassay in 75 preterm or term newborns within the first 2 days of life, in 97 healthy infants aged from 3 days to 12 months, in 40 septic infants and in 38 healthy adult subjects. The mean fibronectin concentration in citrated plasma of normal adults was 318 +/- 84 ml/l. Healthy eutrophic term newborns 1-2 days old had approximately one-third of the fibronectin concentration of adults. There was no significant difference in the values between healthy term and eutrophic preterm newborns or between eutrophic and hypotrophic newborns. The plasma fibronectin increased strongly over the 1st month of life. No significant difference was observed between fibronectin levels in infant boys and girls. The values in septic newborns and septic older infants were significantly lower when compared with those of age-matched healthy controls. It is speculated that this deficiency, because of linkage to fibrin in disseminated intravascular coagulation or due to increased utilisation as a nonspecific opsonin and sequestration at sites of tissue injury, may contribute to organ failure in septicaemia.


Meeting the Tobacco Cessation Coverage Requirement of the Patient Protection and Affordable Care Act: State Smoking Cessation Quitlines and Cost Sharing.
We explored whether various key stakeholders considered cost sharing with state telephone-based tobacco cessation quitlines, because including tobacco cessation services as part of the required essential health benefits is a new requirement of the Patient Protection and Affordable Care Act (ACA). We analyzed qualitative data collected from interviews conducted in April and May of 2014 with representatives of state health departments, quitline service providers, health plans, and insurance brokers in 4 US states. State health departments varied in the strategies they considered the role their state quitline would play in meeting the ACA requirements. Health plans and insurance brokers referred to state quitlines because they were perceived as effective and free, but in 3 of the 4 states, the private stakeholder groups did not consider cost sharing. If state health departments are going to initiate cost-sharing agreements with private insurance providers, then they will need to engage a broad array of stakeholders and will need to overcome the perception that state quitline services are free.


Binding of nicotinamide adenine dinucleotide by the renal brush border membrane from rat kidney cortex.
The characteristics of nicotinamide adenine dinucleotide (NAD) binding on brush border membranes prepared from rat renal cortex were investigated with the use of radioactively labelled NAD, [adenine-2,8-3H]NAD+, as a ligand. (1) We found that NAD binds on brush border membrane and that the extent of NAD binding is linearly proportional to the brush border membrane protein, and progressively increases with concentration of NAD in the medium. (2) The rate of NAD binding was dependent on temperature. At 20 degrees C, the equilibrium binding was obtained at 15 min, while NAD binding at 0 degree C was slower, but the final level of binding reached at 120 min was similar to that plateau of binding observed at 20 degrees C. Brush border membrane inactivated by heating at 95 degrees C for 3 min did not bind NAD. Binding of NAD on brush border membranes was reversed by simple dilution or by the addition of unlabelled NAD. Both alpha-NAD and beta-NAD stereoisomers displaced bound [3H]NAD. Reduced NAD (NADH) caused less displacement of bound NAD than oxidized NAD+. Adenine, nicotinamide, pyrophosphate, of 5'-AMP did not displace bound NAD. (3) The NAD binding to brush border membranes was nearly saturable, approximating saturation at 10(-4) M NAD. Kinetic analysis by Scatchard plot indicates two sets of NAD binding sites in brush border membranes: a high-affinity binding site (Kd = 1.9 . 10(-5) M) and a low-affinity binding site (Kd = 2.2 . 10(-3) M). (4) Unlike concentrative uptake of D-[14C]glucose by brush border membrane vesicles, binding of NAD was not dependent on the presence of an outside-in sodium gradient [Na+0 greater than Na+i], nor was it abolished by repeated freezing and thawing of brush border membranes. Unlike D-[14C]glucose uptake, NAD binding by brush border membranes did not change upon decrease of intravesicular volume in hypertonic media. These observations indicate that NAD association with brush border membranes is true binding rather than intravesicular uptake of this compound. (5) The presence of specific binding sites in renal brush border membrane capable of binding of NAD with a high degree of affinity suggests that such sites may be involved in previously observed (Kempson, S.A., Colon-Otero, G., Ou, S.L., Turner, S.T. and Dousa, T.P. (1981) J. Clin. Invest. 67, 1347) modulatory effect of NAD on sodium-gradient-dependent uptake of phosphate across luminal brush border membrane of proximal tubules.


Identification of an miRNA candidate reflects the possible significance of transcribed microsatellites in the hairpin precursors of black pepper.
Plant miRNAs (18-24nt) are generated by the RNase III-type Dicer endonuclease from the endogenous hairpin precursors ('pre-miRNAs') with significant regulatory functions. The transcribed regions display a higher frequency of microsatellites, when compared to other regions of the genomic DNA. Simple sequence repeats (SSRs) resulting from replication slippage occurring in transcripts affect the expression of genes. The available experimental evidence for the incidence of SSRs in the miRNA precursors is limited. Considering the potential significance of SSRs in the miRNA genes, we carried out a preliminary analysis to verify the presence of SSRs in the pri-miRNAs of black pepper (Piper nigrum L.). We isolated a (CT) dinucleotide SSR bearing transcript using SMART strategy. The transcript was predicted to be a 'pri-miRNA candidate' with Dicer sites based on miRNA prediction tools and MFOLD structural predictions. The presence of this 'miRNA candidate' was confirmed by real-time TaqMan assays. The upstream sequence of the 'miRNA candidate' by genome walking when subjected to PlantCARE showed the presence of certain promoter elements, and the deduced amino acid showed significant similarity with NAP1 gene, which affects the transcription of many genes. Moreover the hairpin-like precursor overlapped the neighbouring NAP1 gene. In silico analysis revealed distinct putative functions for the 'miRNA candidate', of which majority were related to growth. Hence, we assume that this 'miRNA candidate' may get activated during transcription of NAP gene, thereby regulating the expression of many genes involved in developmental processes.


