Micronutrient intakes in the Dutch diet: foods, fortified foods and supplements in a cross sectional study.
This study investigates intakes of risk micronutrients from non-fortified foods, fortified foods and food supplements in different age and gender sub-groups of the Dutch population. This is a secondary analysis of the Dutch National Food Consumption Survey (DNFCS 2012-2016, N = 4313, 1-79 years). The proportion of the population with Habitual Intakes below the Estimated Average Requirement (EAR) and above the Upper Level (UL) for calcium, iron, zinc, vitamin A, vitamin B6, folate, vitamin D and vitamin E from non-fortified foods, fortified foods and total intake including food supplements was calculated using Statistical Program to Assess Dietary Exposure (SPADE). More than 50% of the population had an intake below the EAR for calcium, iron, vitamin D and folate. Intakes were inadequate for certain sub-groups for the other vitamins and minerals. Adolescents and women were the population sub-groups most likely to have an intake below the EAR. For zinc, vitamin A and folic acid, more than 1% of toddlers exceeded the UL from the total intake. A negligible proportion exceeded the UL for the other vitamins and minerals. Inadequate intakes were found for several micronutrients in various population sub-groups despite an apparently well-nourished population. Intakes of zinc, folic acid and vitamin A from food supplements in toddlers and preschoolers should be investigated further to ensure they do not exceed recommended amounts. These results can be used to inform policy makers and to design nutritional interventions to improve micronutrient intakes in the Netherlands.


Uric acid level increases in humans engaged in gambling: a preliminary report.
The effect of gambling and gaming on plasma levels of uric acid was studied. Blood samples were obtained from normal subjects while they gambled for money or while they played checkers without betting. There was an interaction of time and activity reflecting primarily an association of increased uric acid levels during gambling over time, compared with gaming and relaxation. This indicates that gambling can increase plasma levels of uric acid.


Nuclear distribution of porphobilinogen deaminase (PBGD) in glioma cells: a regulatory role in cancer transformation?
Recently, considerable interest has been directed to red-fluorescence photodiagnosis of brain and other tumours during surgery using the protoporphyrin IX natural precursor, 5-aminolaevulinic acid. In the present study we focused on the role of the rate-limiting enzyme porphobilinogen deaminase in glioma C6 cell activity, differentiation and sub-cellular distribution. Over-expression of the human housekeeping porphobilinogen deaminase in the glioma cells, using the housekeeping-porphobilinogen deaminase plasmid, induced a G1 cell cycle attenuation accompanied by increases in enzyme activity and c6 differentiation toward astrocytes. Visualisation of subcellular localisation of the porphobilinogen deaminase using the independent techniques of fluorescence immuno-staining with specific anti-human porphobilinogen deaminase antibodies and cellular expression of porphobilinogen deaminase fused to green fluorescent protein, revealed (unexpectedly) a major fraction of porphobilinogen deaminase in the nucleus and only a minor fraction in the cytoplasm. Both C and N terminals of porphobilinogen deaminase fused to green fluorescent protein revealed a major fraction of the newly synthesized fused porphobilinogen deaminase in the nucleus. Furthermore, newborn rat brain cells grown in a primary culture showed the same localisation pattern of porphobilinogen deaminase in the nuclei. Stimulation of C6 glioma cell differentiation by butyrate induced a marked decrease in porphobilinogen deaminase both in the nucleus and in the cytoplasm as determined by Western blotting and fluorescence immuno-localisation. These findings suggest a possible dual role for housekeeping porphobilinogen deaminase in fast dividing glioma cells, one related to the porphyrin synthesis pathway and another coupled to nuclear function, which might be linked to tumorigenesis.


Concomitant achondroplasia and developmental dysplasia of the hip.
Achondroplasia (ACH) is the most common form of hereditary dwarfism and presents with multiple musculoskeletal anomalies but is not normally associated with premature hip arthritis. Developmental dysplasia of the hip (DDH) is a spectrum of disease resulting in shallow acetabular depth and a propensity for chronic femoral subluxation or dislocation; it is among the most common causes of premature arthritis. This case report describes the diagnosis of symptomatic DDH in a patient with ACH and highlights difficulties of primary total hip arthroplasty (THA) as a treatment option. Intraoperative radiographic imaging is advised to ensure proper prosthesis placement. Femoral osteotomy may aid visualization, reduction, and avoidance of soft tissue injury. Concomitant ACH and DDH is a challenging problem that can be successfully treated with modified THA.


Laparoscopic ventral hernia repair using a novel intraperitoneal lightweight mesh coated with hyaluronic acid: 1-year follow-up from a case-control study using the Hernia-Club registry.
A case-control study was performed to compare laparoscopic ventral hernia repair (LVHR) using the Ventralight ST™ lightweight surgical mesh with LVHR using other types of mesh. Adult patients undergoing intraperitoneal implantation of Ventralight ST™ during LVHR (Ventralight ST™ group; VG) over a 2-year period (2011-2013) were identified from the prospective French Hernia-Club registry. Patients undergoing elective LVHR using other types of intraperitoneal mesh in the first semester of 2013 formed the control group (CG). Patient, hernia and surgical characteristics, and postoperative outcomes after 8 days, 1 month, and 1 year were compared between the two groups. The VG comprised 90 LVHRs in 85 patients, and the CG 86 LVHRs in 81 patients. Patient, hernia and surgical characteristics were similar between the two groups, apart from the method of mesh fixation and the number of procedures involving fascial closure. A low rate of minor complications was observed in both groups at 1 month [4.4 % (VG) and 2.3 % (CG)], and the level of postoperative pain was similar in the two groups at Day 8 and 1 month. After 1 year, no complications, recurrences or cases of chronic pain had occurred in either group, and Quality-of-Life outcomes were similar. Patients rated their procedure as excellent or good in 96 % (VG) and 92 % (CG) of cases. Ventralight ST™ mesh is effective and well tolerated in LVHR, producing very low complication and recurrence rates in the short and medium term. The results are comparable to those achieved with other types of mesh.


Early developmental origins of impaired lung structure and function.
Epidemiological studies show that exposure to factors that restrict fetal growth or lead to low birthweight can alter lung development and have later adverse effects on lung function and respiratory health. The major causal factors include reduced nutrient and oxygen availability, nicotine exposure via maternal tobacco smoking and preterm birth, each of which can affect critical stages of lung development. Experimental studies show that these environmental insults can permanently alter lung structure and hence lung function, increasing the risk of respiratory illness and accelerating the rate of lung aging. Further studies are required that address the molecular and cellular mechanisms by which these factors adversely affect lung development and whether such effects can be blocked or reversed. Ultimately however, a major goal should be to prevent prenatal compromises through clinical monitoring, and in the case of smoking through education, thereby ensuring that each fetus has the best possible environment in which to develop.


On the blockade of acetylcholine release at mouse motor nerve terminals by beta-bungarotoxin and crotoxin.
1. beta-Bungarotoxin and crotoxin are phospholipose A2 neurotoxins, which block irreversibly the evoked release of acetylcholine from motor nerve terminals of mouse triangularis sterni preparations. 2. Extracellular recording of nerve terminal action potentials reveal that inhibition of transmitter release is not associated with failure of the action potential to invade nerve terminals. 3. When evoked transmitter release (measured as intracellularly recorded endplate potentials) was blocked by beta-bungarotoxin, spontaneous acetylcholine release was stimulated as in control experiments by K(+)-induced depolarization and by the Ca2(+)-ionophore A23187. 4. The site of action of the toxins remains to be elucidated but would appear to be associated with the coupling of action potential induced-depolarization to the release mechanism, rather than with the release mechanism itself.


Cognitive and educational outcome of very-low-birthweight children in early adolescence.
A cohort of 138 very-low-birthweight (VLBW) 12-year-old children and matched control children were assessed on objective cognitive and educational measures. School performance was rated by teachers and by the children themselves. VLBW children were shown to have lower IQ scores, and poorer scores on all objective educational measures compared with control children. Controlling for IQ differences, mathematics and reading-comprehension scores remained significantly lower for VLBW children. Teachers rated VLBW children lower in all curriculum areas. Significantly more VLBW children were found to be 'failing' in one or more subject and an increased proportion compared with the control children had received remedial education. The VLBW group showed no evidence of 'catch up' between 6 and 12 years of age. Multiple regression analyses were used to identify predictors of cognitive and educational outcome. The duration of mechanical ventilation in the neonatal period was inversely related to outcome. Full-Scale IQ at 6 years, motor-skills score at 6 years, and head circumference at 12 years all predicted outcome at 12 years, as did maternal education, family income and size. Individually, many VLBW children perform satisfactorily, but as a group VLBW children appear to be at a long-term disadvantage to peers in the areas of cognitive and educational performance.


Evaluation of the impacts of road runoff in a Mediterranean reservoir in Portugal.
Road runoff is a linear diffuse source of pollution, with very specific characteristics. This study intends to improve the understanding of road runoff impacts in water bodies in Portugal. The chosen case study is S. Domingos reservoir catchment. The study analyzed land uses, the presence of pollution sources, and gathered temporal water quality data and performed site measurements and sample collection. The water quality data for the reservoir was provided by the national water quality monitoring system from the Portuguese Water Institute. The parameters selected were TSS, COD, NO3 (-), Cl(-), and Cu. The results obtained revealed that the presence of IP6 highway at S. Domingos catchment affects the water quality; however, the impacts are not significant due to the high dilution effect of the reservoir volume. Agriculture, the main land use of the catchment, is responsible for introducing pollutants such as TSS, Cl(-), COD, N, and P in the local water streams and at the reservoir. TSS, COD, and Cu are pollutants generated by the road. The success of the study was very much dependent on the availability of 12 years of historic water quality data for S. Domingos reservoir, and the use of the moving average method. Taking into consideration the high variability of hydrological variables in Mediterranean climates, the concentration of pollutants in the water bodies must always be assessed in a significant time period.


Hematologic responses to exercise and training.
Hematology has been widely used in attempts to provide information about disease states, performance problems, and fitness in performance horses. However, owing to factors such as the temperament of the horse and time of collection and feeding, considerable variation in the hemograms can be found. This article reviews some of the hematologic responses to exercise and training.


