Serial dependencies and Markov properties of neuronal interspike intervals from rat cerebellum.
Using three different approaches, each with different theoretical assumptions, we showed that mammalian neuronal spike trains contain serial ordering. We demonstrated that: (1) when intervals are categorized according to whether their durations are short, medium, or long, sequential groupings of adjacent interval categories exhibit Markov dependencies, extending to at least the 4th order; (2) the observed incidence of specified patterns of these groups of adjacent interval categories differs from the independent case, based on Chi square goodness-of-fit tests, and by using similar procedures; (3) there is divergence from independence when adjacent interval patterns are described in terms of relative lengths of adjacent intervals. The statistical indicators of serial dependence were significantly greater when applied to the original data than when applied to the same data after shuffling. Each of these approaches leads to the notion that "information" is carried in clusters of adjacent intervals ("bytes" or "words") and moreover, we can identify which specific patterns of interspike intervals contribute most to the statistical significance (i.e., those clusters that are potential candidates for "information carriers"). In most of the ten neurons, the "memory" of the system appears to be at least 36--45 msecs.


[Reconstruction of posttraumatic skull and facial bones injuries with the use of perforated titanium plates and meshes].
The given way of reconstruction of posttraumatic injuries showed predicted, long-term results and can be recommended for application in specialized establishments on bases of hospitals. Use of the data of computer tomography during the preoperative and postoperative period allows to estimate the volume of missing bone tissue. It also allows to define the volume of autogenous bone required for completion. Allows to define parameters of thickness, height, degree of curvature of autogenous bone, and also to select the optimum size of titanium plate or mesh. Application of perforated titanium plates ams meshes, made of high-purity the titan, allows to correct complex defects of maxillofacial area with minimization of complications in the postoperative period.


Beta-amyloid precursor protein immunohistochemistry in the evaluation of pediatric traumatic optic nerve injury.
The pathologic markers of nonaccidental injury (NAI) of the central nervous system (CNS) of infants and young children include subdural, subarachnoid, and retinal hemorrhages. Immunohistochemical staining for beta-amyloid precursor protein (betaAPP) has been used to investigate traumatic axonal injury of the brain, brain stem, and spinal cord injuries, and has potential as an additional indicator of traumatic head injury. A single study has reported that betaAPP immunostaining of the optic nerve in CNS NAI reveals axonal damage. The purpose of our study was to explore further the utility of betaAPP immunostaining of optic nerves for the detection of traumatic axonal injury. We used hematoxylin-eosin and betaAPP immunostaining to evaluate the eyes and optic nerves in 18 cases of CNS nonaccidental blunt force head injury, 4 cases of homicidal blunt force abdominal injury (BFAI), 1 homicidal suffocation, 1 case of sudden infant death syndrome, 1 near-drowning, 1 overlay (clinical history: "found under sleeping mother in bed"), 1 motor vehicle accident, and 6 natural deaths in children < or =5 years of age. Evaluation of the cases of CNS NAI revealed 17 of 18 (94%) with subdural hemorrhage; 15 of 18 (83%), subarachnoid hemorrhage; 17 of 18 (94%), retinal hemorrhage; 16 of 18 (88%), perioptic nerve hemorrhage; and 6 of 18 (33%), optic nerve betaAPP immunoreactive axonal swellings. The only nontraumatic case that demonstrated betaAPP immunoreactive axonal swellings was the near-drowning. No cases of BFAI, suffocation, overlay, or natural deaths revealed any retinal or perioptic nerve hemorrhage or significant optic nerve betaAPP immunoreactivity. Global hypoxic-ischemic injury was present in 21 cases, of which 19 had evidence of brain swelling, and 7 demonstrated betaAPP immunoreactive axonal swellings. These findings confirm the presence of optic nerve axonal injury in some cases of fatal pediatric CNS NAI.


