Combination of texture and color cues in visual segmentation.
The visual system can use various cues to segment the visual scene into figure and background. We studied how human observers combine two of these cues, texture and color, in visual segmentation. In our task, the observers identified the orientation of an edge that was defined by a texture difference, a color difference, or both (cue combination). In a fourth condition, both texture and color information were available, but the texture and color edges were not spatially aligned (cue conflict). Performance markedly improved when the edges were defined by two cues, compared to the single-cue conditions. Observers only benefited from the two cues, however, when they were spatially aligned. A simple signal-detection model that incorporates interactions between texture and color processing accounts for the performance in all conditions. In a second experiment, we studied whether the observers are able to ignore a task-irrelevant cue in the segmentation task or whether it interferes with performance. Observers identified the orientation of an edge defined by one cue and were instructed to ignore the other cue. Three types of trial were intermixed: neutral trials, in which the second cue was absent; congruent trials, in which the second cue signaled the same edge as the target cue; and conflict trials, in which the second cue signaled an edge orthogonal to the target cue. Performance improved when the second cue was congruent with the target cue. Performance was impaired when the second cue was in conflict with the target cue, indicating that observers could not discount the second cue. We conclude that texture and color are not processed independently in visual segmentation.


Impaired colonic fermentation of carbohydrate after ampicillin.
The aim of this study was to investigate the effect of ampicillin on the ability of the human colon to ferment carbohydrate. The effect of ingesting a drink containing 20 g of lactulose on stool output and breath hydrogen production was measured in 13 normal volunteers before and during administration of ampicillin (2 g/day). Small bowel and whole gut transit times were also measured to exclude any direct effect of ampicillin on motor activity. Ingestion of lactulose did not increase stool weight or frequency under control conditions, but during administration of ampicillin, lactulose caused increases in stool weight (p less than 0.02) and frequency (p less than 0.01), in the percentage of unformed stools (p less than 0.001), and in the excretion of galactose and fructose in stool samples collected from 2 volunteers. Administration of ampicillin also significantly reduced the area under the breath hydrogen profile (p less than 0.03). Mouth-to-cecum transit of the lactulose drink was prolonged during ampicillin ingestion (p less than 0.01) but there was no significant change in the whole gut transit time. These results suggest that ampicillin impairs colonic fermentation of carbohydrate and a diet high in unabsorbable carbohydrate increases the risk of antibiotic-associated diarrhea.


Screening for Postpartum Depression in a Neonatal Intensive Care Unit.
Postpartum depression (PPD) is a common mental health condition that affects approximately 13% of postpartum women in the United States. However, the prevalence in the neonatal intensive care unit (NICU) has been shown to be higher. Routine screening for maternal PPD is recommended at infant primary care well-child visits up to 6 months of age. The absence of a routine PPD screening program in a level IV NICU created a large gap in screening in an at-risk population. To develop and implement a screening program in the NICU to increase the identification of maternal PPD symptoms and to develop both a referral algorithm for NICU staff to follow and a referral resource packet to be given to mothers with positive PPD screenings. Mothers with infants in the NICU were screened for PPD using the Edinburgh Postnatal Depression Scale (EPDS). Bedside nurses administered the screening tool and used a referral algorithm to determine appropriate follow-up. EPDS scores of 10 or more were considered positive and indicated a need for referral. The overall EPDS screening compliance was 66% with a positive rate of 26%. Nurses followed the referral algorithm appropriately 100% of the time. It was confirmed that 93% of the mothers with positive EPDS screenings sought help from a mental health provider. Routine maternal PPD screening should be implemented in all NICU settings. Postpartum mental health issues should not be the sole responsibility of obstetricians, mental health providers, or maternal primary care providers.


Association of Operative Volume and Odds of Surgical Complication for Patients Undergoing Repair of Pectus Excavatum at Children's Hospitals.
To determine whether procedure-specific provider volume is associated with outcomes for patients undergoing repair of pectus excavatum at tertiary care children's hospitals. We performed a cohort study of patients undergoing repair of pectus excavatum between January 1, 2013 and December 31, 2019, at children's hospitals using the Pediatric Health Information System database. The main exposures were the pectus excavatum repair volume quartile of the patient's hospital and the pectus excavatum repair volume category of their surgeon. Our primary outcome was surgical complication, identified using International Classification of Diseases, Ninth Revision, Clinical Modification, and International Classification of Diseases, Tenth Revision, Clinical Modification codes from Pediatric Health Information System. Secondary outcomes included high-cost admission and extended length of stay. In total, 7183 patients with an average age of 15.2 years (SD 2.0), 83% male, 74% non-Hispanic White, 68% no comorbidities, 72% private insurance, and 82% from metro areas were analyzed. Compared with the lowest-volume (≤10 cases/year) quartile of hospitals, patients undergoing repair of pectus excavatum at hospitals in the second (>10-18 cases/year), third (>18-26 cases/year), and fourth (>26 cases/year) volume quartiles had decreased odds of complication of OR 0.52 (CI 0.34-0.82), 0.51 (CI 0.33-0.78), and 0.41 (CI 0.27-0.62), respectively. Patients with pectus excavatum who underwent repair by surgeons in the second (>1-5 cases/year), third (>5-10 cases/year), and fourth (>10 cases/year) volume categories had decreased odds of complication of OR 0.91 (CI 0.68-1.20), OR 0.73 (CI 0.51-1.04), and OR 0.55 (CI 0.39-0.76), respectively, compared with the lowest-volume (≤1 case/year) category of surgeons. Procedure-specific case volume is an important factor when considering providers for elective surgery, even among specialized centers providing comprehensive patient care.


Cerebrovascular and metabolic effects of bradykinin, ATP and hypercapnia in the goat.
Cerebral blood flow (CBF) and cerebral O2 metabolism (CMRO2) changes were measured in these studies during treatment with three reputed cerebral vasodilators: bradykinin, adenosine triphosphate (ATP) and increased arterial PCO2. Intracerebrovascular bradykinin infusions increased CMRO2 and CBF to a similar degree. Intramaxillary ATP infusions increased CBF to an extent greater than that required for increases seen in CMRO2. Hypercapnia increased CBF without a significant change in CMRO2. Results suggest that increases in cerebral metabolism may mediate most, some and none of the cerebrovascular changes produced by bradykinin, ATP or hypercapnia, respectively.


MR-guided focused ultrasound surgery: A novel non-invasive technique in the treatment of adenomyosis -18 month's follow-up of 12 cases.
Adenomyosis is a gynecological condition of the uterus, characterized by the presence of ectopic endometrial tissue in the myometrium. Hysterectomy, uterine artery embolization, and endometrial ablation therapy are the various surgical treatment options available for adenomyosis. A novel and globally upcoming technique is MR-guided focused ultrasound surgery "MRgFUS," which is a promising non-invasive surgical treatment option. This study was carried out to determine the effectiveness of MRgFUS in the symptomatic management of adenomyosis. This study was carried out as a long-term follow-up study among 12 cases of adenomyosis, which were treated by MR-guided focused ultrasound. In all these participant's, three parameters - symptom severity score (SSS), menstrual pain score accessed using visual analogue score (VAS), and number of approximate pads used during menstruation were recorded prior to the treatment and on follow-up at 3, 9, and 18 months, respectively. The Friedman's test was used to test the difference in the values of scores before and after treatment. There was a significant improvement in the SSS, VAS, and the numbers of sanitary napkins used after surgery and sustained during the long-term follow-up. These values were statistically significant (P < 0.05). MRgFUS can be used in successful treatment of adenomyosis/focal adenomyoma by careful selection of the participant, good planning, and proper monitoring of the technique during ablation.


Photosynthetic action spectra of the energy storage in bundle sheath cells of Zea mays.
Photosynthetic action spectra (Formula: see text), (Carpentier, R., Larue, B. and Leblanc, R. (1984) Arch. Biochem. Biophys. 228, 534-543.), from 400 to 750 nm were studied in bundle sheath cells of maize. Photosynthetic action spectra in the presence of 10 mM ascorbate or 4 mM ribose-5-phosphate were increased and shifted through all the spectra. After the addition of 10 microM DCMU photosynthetic action spectra were remarkably diminished. On the basis of these results we suggest that the role of PSII in BS chloroplasts will be to prevent the overoxidation of PSI. It appears that in addition to PSII some endogen electron donor may regulate the PSI activity in bundle sheath cells.


Climbing fibers in mouse cerebellum co-cultured with inferior olive.
Cerebellar explants derived from neonatal mice were co-cultured with medulla containing inferior olive. The explants exhibited extracellular climbing fiber-like responses to electrical stimulation. On ultrastructural examination, many terminals with a high packing density of round, clear vesicles in a dark filamentous cytoplasm were present. Similar terminals, characteristic of climbing fibers, had not been identified in previous studies with cerebellar explants incorporating dorsal pons, but excluding medulla. The climbing fiber terminals formed appropriate synapses with Purkinje cell dendritic spines. The findings suggest that when climbing fibers are introduced into cerebellar cultures, accurate functional and morphological units are established.


Impact of price and thickness on consumer selection of ribeye, sirloin, and top loin steaks.
Consumers (n=316) were recruited from college football picnickers to select ribeye, sirloin, and top loin steaks from 3 price groups based on thickness (n=10 steaks per price/type combination). Constant weight steaks were assigned to these groups: P1, thinnest, $19.80/kg ribeye and top loin, $10.99/kg sirloin; P2, average thickness, $22.00/kg ribeye and top loin, $13.19/kg sirloin; P3, thickest, $24.21/kg ribeye and top loin, $15.40/kg sirloin. Consumers selected 3 steaks per type and ranked selection criteria (price, color, marbling, thickness, texture). Percentage of steaks chosen from each price group did not differ (P>0.05), but consumers tended to select thinner ribeye steaks (P1 and P2) and thicker sirloin steaks (P2 and P3). Across all steak types, a greater number of consumers reported that marbling, color, and thickness were more important than price and visual texture. Data indicate that consumers may select steaks that display their preferred attributes, even if the steaks cost more.


[Established classification systems of posterior malleolar fractures : A systematic literature review].
Posterior malleolar fractures are found in almost 50% of all ankle fractures. The high clinical relevance of these joint fractures is explained by the significantly worse clinical and functional outcome. There is still a lack of unified opinion regarding the classification and treatment of these fractures. The aim of this article is to provide a systematic literature review of clinical studies that investigated posterior malleolar fractures and classified them using one of the three established classifications according to Haraguchi, Bartonicek/Rammelt, or Mason. PubMed was searched without time limits. The systematic literature search was performed according to the current criteria of Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA). The methodological quality of the included studies was quantified using the modified Coleman score. A total of 27 studies with a total of 2220 patients were included in this systematic literature review. Trimalleolar fractures showed a significantly less favorable prognosis than other ankle fractures. The quality of reduction was the most important prognostic factor for the clinical outcome. None of the three classifications examined has become established in the literature. Most of the classifications are weak or should not be used with respect to a derivable treatment algorithm or a prognosis with respect to the outcome. Only the classification according to Bartonicek/Rammelt is suitable to become established in the literature and in clinical practice due to its derivable treatment algorithm.