Experimental evidence that sperm maturation drives protandry in an ectotherm.
Protandry, i.e., the earlier arrival to breeding areas of males than females, has attracted a lot of scientific attention. However, evidence for the evolutionary hypotheses of protandry is surprisingly scarce. Here, we experimentally manipulate the time of emergence from hibernation of males, relative to females, in the common lizard, Zootoca vivipara. We test whether the timing of emergence affects sperm maturation and mating success, to disentangle among proposed selective advantages of protandry. Our results experimentally demonstrate that the timing of emergence affects the date of sperm presence. Moreover, the degree of protandry affected whether males had sperm upon their first encounter with females, but it did not affect the probability of copulating. Mating occurred independent of male fertility and mating during infertility was least common in early emerging males. Early emergence from hibernation by males, relative to females, thus increases the male's chance of fertilising eggs and later emergence from hibernation by females reduces the female's probability of mating with infertile males. These results point to direct reproductive benefits of protandry in males and females, where earlier emergence is predicted to increase the male's opportunities to inseminate mates, and later emergence reduces the female's probability of copulating with infertile males. This suggests that protandry evolved due to the time required for sperm maturation after emergence from hibernation.


Subcortical DNET in a Patient With an Enzymatic Deficiency: A Rare Case and Review of the Literature.
This case report describes a toddler with a medical history of biotinidase deficiency who presented with atypical seizures due to a brain tumor. This is a case report. Electroencephalogram revealed a frontal lobe mass, with magnetic resonance imaging confirmation of a mass extending from the frontal lobe into the genu and anterior corpus callosum. She underwent a near-total resection, and pathology identified a dysembryoplastic neuroepithelial tumor. The patient is now seizure free and clinically doing well. Children with biotinidase deficiency and atypical seizures should receive a full electroencephalogram evaluation, as brain tumors continue to be on the differential for seizures in this patient population.


Unveiling TMEM106B: SARS-CoV-2's secret entrance to the cell.
The lysosomal membrane protein TMEM106B functions as a proviral factor in SARS-CoV-2 infection, though it was not known how. In this issue of Cell, Baggen et al. demonstrate that TMEM106B serves as an ACE2-independent receptor for SARS-CoV-2 entry by promoting the fusion of the viral membrane with the lysosomal membrane.


Pulmonary capillary reserve and exercise capacity at high altitude in healthy humans.
We determined whether well-acclimatized humans have a reserve to recruit pulmonary capillaries in response to exercise at high altitude. At sea level, lung diffusing capacity for carbon monoxide (DLCO), alveolar-capillary membrane conductance (DmCO), and pulmonary capillary blood volume (V c) were measured at rest before maximal oxygen consumption ([Formula: see text]) was determined in seven adults. Then, DLCO, DmCO and V c were measured pre- and post-exhaustive incremental exercise at 5150 m after ~40 days of acclimatization. Immediately after exercise at high altitude, there was an increase in group mean DmCO (14 ± 10%, P = 0.040) with no pre- to post-exercise change in group mean DLCO (46.9 ± 5.8 vs. 50.6 ± 9.6 ml/min/mmHg, P = 0.213) or V c (151 ± 28 vs. 158 ± 37 ml, P = 0.693). There was, however, a ~20% increase in DLCO from pre- to post-exercise at high altitude (51.2 ± 0.2 vs. 61.1 ± 0.2 ml/min/mmHg) with a concomitant increase in DmCO (123 ± 2 vs. 156 ± 4 ml/min/mmHg) and V c (157 ± 3 vs. 180 ± 8 ml) in 2 of the 7 participants. There was a significant positive relationship between the decrease in [Formula: see text] from sea level to high altitude and the change in DLCO and lung diffusing capacity for nitric oxide (DLNO) from rest to end-exercise at high altitude. These data suggest that recruitment of the pulmonary capillaries in response to exercise at high altitude is limited in most well-acclimatized humans but that any such a reserve may be associated with better exercise capacity.


Interobserver Reliability of Peripheral Muscle Strength Tests and Short Physical Performance Battery in Patients With Chronic Obstructive Pulmonary Disease: A Prospective Observational Study.
To evaluate the interobserver reliability of the Short Physical Performance Battery (SPPB) and hand dynamometry when measuring isometric muscle strength in people with chronic obstructive pulmonary disease (COPD). Reliability study. Each patient was assessed by a pulmonology physician and a physical therapist in 2 separate sessions 7 to 14 days apart (mean, 9.8±0.8d). Each rater was blinded to the other's results. Pneumology unit of a public hospital. Random sample of outpatients with stable COPD (N=30). Not applicable. SPPB and muscle strength (kg) using electronic handgrip and handheld dynamometers. Reliability was assessed with intraclass correlation coefficients (ICCs), standard error of measurement values, and Bland-Altman plots. ICCs were calculated for the SPPB summary score and for its 3 subscales. The ICCs for the overall reliability of the SPPB summary score and for grip and quadriceps strength were .82 (95% confidence interval [CI], .62-.91), .97 (95% CI, .93-.98), and .76 (95% CI, .49-.88), respectively. The standard error of measurement values were .55 points, 1.30kg, and 1.22kg, respectively. The mean differences between the rater's scores were near zero for grip strength and SPPB summary score measures. The ICCs for the SPPB subscales were .84 (95% CI, .66-.92) for the chair subscale, .75 (95% CI, .48-.88) for gait, and .33 (95% CI, -.42 to .68) for balance. Interobserver reliability was good for quadriceps and handgrip dynamometry and for the SPPB summary score and its chair stand and gait speed subscales. Both pulmonary physicians and physical therapists can obtain and exchange the scores. Because the reliability of the balance subscale was questionable, it is better to use the SPPB summary score.


BACE-2 is overexpressed in Down's syndrome.
Brain deposition of the amyloid-beta protein (Abeta) is a frequent complication of Down's syndrome (DS) patients. Abeta peptide is generated by endoproteolytic processing of Abeta precursor protein by gamma and beta secretases. Recently a transmembrane aspartyl protease, BACE, has been identified as the beta-secretase, and its homologous BACE-2 has also been described. BACE-2 gene resides on chromosome 21 in the obligate DS region. It cleaves Abeta precursor protein at its beta site and more efficiently at a different site within Abeta. In the present study we characterized the BACE-2 gene and protein expression in the DS patients and healthy control. We analyzed, by using a nonradioactive ribonuclease protection assay, the levels of BACE-2 mRNA expression in primary skin fibroblasts. The analysis revealed a 2.6-fold increase in BACE-2 mRNA levels in the DS group compared to the levels observed in the control group. Western blot analysis revealed no difference between DS and control in BACE-2 protein levels in the intracellular compartment. In the medium conditioned by fibroblast, we revealed an evident secretion of BACE-2 protein, represented by two different molecular weights, remarkably increased in DS fibroblasts. BACE-2 overexpression was also confirmed in the DS fetal brains and human neural embryonic DS stem cells in which conditioned media BACE-2 was secreted. These data highlight the importance of the extracellular compartment where BACE-2 overexpression could play a role in plaque formation in DS patients.


Theoretical investigations of the electronic structures of carbazole-based triphenylphosphine oxide derivatives, potential bipolar host materials in blue-phosphorescent devices.
Density functional theory calculations were performed to investigate the electronic structures of bipolar host materials comprising a backbone of linked acceptor moieties where each acceptor was also linked to a pendant donor moiety. The acceptor was triphenylphosphine oxide with two of its phenyls substituted with fluorine atoms or nitrile groups (CN). The donor was carbazole (CZ) substituted, or not, with t-butyl groups. The HOMO and LUMO energy levels of these host molecules were mainly influenced by their respective hole- and electron-transport units. The t-butyl substituents on the CZ moieties had an adverse effect on the triplet energies (E T) of the host molecules, especially for molecules where the phenyls of the backbone chain were substituted with CN groups. While introducing CN substituents onto the backbone chain decreased the energy difference between the lowest singlet and triplet excited states (ΔE ST), it also caused the energy gap between the HOMO and LUMO to narrow. Among the host molecules investigated, that in which one of the phenyls in the acceptor moiety was linked to the donor while the other two phenyls in the acceptor were substituted with CN substituents exhibited the highest E T, balanced charge transport, a low charge-injection barrier, and a small ΔE ST, and is therefore a promising candidate host material for use in blue-phosphorescent devices. Graphical Abstract Density functional theory calculations were performed to explore the electronic properties of bipolar host materials comprising a backbone of linked acceptor moieties where each acceptor was also linked to a pendant donor moiety. All of the designed molecules with high triplet energies were found to be suitable for use as host materials when matched with a blue-light guest material. The results demonstrate that the host molecule in which one of the phenyls in the triphenylphosphine oxide acceptor moiety was linked to the carbazole donor while the other two phenyls in the acceptor moiety were substituted with CN substituents yields the highest blue-phosphorescent device performance, as this host molecule has interesting features such as a high E T, balanced charge transport, a low charge-injection barrier, and a small ΔE ST.


A homozygous EVC mutation in a prenatal fetus with Ellis-van Creveld syndrome.
Ellis-van Creveld (EvC) syndrome, caused by variants in EVC, is a rare genetic skeletal dysplasia. Its clinical phenotype is highly diverse. EvC syndrome is rarely reported in prenatal stages because its presentation overlaps with other diseases. A Chinese pedigree diagnosed with EvC syndrome was enrolled in this study. Whole-exome sequencing (WES) was applied in the proband to screen potential genetic variant(s), and then Sanger sequencing was used to identify the variant in family members. Minigene experiments were applied. WES identified a homozygous variant (NM_153717.3:c.153_174 + 42del) in EVC which was inherited from the heterozygous parents and confirmed by Sanger sequencing. Further experiments demonstrated that this variant disrupts the canonical splicing site and produces a new splicing site at NM_153717.3: c.-164_174del, which ultimately leads to a 337 bp deletion at the 3' end of exon 1 and loss of the start codon. This is the first reported case of EvC syndrome based on a splicing variant and detailed delineation of the aberrant splicing effect in the fetus. Our study demonstrates the pathogenesis of this new variant, expands the spectrum of EVC mutations, and demonstrates that WES is a powerful tool in the clinical diagnosis of diseases with genetic heterogeneity.


Mechanistic impacts of long-term gamma irradiation on physicochemical, structural, and mechanical stabilities of radiation-responsive geopolymer pastes.
The mechanistic effects of long-term γ irradiation on the mineralogical, microstructural, structural, physical, and chemical properties of 40 wt% blast furnace slag + 60 wt% fly ash geopolymer pastes have been examined. Ambient curing for 28 days during normal equilibration was followed by exposure to 60Co irradiation (1574, 4822, 10,214 kGy). The material characteristics are controlled largely through the competing mechanisms of beneficial equilibration at initial lower dosages, which enhances gelation and crosslinking, and detrimental equilibration at subsequent higher dosages, which causes structural and microstructural destabilisation. Irradiation for 2 months (1574 kGy) increases the compressive strength ~45% (~57 to ~83 MPa) through conversion of less-crosslinked (Q0/Q1/Q1') to more-crosslinked (Q2/Q3/Q4) silicate species. The transition between these regimes occurs after ~5 months of irradiation (~4000 kGy). Beyond this, the rates of beneficial equilibration and detrimental equilibration equalise upon completion of normal geopolymerisation. Additional geopolymerisation from γ irradiation is controlled by the rate-limiting release of Si4+ from the unreacted aluminosilicates and silicates and their rapid incorporation in the geopolymer network. The aqueous leaching of the geopolymer pastes is not affected significantly by γ irradiation. These data reveal the potential for these materials as intermediate-level wasteforms that can outperform Portland cement-based materials.