In vitro antioxidant and antidiabetic activities of zinc oxide nanoparticles synthesized using different plant extracts.
Phytofabricated green synthesis of zinc oxide (ZnO) nanoparticles using different plant extracts of Azadirachta indica, Hibiscus rosa-sinensis, Murraya koenigii, Moringa oleifera, and Tamarindus indica for biological applications has been reported. ZnO nanoparticles were also synthesized by chemical method to compare the efficiency of the green synthesized nanoparticles. FT-IR spectra confirmed the functional groups involved in the green synthesis of ZnO nanoparticles and the powder XRD patterns of the ZnO nanoparticles revealed pure wurtzite structure with preferred orientation at (100) reflection plane. SEM and TEM analysis revealed the spherical shape of the synthesized ZnO nanoparticles with the particle size between 54 and 27 nm. The antioxidant activity was evaluated by five different free radical scavenging assays. The present study also intends to screen α-amylase and α-glucosidase activity of ZnO nanoparticles synthesized using natural sources, which may minimize the toxicity and side effects of the inhibitors used to control diabetes. The ZnO nanoparticles synthesized using T. indica extract displayed remarkable antioxidant and antidiabetic activities.


Magnetite-Amyloid-β deteriorates activity and functional organization in an in vitro model for Alzheimer's disease.
The understanding of the key mechanisms behind human brain deterioration in Alzheimer' disease (AD) is a highly active field of research. The most widespread hypothesis considers a cascade of events initiated by amyloid-β peptide fibrils that ultimately lead to the formation of the lethal amyloid plaques. Recent studies have shown that other agents, in particular magnetite, can also play a pivotal role. To shed light on the action of magnetite and amyloid-β in the deterioration of neuronal circuits, we investigated their capacity to alter spontaneous activity patterns in cultured neuronal networks. Using a versatile experimental platform that allows the parallel monitoring of several cultures, the activity in controls was compared with the one in cultures dosed with magnetite, amyloid-β and magnetite-amyloid-β complex. A prominent degradation in spontaneous activity was observed solely when amyloid-β and magnetite acted together. Our work suggests that magnetite nanoparticles have a more prominent role in AD than previously thought, and may bring new insights in the understanding of the damaging action of magnetite-amyloid-β complex. Our experimental system also offers new interesting perspectives to explore key biochemical players in neurological disorders through a controlled, model system manner.


Time course and effect of sodium intake on vascular and hormonal responses to enalapril (MK 421) in normal subjects.
Enalapril (MK 421) is a long-acting angiotensin converting-enzyme inhibitor which specifically lacks the sulfhydryl group of captopril. We measured arterial pressure and hormonal responses that occurred in 22 normotensive subjects treated with increasing doses of enalapril (2.5, 5, 10, and 20 mg) once daily, who were on either low (10 mEq) or high (200 mEq) sodium diets. In sodium-restricted subjects (n = 12), mean diastolic blood pressure declined from control levels in a dose-related fashion during the first 2 h. The mean 24-h diastolic blood pressure values were significantly lower than control (p less than 0.01) at all doses, with the greatest declines occurring with the 10 and 20 mg doses. Accompanying the decline in blood pressure was a significant increase in plasma renin activity (PRA) and reduction in plasma angiotensin II (AII) and aldosterone levels. As with blood pressure, the greatest changes were observed with the 5, 10, and 20 mg doses. However, only the 20 mg dose of enalapril produced prolonged and significant PRA increments (p less than 0.01) and AII decrements (p less than 0.05) of at least 24 h in duration. In sodium-replete subjects (n = 10), a similar pattern of diastolic blood pressure responses was observed; however, the effect of the drug was not so profound. No significant decrease in AII occurred at any dose of enalapril; however, PRA increased modestly but significantly (p less than 0.01) after administration of 5, 10, and 20 mg enalapril. Plasma aldosterone declined modestly but significantly, 2 (p less than 0.05) and 4 (p less than 0.01) h after the 10 mg dose.(ABSTRACT TRUNCATED AT 250 WORDS)


Immunotoxicological effects of inorganic arsenic on gilthead seabream (Sparus aurata L.).
Arsenic (As) has been associated with multitude of animal and human health problems; however, its impact on host immune system has not been extensively investigated. In fish, there are very few works on the potential risks or problems associated to the presence of arsenic. In the present study we have evaluated the effects of exposure (30 days) to sub-lethal concentrations of arsenic (5 μM As₂O₃) in the teleost fish gilthead seabream (Sparus aurata), with special emphasis in the innate immune response. The arsenic concentration was determined using atomic fluorescence spectrometry (AFS) in liver and muscle of exposed fish showing As accumulation in the liver after 30 days of exposure. The hepatosomatic index was increased at significant extent after 10 days but returned to control values after 30 days of exposure. Histological alterations in the liver were observed including hypertrophy, vacuolization and cell-death processes. Focusing on the immunological response, the humoral immune parameters (seric IgM, complement and peroxidase activities) were no affected to a statistically significant extent. Regarding the cellular innate parameters, head-kidney leucocyte peroxidase, respiratory burst and phagocytic activities were significantly increased after 10 days of exposition compared to the control fish. Overall, As-exposure in the seabream affects the immune system. How this might interfere with fish biology, aquaculture management or human consumers warrants further investigations. This paper describes, for the first time, the immunotoxicological effects of arsenic exposure in the gilthead seabream, which is a species with the largest production in Mediterranean aquaculture.


Evidence for the involvement of alpha-adrenoceptor blockade in the antihypertensive action of diazoxide in the renal hypertensive rat.
The effects of diazoxide on the blood pressure and heart rate of conscious renal hypertensive rats have been investigated. The antihypertensive action of diazoxide has been studied in relation to the effects of diazoxide pretreatment on pressor responses to stimulation of the complete sympathetic outflow and to injections of noradrenaline, phenylephrine, angiotensin and serotonin in pithed rats. In pithed preparations, pressor responses to sympathetic nerve stimulation, and to injected noradrenaline and phenylephrine were significantly reduced by diazoxide pretreatment, at a time corresponding to maximal reduction of blood pressure in conscious animals. At this time there was no significant reduction of pressor responses to injected angiotensin or serotonin. These findings suggest a contribution of alpha-adrenoceptor blockade to the antihypertensive activity of diazoxide.