Exposure of rats to high concentrations of 1,1,1-trichloroethane and its effects on brain lipid and fatty acid composition.
Exposure of rats to 1,1,1-trichloroethane (TRI) (1200 p.p.m.) for 30 days resulted in changes in the fatty acid pattern of the brain ethanolamine phosphoglyceride. A decrease was observed in stearic acid (18:0) and arachidonic acid (20:4), while the 22-carbon (n-3) fatty acids were increased. These changes in the fatty acid pattern were similar to that observed previously in the rat for another solvent, perchloroethylene, at a lower exposure concentration (320 p.p.m). Both these solvents are little metabolised and it seems that a common mechanism exists whereby these solvents alter the fatty acid pattern of brain phospholipid upon exposure. The relatively low uptake of TRI makes a high exposure level (1200 p.p.m.) necessary to attain a blood concentration high enough for the changes to appear.


Radiotherapy for small cell carcinoma of the esophagus: outcomes and prognostic factors from a retrospective study.
Small cell carcinoma of the esophagus (SCCE) is characterized by its progressive feature and poor prognosis. There is no consensus on a standard therapeutic modality for SCCE. In this study, we aimed to characterize the outcomes of primary SCCE patients treated by radiation therapy as part of treatment and investigate prognostic factors. We retrospectively analyzed the data of 42 SCCE patients who were treated by RT as part of treatment at the Sun Yat-sen University Cancer Center from 2001 to 2014. The Kaplan-Meier and log-rank method were used to analyze survival. Cox's hazard regression model was applied to determine prognostic factors. Of the 42 enrolled patients, 25 had limited disease (LD) and 17 with extensive disease (ED). The overall response rate (CR + PR) was 60.0% (21/35). The median overall survival time (OS) for whole and LD group were 12.9 and 36.8 months. The 1-, 3- and 5-year OS rates of the whole cohort were 64.9, 31.3, and 13.9%, respectively. OS was significantly longer in patients with ECOG performance score (ECOG PS) < 2 (p = 0.001), lesion length ≤ 5 cm (p = 0.001), and LD (p = 0.049). In the patients with LD, multivariate analysis indicated that combined with chemotherapy (P = 0.046) and higher radiation dose (P = 0.027) predicted better prognosis in OS. The overall rate of grade 3-4 toxicities in the whole cohort was 37.5%. In total, 65% (17/26) patients with recurrent disease died with the metastasis with or without the primary recurrence. RT was one of the effective and safe treatments for locoregional control of SCCE. Lower ECOG PS score, shorter lesion length, treated with chemotherapy, and a higher dose of RT were identified as favorable independent prognostic factors.


Light scattering from cells: the contribution of the nucleus and the effects of proliferative status.
As part of our ongoing efforts to understand the fundamental nature of light scattering from cells and tissues, we present data on elastic light scattering from isolated mammalian tumor cells and nuclei. The contribution of scattering from internal structures and in particular from the nuclei was compared to scattering from whole cells. Roughly 55% of the elastic light scattering at high-angles (> 40 degrees) comes from intracellular structures. An upper limit of 40% on the fractional contribution of nuclei to scattering from cells in tissue was determined. Using cell suspensions isolated from monolayer cultures at different stages of growth, we have also found that scattering at angles greater than about 110 degrees was correlated with the DNA content of the cells. Based on model calculations and the relative size difference of nuclei from cells in different stages of growth, we argue that this difference in scattering results from changes in the internal structures of the nucleus. This interpretation is consistent with our estimate of 0.2 micron as the mean size of the scattering centers in cells. Additionally, we find that while scattering from the nucleus accounts for a majority of internal scattering, a significant portion must result from scattering off of cytoplasmic structures such as mitochondria.


No age-related changes in human benzodiazepine receptor binding measured by PET with [11C]Ro 15-4513.
The effects of age on the binding of [11C]Ro 15-4513, a partial inverse agonist of the central benzodiazepine receptor, were studied. Sixteen healthy male volunteers (21-78 years old) participated. Regional radioactivity in the brain was followed for 45 min by positron emission tomography after a bolus injection of [11C]Ro 15-4513. Similar tracer kinetics were observed in both young and old subjects. For the quantification of receptor binding in vivo, a compartment model, in which radioactivity in the pons was used as an input function, was applied. There were no significant changes in the binding potentials with age (P > 0.1) in ten brain regions. These observations delineate an interesting difference between central benzodiazepine (BZ) receptors and other neurotransmitter receptors in the human brain measured by PET that have been shown to have a reduction with age.


A histochemical demonstration of the Na+ + K+-ATPase activity in the thyroid and the effect of cyclic adenosine monophosphate (c-AMP).
With a suitable modification of the Farquhar and Palade technique the Na+ + K+-ATPase activity in guinea-pig thyroid is demonstrated. The addition of c-AMP (5 X 10(-6) M or 1.5 X 10(-5) M) to the incubation media produced an apparent intensification of the Na+ + K+ -ATPase activity in the thyroid.


Mesoporous bioactive glasses for bone healing and biomolecules delivery.
Impact of bone diseases and injury is increasing at an enormous rate during the past decades due to increase in road traffic accidents and other injuries. Bioactive glasses have excellent biocompatibility and osteoconductivity that makes it suitable for bone regeneration. Researches and studies conducted on several bioactive glasses gives an insight on the need of multi-disciplinary approaches involving various scientific fields to attain its full potential. Of late, a next generation bioactive glass called as mesoporous bioactive glass (MBG) has been developed with higher specific surface area and control over mesoporous structure that presents a new material for bone regeneration. A brief discussion and overview on the potential use of MBG as a suitable material for bone tissue regeneration and biomolecule delivery is included. Additionally, possible control of the structural and functional property based on composition and fabrication techniques are also covered. According to recent researches, MBG-implant interaction with bone forming cells for cellular growth and differentiation as well as its effect on delivery of growth factor, both in vitro and in vivo, are optimistic; yet, the complete efficacy of this material is still to be explored. Hence, in this article we will review the current development and its applications for bone tissue engineering (TE).


Superabsorbent sodium carboxymethyl cellulose membranes based on a new cross-linker combination for female sanitary napkin applications.
The main intent of this investigation was to retain the strength and superabsorbency of natural and non-toxic biodegradable polymers using an innovative combination of cross-linkers for application as the absorbent core of sanitary napkins. For this, sodium carboxymethyl cellulose (NaCMC) and starch were blend to form membranes by phase inversion and lyophilisation, using an optimized cross-linker combination of sodium trimetaphosphate (STMP) and aluminium sulphate (AlS). Optimal cross-linking of NaCMC and starch hampered membrane dissolution and disintegration, yielding a microtextured surface morphology. The membranes were biodegradable and yet possessed the requisite flexibility and mechanical strength for the proposed application, without compromise of superabsorbency. Lyophilised membranes possessed higher immediate water and blood sorption with ∼50% water retention capabilities when compared to the phase inversion technology. The results suggest that the developed membranes can be a cost-effective degradable alternative to the commercial polyacrylate-based nonbiodegradable sanitary products.


Partial oxidations with NO(2) catalyzed by large gold particles.
Large gold particles catalyze alkene epoxidation by NO(2) under mild conditions, oxygen adatoms being the likely active species.


Coronary arteriography; method of presentation of the arteriogram report and a scoring system.
A coronary arteriographic report presentation consisting of a diagram on which the radiologist draws the coronary arterial anatomy of each individual case is described. The diagram allows a clear visual presentation of all the information gained from the analysis of the original arteriographic study including anatomical variations, the position and importance of each artery in terms of the myocardium it supplies, the sites and severity of obstructions and the presence of collateral pathways. A myocardial scoring system which expresses the severity of left ventricular arterial obstructive disease is also presented. The myocardial score takes into account not only the degree of stenosis of any number of arterial branches, but also their importance in terms of the amount of myocardium supplied.


Iatrogenic entrapment of the femoropopliteal bypass.
Three cases of infragenicular femoropopliteal bypass grafts are presented in which iatrogenic entrapment of the distal portion of the graft occurred between the medial head of the gastrocnemius muscle and the posterior surface of the tibia. The condition should be suspected if ischemia of the leg develops postoperatively when the knee is hyperextended and is improved when the knee joint is flexed. Measurements of the ankle pressure index or Pulse Volume Recorder tracings at the ankle in both flexed and extended positions will confirm the diagnosis. The entrapment of the bypasses in these three patients was easily corrected by transection of the medial head of the gastrocnemius muscle. Relief of the occlusion of the bypass can be easily demonstrated by noninvasive studies.


Enhanced TGF-beta1 is involved in 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induced oxidative stress in C57BL/6 mouse testis.
2,3,7,8-Tedtrachlorodibenzo-p-dioxin (TCDD) is one of the most toxic endocrine disruptors and has been reported to induce oxidative stress in the reproductive organs. However, the mechanism by which TCDD induces oxidative stress is unclear. The aim of this study is to examine the role of the general cytokine, TGF-beta1, in TCDD-induced oxidative stress in the male reproductive system. To examine the effect of TCDD on antioxidant enzyme activity, we administered TCDD orally to C57BL/6 mice at 1 microgkg/day for 4 days. Using Smad2-siRNA, we examined the involvement of Smad and non-Smad pathways in TCDD-induced oxidative stress. We also measured the mRNA levels of typical antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase) and analyzed the activation of TGF-beta1, and the downstream signals, Smad2, Smad4, transcription factors (c-Jun, ATF3), and three major MAPKs (JNK, ERK, p38). After TCDD treatment, the mRNA levels of antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase) were significantly decreased. In addition, TGF-beta1 activity increased and the receptor-activated protein, Smad2, was activated while Smad4 was not. The levels of major transcription factors, c-Jun and ATF3, and the regulator of these transcription factors, MAPK, were also increased by TCDD administration. The mRNA levels of the 3 antioxidant enzymes in the Smad2-siRNA and TCDD co-treated group were higher than that of the TCDD-only treated group but still decreased when compared to control. C-Jun and ATF3 levels were also increased in Smad2-siRNA and TCDD co-treated testes compared to control. However, the levels of c-Jun and ATF3 were lower than those in the group treated with TCDD only. Of the three MAPKs which showed increase in expression after TCDD treatment, p38 was the only one that showed a decrease with Smad2 inhibition, while both ERK and JNK expression were unaffected. In conclusion, we found that the activated TGF-beta1-Smad pathway is involved in TCDD-induced oxidative stress. Furthermore, the effects of TCDD on the testes are caused by the coordinated action of both Smad and non-Smad pathways.