Co-construction of oxygen doping and van der walls heterojunction in O-CB/ZnIn2S4 promoting photocatalytic production and activation of H2O2 for the degradation of antibiotics.
The in situ production of H2O2 by photocatalysis have shown a sustainable strategy for water remediation, but the peroxide evolution capacity are still unsatisfactory. Herein, we ingeniously design oxygen-doped carbon black/zinc indium sulfide (O-CB/ZnIn2S4) composites for photocatalytic production and activation of H2O2 to degrade antibiotics. The rich oxygen dopants and van der walls heterojunction between O-CB and ZnIn2S4 promoted charge transfer, oxygen adsorption and reduction for peroxide generation. The optimized O-CB/ZnIn2S4-2 composites exhibited ultrahigh H2O2 production rate (1985 μmol/g/h) in pure water (pH=7) without sacrificial reagents and aeration assistance, which was 2 times, 3 times, and 12 times higher than CB/ZnIn2S4-2, ZnIn2S4 and O-CB, respectively. Additionally, O-CB/ZnIn2S4-2 composites exhibited considerable amount of OH of 30 μmol/L in 60 min, which was originated from the reduction of innergenerate-H2O2 by photogenerated electrons and direct photolysis. The degradation and quenching experiments shows that the innergenerate-H2O2 contributed to the rapid degradation and deep mineralization of tetracycline antibiotics(tetracycline, oxytetracycline, chlortetracycline hydrochloride). Moreover, intermediates analysis and toxicity estimation further confirm the significant mineralization and toxicity decrease during the degradation of oxytetracycline by O-CB/ZnIn2S4-2. The work provides deep insights into the crucial role of dopants and heterojunction in promoting H2O2 production and activation.


Imaging epileptogenic tubers in children with tuberous sclerosis complex using alpha-[11C]methyl-L-tryptophan positron emission tomography.
Several reports have indicated that cortical resection is effective in alleviating intractable epilepsy in children with tuberous sclerosis complex (TSC). Because of the multitude of cortical lesions, however, identifying the epileptogenic tuber(s) is difficult and often requires invasive intracranial electroencephalographic (EEG) monitoring. As increased concentrations of serotonin and serotonin-immunoreactive processes have been reported in resected human epileptic cortex, we used alpha-[11C]methyl-L-tryptophan ([11C]AMT) positron emission tomography (PET) to test the hypothesis that serotonin synthesis is increased interictally in epileptogenic tubers in patients with TSC. Nine children with TSC and epilepsy, aged 1 to 9 years (mean, 4 years 1 month), were studied. All children underwent scalp video-EEG monitoring, PET scans of glucose metabolism and serotonin synthesis, and EEG monitoring during both PET studies. [11C]AMT scans were coregistered with magnetic resonance imaging and with glucose metabolism scans. Whereas glucose metabolism PET showed multifocal cortical hypometabolism corresponding to the locations of tubers in all 9 children, [11C]AMT uptake was increased in one tuber (n=3), two tubers (n=3), three tubers (n=1), and four tubers (n=1) in 8 of the 9 children. All other tubers showed decreased [11C]AMT uptake. Ictal EEG data available in 8 children showed seizure onset corresponding to foci of increased [11C]AMT uptake in 4 children (including 2 with intracranial EEG recordings). In 2 children, ictal EEG was nonlocalizing, and in 1 child there was discordance between the region of increased [11C]AMT uptake and the region of ictal onset on EEG. The only child whose [11C]AMT scan showed no regions of increased uptake had a left frontal seizure focus on EEG; however, at the time of his [11C]AMT PET scan, his seizures had come under control. [11C]AMT PET may be a powerful tool in differentiating between epileptogenic and nonepileptogenic tubers in patients with TSC.


Uptake and metabolism of retinol in isolated cells of germinal epithelium in vitro.
Retinyl esters were quantitatively the most significant product formed in short term incubations of isolated rat germinal cells administered 3H-retinol. 3H-retinyl palmitate was found to be the single most abundant metabolite accounting for approximately 80% of the total label 2 h after administration of 3H-retinol bound to bovine serum albumin. Differences were found in the relative activity of retinol uptake and metabolism between the various subpopulations of germinal cells separated by the staput sedimentation technique. The strongest correlation was between the magnitude of 3H-retinyl palmitate synthesis and the distribution of round spermatids. Large pachytene spermatocytes also appeared to correlate with 3H-retinyl palmitate synthesis although this correlation was ambiguous due to the presence of a small population of Sertoli cells and spermatogonia in these fractions. The concentration of cellular 3H-retinol was more than 10 fold greater in germinal cells administered 3H-retinol bound to bovine serum albumin than when 3H-retinol bound to serum retinol-binding protein was administered, and likewise the concentration of cellular 3H-retinyl palmitate was approximately 30 fold higher. In comparison to germinal cells, Sertoli cells administered 3H-retinol bound to serum retinol-binding protein incorporated 20 fold more 3H-retinol and synthesized more 3H-retinyl palmitate. However, both germinal cells and Sertoli cells were found to have incorporated similar concentrations of total label when administered 3H-retinol bound to bovine serum albumin. (ABSTRACT TRUNCATED AT 250 WORDS)


The blackening process of black-odor water: Substance types determination and crucial roles analysis.
Black-odor water is a serious environmental issue in many developing counties. Iron sulfides and chromophoric dissolved organic matter are considered possible blackening substances. However, the specific type of blackening iron sulfides and the contributions of blackening substances are unclear. This study performed a laboratory simulation experiment to identify the blackening iron sulfides and quantify the contribution of blackening substances. The environmental conditions for forming blackening substances and their blackening process were also determined. We demonstrated that the black iron sulfide was mackinawite. Humic acid is another substance that absorbs light. The equivalent contributions of mackinawite and humic acid were 18.94 m-1/mg Fe2+ and 1.11 m-1/mg DOC, respectively. A pH of more than 6 is a precondition for producing mackinawite. The production of black substances is the foundation of the blackening process, but the suspension of black substances is essential in causing water blackening. Fulvic acid stabilizes the suspension by changing the surface charge of blackening substances. Moreover, blackening substances can also be suspended with microbial flocs. Determining blackening substances and their role during the blackening process would allow for developing precise and targeted control technologies, improving urban water over the long term.


Is the presence of AA amyloidosis associated with impaired coronary flow reserve?
Systemic amyloid A protein (AA) amyloidosis may occur as a complication of many chronic inflammatory disorders. Patients receiving inadequate anti-inflammatory and immunosuppressive therapies have an increased risk of developing systemic AA amyloidosis. Inflammation plays a role in all stages and the thrombotic complications of atherosclerosis. In the absence of epicardial coronary stenosis, coronary flow reserve (CFR) reflects coronary microvascular dysfunction. In the present study, we hypothesized that amyloid advanced subclinical inflammation in chronic inflammatory diseases (CID) patients may further affect coronary microcirculation. Thirty-two patients with biopsy-diagnosed renal AA, 73 patients with non-amyloid CID, and a group of healthy volunteers were included in the study. The measurements of coronary flow velocity were performed by a single investigator with expertise in transthoracic Doppler harmonic echocardiography (TTDE). The AA amyloidosis subgroup had significantly lower CFR values than other non-amyloid CID patients and the control individuals (1.8 (1.5-2.1) vs. 2.1 (2.0-2.4) and 3.0 (2.8-3.2), p < 0.001). Multivariate logistic regression analysis indicated that the presence of AA amyloidosis and elevated hs - CRP independently predict impairment of the CFR (p < 0.05). The presence of AA amyloidosis is related to decreased CFR values and the presence of AA amyloidosis and elevated hs - CRP independently predict impairment of the CFR. Therefore, patients with AA amyloidosis may have an increased risk of developing coronary artery diseases.


PKC epsilon as a neonatal target to correct FXS-linked AMPA receptor translocation in the hippocampus, boost PVN oxytocin expression, and normalize adult behavior in Fmr1 knockout mice.
Fragile X Syndrome (FXS) is an inherited developmental disorder caused by the non-expression of the Fmr1 gene. FXS is associated with abnormal social and anxiety behavior that is more prominent among males. Given that oxytocin (OXT) regulates both social and anxiety behavior, we studied the effect of FXS in the hypothalamic paraventricular nucleus (PVN), the major central source of OXT. We observed a significant suppression of protein kinase C epsilon (PKCε) (34%) in the ventral hippocampal CA1 region of postnatal day-18 (P18) male Fmr1 knockout (KO) mice, which displayed social behavior deficits and hyper-anxiety in adulthood. These mice also displayed a 39% increase in cell surface α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor (AMPAR) at P18 (measured by the surface level of the AMPAR subunit GluR2), thereby indicating excitation of the CA1 neurons. It is known that neuronal activation at CA1 is linked to an inhibition of the PVN neurons. As expected, these mice also displayed a 25% suppression of oxytocin+ (OXT+) cells in the PVN at P20. Stimulating PKCε during postnatal days 6-,14 (P6-14) mice using a selective activator, dicyclopropyl-linoleic acid (DCP-LA), corrected AMPAR externalization in CA1 and suppression of OXT+ cell number in PVN in a PKCε dependent manner. Most notably, neonatal DCP-LA treatment rescued social behavior deficits and hyper-anxiety, displayed by adult (≥P60) male but not female KO mice. Thus, neonatal stimulation of PKCε could be a strategy to correct endophenotypic anomalies during brain development and aberrant adult behavior of the FXS males to the wild-type levels.


Differentially-expressed genes in Candida albicans exposed to ε-poly-L-lysine.
Candida albicans is an opportunistic human pathogen whose disinfection is a challenge. ε-Poly-L-lysine (ε-PL), an antagonistic agent, can disrupt cell membranes and inhibit the growth of C. albicans. Genes that were differentially-expressed in response to ε-PL were isolated from C. albicans and identified by suppression subtractive hybridization. Ten subtracted clones, that share >98 % homology with known genes of C. albicans, were isolated. Among these, four genes encoded cell wall-associated proteins. Real-time quantitative PCR and northern blot hybridization suggest that these genes are involved in the response to ε-PL. These findings will help to determine the mechanism of the antimicrobial activity of ε-PL against C. albicans.