Rates of cyanide binding to the catalytic intermediates of mammalian cytochrome c oxidase, and the effects of cytochrome c and poly(L-lysine).
Rate constants of cyanide binding to 'fast' oxidase have been measured in the fully-oxidised (O), peroxy (P) and ferryl (F) states at pH 8.0. Values of 2.2, 8 and 10 M-1 s-1, respectively, were obtained. Thus, none of these states appears to exhibit a rate that would identify it as the species responsible for the extremely rapid cyanide binding observed during turnover. On the other hand, with 'oxidised' enzyme as prepared, containing a very small fraction of one-electron-reduced (E state) oxidase, a corresponding fraction of enzyme exhibited spectral changes consistent with cyanide binding with a rate constant in excess of 10(4) M-1 s-1. Evidence is presented suggesting that mediation of electron transfer from one-electron-reduced, cyanide-liganded enzyme to free, ferric oxidase, rather than a global protein conformational change of the enzyme, is responsible for the greatly enhanced cyanide binding rates seen in the presence of cytochrome c or poly(L-lysine). Inter-oxidase electron exchange in 'oxidised' enzyme can result in a complicated dependence of the binding rate on cyanide concentration. We have demonstrated that this may give rise to a saturation of the rate of cyanide binding.


Dietary flaxseed (Linum usitatissimum) oil supplementation affects growth, oxidative stress, immune response, and diseases resistance in rainbow trout (Oncorhynchusmykiss).
This paper describes the effects of flaxseed (Linum usitatissimum) oil (FSO) as a feed additive on growth performance, oxidative stress, immunity, and disease resistance in rainbow trout (Oncorhynchus mykiss). Eight-hundred-and-forty rainbow trout individuals (mean weight: 25.66 ± 1.33 g) were fed with different doses of FSO (0.5, 1, and 1.5%) ad libitum two times a day for 9 weeks. At the end of the feeding, growth performance was evaluated and the fish were challenged with two different bacteria (Yersinia ruckeri and Aeromonas hydrophila). At the end of the 3rd, 6th, and 9th weeks, blood and tissue samples were taken from 9 fish per treatment to evaluate innate immune response, cytokine gene expression levels, antioxidant enzyme activities and lipid peroxidation levels, and digestive enzyme activities. Determination of haematological parameters and histological examination was also carried out to evaluate the general health status of the fish. Results showed that the final weight and specific growth rate of FSO-supplemented fish increased significantly (p < 0.05). FSO-supplemented fish showed higher resistance to Y. ruckeri than the control group (p < 0.05). However, survival rates of all groups in A. hydrophila challenge test were similar (p > 0.05). Among the investigated innate immune response parameters, the potential killing activity of phagocytes, myeloperoxidase activity, and lysozyme activity increased in the FSO-supplemented groups (p < 0.05). Almost all cytokine gene expression levels in the experimental groups up-regulated especially after 9 weeks of feeding in the head kidney and intestine (p < 0.05). Similarly, superoxide dismutase and catalase activities were found to be significantly higher in the FSO group than in the control (p < 0.05) whereas, the lipid peroxidation levels drastically declined as a result of the FSO supplementation (p < 0.05). These results suggest that FSO can improve growth, enhance immune response, and lower oxidative damage in rainbow trout when supplemented at the rates of 0.5-1.5% for 9 weeks.


Hand hygiene in rural Indonesian healthcare workers: barriers beyond sinks, hand rubs and in-service training.
Few attempts to increase healthcare workers' hand hygiene compliance have included an in-depth analysis of the social and behavioural context in which hand hygiene is not undertaken. We used a mixed method approach to explore hand hygiene barriers in rural Indonesian healthcare facilities to develop a resource-appropriate adoption of international guidelines. Two hospitals and eight clinics (private and public) in a rural Indonesian district were studied for three months each. Hand hygiene compliance was covertly observed for two shifts each in three adult wards at two hospitals. Qualitative data were collected from direct observation, focus group discussions and semistructured in-depth and informal interviews within healthcare facilities and the community. Major barriers to compliance included longstanding water scarcity, tolerance of dirtiness by the community and the healthcare organisational culture. Hand hygiene compliance was poor (20%; 57/281; 95% CI: 16-25%) and was more likely to be undertaken after patient contact (34% after-patient contact vs 5% before-patient contact, P<0.001) and 'inherent' opportunities associated with contacts perceived to be dirty (49% 'inherent' vs 11% 'elective' opportunities associated with clean contacts, P<0.001). Clinicians frequently touched patients without hand hygiene, and some clinicians avoided touching patients altogether. The provision of clean soap and water and in-service training will not overcome strong social and behavioural barriers unless interventions focus on long term community education and managerial commitment to the provision of supportive working conditions.


Drug Tissue Distribution of TUDCA From a Biodegradable Suprachoroidal Implant versus Intravitreal or Systemic Delivery in the Pig Model.
To determine local ocular tissue levels of the bile acid, tauroursodeoxycholic acid (TUDCA), in the pig model using oral, intravenous (IV), intravitreal injection (IVitI) and low- and high-dose suprachoroidal, sustained-release implants (SCI-L or SCI-H). Forty-six pigs (92 globes) were included in the study. TUDCA was delivered orally in 5 pigs, IV in 4, IVitI in 6, SCI-L in 17, and SCI-H in 14. Testing timeframes varied from the same day (within minutes) for IV; 1 to 6 days, oral; and 1 to 4 weeks, IVitI and SCI. Enucleated globes were dissected, specimens from specific tissues were separated, and TUDCA was extracted and quantified using mass spectrometry. The highest TUDCA tissue levels occurred after IV delivery in the macula (252 ± 238 nM) and peripheral retina (196 ± 171 nM). Macular choroid and peripheral choroid levels were also high (1032 ± 1269 and 1219 ± 1486 nM, respectively). For IVitI delivery, macular levels at day 6 were low (0.5 ± 0.5 nM), whereas peripheral choroid was higher (15.3 ± 16.7 nM). Neither the SCI-L nor SCI-H implants delivered meaningful macular doses (≤1 nM); however, peripheral retina and choroid levels were significantly higher. Bile acid isoforms were found in the serum specimens. The highest TUDCA tissue levels in the pig model were obtained using IV delivery. Oral delivery was associated with reasonable tissue levels. Local delivery (IVitI and SCI) was able to achieve measurable local ocular tissue levels. Diffusional kinetics from the suprachoroidal space follow the choroidal blood flow, away from the macula and toward the periphery.