Genome-wide analysis of Bkm sequences (GATA repeats): predominant association with sex chromosomes and potential role in higher order chromatin organization and function.
Bkm (Banded krait minor) satellite DNA sequences (GATA repeats) have been shown to be associated with the sex determining chromosomes of various eukaryotes and have been implicated in the evolution and differentiation of sex chromosomes in snakes. The objective of the study is to analyze the GATA repeats of human genome specifically, the Y-chromosome, and other model organisms to understand the possible function and potential role in higher order chromatin organization. Our extensive analysis of GATA repeats in the prokaryotic and eukaryotic genomes, which have been completely sequenced so far, has revealed that GATA repeats are absent in prokaryotes and have been gradually accumulated in higher organisms during the course of evolution. In human, the Y-chromosome has the highest GATA repeat density, which predominantly exists in the Yq centromeric region. Generally, occurrence of repeats in the genomes decreases steadily as the length of the repeat increases. In contrast, we report, that the occurrence of GATA repeats increases as the length of the repeat increases from six tandem repeats onwards and peaks at (GATA)(10-12). This has not been observed with any other simple repeat. Distribution of (GATA)(10-12) along the chromosome and their close proximity to Matrix Associated Regions (GATA-MAR) suggests that it may be demarking chromatin domains for a coordinated expression of genes residing in these domains.


The Association of Firearm Caliber With Likelihood of Death From Gunshot Injury in Criminal Assaults.
A foundational issue in firearms policy has been whether the type of weapon used in an assault affects the likelihood of death. To determine whether the likelihood of death from gunshot wounds inflicted in criminal assaults is associated with the power of the assailant's firearm as indicated by its caliber. Cross-sectional study with multivariate analysis of data on shooting cases extracted by the authors from police investigation files for assaults that took place in Boston, Massachusetts, between January 1, 2010, and December 31, 2014. These data were analyzed between October 1, 2017, and February 18, 2018. In all cases the victim sustained 1 or more gunshot wounds in circumstances that the Boston Police Department deemed criminal. The working sample included all 221 gun homicides and a stratified random sample of 300 nonfatal cases drawn from the 1012 that occurred during the 5-year period. Seven nonfatal cases were omitted because they had been misclassified. The primary source of variation was the caliber of the firearm used to shoot the victim. Whether the victim died from the gunshot wound(s). The final sample of 511 gunshot victims and survivors (n = 220 fatal; n = 291 nonfatal) was predominantly male (n = 470 [92.2%]), black (n = 413 [80.8%]) or Hispanic (n = 69 [13.5%]), and young (mean [SD] age, 26.8 [9.4] years). Police investigations determined firearm caliber in 184 nonfatal cases (63.2%) and 183 fatal cases (83.2%). These 367 cases were divided into 3 groups by caliber: small (.22, .25, and .32), medium (.38, .380, and 9 mm), or large (.357 magnum, .40, .44 magnum, .45, 10 mm, and 7.62 × 39 mm). Firearm caliber had no systematic association with the number of wounds, the location of wounds, circumstances of the assault, or victim characteristics, as demonstrated by χ2 tests of each cluster of variables and by a comprehensive multinomial logit analysis. A logit analysis of the likelihood of death found that compared with small-caliber cases, medium caliber had an odds ratio of 2.25 (95% CI, 1.37-3.70; P = .001) and large caliber had an odds ratio of 4.54 (95% CI, 2.37-8.70; P < .001). Based on a simulation using the logit equation, replacing the medium- and large-caliber guns with small-caliber guns would have reduced gun homicides by 39.5%. Firearms caliber was associated with the likelihood of death from gunshot wounds in criminal assault. Shootings with larger-caliber handguns were more deadly but no more sustained or accurate than shootings with smaller-caliber handguns. This conclusion is of direct relevance to the design of gun policy.


UV-independent p53 mutations in sebaceous carcinoma of the eyelid.
Sebaceous carcinoma of the eyelid is a potentially fatal malignancy that has been associated with p53 gene mutations. The purpose of this study is to determine the frequency of p53 mutations in sebaceous carcinoma of the eyelid and to determine whether there is any relationship between the presence of p53 mutations and tumor invasiveness. Retrospective case series. Fourteen samples of sebaceous carcinoma that had been resected from Caucasian patients between 1994 and 2010 were analyzed for p53 gene mutations with PCR and Sequencher software. Patient charts were reviewed to draw clinicopathologic correlations in relation with the presence of p53 gene mutations. Seven of 14 (50%) sebaceous carcinoma samples were found to have p53 gene mutations. None of the samples had tandem mutations, which are caused by UV exposure. No statistically significant trend was found between the presence of p53 mutations and metastasis, recurrence, tumor size, TNM stage, and pagetoid spread. There was a similar frequency of p53 gene mutations found in stage T1, T2, and T3 tumors. p53 Mutations are found in a high percentage of sebaceous carcinomas in the Caucasian population. The absence of tandem mutations is consistent with the belief that sebaceous carcinoma develops as a UV-independent process. There does not appear to be a significant correlation between the presence of p53 mutations and tumor size, recurrence, metastasis, pagetoid spread, or location. The similar frequency of p53 mutations in both low- and high-stage tumors implies that p53 gene mutations may be involved in early stages of carcinogenesis of sebaceous carcinoma.