Effects of proton pump inhibitor on gastric mucosa hemodynamics and tissue oxygenation in anesthetized rats.
Proton pump inhibitors have been reported to have a cytoprotective action in addition to the anti-secretory action of acid. The precise mechanism, however, remains obscure. In this study, the effects of proton pump inhibitors (omeprazole and NC-1300) on gastric mucosa hemodynamics and tissue oxygenation were investigated using organ reflectance spectrophotometry in a hemorrhagic shock-reperfusion model involving anesthetized rats. Neither drug affected gastric mucosa hemodynamics nor tissue oxygenation in the basal state before hemorrhage. During the hemorrhagic shock state, however, these drugs maintained tissue oxygenation and reduced ulcer formation, although they did not show a significant effect on gastric mucosa blood volume. The results suggest that both proton pump inhibitors have an anti-ulcer action by maintaining mucosal oxygenation in addition to the anti-secretory activity of acid.


Development of novel oridonin analogs as specifically targeted NLRP3 inflammasome inhibitors for the treatment of dextran sulfate sodium-induced colitis.
Abnormal activation of the NLR family pyrin domain containing 3 (NLRP3) inflammasome is closely associated with a variety of inflammatory diseases. Herein, we describe the discovery and optimization of a series of NLRP3 inflammasome inhibitors based on the oridonin skeleton. These inhibitors exhibited moderate to potent inhibitory activity against interleukin 1β (IL-1β) release. Compound E6 showed the strongest inhibitory activity and better safety range against IL-1β (IC50 = 0.45 ± 0.02 μM, selectivity index = 36.49). Compared with oridonin, the activity and selectivity index of compound E6 increased 11.5 and 7.2 times, respectively. Compound E6 also exhibited broad-spectrum activity and specificity. Compound E6 mainly reduced the release of IL-1β by targeting the NLRP3 protein, thereby inhibiting the NLRP3-caspase 1-gasdermin D (GSDMD), as well as inhibiting the caspase 4-GSDMD signaling pathway. Further studies revealed an important therapeutic effect of E6 on dextran sulfate sodium-induced colitis. Compound E6 may be promising for the treatment of NLRP3-related diseases including inflammatory bowel disease.


Removal of osseointegrated dental implants: a systematic review of explantation techniques.
This systematic review aims to evaluate current literature regarding available techniques for removal of osseointegrated implants in terms of explantation's success, complications, and bone loss. Two reviewers conducted a systematic literature search through electronic databases (PubMed and EMBASE), complimented by manual and grey literature searches. Successful explantation was defined as the primary outcome. Complications and availability of residual bone for immediate implantation were defined as secondary outcomes. Eighteen articles, comprising 372 implants and 241 patients, were included. Five techniques were identified: reverse torque, trephines, burs, piezosurgery, and laser-assisted explantation. Peri-implantitis was the most common reason for explantation, followed by crestal bone loss, fracture, and malpositioning. The reverse torque was the most frequently reported technique (284 implants) with 87.7% success rate. Burs were used for explantation of 49 implants with a 100% success rate, while trephines were utilized for removal of 35 implants with 94% success. Piezosurgery (11 implants) and Er.Cr:YSGG laser (1 implant) showed 100% success. One study reported perforation of the sinus floor following trephine explantation, while another reported fracture of 3 implants following reverse torque application. Further analysis was hindered by the quality of the available studies and their lack of data. Reverse torque seems the most conservative, and in the authors' opinion, should be the first choice for explantation despite its inferior success rate. Additional studies with randomized controlled designs and larger sample sizes are required. Dental implants have become the leading choice to replace missing teeth with gradually increasing numbers of complications and failures. An effective, conservative, and economic explantation technique is necessary to allow a successive implant placement.


Determination of vertical interproximal bone loss topography: correlation between indirect digital radiographic measurement and clinical measurement.
Diagnosis and accuracy in determining the exact location, extent and configuration of bony defects of the jaw are of utmost importance to determine prognosis, treatment planning and long-term preservation of teeth. If relatively accurate diagnosis can be established by radiography, proper treatment planning prior to treatment procedures will be possible. The aim of the present study was to assess the correlation between indirect digital radiographic measurements and clinical measurements in determining the topography of interproximal bony defects. Twenty interproximal bony defects, preferably in the mandibular and maxillary 5↔5 area were selected and radiographed using the parallel periapical technique. The radiographs were corrected and digitized on a computer using "Linear Measurement" software; then the three parameters of the base of defect (BD), alveolar crest (AC) and cementoenamel junction (CEJ) were determined using a software. Subsequent to radiographic measurements, clinical measurements were carried out meticulously during flap procedures. Then linear measurements were carried out using a periodontal probe to determine the defect depth and its mesiodistal width. Then the amount of correlation between these two measurements was assessed by Pearson's correlation coefficient. The correlation between clinical and radiographic measurements in defect depth determination, in the evaluation of defect angle and in determination of defect width were 88%, 98% and 90%, respectively. Indirect digital radiographic technique can be used to diagnose intra-osseous defects, providing a better opportunity to treat bony defects.


[Role of opiate peptides in regulation of the lymphocyte proliferative activity in patients with dyscirculatory encephalopathy in the late period after irradiation].
The authors have studied the endorphins effects on lymphocyte proliferation of 55 Chernobyl male workers aged 36-69 yrs and exposed to radiation dosed from 0.25 to 3.8 Sv. These patients have been found to have discirculatory encephalopathy in comparison with 30 non-exposed workers and 25 healthy volunteers. Physiological concentrations of alpha- and beta-endorphins intensify the spontaneous and mitogen-dependent proliferation of T-lymphocytes. Intensifying effect of the opiate peptides is being blocked by naloxone. Obtained data demonstrate the unidirectional opiates action, however the beta-endorphine effect dominates. The detected effect of endorhines are shown both among exposed to ionizing radiation and non-exposed. The irradiation higher than 1 Sv results in disturbance of the endorphine reception by T-cells with blockage of the influence of naloxone. It confirms the presence of radiation effects in opiate regulation of the lymphocyte proliferation.


The clinical spectrum of cardiac fibroma with diagnostic and surgical considerations: noninvasive imaging enhances management.
A cardiac fibroma was successfully resected from the interventricular septum of a 25-year-old woman. The clinical data were correlated with a review of the data on 144 other patients, thereby providing a clinical profile and management strategy for this type of tumor. Initial manifestations of a fibroma were determined to be congestive heart failure (21%), tachyarrhythmias (13%), and chest pain (3.5%). A majority of patients were asymptomatic (36%) with abnormal physical findings or an abnormal chest roentgenogram. Finding the tumor at autopsy incidentally or on sudden death (23%) indicated the lethal potential. A few (3.5%) of the reports on patients with cardiac fibroma were without clinical data. Noninvasive imaging by echocardiography, computed tomography, and nuclear magnetic resonance improved the diagnosis. Surgical treatment was successful in 53 of the 84 patients for whom it was attempted.


Cux-1 and Cux-2 control the development of Reelin expressing cortical interneurons.
Homeodomain transcription factors play important roles in the specification and differentiation of neuronal subpopulations. In the cerebral cortex, the expression patterns of Cux-1 and Cux-2 in the medial ganglionic eminence (MGE) suggest a role for these transcription factors in the development of interneurons, a heterogeneous neuronal population. In this report, we describe expression of Cux-1 and Cux-2 proteins in Reelin-secreting interneurons of the cortical plate, but not in calretinin or parvalbumin subpopulations. The role of Cux genes in the development of Reelin positive neurons was studied using Cux-1 and Cux-2 knockout mice. These experiments demonstrate that Cux-1-/-; Cux-2-/- double mutation is embryonically lethal. Although this phenotype is highly penetrant, a small proportion of mice develop to birth (P0). Analysis of these animals demonstrate that expression of Reelin is completely absent in layers II-IV of Cux-1-/-; Cux-2-/- double mutant mice, but it is not affected in the cortex of Cux-1-/- or Cux-2-/- single mutants. No Cux-1-/-; Cux-2-/- double-mutant were collected after P0. Since, GABA-ergic populations mature at late postnatal stages, this did not allow us to analyze the expression of subclass specific markers and define the affected interneuron subpopulations. Our analysis of Cux-1-/-; Cux-2-/- double mutant thus demonstrates essential yet redundant roles for Cux-1 and Cux-2 in specifying Reelin expressing cortical interneurons.


Disordered eating behaviours and attitudes among adolescents in a middle-income country.
Adolescent-disordered eating behaviours and attitudes (DEBA) are noted to be increasing in prevalence internationally. The aim of this study was to explore the DEBAs among Jamaican adolescents and identify those adolescents most at risk. 521 high school participants (females, n = 292), ages 11-19 years, completed measures assessing socio-demographic factors, self-esteem, symptoms of anxiety and depression, behavioural factors, and anthropometry. Weight-related behaviours and attitudes were explored using the Eating Attitudes Test (EAT-26). Thirty-one percent of participants reported engaging in at least one disordered eating behaviour, with bingeing as the most common. Female participants had significantly higher mean body mass index (p < 0.01) and mean EAT-26 score (p < 0.05) compared to males. Adolescents with EAT-26 score ≥ 20 were more desirous of being thinner (p < 0.01) and having a lighter skin complexion (p < 0.05). A greater proportion of adolescents with an EAT-26 score ≥ 20 had engaged in self-harm (p < 0.05), had smoked cigarettes (p < 0.05), had been sexually active (p < 0.01), and gave a history of sexual abuse (p < 0.01). Adolescents with overweight/obesity reported higher use of chemical weight manipulation (laxatives, diuretics, and diet pills) (p = 0.01). Our data are consistent with the global figures showing both male and female adolescents endorsing disordered eating behaviours and attitudes (DEBAs). While this study highlights weight and shape dissatisfaction and associated DEBAs, it also raises the concern of an association with skin bleaching and elevated EAT-26 scores among Jamaican adolescents. Level V: cross-sectional descriptive study.