Process intensification approaches in wastewater and sludge treatment for the removal of pollutants.
Process Intensification (PI) is the modification or integration of conventional or novel processes within a single unit operation in order to improve product quality and reduce waste. PI offers numerous advantages, including a reduction in the initial and operational costs, an improvement in product quality/quantity, the generation of less waste, and an increase in process safety. The synergistic effect of PI in comparison to the conventional procedure ensures maximizing resource efficiency. PI can be accomplished in two ways: either by integrating various processes or by modifying the design of equipment to improve operational efficiency. In this regard, the present review provides a comprehensive insight into the application of PI in wastewater and sludge treatment methods and discusses the operational advantages. This review provides a comprehensive list of different PI approaches applied in wastewater and sludge treatment to remove pollutants and the various equipment, techniques and reactors used in PI. The second section addresses the challenges of PI in wastewater treatment that removes dyes, pesticides, organic and inorganic pollutants, micro- and nano-plastics, persistent organic pollutants, pharmaceutical and personal care pollutants.


[Renal-urinary calculosis in children. Its etiology, pathogenesis, pathological anatomy, clinical picture and diagnosis].
The paper points the etiological, pathogenetical and anatomo-pathological aspects of children's urolithiasis. A special attention was made a clinical symptomatology and a diagnosis scheme.


Effect of lentiviruses carrying enhanced green fluorescent protein injected into the scala media through a cochleostomy in rats.
The purposes of the current study were to assess the feasibility of post-auricular microinjection of lentiviruses carrying enhanced green fluorescent protein (EGFP) into the scala media through cochleostomies in rats, determine the expression of viral gene in the cochlea, and record the post-operative changes in the number and auditory function of cochlear hair cells (HCs). Healthy rats were randomly divided into two groups. The left ears of the animals in group I were injected with lentivirus carrying EGFP (n=10) via scala media lateral wall cochleostomies, and the left ears of the animals in group II were similarly injected with artificial endolymph (n=10). Prior to and 30 days post-injection, auditory function was assessed with click-auditory brainstem response (ABR) testing, EGFP expression was determined with cochlear frozen sections under fluorescence microscopy, and survival of HCs was estimated based on whole mount preparations. Thirty days after surgery, click-ABR testing revealed that there were significant differences in the auditory function, EGFP expression, and survival of HCs in the left ears before and after surgery in the same rats from each group. In group I, EGFP was noted in the strial marginal cells of the scala media, the organ of Corti, spiral nerves, and spiral ganglion cells. Lentiviruses were successfully introduced into the scala media through cochleostomies in rats, and the EGFP reporter gene was efficiently expressed in the organ of Corti, spiral nerves, and spiral ganglion cells.


Formes multiples de la lysyl-tARN-ligase de levure et leurs sous-unites.
When Yeast lysyl-tRNA-ligase is extracted in the presence of protease inhibitor (PMSF) a homogeneous species of enzyme is obtained, the subunits of which have a mass of 70 000 daltons. Endogenous degradation produces lighter active species of the enzyme, dimers with subunits in the range 50 000-60 000 daltons. Partial trypsinolysis mimics this degradation, which is therefore thought to occur through proteolysis.


A self-selected 16:8 time-restricted eating quasi-experimental intervention improves various markers of cardiovascular health in middle-age male cyclists.
Time-restricted eating (TRE) is a dietary intervention that may offer some protection against cardiovascular disease (CVD), while also preserving performance in athletes. To date however, research on TRE in an active population has only been conducted in college-age cohorts and the effects of TRE in an older, trained population are less understood. Therefore, the aim of this study was to compare the effects of a 4-wk, 16:8 TRE intervention on markers of CVD risk in middle-age, male cyclists. Participants (N = 12; age, 51.9 ± 8.6 y; training duration/wk, 375 ± 140 min; peak aerobic capacity, 41.8 ± 5.6 mL/kg/min) reported to the laboratory for two sessions (i.e., at baseline and post-TRE) where blood was drawn from an antecubital vein after an 8-h overnight fast. Dependent variables measured at baseline and post-TRE included insulin, cortisol, brain-derived neurotropic factor, free testosterone, thyroxine, triiodothyronine, C-reactive protein, advanced oxidative protein products, glutathione, tumor necrosis factor (TNF)-α, glucose, and a full lipid profile. Compared with baseline, TRE significantly lowered TNF-α (12.3 ± 3.4 versus 9.2 ± 2.4 pg/mL; P = 0.02) and glucose concentrations (93.4 ± 9.7 versus 87.5 ± 7.9 mg/dL; P = 0.01), as well as significantly elevated high-density lipoprotein cholesterol levels (45.7 ± 13.7 versus 49.2 ± 12.3 mg/dL; P = 0.04), respectively. No further significant changes were observed between the remaining variables (all P > 0.05). Overall, these data suggest that incorporating a 4-wk TRE intervention with habitual endurance training can significantly improve some markers of CVD risk and may compliment the robust health benefits derived from a regular exercise regimen.


The role of BCG vaccine in tuberculosis control.
The present communication deals with the various important issues about the BCG vaccine being using for the control of tuberculosis. The first issue is of BCG vaccine. BCG daughter strains, namely, French, Glaxo, Japanese and many others, inspite of minor differences evoke similar immune responses and none of the strains is superior to other.


Splenic arteries and veins in pediatric sickle cell disease.
The goal of this study was to verify the existence and prevalence of large vessel lesions outside the central nervous system in young patients with sickle cell disease. Thus, 17 spleens resected because of episodes of sequestration or infarction and 41 controls were studied. Anomalies of arteries and veins were detected in all spleens from sickle cell disease patients, but no definite correlation with age, sex, type of sickle hemoglobin, or frequency of sequestration episodes could be established. The most consistent lesions were intimal proliferation affecting large arteries and veins, reduplication of the internal elastic lamina of large arteries, and a lesion not previously documented in this condition, that of subendothelial infiltration of the large veins by activated T cells. Endotheliitis showing some similarity with the one seen in sickle cell disease spleens was noted in 5 of 41 spleens of patients who did not suffer from sickle cell disease. However, when present it was usually mild. Very limited damage to the arterial elastica was noted in only 1 of the 41 controls. Minimal endothelial proliferation was seen in 2 of 41 controls.


Five genes as a novel signature for predicting the prognosis of patients with laryngeal cancer.
In this study, we purpose to investigate a novel five-gene signature for predicting the prognosis of patients with laryngeal cancer. The laryngeal cancer datasets were obtained from The Cancer Genome Atlas (TCGA). Both univariate and multivariate Cox regression analysis was applied to screening for prognostic differential expressed genes (DEGs), and a novel gene signature was obtained. The performance of this Cox regression model was tested by receiver operating characteristic (ROC) curves and area under the curve (AUC). Further survival analysis for each of the five genes was carried out through the Kaplan-Meier curve and Log-rank test. Totally, 622 DEGs were screened from the TCGA datasets in this study. We construct a five-gene signature through Cox survival analysis. Patients were divided into low- and high-risk groups depending on the median risk score, and a significant difference of the 5-year overall survival was found between these two groups (P < .05). ROC curves verified that this five-gene signature had good performance to predict the prognosis of laryngeal cancer (AUC = 0.862, P < .05). In conclusion, the five-gene signature consist of EMP1, HOXB9, DPY19L2P1, MMP1, and KLHDC7B might be applied as an independent prognosis predictor of laryngeal cancer.


Voice Needs and Voice Demands of Professional Newsreaders in Southern India.
Newsreaders are elite vocal professionals who are highly dependent on their voice quality to meet professional commitments. Globally, the voice needs and demands of newsreaders could vary depending on technology and cultural variations. This study documents voice demands, voice needs, and vocal and nonvocal habits of professional newsreaders in Chennai, southern India through a questionnaire-based interview. Prospective, case-control study design. Forty-seven professional newsreaders and 47 non-newsreaders participated in the questionnaire-based interview that elicited information relevant to their profession and voice use. Majority of the newsreaders were not formally trained for newsreading. A significantly larger percentage of female newsreaders felt their jobs to be vocally demanding. Most newsreaders also had other full-time jobs that required a lot of speaking. Ninety-four percent of newsreaders consciously altered their voices while rendering news, and majority of them reported their voices to have changed considerably since they began newsreading. When compared with non-newsreaders, a significantly larger number of newsreaders were aware of voice problems, and many experienced some type of vocal technical difficulties. Seventy-seven percent of newsreaders took active measures to conserve their voice as opposed to non-newsreaders. Majority reported that sitting upright and erect while reading news helped produce the best vocal output for newsreading. The findings on voice needs and vocal and nonvocal habits among newsreaders in Chennai, India, provide valuable first-time information from this part of the world. These have potential application for voice professionals, voice trainers, and prospective aspirant newsreaders in developing strategies for voice care and in preventing voice problems.


Obesity and Diabetic Complications: A Study from the Nationwide Diabetes Report of the National Program for Prevention and Control of Diabetes (NPPCD-2021) Implications for Action on Multiple Scales.
Obesity plays a major role in the pathogenesis and development of macro- and microvascular complications of type 2 diabetes (T2D) and type 1 diabetes (T1D). We aimed to assess the association between obesity and macrovascular and microvascular complications of diabetes. This study consisted of 111,830 patients (age range: 1-106) with diabetes including 10,641 T1D (3187 obese [38.2% men] and 7454 non-obese [45.5% men]) and 101,189 T2D (51,873 obese [27.5% men] and 49,316 non-obese [33.4% men]) from the National Program for Prevention and Control of Diabetes (NPPCD-2021) in Iran, who attended academic tertiary care outpatient clinics from February 2016 to April 2021. A pooled logistic regression model was used to examine the association between obesity and diabetic complications. Among patients with T1D, a significant association was found between obesity and cardiovascular disease (CVD), neuropathy, nephropathy and retinopathy (OR= 1.75, 1.56, 1.80 and 1.92, P-value= 0.001, 0.004, 0.001 and <0.001, respectively). In T2D, a statistically significant association was found between obesity and CVD, neuropathy and nephropathy (OR= 1.63, 1.98, 1.21, respectively, P-values <0.001). Obesity was independently associated with CVD, neuropathy and nephropathy in patients with T1D and T2D and with retinopathy only in T1D, to different degrees. The association between obesity and retinopathy and neuropathy was the strongest among T1D and T2D, respectively. Findings from this study suggest that obesity affects diabetic complications differently among the two types of diabetes, in terms of epidemiology and pathophysiology. This signifies the importance of different preventive and therapeutic approaches to obesity in T1D compared to T2D, on a national and global scale.