Planning anesthesia of a child with a rare disease: useful tools.
Up to 8,000 rare diseases are currently described in the scientific literature. The presence of a rare disease constitutes an additional challenge for the practitioner given its implications on the management of anesthesia. Moreover, it is not possible for an anesthesiologist to know them all especially as the sources of information are scattered. This narrative review aims at proposing pre-anesthetic evaluation clear tools to summarize the individual aspects of a known or suspected rare disease in a patient and to define an adapted anesthetic strategy. It also describes a decision-making process, called « the rare disease reflex », to guide the practitioner to quickly initiate diagnostic investigations in the presence of unusual perioperative clinical signs suggestive of an undiagnosed rare disease.


Poly-tobacco use among HIV-positive smokers: implications for smoking cessation efforts.
Poly-tobacco use is defined as cigarette and other tobacco consumption with either product used daily or nondaily. While concurrent use of different types of tobacco has been documented within the general population, less is known about poly-tobacco use among HIV-positive smokers and its impact on smoking cessation efforts. To characterize the profile of poly-tobacco users (PTU) in a sample of HIV-positive smokers participating in a cessation program. The study sample consisted of 474 HIV-positive smokers enrolled in a 2-group randomized controlled trial of cigarette smoking cessation comparing a cell phone-based intervention to usual care. Prevalence was determined, and risk factors for poly-tobacco use were evaluated using logistic regression. In this cohort of HIV-positive cigarette smokers, 21.6% of participants were PTU, with cigars (73.4%) the most common tobacco product consumed. Among PTU, 73.5% used other form(s) of tobacco some days, and 26.5% use them every day. Perceived discrimination and unemployment were significantly associated with poly-tobacco use after adjusting for other demographic, behavioral, and psychosocial factors. Analysis showed that participants in the cell phone group (vs. usual care) were more likely to report 24-hr abstinence, both among monocigarette users (16.6% vs. 6.3%, p < .001) and PTU (18.5% vs. 0%, p < .001). Poly-tobacco use prevalence among adult HIV-positive smokers was considerably higher than in the general population. Special attention must be placed on concurrent use of cigarettes and cigars among HIV-positive smokers. Because PTU are a unique population less likely to succeed in brief smoking cessation interventions, effective cessation programs are needed.


Complete resolution of lumbar disc sequestration with Ayurveda management: A case report.
Lumbar disc herniation (LDH) is the most common spinal disorder among which disc sequestration is a severe type where the herniated disc fragment migrates and is completely separated from the parent disc. A 46-year-old female patient with severe lower back pain radiating to right lower limb, disability, and numbness in the affected extremity came to Panchakarma O.P.D of our hospital. She was a chronic case of disc sequestration where her symptoms were severely aggravated after a sudden jolt felt on her lower back while traveling on a motorcycle. The patient's Oswestry disability index (ODI) score was 90 % which indicates a bed-bound condition and even Schobar's test indicated a severe reduction in lumbar flexion capability. MRI showed postero-central herniation with disc sequestration at L5-S1 caused compression on the subarachnoid space and traversing S1 nerve roots. She was treated according to Ayurveda treatment principles and underwent Panchakarma like medicated enema (Basti) and fomentation of a lumbosacral region with oil (Kati Basti). She also received different oral medications on successive follow-ups. After 6 months of Ayurveda treatment, the patient showed remission in lower back pain (LBP), radiculopathy, and numbness. Her ODI score was reduced to 6 %. The MRI repeated post-treatment showed complete interval resolution of disc sequestration and no neurological compression was observed.