Clinical significance of abnormalities of the gastrointestinal tract detected by abdominal ultrasound.
In order to define the clinical significance and the need for further clinical work-up in patients where abnormalities of the stomach or bowel are found by ultrasound, we performed a prospective study on 100 patients with such findings. Of all patients, 35% were found to have a malignant tumor, 73% had a diagnosis as made by reference methods which was probably (18%) or definitively (55%) related to the US finding. Eighteen percent had definitive false positive findings, in 9% no final diagnosis was obtained. Thus, a positive predictive value of 80% was calculated for the US finding of a mass or a target sign related to bowel or stomach in US. The positive predictive value was lowest for target signs related to the bowel (75%) and highest for bowel conglomerates (100%). Patients with target signs of the stomach, bowel conglomerates, or masses were more likely to have malignant disorders (72%) than those with target signs related to the bowel (16%). We conclude from this study that the ultrasound finding of a target sign or a mass related to stomach or bowel has a high clinical relevance and should in any case worked up by appropriate investigations when clinical consequences are possible.


Pulmonary Implications of Pediatric Spinal Deformities.
"Pediatric spinal deformities may be associated with pulmonary complications in a patient's lifetime. A review of the diagnosis of spinal abnormalities includes classifications of scoliosis and kyphosis, correlating physical examination findings and radiographic interpretation. The natural history of untreated spine deformities is reviewed along with the associated altered pulmonary compromise. Treatment options for children affected by spinal deformities are discussed, including the relative indications, the efficacy, pros and cons of different treatment options, along with the evidence to support these. This overview of spine deformities includes research outcomes to support the care of these pediatric patients."


Exposure to a controlled adverse environment impairs the ocular surface of subjects with minimally symptomatic dry eye.
Adverse environmental conditions elicit dry eye (DE)-related signs and symptoms. The purpose of this work is to determine whether these conditions can alter a normal-to-borderline ocular surface in subjects with DE symptoms. Ten minimally symptomatic contact lens (CL)-wearing subjects were exposed, without (WO-) and with (W-)CLs, to a controlled adverse environment (CAE) of 22.0 +/- 2.0 degrees C and 19.0% +/- 4.0% relative humidity (RH) for 2 hours in an environmental chamber (EC). One month later, the same subjects were placed in an indoor normal environment (INE) of 24.2 +/- 1.3 degrees C and 34.8% +/- 2.9% RH for 2 hours. DE-related signs and symptoms were evaluated before and after each exposure. The reversibility of changes provoked by CAE or INE was also evaluated. Without CL wear, significant changes were found in DE signs (noninvasive tear break-up time [NIBUT], conjunctival hyperemia and phenol red thread test) after CAE exposure, but not found after INE exposure. However with CL wear, the same tests were altered after both CAE and INE exposure. Most of these changes returned to normal values within 1 month after environmental exposure. Significant changes in comfort and the ocular surface tests were found after 2 hours of exposure to CAE. These results show the negative impact that an adverse environment, especially low RH, can have on the ocular surface. These alterations were fully reversible. This indicates that the CAE is a safe and functional condition in which to standardize DE diagnostic tests and evaluate therapeutics.


Serodiagnosis of sheeppox and goatpox using an indirect ELISA based on synthetic peptide targeting for the major antigen P32.
Sheeppoxvirus (SPPV), goatpoxvirus (GTPV) and lumpy skin disease virus (LSDV) of cattle belong to the Capripoxvirus genus of the Poxviridae family and can cause significant economic losses in countries where they are endemic. Despite the considerable threat that these viruses pose to livestock production and global trade in sheep, goats, cattle and their products, convenient and effective serodiagnostic tools are not readily available. Toward this goal, two synthetic peptides corresponding to the major antigen P32 were synthesized. These synthetic peptides were then used as antigen to develop an ELISA method to detect anti-SPPV and GTPV antibodies. The results indicated that the optimal concentration of coated recombinant antigen was 0.2 μg per well for a serum dilution of 1:10. The ELISA performed favorably when sera from sheep immunized experimentally were tested. This assay offers the prospect of synthetic peptide as antigens for indirect ELISA to detect SPPV and GTPV antibody in sheep and goat sera.


Effects of heat stress on the chemical composition, oxidative stability, muscle metabolism, and meat quality of Nile tilapia (Oreochromis niloticus).
The present study investigated the effects of chronic heat stress (HS) on the chemical composition, oxidative stability, muscle metabolism, and meat quality of Nile tilapia (Oreochromis niloticus). Compared with the control (26 °C), chronic HS (32 °C) lowered growth performance, the contents of whole-body lipid, muscle protein, and muscle lipid. Also, HS significantly increased the contents of reactive oxygen species (ROS) and decreased antioxidative status, causing a decline in meat quality, including increased lipid and protein oxidation, the centrifugal water loss, and cooking loss as well as decreased the fragmentation index and pH at 24 h, which may be attributed to induced apoptosis by excessive ROS in Nile tilapia meat. Moreover, metabolomic analysis showed HS lowered flavor and nutritional value by affecting amino acid, lipid, and nucleotide metabolism. These results reveal that HS adversely affects oxidative stability, meat quality, flavor, and nutrition, warranting its recognition and prevention.