The significance of persistent newly developed autoantibodies in JIA patients under long-term anti-TNF treatment.
To study the significance of persistent (12 months) new autoantibodies, in Juvenile Idiopathic Arthritis (JIA) patients treated with either Infliximab (INFL) or Etanercept (ET) for 2 years. 26 children under INFL (n=12) or ET (n=14) were prospectively studied. A large panel of autoantibodies was tested using indirect immunofluorescence (ANA, anti-dsDNA, anti-ENA, SMA, LKM, AMA, PCA, anti-R1, ATA), ELISA (ANA, anti-ENA, anti-cardiolipin, ANCA), immunoblotting assay (anti-ENA: anti-Ro, anti-La, anti-Sm, anti-URNP, anti-Jo, anti-Scl70, anti-centromere, anti-ribosomal and anti-histone) and rate nephelometry (RF). Apart from the positive patients for ANA (13/26) and RF (2/26) prior to anti-TNF treatment, 6/26 patients (23%) developed new autoantibodies (SMA, anti-R1, ATA) which persisted for 12-50 months. None developed antibodies to nuclear antigens. In only one case, ATA was associated with the development of Hashimoto's thyroiditis. These findings indicate that in JIA patients in contrast to adult RA patients, development of new autoantibodies to various nuclear antigens is rare. Other non relevant to rheumatic diseases autoantibodies, may appear and persist for >12 months, but very rarely they may be related to clinical entities, especially in the presence of a positive family history of autoimmunity.


ERK2 phosphorylation of serine 77 regulates Bmf pro-apoptotic activity.
B-cell lymphoma 2 (Bcl-2) homology 3 (BH3)-only proteins represent a class of pro-apoptotic factors that neutralize pro-survival Bcl-2 proteins, and, in some cases, directly activate Bax. The mechanisms of control and the role of BH3-only proteins, such as Bcl-2 like protein 11 extra large and Bad are well studied. By contrast, relatively little is known about the regulation and role of Bcl-2 modifying factor (Bmf). The B-RAF oncogene is mutated in ∼8% of human tumors. We have previously shown that Bmf is upregulated at the transcript level and is required for apoptosis induced by targeting B-RAF signaling in tumor cells harboring mutant B-RAF. In this study, we show that Bmf is regulated at the post-translational level by mutant B-RAF-MEK-ERK2 signaling. Extracellular signal-regulated kinase (ERK2) directly phosphorylates Bmf on serine 74 and serine 77 residues with serine 77 being the predominant site. In addition, serine 77 phosphorylation reduces Bmf pro-apoptotic activity likely through a mechanism independent of altering Bmf localization to the mitochondria and/or interactions with dynein light chain 2 and the pro-survival proteins, B-cell lymphoma extra large, Bcl-2 and Mcl-1. These data identify a novel mode of regulation in Bmf that modulates its pro-apoptotic activity in mutant B-RAF tumor cells.


Under-ascertainment of mosaic carriers of balanced homologous acrocentric translocations and isochromosomes.
Acrocentric rearrangements are the most common chromosome abnormalities in humans. Carriers of homologous acrocentric rearrangements (Robertsonian translocations (ROBs) between homologous chromosomes and isochromosomes) are at very high risk of having multiple spontaneous abortions and chromosomally abnormal offspring. Parents of fetuses and children with unbalanced homologous acrocentric rearrangements are rarely found to be carriers or mosaic for the same rearrangement. Even though recurrent miscarriages may indicate a carrier parent, carriers are rarely identified. Comparison of non-chromosome 21 homologous rearrangements to rea(21q21q) culled from the literature revealed a 7-fold decrease in the number of mosaic cases among the parents of non-rea(21q21q) offspring. This under-ascertainment in parents may be due to low level mosaicism confined to the gonads, a true biological difference between chromosome 21 rearrangements and other homologous acrocentric rearrangements, or simply to the lack of rigorous clinical investigation of the parental karyotypes to uncover mosaicism. We recommend that polymorphic marker analysis be applied to apparently de novo acrocentric rearrangements to distinguish those resulting from biparental postzygotic formation from those resulting from meiotic formation; the latter of which may indicate a potential carrier parent. Parental chromosomal constitutions could then be screened in a large number of cells and in more than one tissue type to identify mosaicism. Identification of mosaicism allows for accurate genetic counseling and discussion of reproductive options. However, given that mosaicism may be restricted to the gonads, prenatal testing is likely to be desired by the family whether or not mosaicism is found.


Relay-type sensing mode: A strategy to push the limit on nanomechanical sensor sensitivity based on the magneto lever.
Ultrasensitive molecular detection and quantization are crucial for many applications including clinical diagnostics, functional proteomics, and drug discovery; however, conventional biochemical sensors cannot satisfy the stringent requirements, and this has resulted in a long-standing dilemma regarding sensitivity improvement. To this end, we have developed an ultrasensitive relay-type nanomechanical sensor based on a magneto lever. By establishing the link between very weak molecular interaction and five orders of magnitude larger magnetic force, analytes at ultratrace level can produce a clearly observable mechanical response. Initially, proof-of-concept studies showed an improved detection limit up to five orders of magnitude when employing the magneto lever, as compared with direct detection using probe alone. In this study, we subsequently demonstrated that the relay-type sensing mode was universal in application ranging from micromolecule to macromolecule detection, which can be easily extended to detect enzymes, DNA, proteins, cells, viruses, bacteria, chemicals, etc. Importantly, we found that, sensitivity was no longer subject to probe affinity when the magneto lever was sufficiently high, theoretically, even reaching single-molecule resolution. Supplementary material (experimental section) is available in the online version of this article at 10.1007/s12274-022-5049-0.


Incentives, health promotion and equality.
The use of incentives to encourage individuals to adopt 'healthier' behaviours is an increasingly popular instrument in health policy. Much of the literature has been critical of 'negative' incentives, often due to concerns about equality; 'positive' incentives, however, have largely been welcomed as an instrument for the improvement of population health and possibly the reduction of health inequalities. The aim of this paper is to provide a more systematic assessment of the use of incentives from the perspective of equality. The paper begins with an overview of existing and proposed incentive schemes. I then suggest that the distinction between 'positive' and 'negative' incentives - or 'carrots' and 'sticks' - is of limited use in distinguishing those incentive schemes that raise concerns of equality from those that do not. The paper assesses incentive schemes with respect to two important considerations of equality: equality of access and equality of outcomes. While our assessment of incentive schemes will, ultimately, depend on various empirical facts, the paper aims to advance the debate by identifying some of the empirical questions we need to ask. The paper concludes by considering a number of trade-offs and caveats relevant to the assessment of incentive schemes.


The "gonadotropin-resistant ovary" syndrome as a cause of secondary amenorrhea and infertility.
A patient with secondary amenorrhea with the gonadotropin-resistant ovary syndrome is described. The physiopathology of the syndrome is investigated and discussed. Ovulation could not be induced by using very high doses of gonadotropins. The presence of a hormone abnormality or of an inhibitor preventing hormone action could not be substantiated. It is suggested that the disease may be due to an autoimmune reaction with antibody formation against the receptor sites for gonadotropins.


Interleukin-6 signal transducer gp130 mediates oncostatin M signaling.
Oncostatin M (OM) is a multifunctional cytokine that is structurally and functionally related to interleukin 6 (IL-6) and leukemia inhibitory factor (LIF). The specific receptor for OM has been demonstrated (by chemical cross-linking) to be a 150-kDa protein in a number of cell lines. The IL-6 signal transducer, gp130, is also an affinity converter for the LIF receptor. It does not bind to either IL-6 or LIF, but associates with the alpha subunits of the receptors and transduces the signals. We examined the possible involvement of gp130 in OM binding and signaling. We demonstrate that: (a) anti-gp130 monoclonal antibodies (mAbs) block the inhibitory effect of OM on A375 cell growth, (b) the binding and cross-linking of 125I-OM to H2981 cells are completely abolished by anti-gp130 mAbs, (c) the cross-linked OM-receptor complex is immunoprecipitated by anti-gp130 mAbs, and (d) COS-7 cells transfected with the full-length cDNA encoding gp130 exhibit increased OM binding and cross-linking, which are also blocked by anti-gp130 mAbs. Therefore, we conclude that the 150-kDa OM binding protein previously characterized in a variety of cell lines is gp130. OM is the natural ligand for gp130 and gp130 mediates the biological responses of OM.


Full-length tropomyosin-related kinase B expression in the brainstem in response to persistent inflammatory pain.
Supraspinal descending pathways from the periaqueductal gray and rostral ventromedial medulla dynamically modulate nociceptive transmission in the spinal dorsal horn. We examined the expression of the brain-derived neurotrophic factor receptor trkB in response to inflammation. No difference was observed in the number of neurons expressing trkB in the periaqueductal gray or rostral ventromedial medulla 3 h after inflammation; however, by 24 h, there was a significant increase in trkB expression in the periaqueductal gray (P < 0.05) and rostral ventromedial medulla (P < 0.05), compared with naïve levels, which persisted to 7 days and returned to naïve levels by 21 days. These results demonstrate a temporal increase in the number of cells expressing trkB in response to persistent inflammation, suggesting a role for trkB signaling in activity-dependent plasticity in the pain modulatory circuitry.


Dormancy in potato tuber meristems: chemically induced cessation in dormancy matches the natural process based on transcript profiles.
Meristem dormancy in perennial plants is a developmental process that results in repression of metabolism and growth. The cessation of dormancy results in rapid growth and should be associated with the production of nascent transcripts that encode for gene products controlling for cell division and growth. Dormancy cessation was allowed to progress normally or was chemically induced using bromoethane (BE), and microarray analysis was used to demonstrate changes in specific transcripts in response to dormancy cessation before a significant increase in cell division. Comparison of normal dormancy cessation to BE-induced dormancy cessation revealed a commonality in both up and downregulated transcripts. Many transcripts that decrease as dormancy terminates are inducible by abscisic acid particularly in the conserved BURP domain proteins, which include the RD22 class of proteins and in the storage protein patatin. Transcripts that are associated with an increase in expression encoded for proteins in the oxoglutarate-dependent oxygenase family. We conclude that BE-induced cessation of dormancy initiates transcript profiles similar to the natural processes that control dormancy.


Geographic/ethnic differences in human herpesvirus-6 antibody patterns.
Serum samples from healthy adults in four geographic/ethnic groups (Ghanaian Blacks, Malaysian Chinese, Malaysian Indians and United States Caucasians) were tested under code for antibodies to human herpesvirus-6 (HHV-6). The prevalence and titer of HHV-6 antibody in the healthy Ghanaians were significantly higher than in the Malaysian Chinese; United States Caucasians and Malaysian Indians had intermediate prevalence and titer of antibodies. Thus far, no specific differences in HHV-6-associated diseases have been noted between geographic/ethnic groups with these marked variations in antibody patterns.