Effect of mutations in lipooligosaccharide biosynthesis genes on virulence of Haemophilus influenzae type b.
Chemical mutagenesis techniques and genetic transformation methods were used to construct isogenic mutants of Haemophilus influenzae type b (Hib) defective in the ability to synthesize lipooligosaccharide (LOS). A mutant (17B) which expressed a LOS molecule with an altered oligosaccharide was less virulent than the wild-type parent strain, as determined by measurement of the ability of these strains to produce bacteremia in infant rats after intranasal challenge. Further mutagenesis of this mutant strain yielded two new mutants with different LOS phenotypes. Mutant 7A was slightly sensitive to the bactericidal activity present in normal infant rat serum and was even less virulent than its immediate parent strain (17B) in the intranasal challenge model. However, both mutants 17B and 7A could produce bacteremia and meningitis when introduced into infant rats by the intraperitoneal route. The other LOS mutant (14A) derived from mutant 17B exhibited a level of virulence equivalent to that of the original wild-type strain. Genetic transformation of wild-type chromosomal DNA into the essentially avirulent mutant 7A and selection of transformants on the basis of their LOS antigenic characteristics resulted in the sequential restoration of full virulence to this mutant. These findings suggest that LOS is involved on at least two different levels in the ability of Hib to produce invasive disease in the infant rat model. Changes in LOS phenotype can independently affect the ability of Hib to produce bacteremia after intranasal challenge and the sensitivity of Hib to killing by normal infant rat serum. These results reinforce the significance of Hib LOS in the expression of virulence by this pathogen.


Monkeypox-Related Stigma and Vaccine Challenges as a Barrier to HIV Pre-Exposure Prophylaxis among Black Sexual Minority Men.
The U.S. monkeypox (mpox) outbreak of 2022 was a unique emergent public health crisis disproportionately affecting Black sexual minority men (BSMM). Similar to other stigmas, mpox-related stigma may have adverse effects on BSMM, including deterring HIV prevention such as PrEP. Our study investigated the experiences and perceptions of BSMM related to mpox, including mpox-associated stigma, and PrEP engagement among BSMM. We conducted qualitative interviews of 24 BSMM attending HIV prevention-related events in the greater D.C. Metropolitan area. In-depth interviews were conducted via phone, and responses to questions specific to the mpox outbreak were analyzed using thematic analysis. We identified three key themes from the analysis: Mpox-related stigma, Mpox vaccine availability concerns, and Mpox vaccine hesitancy. Participants also described relationships between each of these three themes and PrEP use. Mpox stigma was particularly relevant as it is related to sexual stigma and is a deterrent to PrEP use. A sense of health system neglect of BSMM, especially related to low mpox vaccine availability, was also described. We identified mpox stigma and challenges related to mpox vaccination as key themes among BSMM, with implications for PrEP use. Future research exploring medical mistrust among BSMM, particularly related to HIV prevention, is recommended.


One-Carbon Ring Expansion of Indoles and Pyrroles: A Straightforward Access to 3-Fluorinated Quinolines and Pyridines.
3-Fluorinated quinolines and pyridines are prevalent pharmacophores, yet their synthesis is often challenging. Herein, we demonstrate that dibromofluoromethane as bromofluorocarbene source enables the one-carbon ring expansion of readily available indoles and pyrroles to structurally diverse 3-fluorinated quinolines and pyridines. This straightforward protocol requires only a short reaction time of ten minutes and can be performed under air atmosphere. Preliminary investigations reveal that this strategy can also be applied to the synthesis of other valuable azines by using different 1,1-dibromoalkanes as the bromofluorocarbene sources.


Quantitative heat dissipation characteristics in current-carrying GaN nanowires probed by combining scanning thermal microscopy and spatially resolved Raman spectroscopy.
Using an approach combining scanning thermal microscopy (SThM) and spatially revolved Raman spectroscopy, we have investigated quantitatively the heat dissipation characteristics in substrate-supported and suspended (with asymmetric type of contacts) current-carrying GaN nanowires with diameters of ∼40-60 nm, where the phonon confinement is expected to play an important role in thermal transport. In particular, this approach allows direct measurements of nanowire-substrate/electrode interface thermal resistances and the nanowire thermal conductivity. On the basis of these results, the nanowire-substrate thermal transfer was suggested to be the main heat dissipation route, counting for ∼80-93% of the total dissipated heat, whereas the nanowire-electrode interface plays a minor role. The relative significance of nanowire-substrate/electrode interfaces in dissipating heat was further demonstrated in suspended nanowire devices. The measured nanowire thermal conductivity (∼40-60 W/mK) is lower than that in bulk GaN, possibly due to the phonon confinement and boundary scattering effects. Besides providing quantitative insight into heat dissipation characteristics, our results also reveal aspects, particularly the topography-related thermal signals and the relative significance of various tip-sample thermal transfer processes, that are important to advancing the applications of SThM technique in nanoscale thermal characterizations.