Serum Trace Element Concentrations in Rheumatoid Arthritis.
Rheumatoid arthritis (RA) is a condition that is associated with oxidative stress. Serum trace elements and their related transport proteins, e.g., albumin and ceruloplasmin, play an important role in the antioxidant defense. Trace element status may therefore be involved in the pathogenesis of RA or be affected by the disease activity of this chronic inflammatory condition. The study participants were 110 patients with RA and 100 sex- and age-matched healthy volunteers. Serum concentrations of albumin, ceruloplasmin, selenium, zinc, copper, and zinc/copper ratio were measured in all subjects. The relationship between these parameters and disease activity score was also assessed. Lower concentrations of serum Alb, Zn, and Se were independently related to disease activity index. High concentrations of serum copper were associated with the presence of RA. Serum Cu concentrations were positively related to disease activity as assessed by the disease activity score. Low serum concentrations of Zn and Se, and high serum Cu concentrations may be associated with the presence of RA or be a consequence of this condition. Of the trace elements that were investigated in the present study, only serum Cu was positively correlated with disease activity.


Does same session EUS-guided tissue acquisition and ERCP increase the risk of pancreatitis in patients with malignant distal biliary obstruction?
Endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasonography-guided tissue acquisition (EUS-TA) are increasingly performed in the same session in patients with malignant biliary obstruction. In this retrospective analysis, we investigated adverse events (AE) after same session ERCP and EUS-TA. Patients with malignant distal biliary obstruction who underwent EUS-TA and/or ERCP with self-expandable metal stent (SEMS) placement from January 2015 to April 2020 were included. Primary outcome was post-procedural pancreatitis (PPP). Secondary outcomes were other procedure-related AE. We included 494 patients, of which 118 patients (24%) underwent same session EUS-TA+ERCP, 51 patients (10%) underwent separate session EUS-TA & ERCP, 90 patients (18%) ERCP-only and 235 patients (48%) EUS-TA only. PPP occurred in 22 patients (19%) after same session EUS-TA+ERCP and in 6 patients (12%) after separate EUS-TA & ERCP (p = 0.270). When adjusted for other known risk factors (i.e., difficult procedure), the difference in PPP remained non-significant (adjusted odds ratio 1.74 (95%-CI 0.65-4.67, p = 0.268). The incidence of other AE was similar, although the overall AE rate was significantly higher after same session EUS-TA+ERCP (36% vs. 20%, p = 0.030). Same session EUS-TA+ERCP did not significantly increase the incidence of PPP, although overall AE were significantly higher. These data warrant further prospective studies.


Characterization of the aroma profiles of oolong tea made from three tea cultivars by both GC-MS and GC-IMS.
Tea cultivar is crucial for oolong tea aroma quality. However, the aroma characteristics of oolong tea made from different cultivars have rarely been studied. The aroma profiles of fresh tea leaves and oolong teas derived from Shuixian (SX), Huangmeigui (HMG) and Zimudan (ZMD) cultivars were comprehensively analyzed by gas chromatography-mass spectrometry, gas chromatography-ion mobility spectrometry (GC-IMS), sensory evaluation and odor activity value (OAV) determination. 12 volatiles (OAV>1) contributed to the overall aroma, of which benzeneacetaldehyde (OAV 2.14) and 3,5-diethyl-2-methylpyrazine (OAV 1.25) were the aroma-active compounds for HMG tea. Significantly more volatiles and stronger floral odor were from HMG and ZMD than the SX tea. Moreover, popcorn-like, creamy odors with high-intensity, and caramel-like odor were only recorded in HMG and ZMD samples. Additionally, 27 volatiles were identified by GC-IMS only, indicating the benefits of combined method for a better understanding of the impact of cultivars on tea aroma profiles.


Plasmodium berghei: ectopic antibody synthesis in splenectomized rodents.
Jirds (Meriones unguiculatus) were able to maintain acquired antimalaria immunity independent of the spleen approximately 4 months after initial infection. The memory cells appeared to become peripheralized, and persist outside the spleen for +/- 10 months if no further antigenic stimulus is applied. With regular stimulation, immunity was maintained indefinitely. In immune splenectomized jirds, the secondary, splenic germinal center function appeared to be taken over by cellular infiltrates in the liver that are organized as "pseudofollicles." They were comprised of macrophages that contained very finely divided malaria pigment and functional B and T cells. These pseudofollicles were located at the vascular triangles of the hepatic lobules. Strings of plasma cells appeared to be differentiated at the edges of the pseudofollicles. Like the splenic germinal centers, the pseudofollicles appeared largest about 10 days after challenge and became completely resorbed after 3 weeks. Similar structures were observed in asplenic aged rats, whether the spleen was removed before or after initial infection. However, rats splenectomized prior to infection developed low-grade chronic parasitemias; rats splenectomized later remained solidly immune, confirming the view that the pseudofollicles replace only the secondary, humoral response of the splenic germinal centers. It is not known at which site the memory for sterilization locates after peripheralization. The liver also appears to assume the splenic function of storage, and possibly detoxification, of clumps of indigestible malaria pigment. The pigment is located in clusters of macrophages dispersed throughout the parenchyma.


Pancreatic resection for cancer-the Heidelberg technique.
Pancreatic cancer is associated with high recurrence rates, and any surgery should aim to prevent local recurrence. However, systematic resection of putatively tumor-infiltrated soft tissue adjacent to the celiac branches and superior mesenteric artery has not regularly been applied in pancreatic head resection. We describe a technique of vessel-oriented pancreatic head resection, allowing for extended removal of lymphatic and neural tissue that is situated in the TRIANGLE in between the celiac trunk, the superior mesenteric artery, and the portal vein. Vessel-oriented dissection or vascular resection facilitates complete removal of putatively tumor-infiltrated soft tissue, thus potentially reducing the risk of isolated local recurrence in pancreatic cancer.