Blood group antigens in the intrahepatic biliary tree. I. Distribution in the normal liver.
The distribution of six blood group-related antigens, A, B, H, Lea, Leb and sialylated Lea antigens, in the intrahepatic biliary tree was studied. These carbohydrate antigens in fixed normal liver tissues were immunostained with the use of highly specific monoclonal antibodies in an avidin-biotin-peroxidase complex method. Bile ducts expressed both ABH and Lewis blood group antigens. However, only Lewis blood group antigens could be detected in the bile ductules. Canaliculo-ductular junctions could be clearly delineated with the anti-Lewis blood group antibodies, especially with anti-Lea antibody. Small Lewis antigen-positive cells were scattered intralobularly. They were adjacent to parenchymal liver cells, mainly in Rappaport zone 1, and apparently in continuity with the portal biliary tree. Sialylated Lea antigen was found in some septal bile ducts. No blood group antigen could be detected in the bile canaliculi. These results indicate that (1) biliary tract of a given size has its own pattern of blood group antigen expression, and (2) biliary epithelial cells are not identical with regard to the phenotypic expression of their structural carbohydrates. In future, it will be possible to classify biliary epithelial cells by their blood group antigen expression.


JTE-522, a cyclooxygenase-2 inhibitor, is an effective chemopreventive agent against rat experimental liver fibrosis1.
The aim of this study was to assess the effects of cyclooxygenase (COX)-2 inhibition on rat experimental liver fibrogenesis. We investigated the inhibitory effects of a selective COX-2 inhibitor, JTE-522, on liver fibrosis induced by a choline-deficient, l-amino acid-defined diet (CDAA). Inhibitory effect was also tested in a second model of thioacetamide (TAA)-induced liver fibrosis. CDAA induced liver fibrosis and preneoplastic foci at 12 weeks and cirrhosis at 36 weeks. Hepatocellular carcinoma was noted in 13 of 15 rats (87%). JTE-522 significantly inhibited fibrosis and development of preneoplastic lesions in a dose-dependent manner and completely inhibited generation of cirrhosis and hepatocellular carcinoma at both low and high doses (10 and 30 mg/kg body wt/day, respectively). JTE-522 administrated only from 12 weeks to 36 weeks also prevented cirrhosis and formation of hepatocellular carcinoma. JTE-522 itself did not cause local or systemic gross or histopathologic changes at 36 weeks. Mechanistic studies indicated that the CDAA model displayed up-regulation of several biomarkers, including COX-2, arachidonate metabolite (prostaglandin E(2)), serum aspartate aminotransferase, and c-myc expression. The model also showed an increased proportion of activated hepatic stellate cells, proliferating cell nuclear antigen index, and CD45-positive inflammatory cells in the liver. JTE-522 effectively diminished these changes. JTE-522 exhibited similar antifibrosis effects in the TAA model. Our results suggest that COX-2 is involved in CDAA- and TAA-induced liver fibrosis. Our data also indicate that JTE-522 is a potent chemopreventive agent of rat liver fibrosis with low toxicity.


Mechanism of a clinically relevant protocol to induce tolerance of cardiac allografts. Perioperative donor spleen cells plus cyclosporine suppress IL-2 and interferon-gamma production.
Many groups have reported that preoperative injection of donor-derived whole spleen cells or major histocompatibility complex antigens prolongs organ allograft survival in experimental models, but the immunosuppressive mechanism(s) responsible remains unclear. A central, confounding issue is how to reconcile documentation of comparable levels of mRNA for IL-2 in suppressed versus control groups with obvious host hyporesponsiveness. We used a model of tolerance induction involving perioperative injection of donor spleen cells and injection of CsA at day 2 after transplant to analyze the serial expression of several proinflammatory cytokines relevant to development of alloresponsiveness within cardiac allografts and recipients' spleens. Four experimental groups of Lewis rats receiving vascularized heterotopic cardiac allografts from Brown Norway (BN) donors were evaluated: (1) untreated controls; (2) animals receiving intraoperative injection of donor BN spleen cells; (3) those receiving a single injection of CsA on day 2 post-Tx; and (4) animals given the combination of intraoperative BN spleen cells and CsA on day 2 post-Tx. Graft survival was significantly prolonged in Lewis rats receiving the combined spleen cell/CsA therapy (mean 64 days, with 40% of grafts surviving > 100 days, n = 15) compared with acute rejection at about 8 days (range 6-13, n = 20) in each of the 3 control groups (P < 0.0001). By comparison with acutely rejecting allografts in the control untreated group at day 7 post-Tx, allografts in rats receiving the combined perioperative spleen cell/CsA treatment showed (1) significantly reduced graft cellularity and interstitial edema; (2) significantly decreased features of immune activation, including infiltration by mononuclear cells expressing IL-2R or proliferating cell nuclear antigen; (3) decreased intragraft expression of the cytokines IL-2 and IFN-gamma; and (4) suppression of endothelial activation as evidenced by both failure of up-regulation of intracellular adhesion molecule-1 and maintenance of thrombomodulin expression by graft endothelium. Analysis of sections of recipients' spleens showed that spleen cell/CsA therapy led to significant reductions versus untreated controls, in expression of IL-2, IFN-gamma, and IL-2R. Similarly, mixed lymphocyte response cultures showed that responder cells from rats receiving combined therapy proliferated by 93-95% less than untreated animals. Our results suggest that the efficacy of this clinically relevant protocol is associated with suppression of IL-2 or IFN-gamma protein production, and that in the absence of such molecules, it appears that T cell-receptor occupancy by alloantigens readily induces a state of anergy in vivo.


Integrative effects of dystrophin loss on metabolic function of the mdx mouse.
Duchenne muscular dystrophy (DMD) is a disease marked by the development of skeletal muscle weakness and wasting. DMD results from mutations in the gene for the cytoskeletal protein dystrophin. The loss of dystrophin expression is not limited to muscle weakness but has multiple systemic consequences. Managing the nutritional requirements is an important aspect of the clinical care of DMD patients and is complicated by the poor understanding of the role of dystrophin, and dystrophic processes, in regulating metabolism. Here, we show that mdx mice, a genetic model of DMD, have significantly reduced fat mass relative to wild type C57BL/10. The alteration in body composition is independent of the presence of skeletal muscle disease, as it is still present in mice with transgenic expression of a fully-functional dystrophin in skeletal muscle. Furthermore, mdx mice do not increase their fat mass or body weight when housed under thermoneutral conditions, in marked contrast to C57BL/10 mice. We also demonstrated that mdx mice have significantly reduced fat metabolism and altered glucose uptake. These significant metabolic changes in dystrophic mice implicate dystrophin as an important regulator of metabolism. Understanding the metabolic functions of dystrophin is important for managing the nutritional needs of DMD patients.


Glucose metabolism gene polymorphisms and clinical outcome in pancreatic cancer.
Altered glucose metabolism is the most common metabolic hallmark of malignancies. The authors tested the hypothesis that glucose metabolism gene variations affect clinical outcome in pancreatic cancer. The authors retrospectively genotyped 26 single nucleotide polymorphisms from 5 glucose metabolism genes in 154 patients with localized disease and validated the findings in 552 patients with different stages of pancreatic adenocarcinoma. Association between genotypes and overall survival (OS) was evaluated using multivariate Cox proportional hazard regression models with adjustment for clinical predictors. Glucokinase (GCK) IVS1 + 9652C > T and hexokinase 2 (HK2) N692N homozygous variants were significantly associated with reduced OS in the training set of 154 patients (P < .001). These associations were confirmed in the validation set of 552 patients and in the combined dataset of all 706 patients (P ≤ .001). In addition, HK2 R844K variant K allele was associated with a better survival in the validation set and the combined dataset (P ≤ .001). When data were further analyzed by disease stage, glutamine-fructose-6-phosphate transaminase (GFPT1) IVS14-3094T>C, HK2 N692N and R844K in patients with localized disease and GCK IVS1 + 9652C>T in patients with advanced disease were significant independent predictors for OS (P ≤ .001). Haplotype CGG of GPI and GCTATGG of HK2 were associated with better OS, respectively, with P values of .004 and .007. The authors demonstrated that glucose metabolism gene polymorphisms affect clinical outcome in pancreatic cancer. These observations support a role of abnormal glucose metabolism in pancreatic carcinogenesis.


Efficacy of perampanel in pediatric epilepsy with known and presumed genetic etiology.
The efficacy of perampanel (PER) in pediatric epilepsy with specific etiologies has not been well established. Here, we investigated outcome and predictors of PER treatment in a pediatric cohort with known and presumed genetic etiology. We included pediatric patients with potential genetic epilepsy who received PER treatment and underwent whole-exome sequencing (WES) from January 2020 to September 2021. All patients were followed up for >12 months. A total of 124 patients were included. Overall response rates were 51.6% and 49.6% at 6 months and 12 months, respectively. Pathogenic or likely pathogenic variants in 27 multiple genes were detected among 58 patients (46.8%) by WES. On performing multivariate logistic regression analysis, only developmental delay (OR = 0.406, P = 0.042) was a negative predictor of treatment response. However, the seizure onset age, positive WES results, and number of ASMs before PER administration were not significantly. Thirteen carriers with variants in the SCN1A gene showed a better response compared to eight patients with other sodium channels (P = 0.007), and to the other 45 patients with positive WES results (OR = 7.124, 95% CI = 1.306-38.860, P = 0.023). Adverse events were only reported in 23 patients, the most common being emotional problems. PER is safe and efficacious in pediatric patients with known and presumed genetic etiology. The response rate is comparable to that reported in other pediatric populations, and lower among those with developmental delay. A gene-specific response to PER is found along with better efficacy links to pathogenic variants in the SCN1A gene.


Dynamic online surveys and experiments with the free open-source software dynQuest.
With computers and the World Wide Web widely available, collecting data through Web browsers is an attractive method utilized by the social sciences. In this article, conducting PC- and Web-based trials with the software package dynQuest is described. The software manages dynamic questionnaire-based trials over the Internet or on single computers, possibly as randomized control trials (RCT), if two or more groups are involved. The choice of follow-up questions can depend on previous responses, as needed for matched interventions. Data are collected in a simple text-based database that can be imported easily into other programs for postprocessing and statistical analysis. The software consists of platform-independent scripts written in the programming language PERL that use the common gateway interface between Web browser and server for submission of data through HTML forms. Advantages of dynQuest are parsimony, simplicity in use and installation, transparency, and reliability. The program is available as open-source freeware from the authors.