[The choice of the revascularization method in the patients with critical ischemia of the lower extremities].
Immediate and remote results of surgical treatment of 407 patients, suffering the lower extremities tissues critical ischemia, were analyzed. In 223 patients (the first group) endovascular revascularization was performed, in 165 (the second group)--the open-access reconstructive operations, in 31 (the third group)--the combined or hybrid interventions. The immediate technical success of operations in all this groups was equal and up to 90%. The lower extremities high amputations and complications rate is trustworthy bigger after operative interventions, then after endovascular. The remote results, including the lower extremities preservation rate and survival indices, did not differ trustworthy in the groups. The reoperations rate in remote period for critical ischemia of the lower extremities recurrences is significantly bigger after endovascular interventions performance. Thus, endovascular and the open-access surgical procedures are equally effective in patients, suffering critical ischemia of the lower extremities, but, choosing the revascularization method, it is necessary to take into account the affection localization and spread, the certain venous conduit presence, as well as the risk and expected span of life.


AttentionViz: A Global View of Transformer Attention.
Transformer models are revolutionizing machine learning, but their inner workings remain mysterious. In this work, we present a new visualization technique designed to help researchers understand the self-attention mechanism in transformers that allows these models to learn rich, contextual relationships between elements of a sequence. The main idea behind our method is to visualize a joint embedding of the query and key vectors used by transformer models to compute attention. Unlike previous attention visualization techniques, our approach enables the analysis of global patterns across multiple input sequences. We create an interactive visualization tool, AttentionViz (demo: http://attentionviz.com), based on these joint query-key embeddings, and use it to study attention mechanisms in both language and vision transformers. We demonstrate the utility of our approach in improving model understanding and offering new insights about query-key interactions through several application scenarios and expert feedback.


Differential dynamics of spatial attention, position, and color coding within the parietofrontal network.
Despite an ever growing knowledge on how parietal and prefrontal neurons encode low-level spatial and color information or higher-level information, such as spatial attention, an understanding of how these cortical regions process neuronal information at the population level is still missing. A simple assumption would be that the function and temporal response profiles of these neuronal populations match that of its constituting individual cells. However, several recent studies suggest that this is not necessarily the case and that the single-cell approach overlooks dynamic changes in how information is distributed over the neuronal population. Here, we use a time-resolved population pattern analysis to explore how spatial position, spatial attention and color information are differentially encoded and maintained in the macaque monkey prefrontal (frontal eye fields) and parietal cortex (lateral intraparietal area). Overall, our work brings about three novel observations. First, we show that parietal and prefrontal populations operate in two distinct population regimens for the encoding of sensory and cognitive information: a stationary mode and a dynamic mode. Second, we show that the temporal dynamics of a heterogeneous neuronal population brings about complementary information to that of its functional subpopulations. Thus, both need to be investigated in parallel. Last, we show that identifying the neuronal configuration in which a neuronal population encodes given information can serve to reveal this same information in a different context. All together, this work challenges common views on neural coding in the parietofrontal network.


Response of osteocalcin and insulin resistance after a hypocaloric diet in obese patients.
Osteocalcin is a hormone with a complex cross-talk between adipose tissue and the skeleton. The aim of the present study was to explore the change of osteocalcin, insulin resistance, and adipocytokines after hypocaloric diet in obese patients. A population of 178 obese patients was analyzed. At basal time and 2 months after the dietary intervention, weight, fat mass, body mass index, basal glucose, insulin, insulin resistance (HOMA), total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, leptin, adiponectin, IL-6, TNF alpha and osteocalcin levels were measured. After dietary treatment, BMI, weight, fat mass, waist circumference, waist to hip ratio, systolic pressure, glucose, HOMA, triglycerides, total cholesterol, leptin and LDL cholesterol decreased significantly. Osteocalcin levels have a significant decrease after weight loss (Osteocalcin (ng/ml); 9.76 ± 5.3 vs 9.31 ± 4.1: p < 0.05). In correlation analysis, a negative association was detected among osteocalcin and age, BMI, fat mass, glucose, C reactive protein, interleukin-6. In the linear regression with age-, sex-, BMI, fat mass- and insulin- adjusted, only C reactive protein concentrations are related with osteocalcin levels -0.21 (CI 95%: -0.40 -0.009). Osteocalcin decreased after a weight loss treatment. Moreover, osteocalcin levels, before and after treatment, were related in a negative way with CRP fat mass, body mass index, age and glucose levels.