Methyl-directed DNA mismatch repair in Escherichia coli.
Some of the molecular aspects of methyl-directed mismatch repair in E. coli have been characterized. These include: mismatch recognition by mutS protein in which different mispairs are bound with different affinities; the direct involvement of d(GATC) sites; and strand scission by mutH protein at d(GATC) sequences with strand selection based on methylation of the DNA at those sites. In addition, communication over a distance between a mismatch and d(GATC) sites has been implicated. Analysis of mismatch correction in a defined system (Lahue et al., unpublished) should provide a direct means to further molecular aspects of this process.


Knockdown of long non-coding RNA TUG1 depresses apoptosis of hippocampal neurons in Alzheimer's disease by elevating microRNA-15a and repressing ROCK1 expression.
Many studies have already suggested the role of long non-coding RNAs (lncRNAs) in Alzheimer's disease (AD), but the functions of lncRNA Taurine Upregulated Gene 1 (TUG1) in AD have been scarcely discussed. This study aims to verify how TUG1 affects hippocampal neurons in AD through modulation of microRNA-15a (miR-15a)/Rho-associated protein kinase 1 (ROCK1). AD mice was modeled through injection of β-amyloid 25-35 (Aβ25-35) into the lateral ventricle. After modeling, the mice were injected with altered TUG1 and/or miR-15a agomir lentiviruses. The spatial learning ability and memory ability of mice were detected through Morris water maze test. Hippocampal neuronal apoptosis and oxidative stress indicators in AD mice were then detected. The hippocampal neuron AD model was induced by Aβ25-35. Next, the neurons were, respectively, transfected with altered TUG1 vector and/or miR-15a mimics to determine the proliferation inhibition and apoptosis of hippocampal neurons. The interactions between TUG1 and miR-15a, and between miR-15a and ROCK1 were assessed using bioinformatic prediction, dual luciferase reporter gene assay and RNA-pull-down assay. In the animal models, Aβ25-35-induced mice exhibited decreased spatial learning and memory ability, obvious pathological injury, promoted hippocampal neuronal apoptosis and decreased antioxidant ability. TUG1 silencing and miR-15a elevation improved spatial learning ability and memory ability, ameliorated pathological injury, depressed neuronal apoptosis, and strengthened antioxidant ability of hippocampal neurons in AD mice. In cellular models, Aβ25-35-treated hippocampal neurons presented inhibited neuronal viability and promoted neuronal apoptosis. TUG1 silencing and miR-15a elevation increased viability and limited apoptosis of Aβ25-35-treated hippocampal neurons. TUG1 specifically bound to miR-15a, and miR-15a targeted ROCK1. Collectively, this study reveals that TUG1 knockdown restricts apoptosis of hippocampal neurons in AD by elevating miR-15a and suppressing ROCK1 expression, and provides a new therapeutic target for AD treatment.


Developmental outcomes of very low birth weight infants with catch-up head growth: a nationwide cohort study.
As the survival rates of very low birth weight (VLBW) infants have increased, their neurodevelopmental outcomes are of concern. This study aims to determine the demographic and perinatal characteristics of premature infant according to head growth, identify clinical factors affecting growth catch-up, and explore differences in developmental outcomes according to catch-up states. This nationwide prospective cohort study of Korean Neonatal Network data analyzed premature infants with very low birth weight (< 1,500 g) between 2014 and 2017. A total of 253 eligible infants who had completed the Bayley Scales of Infant and Toddler Development, Third Edition, were assigned into two groups: a catch-up (CU) group with a head circumference above the 10th percentile and a no catch-up (NCU) group with a head circumference below the 10th percentile at 18-24 months of corrected age (CA). Most (81.4%, 206/253) premature infants exhibited catch-up growth at 18-24 months of CA. Rates of microcephaly, intraventricular hemorrhage (IVH), bronchopulmonary dysplasia (BPD), sepsis, necrotizing enterocolitis (NEC), length of NICU stay, ventilation care, and parenteral nutrition were significantly greater in the NCU group (P < 0.05). On multiple linear regression analysis, BPD status was the most influential clinical factor affecting catch-up head growth after adjusting for gestational age, birth weight, and birth head circumference (adjusted OR 4.586, 95% CI 1.960-10.729). At 18-24 months of CA, the NCU group exhibited lower developmental indices and a higher rate of developmental delay than the CU group. Motor developmental delay was the most significant factor relevant to catch-up head growth, and the motor development difference between the two groups was only statistically significant after adjusting for four major neonatal morbidities: IVH, BPD, sepsis, and NEC status (adjusted OR 10.727, 95% CI 1.922-59.868). As association was observed between head growth catch-up status and developmental outcomes in VLBW infants at 18-24 months of CA. Key clinical factors associated with catch-up status included BPD and NEC status, length of parenteral nutrition, and ventilator care. Further study is needed to establish causality and explore additional factors that may influence developmental outcomes in this population.


The association between body mass index and health-related quality of life: data from CaMos, a stratified population study.
Deviation from normal weight is associated with health risks, but less is known about the association between weight and health-related quality of life (HRQOL). We investigated this in the context of a population-based study, using a standard five-category weight classification system based on body mass index (BMI). The Canadian Multicentre Osteoporosis Study is a randomly selected sample of men and women over 25 years of age from nine centres across Canada. Data were obtained by interview, and height and weight were measured and used to calculate BMI. HRQOL was measured using the SF-36. Multivariable linear regression was used to identify the association between BMI category and SF-36 scores after controlling for potential confounders. Complete data were available for 6,302 women and 2,792 men. Mean BMI for every age and gender group exceeded healthy weight guidelines. For women, being underweight, overweight or obese was associated with poorer HRQOL in most SF-36 outcomes while for men, this was associated with poorer HRQOL in some domains and with higher HRQOL in others. A significant proportion of the population may be putting their health at risk due to excess weight, which may have a substantial negative effect on HRQOL, particularly in women. This underscores the need for continued public health efforts aimed at combating overweight and obesity.


Multidisciplinary approach as a treatment option for abdominal wall reconstruction in patients with heart failure: A case report.
Incisional hernias are among the most frequent complications of abdominal surgery, with an incidence of 4-10 % of patients [1]. The multidisciplinary approach according to the patient's needs and their comorbidities has been shown to improve postoperative outcomes. This case report highlights the importance of a multidisciplinary approach including cardiology, general surgery, plastic surgery anesthesiology and intensive care unit for abdominal wall reconstruction in a patient with heart failure and reduced ejection fraction. We present a case of a 61-year-old patient with long-standing incisional hernia, without surgical correction due to the patient's condition and multiple comorbidities, advanced heart failure with reduced left ejection fraction (10-15 %) who underwent a multidisciplinary approach by cardiology, plastic surgery, anesthesiology, intensive care unit, and general surgery. The patient underwent abdominal wall reconstruction without complications. Due to multiple comorbidities, the patient was admitted in the ICU in the immediate postoperative period. He was discharged 9 days after surgery. The patient did not report long-term complications. Heart failure is associated with an increased risk of cardiovascular complications during surgical hospitalization. In patients with multiple comorbidities, the multidisciplinary approach represents an essential strategy in order to improve the surgical outcome, reduce costs to the health care system, and improve the patient's quality of life.


Effects of sperm pretreatment and embryo activation methods on the development of bovine embryos produced by intracytoplasmic sperm injection.
The aim of the study was to examine the effects of different embryo activation methods and sperm pretreatments on the activation and development of bovine embryos produced by intracytoplasmic sperm injection (ICSI). Four activation agents, i.e., calcium ionophore (A23187), ionomycin (Ion), electric pulse (EP) and ethanol (Eth) were used in various combinations to activate bovine ICSI embryos. The normal fertilization rate was similar in bovine ICSI embryos activated by A23187+Eth, Ion+Eth, Ion+EP+Eth, and 2-Ion (Ion administered two times)+Eth. Increasing the frequency of ionomycin stimulation from two (2-Ion+Eth) to three times (3-Ion+Eth) significantly (p<0.05) increased the cell number per embryo at the blastocyst stage. In addition, spermatozoa were pretreated with dithiothreitol (DTT), glutathione (GSH) or GSH+lysolecithin (LL) and used for producing bovine ICSI embryos. The blastocyst rate of bovine ICSI embryos produced from sperm pretreated with GSH was significantly (p<0.05) higher than those of embryos produced from sperm pretreated with DTT and GSH+LL. In conclusion, the embryo activation methods and sperm pretreatments examined in the present study did not affect the normal fertilization rate of bovine ICSI embryos. However, activation with 3-Ion+Eth and sperm pretreatment with GSH increased the cell number per embryo at blastocyst stage and the blastocyst rate, respectively, in bovine ICSI embryos.


A sensitive radioimmunoassay for a component of mouse casein.
Mouse casein (m.w. 22,000 daltons) has been purified by employing Sephadex G-100 and DEAE-cellulose column chromatographies. A sensitive radioimmunoassay method has been developed by using [125I]-labelled casein and antiserum elicited in rabbits after injection of glutaraldehyde-treated casein. The assay method is capable of detecting as little as 0.1 ng of casein. The use of the present radioimmunoassay method in detecting casein production in cultured mouse mammary explants has also been demonstrated.


Synthesis of 6-arylvinyl analogues of the HIV drugs SJ-3366 and Emivirine.
This paper reports the synthesis and the antiviral activities of a series of 6-arylvinyl substituted analogues of SJ-3366, a highly potent agent against HIV. The objective was to investigate whether substitution of the 6-arylketone with a 6-arylvinyl group could lead to an improved antiviral activity against HIV-1. The most active compounds 1-ethoxymethyl, 1-(2-propynyloxymethyl), and 1-(2-methyl-3-phenylallyloxymethyl) substituted 6-[1-(3,5-dimethylphenyl)vinyl]-5-ethyl-1H-pyrimidine-2,4-dione (5b, 16, and 18) showed activities against HIV-1 wild type in the range of Efavirenz, and moderate activities against Y181C and Y181C+K103N mutant strains were also observed.


2-(2-Carb-oxy-eth-yl)-1,3-dioxoisoindoline-5,6-dicarb-oxy-lic acid methanol monosolvate.
In the title compound, C(13)H(9)NO(8)·CH(3)OH, the main mol-ecule possesses three carb-oxy-lic acid groups, which are asymmetrically distributed around the mol-ecule core. This results in hydrogen-bonding motifs ranging from a chain to various rings. The combination of the chain motif together with a carb-oxy-lic dimer R(2) (2)(8) ring motif creates a ribbon of mol-ecules propagating along the c-axis direction. A second ribbon results from the combination of the chain motif together with a methanol solvent mol-ecule and carboxyl-containing R(4) (4)(12) ring motif. These two ribbons combine alternately, forming a hydrogen-bonded layer of mol-ecules parallel to (2[Formula: see text]0).