Cocaine exposure alters H2S tissue concentrations in peripheral mouse organs.
Hydrogen sulfide (H2S) is well-known as a physiological mediator in the mammalian brain and peripheral tissues. Among several factors that change the concentration of H2S, oxidative stress and generation of reactive oxygen species, which accompany neurochemical actions of drugs of abuse, are of recent interest. Limited data on the connection of cocaine and H2S levels prompted us to investigate the effect of this psychostimulant on the H2S concentration in the mouse brain and peripheral organs. Male BALB/C mice were given several cocaine dosage and treatment regimens, and the free and acid-labile H2S tissue concentrations were determined with a modified spectrophotometric method of Siegel. We demonstrated the dose- and treatment-dependent decreases in the H2S level in the heart (83% of control level), and in the liver and kidney (17-34% of control levels) homogenates, but no changes were seen in the mouse brain. The strongest effect occurred after repeated administration of cocaine (20mg/kg) in all peripheral tissues. A reduction in the peripheral tissue H2S level in the heart, liver and kidney homogenates after repeated injections of cocaine may be the result of a strong toxic effect of the drug.


Enhancing Recovery in Congenital Cardiac Surgery.
The benefits of a comprehensive enhanced recovery after surgery (ERAS) program for patients with congenital heart disease are largely unknown. This study evaluated adherence and to outcomes of a recently implemented enhanced recovery program (ERP) in congenital cardiac surgery. Patients undergoing elective procedures for simple and moderately complex congenital cardiac surgery have followed institutional ERP guidelines since October 2018. Adherence to guidelines over a 12-month period (P2) was compared with implementation data (P1, 5 months). The association of outcomes with continuous time was estimated using linear regression. Among 559 patients (representing 40% of the cardiac surgical volume) following the ERP over a period of 17 months, no differences in patient characteristics were observed between periods, except a higher incidence of previous operations in P2. Adherence to many aspects of guidelines improved from P1 to P2. The following improvements were notable: operating room extubation, 27% in P2 vs16% in P1 (P = .006); and a decrease in median ventilation time, 6.0 hours (interquartile range [IQR], 0-9.2 hours) in P2 vs 7.6 hours (IQR, 3.8-12.3 hours) in P1 (P = .002). In addition, there was a reduction in opioids, reported as oral morphine equivalents, that was most significant for intraoperative oral morphine equivalents: 5.00 mg/kg (IQR, 3.11-7.60 mg/kg) in P2 vs 6.05 mg/kg (IQR, 3.77-9.78 mg/kg) in P1 (P = .001). There was no difference in overall intensive care unit and postoperative lengths of stay, except in lower-risk surgical procedures. Surgical outcomes were similar in the 2 periods. An enhanced recovery program reduced the use of opioids, led to more extubation in the operating room, and reduced mechanical ventilation duration in patients undergoing congenital cardiac surgery.


Adaptations and Safety Modifications to Perform Safe Minimal Access Surgery (MIS: Laparoscopy and Robotic) During the COVID-19 Pandemic: Practice Modifications Expert Panel Consensus Guidelines from Academia of Minimal Access Surgical Oncology (AMASO).
The pandemic of COVID-19 across the globe triggered national lockdowns hampering normal working for all the essential services including healthcare. In order to reduce transmission and safety of patients and healthcare workers, the elective surgeries have been differed. The visits to the hospitals for follow-ups and consultations received temporary halt. However, we cannot halt the treatment for cancer patients who may or may not be COVID-19 positives. These are emergencies and should be treated ASAP. Conducting emergency surgeries during pandemic like COVID-19 is challenge for surgeons and the entire hospital infrastructure. The available information about COVID-19 and its propensity of contamination through droplets and aerosol need some modifications for conducting surgeries successfully without contaminating the hospital buildings, protecting healthcare teams and the patient. With these objectives, some modifications in the operating theater including surgical techniques for minimal access, laparoscopy, and robotic surgery are proposed in this review article. This review article also discusses the safety measures to be followed for the suspected or confirmed COVID-19 patient and the guidelines and recommendations for healthcare teams while treating these patients. Although there is little evidence of viral transmission through laparoscopic or open approaches, modifications to surgical practice such as the use of safe smoke evacuation and minimizing energy device used to reduce the risk of exposure to aerosolized particles to healthcare team are proposed in this review article.


Discovery of the Novel Entecavir-Resistant Hepatitis B Virus Reverse Transcriptase A181C Substitution From an Integrated Genotypic Analysis.
Entecavir (ETV) is a first-line therapy for chronic hepatitis B virus (HBV), demonstrating potent suppression of HBV DNA and a high barrier to viral resistance. Previous studies revealed that ETV-resistant (ETVr) HBV DNA resulted from substitutions in the HBV reverse transcriptase (RT) at positions rtT184, rtS202, or rtM250 in combination with lamivudine resistance (LVDr) substitutions rtM204I/V±rtL180M. In vitro, viral variants exhibit varying degrees of ETV susceptibility and replication capacity depending on specific resistance substitutions. To explore the potential for additional pathways to ETVr, HBV RT sequences from 982 evaluable patients enrolled in 17 ETV clinical studies were analyzed. Thirty novel emergent substitutions at amino acid positions not previously associated with HBV nucleos(t)ide drug resistance were observed in at least 2 patients and were identified in patient-derived HBV with a wild-type, LVDr, or ETVr RT sequence. Phenotypic analysis of these substitutions indicated that they had no effect on ETV susceptibility. Phenotypic analysis was also performed on patient-derived HBV RT sequences from 10 LVD-naive and 13 LVD-experienced patients with virologic breakthrough and emergent novel substitutions while on ETV treatment. One LVD-experienced patient-derived HBV RT harboring LVDr substitutions rtL180M+rtM204V with rtA181C displayed reduced ETV susceptibility (122-fold greater than wild-type HBV) and remained susceptible to adefovir and tenofovir. HBV harboring the rtA181C substitution without LVDr substitutions rtL180M+rtM204V remained susceptible to inhibition by ETV, adefovir, and tenofovir, although cross-resistance to LVD and telbivudine was observed. Conclusion: An integrated genotypic analysis of HBV RT sequences from patients with chronic HBV treated with ETV led to the discovery of the novel ETVr substitution rtA181C. This substitution was always detected in combination with LVDr substitutions rtL180M+rtM204V in ETV-treated patients.