The frequency of prediabetes and contributing factors in patients with chronic kidney disease.
Uremia is a prediabetic state, but abnormal glucose metabolism and relative risk factors in non-diabetic chronic kidney disease (CKD) patients are not studied extensively. This study aimed to evaluate prediabetes and contributing factors in patients with CKD. We studied the frequency of prediabetes (defined as fasting plasma glucose 100-125 mg/dl and 2-h plasma glucose 140-199 mg/dl) and contributing risk factors in 91 (34 women and 57 men) non-diabetic CKD (GFR < 60) patients who were referred to Sina Hospital between November 2010 and November 2011. Impaired fasting glucose and impaired glucose tolerance were regarded as prediabetic state. Thirty-eight patients (41.8%), 28 male and 10 female, with mean age of 57.4 ± 17.1 yr, had prediabetes. Among these, 18.7% had impaired fasting glucose, 7.7% impaired glucose tolerance, and 15.4% combined impaired fasting glucose and impaired glucose tolerance. CKD patients with impaired glucose tolerance had more frequently hypertriglyceridemia (85.7% vs. 42.0%, p = 0.001), hypertension (66.6% vs. 31.4%, p = 0.004), and metabolic syndrome according to National Cholesterol Education Program Adult Treatment Panel III (52.3% vs. 25.7%, p = 0.02). Also, mean systolic blood pressure (134.2 ± 13.9 vs. 124.5 ± 20.0, p = 0.004) was higher in CKD patients with impaired glucose tolerance compared to CKD patients with normal glucose. Prediabetes is a frequent condition in CKD patients. Also, hypertriglyceridemia and hypertension are more prevalent in prediabetic CKD patients than in non-diabetic CKD patients.


A history of medical and biological imaging with polyvinylidene fluoride (PVDF) transducers.
Polyvinylidene fluoride (PVDF) is a ferroelectric polymer with unique properties suitable for use in a wide range of medical and biological imaging applications. Most notable among these is its low acoustic impedance, which matches that of the body reasonably well, and its flexible mechanical properties. This paper traces the exploitation of PVDF as a transducer material from its early beginnings for thyroid and breast imaging to its current well-established applications in ultrasound biomicroscopy. Although PVDF's electromechanical properties fall short of composite ceramic materials in the traditional diagnostic frequency range, it has significant advantages in the 25-to 100-MHz range. Design criteria for high frequency transducers are reviewed, and examples of relevant medical and biological images are used to illustrate the excellent image quality obtained with this remarkable material.


Adaptation of Leishmania cells to in vitro culture results in a more efficient reduction and transport of biopterin.
Leishmania major and Leishmania donovani cells freshly isolated from infected animals divided slowly as axenic promastigotes but the addition of biopterin in the culture medium greatly enhanced their growth. However, when cells were subjected to serial passages and adapted to culture, this growth-promoting effect of biopterin was no longer observed. Genetic analysis of these culture-adapted Leishmania cells demonstrated that the genes coding for the pterin reductase PTR1 or for the biopterin transporter BT1 were over-expressed. This suggests that Leishmania cells adapted to culture were more efficient in utilizing biopterin, an essential growth factor in Leishmania.