Fermentation of lactose and its constituent sugars by Escherichia coli WDHL: impact on hydrogen production.
Fermentations of lactose, glucose and galactose using Escherichia coli WDHL, a hydrogen over producer strain, were performed. With glucose as substrate pyruvate was mainly routed to the lactate pathway, resulting in hydrogen production and yield of 1037 mL and 0.30 mol H(2)/mol of glucose, respectively. When galactose was the substrate, the pyruvate formate lyase pathway was the main route for pyruvate and a fermentation yield of 1.12 mol H(2)/mol of galactose and a hydrogen production of 2080 mL were obtained. The fermentation of lactose or glucose plus galactose showed a similar yield of 1.02 mol H(2)/mol of hexose consumed. This work clearly demonstrated that the kinetics of hydrogen and metabolites production as well as the hydrogen yield were affected by the type of sugar used as substrate as reflected by the deviations from the metabolic hydrogen-production pathway.


Effects of odanacatib on bone matrix mineralization in rhesus monkeys are similar to those of alendronate.
Odanacatib (ODN) is a selective and reversible inhibitor of cathepsin K which is an important enzyme for the degradation of collagen I. Aim of the present work was the head-to-head comparison between the effects of ODN and alendronate (ALN) on bone mineralization density distribution (BMDD), based on quantitative backscattered electron imaging in relation to changes in histomorphometric mineralizing surface per bone surface (MS/BS) in 12-22 years old ovariectomized rhesus monkeys. Trabecular and cortical BMDD derived parameters from vertebrae and proximal tibiae were compared among vehicle (VEH, n = 8), odanacatib low dose (ODN-L, n = 8), odanacatib high dose (ODN-H, n = 8), and alendronate (ALN, n = 6) treated animals. Additionally, data from an intact, non-treated group of animals are shown (INT, n = 8). In trabecular bone from the vertebra and metaphyseal tibia, the BMDD of the ODN and ALN treatment groups was shifted toward higher mineralization densities (p < 0.001) consistent with the significant reduction of MS/BS (p < 0.05 in ODN-H and ALN) compared to VEH. Vertebral trabecular CaMean (average degree of mineralization) was significantly higher in ODN-L (+ 6.5%), ODN-H (+ 6.1%), and ALN (+ 6.7%, all p < 0.001). Tibial osteonal cortical bone revealed also significantly increased CaMean for ODN-L (+ 1.4%, p < 0.05), ODN-H (+ 2.2%, p < 0.05), and ALN (+ 3.4%, p < 0.001) versus VEH, while primary cortical bone (devoid of secondary osteons) did not show any significant differences between the study groups. The percentage of primary bone area in the tibial cross-sections (on average 45 ± 12%) was also not significantly different between the study groups (p = 0.232). No significant differences in any BMDD parameters of all studied skeletal sites between ODN and ALN treatment were found. Correlation analysis revealed that MS/BS was highly predictive for trabecular BMDD in vertebral bone. The higher MS/BS, the lower was CaMean. Our findings are consistent with the inhibition of bone resorption of ODN and ALN in trabecular and osteonal compartments.


Corticosteroids stimulate an increase in phospholipase A2 inhibitor in human serum.
A corticosteroid induced increase in a circulating inhibitor of serum phospholipase A2 activity is described. Inhibitor activity was found to be normally present in serum in agreement with the findings of other workers, and this activity was significantly increased by either acute or chronic administration of corticosteroids. The possible relation of this inhibitor to the known inhibitory effects of lipocortin and sphingomyelin on phospholipase A2 activity is briefly discussed.


Contrast media in intussusception.
Pediatric radiologists in 40 children's hospitals in North America were interviewed to determine their choice of contrast media in the diagnosis and treatment of intussusception. The respondents indicated that barium was utilized in the vast majority of instances. Almost all indicated that they would proceed with barium enema even if there is unequivocal evidence of small bowel obstruction on the plain film examination. In over 14,000 cases of intussusception, there were 55 perforations, an incidence of approximately 1 in 250. The perforations in general were well tolerated, although there was one death.


The emotional counting Stroop paradigm: a functional magnetic resonance imaging probe of the anterior cingulate affective division.
The emotional counting Stroop (ecStroop) functional magnetic resonance imaging (fMRI) activation paradigm was designed to recruit the anterior cingulate affective division (ACad). Nine normal, healthy male and female subjects (mean age 24.2 years) reported via button press the number of neutral and negative words that appeared on a screen while reaction time and fMRI data were acquired. We observed a) greater ACad activation for negative versus neutral words during initial presentation blocks; b) lower overall ACad signal intensity during task performance (i.e., both negative and neutral words) compared to the baseline fixation condition; and c) no reaction time increase to negative versus neutral words. In a companion study of a cognitive version of the counting Stroop (Bush et al 1998), these same 9 subjects a) activated the more dorsal anterior cingulate cognitive division; b) also showed the overall decrease in ACad signal intensity; and c) demonstrated a reliable reaction time effect. Taken together, these data offer a within-group spatial dissociation of AC function based upon information content (i.e., cognitive vs. emotional) and/or presence of behavioral interference. We propose that the ecStroop will be a useful fMRI probe of ACad function in anxiety disorders.


Potential antioxidant mechanism of action for metronidazole: implications for rosacea management.
Chronic inflammation is believed to account for some symptoms of rosacea. The efficacy of topical metronidazole in the treatment of rosacea may be due to its antimicrobial as well as anti-inflammatory activity. Neutrophils release potent inflammatory mediators, including reactive oxygen species (ROS), and intrafollicular neutrophils have been observed in stage II disease. ROS and other free radicals may contribute to intrinsic and extrinsic aging, both of which accentuate clinical manifestations of rosacea. If, as in vitro data suggest, metronidazole has antioxidant activity, it may help subdue the oxidative tissue damage of intrinsic and extrinsic aging as well as prevent and treat rosacea symptoms.


Hyperlipidemia in COPD is associated with decreased incidence of pneumonia and mortality: a nationwide health insurance data-based retrospective cohort study.
COPD is often associated with various comorbidities that may influence its outcomes. Pneumonia, cardiovascular disease (CVD), and cancer are the major causes of death in COPD patients. The objective of this study is to investigate the influence of comorbidities on COPD by using the Taiwan National Health Insurance database. We retrospectively analyzed the database in 2006 of one million sampling cohort. Newly diagnosed patients with COPD with a controlled cohort that was matched by age, sex, and Charlson comorbidity index (CCI) were included for analysis. In total, 1,491 patients with COPD were included for analysis (61.8% male). Patients with COPD had higher incidences of pneumonia (25.7% vs 10.4%; P<0.0001), CVD (15.1% vs 10.5%; P<0.0001), and mortality rate (26.6% vs 15.8%; P<0.001) compared with the control group in the 4-year follow-up. In patients with COPD, CCI ≥3 have a higher incidence of pneumonia (hazard ratio [HR] 1.61; 95% confidence interval [CI] 1.23-2.09; P<0.0001), CVD (HR 1.73; 95% CI 1.24-2.41; P=0.001), and mortality (HR 1.12; 95% CI 1.12-1.83; P=0.004). Among the major comorbidities of COPD, hyperlipidemia was associated with decreased incidence of pneumonia (HR 0.68; 95% CI 0.5-0.93; P=0.016) and mortality (HR 0.64; 95% CI 0.46-0.90; P=0.009), but was not associated with increased risk of CVD (HR 1.10; 95% CI 0.78-1.55; P=0.588). Our results demonstrate that COPD is associated with increased incidence of pneumonia, CVD, and mortality. In patients with COPD, higher CCI is associated with increased incidence of pneumonia, CVD, and mortality. However, COPD with hyperlipidemia is associated with decreased incidence of pneumonia and mortality.


The role of the responsiveness of animal stock to certain secretagogues in evaluating antisecretory drugs. Experiments in the lumen-perfused rat.
The gastric secretion pattern resulting from histamine, pentagastrin and carbachol infusion was studied in lumen-perfused anesthetised male Wistar rats. The differences between the results of this study and other published results and among the latter demonstrate the necessity of knowing the acid secretion patterns in given laboratory conditions before attempting to assess the antisecretory activity of any drug.


Is it worthwhile to fully evaluate the stomach in every ultrasound examination of the abdominal cavity?
To evaluate the usefulness of abdominal sonography in the fasting state with no hypotonic agents in the detection and exclusion of gastric lesions. One-hundred patients with normal upper gastrointestinal endoscopy, 94 patients with a major gastric abnormality (including 59 intraluminal tumors, three submucosal masses, 29 ulcers, two polyps and one hypertrophied gastric mucosa) and 75 patients with minor gastric abnormalities (mainly gastritis) were enrolled into the study. Of the 100 normal patients, ultrasound showed four false positive results with 96% specificity of the examination. Within the major gastric lesion group, ultrasound was true positive in 55 of 59 tumors, 15 of 29 ulcers, three of three submucosal masses and the case of giant gastric mucosa. It was negative in the detection of gastric polyps. It could detect only 8% of minor gastric abnormalities. Abdominal sonography in the fasting state, if carefully performed, is sufficiently accurate in detection and exclusion of major gastric lesions. Therefore, although it cannot replace endoscopic and barium studies of the stomach, careful evaluation of the stomach is recommended in every sonographic evaluation of the abdominal cavity.


Surgical Treatment of Nasal Obstruction in Rhinoplasty.
The key to a successful septorhinoplasty includes an understanding of nasal anatomy and physiology. This allows the surgeon the ability to properly address both form and function during the operation. History and physical examination are paramount in diagnosing and subsequently treating the epicenter of obstruction, which is commonly found among the internal and external nasal valve, the septum, or the turbinates. Treatment of each of these areas is nuanced and multiple approaches are discussed to provide an understanding of the current surgical techniques that allow for excellent functional and cosmetic rhinoplasty results.


Cytogenetic studies in wheat. XV. Location of rust resistance genes in VPM1 and their genetic linkage with other disease resistance genes in chromosome 2A.
Inheritance studies showed that the VPM1-derived seedling resistances to stem rust, stripe rust, leaf rust, and powdery mildew were controlled by single genes; the genes for rust resistance were designated Sr38, Yr17, and Lr37, respectively, whereas the gene for resistance to powdery mildew was postulated to be Pm4b. Sr38, Yr17, and Lr37 were shown to be closely linked and distally located in the short arm of chromosome 2A. They showed very close repulsion linkage with Lr17 and were genetically independent of other genes known to be located in chromosome 2A. Previously unmapped, Yr1 appeared to be distally located in the long arm of chromosome 2A.