Conspiracy beliefs, regulatory self-efficacy and compliance with COVID-19 health-related behaviors: The mediating role of moral disengagement.
Although recent studies on the 2019 coronavirus disease (COVID-19) have highlighted the negative effects of moral disengagement on intentions to comply with COVID-19 containment measures, little is known about the mediating role of moral disengagement in the relationship between regulatory self-efficacy in complying with the containment measures, beliefs in conspiracy theories and compliance with COVID-19 health-related behaviors. Data were collected from 1164 young adults (women, N = 796; 68.4%; mean age 25.60 ± 4.40 years) who completed an online survey from 15th May to 22nd June 2021. Results of the multi-group path analyses indicated that higher beliefs in conspiracy theories were associated with lower compliance with COVID-19 health-related behaviors, whereas higher self-efficacy beliefs in complying with the containment measures were associated with higher compliance with COVID-19 health-related behaviors. Moral disengagement significantly mediated the associations between beliefs in conspiracy theories, regulatory self-efficacy, and compliance with COVID-19 health-related behaviors. Finally, the tested model was gender-invariant. Findings suggest that public health authorities and social care professionals should promote interventions aimed at improving regulatory self-efficacy, emphasizing the moral significance of respecting or ignoring the recommended COVID-19 measures (e.g., physical distance in public), and enhancing people's concern for the potential harms of their immoral actions.


Metric biases in body representation extend to objects.
We typically misestimate the dimensions of our body e.g., we perceive our fingers as shorter, and our torso as more elongated, than they actually are. It stands to reason that those metric biases may also extend to objects that we interact with, to facilitate attunement with the environment. To explore this hypothesis, we compared the metric representations of seven objects and the subjects' own hand using the Line Length Judgment task, in six experiments involving 152 healthy subjects. We evaluated the size estimation errors made for each target (hand or previously observed objects) by asking subjects to compare the vertical or horizontal dimension of a specific target against the length of a vertical or horizontal line. As expected, we showed that the hand is misperceived in its dimensions. Interestingly, we found that metric biases are also present for daily-life objects, such as a mobile phone and a coffee mug, and are not affected by familiarity with the objects. In contrast, objects that are less likely to be manipulated, either because they are potentially harmful or disgusting, were differently represented. Furthermore, the propensity to interact with an object, rated by an independent sample of subjects, best predicted the pattern of metric biases associated with that object. Taken together, these findings support the hypothesis that biases affecting the hand representation extend to objects that elicit action-oriented behavior, highlighting the importance of studying the body as integrated and active in the environment.


ARID1A serves as a receivable biomarker for the resistance to EGFR-TKIs in non-small cell lung cancer.
ARID1A is a key component of the SWI/SNF chromatin remodeling complexes which is important for the maintaining of biological processes of cells. Recent studies had uncovered the potential role of ARID1A alterations or expression loss in the therapeutic sensitivity of cancers, but the studies in this field requires to be further summarized and discussed. Therefore, we proposed a series of mechanisms related to the resistance to EGFR-TKIs induced by ARID1A alterations or expression loss and the potential therapeutic strategies to overcome the resistance based on published studies. It suggested that ARID1A alterations or expression loss might be the regulators in PI3K/Akt, JAK/STAT and NF-κB signaling pathways which are strongly associated with the resistance to EGFR-TKIs in NSCLC patients harboring sensitive EGFR mutations. Besides, ARID1A alterations or expression loss could lead to the resistance to EGFR-TKIs via a variety of processes during the tumorigenesis and development of cancers, including epithelial to mesenchymal transition, angiogenesis and the inhibition of apoptosis. Based on the potential mechanisms related to ARID1A, we summarized that the small molecular inhibitors targeting ARID1A or PI3K/Akt pathway, the anti-angiogenic therapy and immune checkpoint inhibitors could be used for the supplementary treatment for EGFR-TKIs among NSCLC patients harboring the concomitant alterations of sensitive EGFR mutations and ARID1A.


Nanodroplet chemical microarrays and label-free assays.
The microarraying of chemicals or biomolecules on a glass surface allows for dense storage and miniaturized screening experiments and can be deployed in chemical-biology research or drug discovery. Microarraying allows the production of scores of replicate slides. Small molecule libraries are typically stored as 10 mM DMSO stock solutions, whereas libraries of biomolecules are typically stored in high percentages of glycerol. Thus, a method is required to print such libraries on microarrays, and then assay them against biological targets. By printing either small molecule libraries or biomolecule libraries in an aqueous solvent containing glycerol, each adherent nanodroplet remains fixed at a position on the microarray by surface tension without the use of wells, without evaporating, and without the need for chemically linking the compound to the surface. Importantly, glycerol is a high boiling point solvent that is fully miscible with DMSO and water and has the additional property of stabilizing various enzymes. The nanoliter volume of the droplet forms the reaction compartment once additional reagents are metered onto the microarray, either by aerosol spray deposition or by addressable acoustic dispensing. Incubation of the nanodroplet microarray in a high humidity environment controls the final water content of the reaction. This platform has been validated for fluorescent HTS assays of protease and kinases as well as for fluorogenic substrate profiling of proteases. Label-free HTS is also possible by running nanoliter HTS reactions on a MALDI target for mass spectrometry (MS) analysis without the need for desalting of the samples. A method is described for running nanoliter-scale multicomponent homogeneous reactions followed by label-free MALDI MS spectrometry analysis of the reactions.


Severe Housing-Cost Burden and Low-Income Young Children's Exposure to Adverse Experiences: A Cross-Sectional Survey of WIC Participants in Los Angeles County.
Substantial literature has documented adverse childhood experiences' (ACEs) link with poor health in childhood and adulthood. Despite many American low-income families spending more than a third of their income toward housing costs, little research has been published about a link between severe housing-cost burden and ACEs. The objective of this study was to examine the association of severe housing-cost burden to the ACEs to which young, low-income children are exposed. Participants were 2-5-year-olds who participated in the Special Supplemental Nutrition Program for Women, Infants and Children (WIC) in Los Angeles County. We used data from the 2017 Los Angeles County WIC Survey, a survey of a random sample of all WIC participants living in Los Angeles County. Separate multiple logistic regression analyses were conducted to examine the association of severe housing-cost burden (very difficult to pay for housing) with the ACEs of financial hardship (household food insecurity, extreme poverty, parent's unemployment and underemployment), household dysfunction (parent's poor mental well-being and parent's separation), housing insecurity (doubled up and residential instability), and parent's experience with homelessness. Sixteen percent of children lived in severe housing-cost burdened households and 14% experienced at least 4 ACEs. After adjusting for sociodemographic characteristics and social support, severe housing-cost burden was associated with an increase in the odds of each of the ACEs. While further research is needed, findings highlight the need for policymakers to provide resources and support for housing-cost burdened children. Also, service providers should identify ACEs among housing cost-burdened children.


Examining the role of different weakness categories for mobility and future falls in older Americans.
Recently developed absolute and body size normalized handgrip strength (HGS) cut-points could be used individually and collectively to predict mobility problems and falls. We examined the associations of (1) each absolute and normalized weakness cut-point, (2) collective weakness categories, and (3) changes in weakness status on future falls in older Americans. The analytic sample included 11,675 participants from the 2006-2018 waves of the Health and Retirement Study. Falls were self-reported. Men were classified as weak if their HGS was < 35.5-kg (absolute), < 0.45 kg/kg (body mass normalized), or < 1.05 kg/kg/m2 (body mass index normalized). While, women were considered weak if their HGS was < 20.0-kg, < 0.337 kg/kg, or < 0.79 kg/kg/m2. Collective weakness categorized those below 1, 2, or all 3 cut-points. The collective weakness categories were also used to observe changes in weakness status over time. Older Americans below each absolute and normalized cut-point had greater odds for future falls: 1.23 (95% confidence interval (CI): 1.15-1.32) for absolute weakness, 1.20 (CI 1.11-1.29) for body mass index normalized weakness, and 1.26 (CI 1.17-1.34) for body mass normalized weakness. Persons below 1, 2, or all 3 weakness cut-points had 1.17 (CI 1.07-1.27), 1.29 (CI 1.18-1.40), and 1.36 (CI 1.24-1.48) greater odds for future falls, respectively. Those in some changing weakness categories had greater odds for future falls: 1.26 (CI 1.08-1.48) for persistent and 1.31 (CI 1.11-1.55) for progressive. Collectively using these weakness cut-points may improve their predictive value. We recommend HGS be evaluated in mobility and fall risk assessments.


New options for bloodstream infections caused by colistin- or ceftazidime/avibactam-resistant Klebsiella pneumoniae.
Concerns regarding carbapenem-resistant Klebsiella pneumoniae (CR-Kp), especially in bloodstream infections (BSIs), are continuing to increase worldwide. Several novel agents with activity against BSI CR-Kp have been approved or are in late-stage clinical development. In this study, the antibacterial effects of ceftazidime/avibactam (CZA), aztreonam/avibactam (AZA), meropenem/vaborbactam (MEV), imipenem-cilastatin/relebactam (ICR) and eravacycline (ERV) against three colistin-resistant CR-Kp (COLR-Kp) and four CZA-resistant CR-Kp (CZAR-Kp) were tested by time-kill assay. Klebsiella pneumoniae ATCC® BAA-1705TM was used as a control strain. Two COLR-Kp isolates carried the blaKPC-2 gene and four CAZR-Kp isolates carried metallo-β-lactamase genes. The results revealed that ERV resulted in re-growth of seven tested isolates. CZA and MEV showed a bactericidal effect against isolates harbouring blaKPC-2. ICR reduced the population of six isolates to >5 log10 CFU/mL compared with the initial count. AZA showed a bactericidal effect (>5 log10 CFU/mL) against seven isolates and a bacteriostatic effect (<3 log10 CFU/mL) against one CZAR-Kp isolate. Therefore, AZA and ICR are effective therapeutic candidates for COLR-Kp and CZAR-Kp isolates.