Parents of schizophrenic individuals: what we say is what we see.
The language used to describe the families of schizophrenic individuals is reviewed briefly. It is suggested that this language has negative connotations and is a legacy of past theory interpreting parents as primary causal agents in schizophrenia. If we are to engage the families of schizophrenic patients in cooperative therapeutic endeavors, we must begin to speak to and about those families in more neutral terms.


Bronchoscopic navigation and tissue diagnosis.
Diagnosis of early-stage lung cancer has become increasingly important as the detection of peripheral pulmonary lesions (PPLs) grows with widespread adoption of CT-based lung cancer screening. Although CT-guided transthoracic needle aspiration has been the standard diagnostic approach for PPLs, transbronchial sampling by bronchoscopy is often performed due to its reduced rate of adverse events. However, the diagnostic yield of conventional bronchoscopy is often poor. Various bronchoscopic technologies have emerged over recent years to address this limitation, including thin/ultrathin bronchoscopes, radial probe endobronchial ultrasound (RP-EBUS), virtual navigation bronchoscopy (VBN), electromagnetic navigation bronchoscopy (ENB), and robotic bronchoscopy. Bronchoscopic transparenchymal nodule access (BTPNA) and transbronchial access tool (TBAT) are novel techniques that leverage navigational bronchoscopic technologies to further improve access to lesions throughout the lung. The devices used for sampling tissue have similarly evolved, such as the introduction of cryobiopsy. These innovative bronchoscopic techniques allows higher diagnostic yield even in small PPLs. Given the complexity of these new techniques and technologies, it is important for physicians to understand their strengths and limitations.


D-Allulose cooperates with glucagon-like peptide-1 and activates proopiomelanocortin neurons in the arcuate nucleus and central injection inhibits feeding in mice.
A rare sugar D-Allulose has sweetness without calorie. Previous studies have shown that D-Allulose improves glucose and energy metabolism and ameliorates obesity. However, underlying mechanisms remain elusive. This study explored the effect of central injection of D-Allulose on feeding behavior in mice. We also examined direct effects of D-Allulose on the neurons in the hypothalamic arcuate nucleus (ARC) that regulate feeding, including the anorexigenic glucagon-like peptide-1 (GLP-1)-responsive neurons and proopiomelanocortin (POMC) neurons. Single neurons were isolated from ARC and cytosolic Ca2+ concentration ([Ca2+]i) was measured by fura-2 microfluorometry. Administration of D-Allulose at 5.6, 16.7 and 56 mM concentration-dependently increased [Ca2+]i in ARC neurons. The [Ca2+]i increases took place similarly when the osmolarity of superfusion solution was kept constant. The majority (40%) of the D-Allulose-responsive neurons also responded to GLP-1 with [Ca2+]i increases. D-Allulose increased [Ca2+]i in 33% of POMC neurons in ARC. D-Allulose potentiated the GLP-1 action to increase [Ca2+]i in ARC neurons including POMC neurons. Intracerebroventricular injection of D-Allulose significantly decreased food intake at 1 and 2 h after injection. These results demonstrate that D-Allulose cooperates with glucagon-like peptide-1 and activates the ARC neurons including POMC neurons. Furthermore, central injection of D-Allulose inhibits feeding. These central actions of D-Allulose may underlie the ability of D-Allulose to counteract obesity and diabetes.


Spatially adaptive blind deconvolution methods for optical coherence tomography.
Optical coherence tomography (OCT) is a powerful noninvasive imaging technique for detecting microvascular abnormalities. Following optical imaging principles, an OCT image will be blurred in the out-of-focus domain. Digital deconvolution is a commonly used method for image deblurring. However, the accuracy of traditional digital deconvolution methods, e.g., the Richardson-Lucy method, depends on the prior knowledge of the point spread function (PSF), which varies with the imaging depth and is difficult to determine. In this paper, a spatially adaptive blind deconvolution framework is proposed for recovering clear OCT images from blurred images without a known PSF. First, a depth-dependent PSF is derived from the Gaussian beam model. Second, the blind deconvolution problem is formalized as a regularized energy minimization problem using the least squares method. Third, the clear image and imaging depth are simultaneously recovered from blurry images using an alternating optimization method. To improve the computational efficiency of the proposed method, an accelerated alternating optimization method is proposed based on the convolution theorem and Fourier transform. The proposed method is numerically implemented with various regularization terms, including total variation, Tikhonov, and l1 norm terms. The proposed method is used to deblur synthetic and experimental OCT images. The influence of the regularization term on the deblurring performance is discussed. The results show that the proposed method can accurately deblur OCT images. The proposed acceleration method can significantly improve the computational efficiency of blind demodulation methods.


The role of intraoperative radiotherapy in pancreatic cancer.
In single-institution studies, IORT at appropriate doses seems to safely improve local control in patients who have locally advanced pancreatic cancer, compared with historical controls. IORT also has been a component of adjuvant treatment programs that have led to excellent local control in resected patients. When considering the use of IORT, it is essential to have an understanding of the physical characteristics of the electron beam and how it can differ with the use of flat and beveled applicators. Although apparent improvement in local control with the use of IORT seems to have produced some improvement in median survival rates, high rates of distant failure continues to prevent a significant improvement in long-term survival. Because effective local control in patients with unresectable pancreatic cancer is a prerequisite to the development of curative therapies, the development of improved systemic therapies in patients with locally advanced pancreatic cancer will likely make local therapies such as the use of IORT even more important in the future.