Woman with Sickle Cell Disease with Current Sigmoid Sinus Thrombosis and History of Inadequate Warfarin Use during a Past Thrombotic Event.
We report a 20-year-old woman with sickle cell disease (SCD) who presented with a severe pulsating headache, nausea, and vomiting. Her history was significant for a past thrombotic event during which she had not used anticoagulation therapy as prescribed. Her mental status was mildly confused. On funduscopic examination, papilledema and retinal hemorrhages were found. Results of a computed tomogram were normal. A lumbar puncture demonstrated increased intracranial pressure (60 cm H(2)O). Magnetic resonance venography demonstrated a right sigmoid sinus thrombosis. Although SCD has been reported as a cause of thrombotic dural venous sinus events, this case increases the knowledge about neurological complications of SCD. The patient was treated with low molecular weight heparin, blood transfusions, acetazolamide, and methylprednisolone, and her symptoms and signs resolved.


BMP regulates vegetal pole induction centres in early xenopus development.
Bone morphogenetic protein (BMP) plays an important role in mesoderm patterning in Xenopus. The ectopic expression of BMP-4 protein hyperventralizes embryos, whereas embryos expressing a BMP-2/4 dominant-negative receptor (DNR) are hyperdorsalized. Mesoderm is initially induced in the marginal zone by cells in the underlying vegetal pole. While much is known about BMP's expression and role in patterning the marginal zone, little is known about its early role in regulating vegetal mesoderm induction centre formation. The role of BMP in regulating formation of vegetal mesoderm inducing centres during early Xenopus development was examined. Ectopic BMP-4 expression in vegetal pole cells inhibited dorsal mesoderm induction but increased ventral mesoderm induction when recombined with animal cap ectoderm in Nieuwkoop explants. 32-cell embryos injected with BMP-4 RNA in the most vegetal blastomere tier were not hyperdorsalized by LiCl treatment. The ectopic expression of Smad or Mix.1 proteins in the vegetal pole also inhibited dorsal mesoderm induction in explants and embryos. Expression of the BMP 2/4 DNR in the vegetal pole increased dorsal mesoderm induction and inhibited ventral mesoderm induction in explants and embryos. These results support a role for BMP signalling in regulating ventral vegetal and dorsal vegetal mesoderm induction centre formation during early Xenopus development.


Exosomes Secreted from HEK293-APP Swe/Ind Cells Impair the Hippocampal Neurogenesis.
This study aimed to investigate the neurotoxicity of exosomes to cultured neuroblastoma and neurons in vitro and to mature and newborn neurons in the hippocampus in vivo. Recent in vitro and in vivo studies have shown that exosomes, small membranous vesicles secreted from many cell types, contain pathogenic proteins including full-length amyloid precursor protein (flAPP) and amyloid precursor protein (APP) metabolites. However, the function of these exosomes in Alzheimer disease (AD) has not been much explored. In the present study, exosomes were harvested from the conditioned medium of HEK293-APP Swe/Ind cells and injected into the hippocampal dentate gyrus region via a stereotactic method to detect their effects on the neuronal survival in vivo. These exosomes containing pathogenic proteins showed high neurotoxicity and could impair neurogenesis in the hippocampus. The data demonstrated that exosomes secreted from sick cells might damage neurogenesis and promote disease progression in AD.


Dietary protein and carbohydrate effects on blood parameters related to stress in cat.
Adult cats were adapted to hypoglucidic semi-purified diets containing casein or soya as the protein source to study the effects of a 2 hr immobilization period. Body weight of cats fed hypoglucidic diets was significantly decreased. The control casein group showed higher plasma dopamine-beta-hydroxylase activity but lower pyridoxal 5'-phosphate level than control soya group. Cats fed hypoglucidic casein diet, plasma glucose, insulin and pyridoxal 5'-phosphate levels were increased whereas cats fed hypoglucidic soya diet, pyridoxal 5'-phosphate levels were decreased and dopamine-beta-hydroxylase activity increased when data were compared to their respective control groups. A 2 hr immobilization period induced hyperglycemia in all groups whereas cats fed soya diets, plasma insulin level and dopamine-beta-hydroxylase activity were significantly increased and pyridoxal 5'-phosphate content significantly decreased. These results demonstrate that dietary casein and soya protein might be differentiated on a physiological basis and immobilization emphasized the biochemical disturbances observed between the groups thus suggesting a greater resistance to stress in casein groups than in soya groups.


Thymineless death and genetic events in mammalian cells.
Thymidylate synthase-negative mutants of cultured mouse FM3A cells were immediately committed to cell death upon thymidine deprivation especially when the cells were synchronized in the S-phase. Thymidine deprivation induced single strand breaks in parental DNA strands, as measured by alkaline sucrose gradient sedimentation, giving rise to two peaks, one with large and the other with short fragments. Increase in the short DNA fragments paralleled that of thymineless death. Thymidine deprivation also accumulated double strand DNA fragments as determined by a method of neutral filter elution, and their extent paralleled that of cell death. Double-strand DNA eluted through the filter sedimented as a single peak both in a neutral and in an alkaline sucrose gradient that coincided with that of the above short DNA fragments. Therefore, the double strand breaks seemed to occur in some defined portions of the genome and in some specific manners in contrast to those induced by X-ray, which occurred rather randomly. Cycloheximide blocked thymineless death and accumulation of the double stranded DNA fragments in parallel. The double strand breaks induced by thymidine starvation were not repaired, but instead advanced on subsequent incubation of the cells in growth medium containing thymidine. Cytogenetically, thymidine deprivation induced chromosome aberrations such as chromatid breaks, chromatid interchanges, and chromosome fragmentation. Also, 5-bromodeoxyuridine deprivation induced sister chromatid exchange. Thymidylate stress also induced loss of a stably integrated human gene in mouse cells, possibly by DNA rearrangements, under the conditions where no point mutations were induced.


Quantifying the interaction of vecuronium with enflurane using closed-loop feedback control of vecuronium infusion.
The influence of different levels of enflurane anaesthesia on infusion requirements of vecuronium was studied in 40 adult surgical patients. Ninety percent neuromuscular block was maintained by computer controlled infusion of vecuronium. During the first 90 min study period all patients received fentanyl-nitrous oxide-oxygen (2:1) anaesthesia. For the following 90 min the patients were randomly assigned to receive enflurane at different end-tidal concentrations: group I, control, fentanyl-nitrous oxide anaesthesia; group II, enflurane 0.3%-nitrous oxide; group III, enflurane 0.6%-nitrous oxide; group IV, enflurane 0.9%-nitrous oxide. Every patient served as his/her own control and the changes of vecuronium infusion requirements were determined individually. When the administration of enflurane was started, vecuronium infusion requirements decreased progressively until 90 min. In group II the infusion rate lowered from 80 +/- 28 to 56 +/- 20 micrograms.kg-1.h-1, in group III from 61 +/- 29 to 34 +/- 17 micrograms.kg-1.h-1 and in group IV from 65 +/- 20 to 30 +/- 14 micrograms.kg-1,h-1. In the control group the infusion rate decreased during the three hour study period from 69 +/- 17 (first 90 min period) to 59 +/- 16 micrograms.kg-1.h-1 (second 90 min period). Enflurane reduces the dose requirements of vecuronium administered by continuous infusion in a dose- and time-dependent manner.


A novel frameshift variant of COCH supports the hypothesis that haploinsufficiency is not a cause of autosomal dominant nonsyndromic deafness 9.
COCH (coagulation factor C homology) encodes cochlin, and certain mutations of COCH cause autosomal dominant nonsyndromic deafness 9 (DFNA9). Hearing loss due to COCH mutation begins in adulthood, and 17 missense mutations and two in-frame mutations have been reported. Studies with animal and cellular models have suggested that the underlying biological mechanism of DFNA9 is the dominant-negative effect of mutated COCH and not haploinsufficiency. However, no human cases of DFNA9 that support this hypothesis have been reported. The proband of the present case was an 18-year-old male with congenital or infantile hearing loss. Targeted next-generation sequencing analysis detected a heterozygous novel frameshift mutation of COCH (c.146dupT, p.C50LfsX8) in the proband, whose hearing loss began earlier than what is typical for DFNA9. His mother also carried the mutation but had normal hearing. Consequently, the mutation was not considered to be the cause of the proband's hearing loss. This family is the first case of a truncating COCH variant and supports the hypothesis that COCH haploinsufficiency is not the cause of hearing loss in humans.


Fine discrimination training alters the causal contribution of macaque area MT to depth perception.
When a new perceptual task is learned, plasticity occurs in the brain to mediate improvements in performance with training. How do these changes affect the neural substrates of previously learned tasks? We addressed this question by examining the effect of fine discrimination training on the causal contribution of area MT to coarse depth discrimination. When monkeys are trained to discriminate between two coarse absolute disparities (near versus far) embedded in noise, reversible inactivation of area MT devastates performance. In contrast, after animals are trained to discriminate fine differences in relative disparity, MT inactivation no longer impairs coarse depth discrimination. This effect does not result from changes in the disparity tuning of MT neurons, suggesting plasticity in the flow of disparity signals to decision circuitry. These findings show that the contribution of particular brain area to task performance can change dramatically as a result of learning new tasks.


The influences of selected soil properties on Pb availability and its transfer to wheat (Triticum aestivum L.) in a polluted calcareous soil.
Accumulated anthropogenic heavy metals in the surface layer of agricultural soils may be transferred through the food chain via plant uptake processes. The objectives of this study were to assess the spatial distribution of lead (Pb) in the soils and wheat plants and to determine the soil properties which may affect the Pb transferring from soil to wheat plants in Zanjan Zinc Town area, northwestern Iran. A total of 110 topsoil samples (0-20 cm) were systematically collected from an agricultural area near a large metallurgical factory for the analyses of physico-chemical properties and total and bioavailable Pb concentrations. Furthermore, a total of 65 wheat samples collected at the same soil sampling locations were analyzed for Pb concentration in different plant parts. The results showed that elevated Pb concentrations were mostly found in soils located surrounding the industrial source of pollution. The bioavailable Pb concentration in the studied soils was up to 128.4 mg kg(-1), which was relatively high considering the observed soil alkalinity. 24.6% of the wheat grain samples exceeded the FAO/WHO maximum permitted concentration of Pb in wheat grain (0.2 mg kg(-1)). Correlation analyses revealed that soil organic matter, soil pH, and clay content showed insignificant correlation with Pb concentration in the soil and wheat grains, whereas calcium carbonate content showed significantly negative correlations with both total and bioavailable Pb in the soil, and Pb content in wheat grains, demonstrating the strong influences of calcium carbonate on Pb bioavailability in the polluted calcareous soils.