First impressions: Integrating faces and bodies in personality trait perception.
Faces and bodies spontaneously elicit personality trait judgments (e.g., trustworthy, dominant, lazy). We examined how trait information from the face and body combine to form first impressions of the whole person and whether trait judgments from the face and body are affected by seeing the whole person. Consistent with the trait-dependence hypothesis, Experiment 1 showed that the relative contribution of the face and body to whole-person perception varied with the trait judged. Agreeableness traits (e.g., warm, aggressive, sympathetic, trustworthy) were inferred primarily from the face, conscientiousness traits (e.g., dependable, careless) from the body, and extraversion traits (e.g., dominant, quiet, confident) from the whole person. A control experiment showed that both clothing and body shape contributed to whole-person judgments. In Experiment 2, we found that a face (body) rated in the whole person elicited a different rating than when it was rated in isolation. Specifically, when trait ratings differed for an isolated face and body of the same identity, the whole-person context biased in-context ratings of the faces and bodies towards the ratings of the context. These results showed that face and body trait perception interact more than previously assumed. We combine current and established findings to propose a novel framework to account for face-body integration in trait perception. This framework incorporates basic elements such as perceptual determinants, nonperceptual determinants, trait formation, and integration, as well as predictive factors such as the rater, the person rated, and the situation.


Language beyond action.
The discovery of mirror neurons in macaques and of a similar system in humans has provided a new and fertile neurobiological ground for rooting a variety of cognitive faculties. Automatic sensorimotor resonance has been invoked as the key elementary process accounting for disparate (dys)functions, like imitation, ideomotor apraxia, autism, and schizophrenia. In this paper, we provide a critical appraisal of three of these claims that deal with the relationship between language and the motor system. Does language comprehension require the motor system? Was there an evolutionary switch from manual gestures to speech as the primary mode of language? Is human communication explained by automatic sensorimotor resonances? A positive answer to these questions would open the tantalizing possibility of bringing language and human communication within the fold of the motor system. We argue that the available empirical evidence does not appear to support these claims, and their theoretical scope fails to account for some crucial features of the phenomena they are supposed to explain. Without denying the enormous importance of the discovery of mirror neurons, we highlight the limits of their explanatory power for understanding language and communication.


Accessible Pipeline for Translational Research Using TCGA: Examples of Relating Gene Mechanism to Disease-Specific Outcomes.
Bioinformatic scientists are often asked to do widespread analyses of publicly available datasets in order to identify genetic alterations in cancer for genes of interest; therefore, we sought to create a set of tools to conduct common statistical analyses of The Cancer Genome Atlas (TCGA) data. These tools have been developed in response to requests from our collaborators to ask questions, validate findings, and better understand the function of their gene of interest. We describe here what data we have used, how to obtain it, and what figures we have found useful.


Surgical implications of atrial septal defect complicating aortic balloon valvuloplasty.
An 80-year-old man underwent percutaneous transluminal balloon valvuloplasty for critical aortic stenosis. The procedure was performed by the antegrade atrial transseptal approach and was complicated by a persistent atrial septal defect. Symptoms recurred 6 months later, restenosis of the aortic valve was confirmed, and the atrial septal defect yielded a substantially greater left-to-right shunt. This complication of percutaneous transluminal balloon valvuloplasty poses important problems in hemodynamic assessment and operative management of patients who undergo subsequent aortic valve replacement.


Lasers in Glaucoma: an Overview.
Lasers have been in use as a treatment modality of glaucoma for more than last four decades. Each passing year has added newer dimensions to the existing laser technologies enhancing their safety and efficacy profile. This has become possible due to continuous research and innovations with proper understanding of the mechanism of action of different variety of lasers as treatment options. Each category of glaucoma has different underlying pathologies. Adequate knowledge and understanding of indications, limitations and hazards of these laser procedures are must before their application for improvising outcome. Recent years have witnessed a revolution this field. A thorough literature search was conducted in PubMed, Medline, the Cochrane Library Database, EMBASE, and Scopus and Google Scholar until May 2020 using the keywords, and all the articles pertaining to the relevant topics were included in this review. Purpose of this review is to summarize the important laser procedures currently in use for managing glaucoma along with updating the readers with recent advances in laser technologies, their extended applications and also analyzing possible future implications.


Anaesthetic considerations in caesarean section for quadruplets.
A case of a caesarean delivery with epidural analgesia of a term parturient with quadruplets is presented. Maternal considerations of hypotension, respiratory embarrassment and aspiration of gastric content and foetal considerations of prematurity and impaired placental function are discussed relative to the use of general anaesthesia or epidural analgesia.


Correlation of EGFR mutations with chromosomal alterations and expression of EGFR, ErbB3 and VEGF in tumor samples of lung adenocarcinoma patients.
Mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) are frequently detected in lung adenocarcinomas with bronchioloalveolar (BAC) differentiation and have been associated with increased response to small molecule EGFR inhibitors in some clinical studies. However, further molecular characterization of tumor cells carrying EGFR mutations (EGFR-mut) is warranted. By DNA sequencing, 120 patients with lung adenocarcinomas (70 tumors with BAC components) were screened for EGFR mutations within exons 18-21. Performing comparative genomic hybridization (CGH) and immunohistochemistry, chromosomal imbalances and protein expression levels of EGFR, ErbB3 and VEGF (vascular endothelial growth factor) were analyzed, respectively. EGFR mutations were detected in 20/120 tumors. Tumors with BAC components carried more frequently EGFR mutations compared to adenocarcinomas without BAC histology (17/70=24% vs 3/50=6.0%; p=0.012). In a subsequent matched-pair analysis, CGH-analysis demonstrated similar mean numbers of chromosomal imbalances for EGFR mutated and wild-type tumors (8.6 vs 7.8 gains; 2.4 vs 2.7 losses), respectively. Furthermore, tumors with mutated EGFR demonstrated gains in chromosomes 7p, 16p and 20q and losses in chromosome 8p. Interestingly, EGFR mutated tumors showed higher VEGF expression (p=0.03) while differences in EGFR expression were not statistically significant. EGFR gene mutations are frequently seen in lung adenocarcinomas with BAC differentiation and can be linked to chromosomal imbalances and increased VEGF expression.


Laparoscopic common bile duct exploration in children is associated with decreased cost and length of stay: results of a two-center analysis.
Our aim was to compare outcomes of children undergoing laparoscopic cholecystectomy with laparoscopic common bile duct exploration (LC+CBDE) to those undergoing laparoscopic cholecystectomy with adjunctive endoscopic retrograde cholangiopancreatography (LC+ERCP). We performed a two-center retrospective chart review of all children (<18 years) undergoing LC+CBDE or LC+ERCP between January 2000 and July 2011. Wilcoxon test was performed on continuous variables and logistic regression modeling on categorical data. A P value < 0.05 was considered significant. Outcomes with a P value < 0.2 were selected for multivariable analysis. Forty-two patients were identified. Twenty-four (57%) underwent LC+ERCP, and eighteen (43%) underwent LC+CBDE. Demographic and clinical factors were well matched between groups. Total operative time was similar between groups (157 min vs. 152 min, P = .26). LC+CBDE patients had zero major complications and five minor complications (retained stone: 3, pancreatitis: 1, late recurrence: 1). LC+ERCP patients experienced two major complications (duodenal perforation: 1, bleeding requiring transfusion: 1), and four minor complications (pancreatitis: 2, retained stone: 2, P = .57). Median length of stay was significantly longer (15.7 days vs. 6.6 days, P = .02), and median hospital cost was significantly higher ($18,132 vs. $12,735, P < .01) in the LC+ERCP group. Multivariable analysis revealed that cost was significantly lower in patients undergoing LC+CBDE (P = .05, OR= 0.71; 95% CI: 0.51-0.97). LC+CBDE at the time of cholecystectomy is associated with decreased length of stay, decreased cost, and has similar or improved morbidity compared to LC+ERCP.


Developing a watershed screening tool to estimate relative contribution of phosphorus to guide management planning.
To support the development of clean water plans, as required by the federal Clean Water Act 303(d) program, the New York State Department of Environmental Conservation (DEC) developed the Loading Estimator of Nutrient Sources (LENS) tool. DEC has prioritized clean water planning for fresh waterbodies experiencing negative impacts due to excessive phosphorus levels. LENS, an Excel based tool, combines several simple steady state models into a single screening tool that may be used to estimate the relative contribution of phosphorus sources within a watershed, waterbody response, and recovery potential of a waterbody. To validate that LENS results are reasonable approximations, LENS loading estimates were statistically compared with loading estimates from more complex watershed models that were used to develop existing clean water plans using simple linear regressions. For this comparison, DEC selected a variety of completed models that have modeled watershed phosphorus loads with different land use compositions and loading from both point and nonpoint sources. This analysis shows that LENS performs reasonably well at estimating the relative loading from a range of source sectors, though cannot replace more robust watershed models. DEC has used LENS to prioritize waterbodies for clean water plans and to guide management actions in watersheds where data is lacking to support more complex modeling efforts. Future expansions of LENS may include modifying the tool to estimate other pollutants (i.e. nitrogen), add the ability to account for internal loading of nutrients within waterbodies; and estimate the contribution of nutrients from groundwater.


Optimizing SPECT SISCOM analysis to localize seizure-onset zone by using varying z scores.
Subtraction ictal single photon emission computed tomography (SPECT) co-registered to magnetic resonance imaging (MRI) (SISCOM) is a useful modality to identify epileptogenic focus. Using this technique, several studies have generally considered the area of highest ictal hyperperfusion, as outlined by thresholding the difference images with a standard z score of 2, to be highly concordant to the epileptogenic focus. In clinical practice, several factors influence ictal hyperperfusion and using different SISCOM thresholds can be helpful. We aimed to systematically evaluate the localizing value of various z scores (1, 1.5, 2, and 2.5) in a seizure-free cohort following resective epilepsy surgery, and to examine the localizing information of perfusion patterns observed at each z score. Twenty-six patients were identified as having ictal-interictal SPECT images, preoperative and postoperative MRI studies, and having remained seizure free for at least 6 months after temporal or extratemporal surgical resection. SISCOM analysis was performed using preoperative MRI studies, and then blindly reviewed for localization of hyperperfused regions. With the added information from postoperative, coregistered MRI, perfusion patterns were determined. Using pair-wise comparisons, we found that the optimal z score for SPECT-SISCOM localization of the epileptogenic zone was 1.5, not the commonly used z score of 2. The z score of 1.5 was 84.8% sensitive and 93.8% specific. The z score of 1.5 had a moderate interrater agreement (0.70). When an hourglass configuration hyperperfusion pattern was present, a trend toward correctly localizing the seizure onset region was suggested (100% of the 11 observed occurrences). Nonetheless this trend was not statistically significant, possibly reflecting the small number of occurrences in our study. SISCOM is a useful modality in evaluating patients for epilepsy surgery. This study shows that the z score of 1.5 represents a highly sensitive and specific SISCOM threshold that should be examined in conjunction with the traditionally used z score of 2 to enhance the chances of correct localization. Further prospective investigations are needed to confirm this finding in large patient series.