Gross Hematuria Following SARS-CoV-2 Infection in IgA Nephropathy: A Report of 5 Cases.
Gross hematuria after upper respiratory tract infections is a well-known characteristic symptom of immunoglobulin A nephropathy (IgAN). In recent years, there have been several reports of existing or newly diagnosed patients with IgAN susceptible to gross hematuria after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. However, reports of patients with IgAN and gross hematuria after SARS-CoV-2 infection are extremely rare despite a considerable number of patients with coronavirus disease 2019 (COVID-19) who preferentially present with upper respiratory symptoms. Here, we report the cases of 5 Japanese patients with IgAN who developed gross hematuria associated with SARS-CoV-2 infection. These patients presented with fever and other COVID-19-related symptoms, followed by the appearance of gross hematuria within 2 days, which lasted for 1-7 days. Acute kidney injury occurred after gross hematuria in 1 case. In all cases, microhematuria was identified before gross hematuria associated with SARS-CoV-2 infection, and it persisted after the gross hematuria episode. Because repeated gross hematuria and persistent microhematuria may lead to irreversible kidney injury, the clinical manifestations of patients with IgAN during the COVID-19 pandemic should be carefully monitored.


REM sleep parameters in the discrimination of probable Alzheimer's disease from old-age depression.
Thirteen dementia of the Alzheimer type (DAT) patients and fifteen old-age major depressive disorder (OAD) patients were investigated by polysomnography. The sleep was recorded during two nights after a 1 week wash-out period of psychotropic drugs. No statistically significant differences between the two groups were found concerning sleep continuity or architecture. The amount of REM sleep was significantly lower in DAT in comparison with OAD patients (11.7% verses 18.5%). Also, total REM density as well as the density of the first REM period were significantly lower in the DAT compared with the OAD patient group (15.8% verses 32.5%, 14.9% verses 38.1%, respectively). REM latency did not differ between both groups. Because REM latency is known from other studies to be shortened in depressed patients due to a cholinergic hyperactivity, the opposite finding, i.e., prolongation of REM latency, was expected for DAT patients. This assumption, however, could not be confirmed in the present study. It is concluded that REM density may better differentiate between DAT and OAD.


Kaempferol tetraglucosides from cabbage leaves.
Four flavonol glycosides were isolated from a leaf extract of cabbage and characterized by chemical and spectroscopic methods including 1H and 13C NMR and negative ion FAB-MS. The common structure of the four compounds was kaempferol 3-O-beta-D-[beta-D-glucopyranosyl(1-->2)glucopyranoside]-7- O-beta-D-[beta-D-glucopyranosyl(1-->4)glucopyranoside]. This compound was found unmodified or acylated at C-2"' (outer glucose in sophorosyl moiety) with either sinapic acid, ferulic acid or caffeic acid. The possible role of diversity in glycosylation and acylation patterns of flavonol glycosides for plant defences against herbivores is discussed.


Extrachromosomal circular DNA and structural variants highlight genome instability in Arabidopsis epigenetic mutants.
Abundant extrachromosomal circular DNA (eccDNA) is associated with transposable element (TE) activity. However, how the eccDNA compartment is controlled by epigenetic regulations and what is its impact on the genome is understudied. Here, using long reads, we sequence both the eccDNA compartment and the genome of Arabidopsis thaliana mutant plants affected in DNA methylation and post-transcriptional gene silencing. We detect a high load of TE-derived eccDNA with truncated and chimeric forms. On the genomic side, on top of truncated and full length TE neo-insertions, we detect complex structural variations (SVs) notably at a disease resistance cluster being a natural hotspot of SV. Finally, we serendipitously identify large tandem duplications in hypomethylated plants, suggesting that SVs could have been overlooked in epigenetic mutants. We propose that a high eccDNA load may alter DNA repair pathways leading to genome instability and the accumulation of SVs, at least in plants.


Public acceptance of obesity prevention policies in the UK.
Half of the UK population will get cancer during their lifetime, with the current survival rate at 50 %. Behavioural factors such as obesity contribute to two-fifths of the UK's most common cancers. Food 'pricing' and 'place and promotion' policies aim to avert this risk by reducing the rate of obesity in the UK. A cross-sectional survey collected data on the acceptance of obesity-related pricing and place and promotion policies from 3293 UK adults in 2016. Cross-tabulations and chi-squared tests were performed to investigate the support for these policies in the four UK countries and different socioeconomic groups. Only two-fifths of respondents supported all policies. Food place and promotion policies were better supported by the public than taxation, with over 70 % support for the promotion of healthy foods as opposed to 40 % support for 'fat tax'. The most deprived social groups were least supportive of all policies. There was not a noticeable difference in policy support between the four UK countries. The support for obesity policies is low, most notably amongst lower socioeconomic groups and for policies involving a price increase, across the UK. Obesity prevention policies could reduce the rate of related cancers, but their success requires public support and acceptance. Increasing tax on unhealthy foods is less well supported in the UK population than policies which affect the in-store placement and promotion of these products. Lower levels of support for all these policies among low-income groups, among whom obesity and cancer rates are highest, indicate a particular need for strategies to increase policy support in these groups.


Electrical responses to taste chemicals across the dorsal epithelium of bullfrog tongue.
Stimulation of the bullfrog tongue with taste chemicals produced a slow change in transepithelial potential difference across the dorsal epithelium. The potential profile was in many respects similar to that of the intracellularly recorded potential changes in taste cells and to the activity of taste fibers in frogs.


The T-box gene Tbx10 exhibits a uniquely restricted expression pattern during mouse embryogenesis.
The human TBX10 gene was previously identified from a genomic DNA sequence containing a partial open reading frame and was mapped to Chromosome 11q13, a chromosomal region associated with multiple inherited developmental disorders. Since mutations in several T-box family genes have been found to underlie distinct inherited developmental disorders, it has been speculated that TBX10 may be a candidate for one of the disease loci at Chromosome 11q13. To investigate the role of TBX10 in development and pathogenesis, we have isolated a full-length human TBX10 cDNA and cloned the mouse ortholog, Tbx10. Sequence analysis of cDNA clones and reverse transcription-polymerase chain reaction products revealed that the previously predicted TBX10 open reading frame (GenBank accession number AH006177) was incorrect. We have characterized the developmental expression patterns of Tbx10 during mouse embryogenesis by using in situ hybridization analyses. Our results show that Tbx10 mRNA expression is highly restricted and exhibits a unique spatio-temporal pattern during hindbrain development. These data will facilitate investigation of the role of TBX10 in development and disease.