Valproate: Not All Boxed Warnings Are Created Equal.
Valproate has undergone significant changes in labeling to the boxed warnings associated with it. This review will analyze evidence regarding the valproate-boxed warnings for teratogenicity, hepatotoxicity, and pancreatitis, with a particular emphasis on the fetal risk. A review of Pubmed, Cochrane Central Register, Google Scholar, manufacturer websites, and product labeling was performed from 1963 to February 2022, using the following search terms: valproate, valproic acid, depakote, teratogenicity, birth defects, fetal risk, hepatotoxicity, and pancreatitis. Relevant English-language studies and those conduced in humans were considered. Product labeling was also reviewed. There is a significant fetal risk following in utero valproate exposure (risk of malformation development: 8.6% in 360 women in North America). Current labeling in the United States recommends co-prescribing effective contraception for women of childbearing age. The risk of hepatotoxicity and pancreatitis is much lower in the general population (1/20 000 and 1/40 000 patients, respectively) compared with those patients with certain risk factors who are taking valproate (1/500). Overstated monitoring recommendations for the potential risk of hepatotoxicity and pancreatitis distracts from a much more common and severe risk of fetal harm. Clinicians must be diligent about discussing this risk with patients and documenting when this discussion occurs. Changes to the current recommendations for monitoring of the boxed warnings associated with valproate therapy should be considered, such as more stringent monitoring requirements for the inherent fetal risk. This could be accomplished through a Risk Evaluation and Mitigation Strategy program or through institution-based policies and procedures. In addition, monitoring recommendations for the risk of hepatotoxicity and pancreatitis should account for contributing risk factors.


Assessment of gold nanoparticle effects in a marine teleost (Sparus aurata) using molecular and biochemical biomarkers.
Gold nanoparticles (AuNP) are increasingly employed in a variety of applications and are likely to be increasing in the environment, posing a potential emerging environmental threat. Information on possible hazardous effects of engineered nanoparticles is urgently required to ensure human and environmental safety and promote the safe use of novel nanotechnologies. Nevertheless, there is a lack of comprehensive knowledge on AuNP effects in marine species. The present study aimed to assess AuNP effects in a marine teleost, Sparus aurata, by combining endpoints at different biological levels (molecular and biochemical). For that purpose, fish were exposed via water for 96h to 4, 80 and 1600μgL(-1) of AuNP (∼40nm) coated with citrate or polyvinylpyrrolidone (PVP). Results revealed a significant impact of AuNP-PVP in the hepatic expression of antioxidant, immune and apoptosis related genes. Total oxidative status was increased in plasma after exposure to the lowest concentration of AuNP-PVP, although without altering the total antioxidant capacity. Furthermore, AuNP did not induce significant damage in the liver since the activity of neither hepatic indicator (aspartate aminotransferase and alkaline phosphatase) increased. Overall, the present study demonstrated that AuNP, even with a biocompatible coating is able to alter oxidative status and expression of relevant target genes in marine fish. Another important finding is that effects are mainly induced by the lowest and intermediate concentrations of the PVP coated AuNP revealing the importance of different coatings.


FOXO3a-dependent Parkin regulates the development of gastric cancer by targeting ATP-binding cassette transporter E1.
Gastric cancer (GC) is one of the most common malignant tumors in China and the third leading cause of cancer-related death. Parkin has been shown to be a tumor suppressor in a variety of malignancies, including GC. However, the mechanism of Parkin in GC remains unclear. In this study, the low expression of Parkin in GC cells and patient tumor tissues was observed, and Parkin inhibited proliferation and migration of GC cells. Additionally, doxorubicin (DOX) upregulated the expression of Parkin and promoted its anticancer effect. Forkhead box O3 (FOXO3a) is a crucial transcription factor that involves in the regulation of cancer cell proliferation, apoptosis, and metabolism. Here, we found that FOXO3a inhibits cell proliferation, migration, and promotes apoptosis in GC by regulating Parkin expression at the transcriptional level. In addition, Parkin inhibited cell proliferation, migration, and promoted apoptosis by inhibiting ATP-binding box protein E1 (ABCE1) expression. In summary, our results demonstrated a new regulatory axis of FOXO3a-Parkin-ABCE1 that modulated GC cell proliferation, migration, and apoptosis, and it can serve as a potential therapeutic target in GC.


Limited-stage diffuse large B-cell lymphoma treated with abbreviated systemic therapy and consolidation radiotherapy: involved-field versus involved-node radiotherapy.
For limited-stage diffuse large B-cell lymphoma (DLBCL), treatment decisions are often influenced by toxicity profiles. One strategy that minimizes chemotherapy-induced toxicities is abbreviated chemotherapy plus consolidation involved-field radiotherapy (IFRT). Involved-node radiotherapy (INRT) is a new concept to DLBCL, aimed to reduce radiotherapy-induced toxicities. We retrospectively review the long-term outcomes of limited-stage DLBCL treated with abbreviated systemic therapy and radiotherapy focusing on field size: IFRT versus INRT. The British Columbia Cancer Agency Lymphoid Cancer Database was used to identify patients diagnosed with limited-stage DLBCL (stage I/II, without B-symptoms; bulk < 10 cm) from 1981 to 2007. Patients were prescribed 3 cycles of chemotherapy plus IFRT (1981-1996) or INRT≤5 cm (1996-2007), defined as INRT to the prechemotherapy involved nodes with margins ≤ 5 cm. A total of 288 patients were identified: 56% were aged >60 years, 34% had stage II disease, 55% had extranodal disease, 19% had elevated lactate dehydrogenase levels, and 15% received rituximab. The two radiotherapy groups were IFRT (138 patients; 48%) and INRT≤5cm (150 patients; 52%); median follow-up was 117 and 89 months, respectively. Distant relapse was the most common site of failure in both groups. After INRT≤5 cm, marginal recurrence was infrequent (2%). Time to progression (P = .823), progression-free survival (P = .575), and overall survival (P = .417) were not significantly different between the radiotherapy cohorts. Radiotherapy field size was not a significant prognostic factor on multivariate analyses. This research is the first known body of work to apply the concept of INRT to limited-stage DLBCL. Reducing the field size from IFRT to INRT≤5 cm maintains a low marginal recurrence risk with no impact on overall outcome.


Validation of the Spanish-language version of the Relevant Outcome Scale for Alzheimer's Disease.
The Relevant Outcome Scale for Alzheimer's Disease (ROSA) is a useful tool for evaluating and monitoring dementia patients. This study aims to evaluate the validity and reliability of the Spanish version of ROSA. Spanish multicentre study involving 39 researchers and including 237 patients with Alzheimer disease (78 mild, 79 moderate, and 80 severe). The patients were tested with the following: Mini-Mental State Examination (MMSE), Fototest, Neuropsychiatric Inventory (NPI), Blessed dementia scale, and a Spanish-language version of ROSA. A subsample of 40 subjects was retested in the 14 days following the initial evaluation. The construct validity was evaluated with the Spearman correlation coefficient (r), internal consistency with Cronbach's alpha (alpha), and test-retest reliability with the intraclass correlation coefficient (ICC). ROSA requires 13.8±7.4minutes to administer and its results show a significant association with the clinical stage of AD (mild, 116.7±23.1; moderate, 92.9±19.8; and severe, 64.3±22.6), and with results on the MMSE (r=0.68), Fototest (r=0.63), NPI (r=0.53), and Blessed dementia scale (r=-0.80). ROSA shows high internal consistency (alpha=0.90) and excellent test-retest reliability (ICC0.97). The Spanish version of ROSA is a brief, valid, and reliable tool permitting overall evaluation of patients with dementia.


Effect of Plasma and Blood Donations on Levels of Perfluoroalkyl and Polyfluoroalkyl Substances in Firefighters in Australia: A Randomized Clinical Trial.
Elevated levels of blood perfluoroalkyl and polyfluoroalkyl substances (PFASs) have been associated with a range of adverse health outcomes. Firefighters have been exposed to PFASs in firefighting foams and have previously been shown to have higher PFAS levels in blood samples than the general population. No interventions have been shown to reduce PFAS levels. To examine the effect of blood or plasma donations on PFAS levels in firefighters in Australia. This 52-week, open-label, randomized clinical trial enrolled participants from May 23 to August 23, 2019. Participants were 285 Fire Rescue Victoria staff or contractors with serum levels of perfluorooctane sulfonate (PFOS) of 5 ng/mL or more who were eligible to donate blood, had not donated blood in the 3 months prior to randomization, and were able to provide written informed consent. Analysis was performed on an intention-to-treat basis from May to July 2021. Firefighters with baseline PFOS levels of 5 ng/mL or more were randomly assigned to donate plasma every 6 weeks for 12 months, donate blood every 12 weeks for 12 months, or be observed only. The primary end points were changes in the serum PFOS and perfluorohexane sulfonic acid (PFHxS) levels after 12 months of plasma or blood donations or after observation only. Secondary end points included changes in serum PFAS levels from week 52 to week 64, changes in other PFASs, and changes in complete blood count, biochemistry, thyroid function, and lipid profile from screening to week 52. A total of 285 firefighters (279 men [97.9%]; mean [SD] age, 53.0 [8.4] years) were enrolled; 95 were randomly assigned to donate plasma, 95 were randomly assigned to donate blood, and 95 were randomly assigned to be observed. The mean level of PFOS at 12 months was significantly reduced by plasma donation (-2.9 ng/mL; 95% CI, -3.6 to -2.3 ng/mL; P < .001) and blood donation (-1.1 ng/mL; 95% CI, -1.5 to -0.7 ng/mL; P < .001) but was unchanged in the observation group. The mean level of PFHxS was significantly reduced by plasma donation (-1.1 ng/mL; 95% CI, -1.6 to -0.7 ng/mL; P < .001), but no significant change was observed in the blood donation or observation groups. Analysis between groups indicated that plasma donation had a larger treatment effect than blood donation, but both were significantly more efficacious than observation in reducing PFAS levels. Plasma and blood donations caused greater reductions in serum PFAS levels than observation alone over a 12-month period. Further research is needed to evaluate the clinical implications of these findings. anzctr.org.au Identifier: ACTRN12619000204145.


Importance of lymph node ratio for locoregional recurrence of squamous cell carcinoma of the buccal mucosa.
There is no published study on the influence of lymph node ratio on locoregional recurrence of squamous cell carcinoma (SCC) of the buccal mucosa. Therefore, we focused in our study on this specific anatomic subsite. We conducted a retrospective chart review of 95 patients from 2003-2013 with treatment-naive SCC of the buccal mucosa. Exclusion criteria were neoadjuvant chemoradiotherapy, perioperative death, N3 disease, unresectable disease, synchronous malignancy, and follow-up <3 months. Statistical analysis was performed using univariate and multivariate analysis. Significant correlations were found between locoregional recurrence and pathologic N classification (P < .001), grading (P = .001), and lymph node ratio (P < .001). Multivariate analysis indicated lymph node ratio as an independent risk factor for locoregional recurrence (P = .002). A cutoff value under 7% led to a 10.383-fold higher risk of incurring a locoregional recurrence. Lymph node ratio is a useful parameter to stratify the risk of locoregional recurrence in patients with SCC of the buccal mucosa.


Clinicopathologic types of epidermolysis bullosa and their nondermatological complications.
The various epidermolysis bullosa syndromes are classified into (1) epidermolytic, (2) lamina lucidolytic (junctional), and (3) dermolytic (dystrophic) subgroups. The mode of inheritance and the clinical manifestations, both cutaneous and noncutaneous, are systematically summarized. This report provides an overview of the diverse epidermolysis bullosa syndromes, particularly from the perspective of their nondermatological manifestations.


Safety evaluation of calcium L-methylfolate.
Calcium L-methylfolate (L-5-MTHF-Ca; CAS Number 151533-22-1) is a source of folate and an alternative to folic acid for use in human food and food supplements. The safety of L-5-MTHF-Ca was evaluated by testing for genotoxicity, subchronic and prenatal developmental toxicity. In in vitro assays L-5-MTHF-Ca was not mutagenic and did not induce other chromosomal events. Additionally, L-5-MTHF-Ca was not genotoxic in the in vivo micronucleus test nor did it induce DNA damage in rat liver cells. In a subchronic toxicity study, rats administered up to 400 mg/kg bw/day of L-5-MTHF-Ca via oral gavage for 13 weeks had no treatment-related mortalities, and no treatment-related effects were identified on behaviour, body weight, food consumption, ophthalmology, haematology, or organ weights. No treatment-related macroscopic or histopathological findings were observed. Calcium and sodium levels increased with increasing dosage, however the slight increases were within historical control ranges and reversible after the recovery period. L-5-MTHF-Ca is neither teratogenic nor embryotoxic. Based on the results of the in vitro and in vivo studies, the safe use of L-5-MTHF-Ca as an ingredient in foods is supported. The no observed adverse effect level was the highest dose in the subchronic toxicity study, i.e. 400 mg/kg bw/day for male and female rats.


Pore-forming activity and structural autoinhibition of the gasdermin family.
Inflammatory caspases cleave the gasdermin D (GSDMD) protein to trigger pyroptosis, a lytic form of cell death that is crucial for immune defences and diseases. GSDMD contains a functionally important gasdermin-N domain that is shared in the gasdermin family. The functional mechanism of action of gasdermin proteins is unknown. Here we show that the gasdermin-N domains of the gasdermin proteins GSDMD, GSDMA3 and GSDMA can bind membrane lipids, phosphoinositides and cardiolipin, and exhibit membrane-disrupting cytotoxicity in mammalian cells and artificially transformed bacteria. Gasdermin-N moved to the plasma membrane during pyroptosis. Purified gasdermin-N efficiently lysed phosphoinositide/cardiolipin-containing liposomes and formed pores on membranes made of artificial or natural phospholipid mixtures. Most gasdermin pores had an inner diameter of 10–14 nm and contained 16 symmetric protomers. The crystal structure of GSDMA3 showed an autoinhibited two-domain architecture that is conserved in the gasdermin family. Structure-guided mutagenesis demonstrated that the liposome-leakage and pore-forming activities of the gasdermin-N domain are required for pyroptosis. These findings reveal the mechanism for pyroptosis and provide insights into the roles of the gasdermin family in necrosis, immunity and diseases.


Evaluation of the time-schedule dependency for the cytotoxic activity of the new vinca alkaloid derivative, S 12363 (vinfosiltine).
S 12363 is a new vinca alkaloid derivative obtained by appending an optically active alpha-aminophosphonate at the C23 position of 04-deacetyl vinblastine. The present study concerns four different human tumour cell lines, which represent the spectrum of vinca alkaloid clinical activity. The influence of time exposure on S 12363 growth inhibition was studied in vitro. Cells were exposed to the drug during the following exposure times: 5, 15, 30 min and 1, 3, 6, 12, 24, 48, 72, 144 h. The concentrations of S 12363 applied were between 1 x 10(-2) and 1 x 10(3) nmol/l. The cytotoxic effects were assessed by using the methyltetrazolium (MTT) semi-automated test. Considering the IC50 values in terms of concentration (C) x time (T), I (C x T)50, it was shown that for an equal growth inhibitory effect (50% of cell death) the increased exposure times required higher cumulative drug exposures. More precisely, only very long exposure (greater than 24 h) resulted in very high I (C x T)50. The drug exposure ratios which correspond to I (C x T)50 values for 144 h divided by the I (C x T)50 values for 0.25 h ranged between 2.8 and 18.3. If T and C had symmetrical effects on the final growth inhibition, the I (C x T)50 ratios should have been equal to one. For all cell lines investigated there were similar dose-response curves following two types of S12363 exposure: a single day exposure or three successive daily exposures, the total C x T values being the same in both experimental situations. The basic pharmacological information provided by the present study may encourage further clinical trials of this potentially interesting new vinca alkaloid.


Induction of stathmin mRNA during liver regeneration.
Stathmin is a 19 kDa phosphoprotein, and is proposed to play a role in signal transduction in response to various extracellular stimuli that promote cellular growth and/or differentiation. We examined stathmin mRNA expression during development and liver regeneration in mice. Stathmin mRNA expression declined during the post-natal period and was undetected in adult liver. 36 h after partial hepatectomy, stathmin mRNA was rapidly induced and remained at elevated levels for at least 10 days. In situ hybridization experiments confirmed that stathmin mRNA expression occurred in hepatocytes. These results indicate that the stathmin gene expression appears to be repressed during the post-natal liver development, and is de-repressed by liver regeneration, which suggests that stathmin may be a good molecular marker of liver plasticity.


Formation of a photocatalytic WO3 surface layer on electrodeposited Al-W alloy coatings by selective dissolution and heat treatment.
In this study, we explored the feasibility of WO3 surface layer formation on electrodeposited Al-W alloy coatings by selective dissolution and heat treatment, with the aim of providing corrosion-resistant Al-W alloy coatings with photocatalytic self-cleaning properties under visible light illumination. The selective dissolution of Al and oxidation of residual W was carried out by immersing Al-W alloy films in an aqueous solution of nitric acid. A nanostructured H2WO4·H2O surface layer was formed on the alloy film by this process. The H2WO4·H2O layer was dehydrated to WO3 by heat treatment, yielding a multilayered WO3/Al-W alloy film with an approximately 300 nm thick WO3 layer. The WO3/Al-W alloy film exhibited photocatalytic self-cleaning, as demonstrated by the photodegradation of stearic acid and methylene blue. We also confirmed that selective dissolution and heat treatment did not significantly diminish the corrosion resistance of the Al-W alloy films.


Quality assessment of refined red palm-pressed mesocarp olein.
Palm-pressed mesocarp oil has been found to contain plenty of naturally occurring valuable phytonutrients. The application and study of the oil are limited, therefore, quality assessment of refined red palm-pressed mesocarp olein (PPMO) is deemed necessary to provide data in widening the applications as a niche products or raw material for the nutraceutical industry. Results showed that refined PPMO has comparable physicochemical properties and oxidative stability with commercial cooking oil, palm olein (PO). The food safety parameters and contaminants (PAH, 3-MCPD ester, 2-MCPD ester, glycidyl ester and trace metals) analyses proven that refined PPMO is safe to be consumed. Besides, refined PPMO contains remarkably greater concentrations of phytonutrients including carotenoids, phytosterols, squalene and vitamin E than PO, postulating its protective health benefits. The overall quality assessment of refined PPMO showed that it is suitable for human consumption and it is a good source for food applications and dietary nutritional supplements.


Ulcer and gastritis.
The literature on peptic ulcer and gastritis in 2000 again focused on the topics of Helicobacter pylori, nonsteroidal anti-inflammatory drugs (NSAIDs), and gastric cancer. New diagnostic tests for H. pylori infection have been evaluated, and rescue therapies for failed H. pylori eradication have been tested. The causal relationship between H. pylori infection and nonulcer dyspepsia, gastric cancer, gastroesophageal reflux disease, and NSAID-related ulcers remained heated topics of debate. In 2000, landmark clinical trials and meta-analyses were published addressing these issues. The role of endoscopy in managing nonulcer dyspepsia was better defined. The role of H. pylori eradication in NSAID/aspirin users was reexamined in high-risk patients. Clinical benefit was finally confirmed for specific inhibitors of cyclooxygenase-2 (COX-2). The millennium year turned out to be a very important one in the advancement of knowledge in this field.


Efficacy and safety of adding gemtuzumab ozogamicin to conventional chemotherapy for adult acute myeloid leukemia: a systematic review and meta-analysis.
Introduction: Compared with the 3 + 7 regimen, the addition of gemtuzumab ozogamicin (GO) has improved survival in patients with acute myeloid leukemia (AML). We conducted a systematic review and meta-analysis to examine the overall efficacy and safety of GO in combination with conventional chemotherapy regimens in patients with AML.Methods: We searched several databases (MEDLINE, Embase, Web of Science and Cochrane Library). Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated for overall survival (OS) and relapse-free survival (RFS); odds ratios (ORs) with 95% CIs were calculated for the other outcomes.Results: Ten records involving 11 randomized controlled trials (RCTs) met the inclusion criteria. GO plus induction chemotherapy significantly increased RFS (HR: 0.84, 95% CI: 0.73-0.98), decreased the incidence of relapse (OR: 0.78, 95% CI: 0.68-0.91) and resistant disease (OR: 0.72, 95% CI: 0.61-0.84), and had no significant effect on the rate of complete remission (CR) with or without incomplete platelet recovery (OR: 1.21, 95% CI: 0.94-1.55), 30-day mortality (OR: 1.25, 95% CI: 0.99-1.57). Subgroup analysis showed significant OS benefits for patients with favorable cytogenetic (HR: 0.50, 95% CI: 0.28-0.89) or given GO at induction stage (HR: 0.91, 95% CI: 0.84-1.00). Compared with other dosing schedule groups, 3 mg/m2 fractionated schedule had a greater RFS benefit (HR: 0.52, 95% CI: 0.36-0.76) and lower relapse risk (OR: 0.48, 95% CI: 0.28-0.84).Conclusions: Adding low-dose GO to induction or both induction and post-remission chemotherapy has considerable efficacy and unequivocal safety for newly diagnosed adult AML.