Extrahepatic platelet-derived growth factor-β, delivered by platelets, promotes activation of hepatic stellate cells and biliary fibrosis in mice.
Platelet-derived growth factor-β (PDGFB) is a mitogen for hepatic stellate cells (HSCs). We studied the cellular sources of PDGFB and the effects of a high-affinity monoclonal antibody against PDGFB (MOR8457) in mouse models of biliary fibrosis. Cellular sources of PDGFB were identified using quantitative reverse-transcription polymerase chain reaction, biochemical, and immunohistologic methods. Mice with advanced biliary fibrosis, MDR2(Abcb4)-null mice, and C57Bl/6 (control) mice were placed on 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-supplemented diets and were given weekly intraperitoneal injections of MOR8457. Platelets were depleted from MDR2-null mice by injection of an antibody against CD41, or inhibited with diets containing low-dose aspirin. Liver tissues were collected and analyzed by quantitative reverse-transcription PCR and histologic and biochemical analyses. Levels of PDGFB protein, but not messenger RNA, were increased in fibrotic livers of MDR2-null mice, compared with control mice. Platelet clusters were detected in the hepatic endothelium, in close proximity to HSCs, and were identified as a source of PDGFB protein in MDR2-null mice. Levels of the PDGFB were increased in serum samples from patients with early stages of liver fibrosis of various etiologies (F1-2, n = 16; P < .05), compared with nonfibrotic liver tissue (F0, n = 12). Depletion of platelets from MDR2-null mice normalized hepatic levels of PDGFB within 48 hours, reducing levels of a marker of HSC activation (α-smooth muscle actin) and expression of genes that promote fibrosis. Diets supplemented with low-dose aspirin reduced circulating serum and hepatic levels of PDGFB and significantly reduced progression of fibrosis in MDR2-null mice over 1 year. MOR8457 produced a dose-dependent decrease in liver fibrosis in MDR2-null mice, reducing collagen deposition by 45% and expression of fibrosis-associated genes by 50%, compared with mice given a control antibody. In vitro, platelets activated freshly isolated HSCs (induction of α-smooth muscle actin and fibrosis-associated genes) via a PDGFB-dependent mechanism. MOR8457 also reduced liver fibrosis in mice placed on DDC-supplemented diets. Platelets produce PDGFB to activate HSC and promote fibrosis in MDR2-null mice and mice on DDC-supplemented diets. Antiplatelet therapy or selective inhibition of PDGFB might reduce biliary fibrosis in patients with liver disease.


Characterization of the laminated layer of in vitro cultivated Echinococcus vogeli metacestodes.
The metacestode (larval) stages of the cestode parasites Echinococcus vogeli and E. multilocularis were isolated from the peritoneal cavity of experimentally infected C57BL/6 mice and were cultured in vitro for a period of up to 4 mo under conditions normally applied for the in vitro cultivation of E. multilocularis metacestodes. In contrast to E. multilocularis, E. vogeli did not exhibit extensive exogenous budding and proliferation but increased in size with a final diameter of up to 10 mm. Most metacestodes contained protoscoleces, singly or in groups, either associated with brood capsules or growing directly out of the germinal layer. Each individual metacestode was covered by an acellular translucent laminated layer that was considerably thicker than the laminated layer of E. multilocularis metacestodes. The ultrastructural characteristics, protein content, and carbohydrate composition of the laminated layer of in vitro cultivated E. vogeli and E. multilocularis were assessed using transmission electron microscopy, lectin fluorescence labeling, and lectin blotting assays. The laminated layer of E. vogeli is, as previously described for E. multilocularis metacestodes, largely composed of N-acetyl-beta-D-galactosaminyl residues and alpha- and beta-D-galactosyl residues, as well as of the core structure of O-linked carbohydrate chains, N-acetylgalactosamine-beta-1,3-galactose. However, in contrast to E. multilocularis, N-linked glycopeptides and alpha-D-mannosyl and/or glucosyl residues were also associated with the laminated layer of E. vogeli. The laminated layer from both species was isolated from in vitro cultivated metacestodes, and the purified fractions were comparatively analyzed. The protein:carbohydrate ratio (1:1) was similar in both parasites; however, the protein banding pattern obtained by silver staining following sodium dodecyl sulfate polyacrylamide gel electrophoresis suggested intrinsic differences in protein composition. A polyclonal antiserum raised against the E. multilocularis laminated layer and a monoclonal antibody, G11, directed against the major E. multilocularis laminated layer antigen Em2 did not cross-react with E. vogeli, indicating distinct compositional and antigenic differences between these 2 parasites.


Expression of genes encoding IGF1, IGF2, and IGFBPs in blood of obese adolescents with insulin resistance.
The development of obesity and its metabolic complications is associated with dys-regulation of various intrinsic mechanisms, which control basic metabolic processes via changes in the expression of numerous regulatory genes. The main goal of this work was to study the association between the expression of insulin-like growth factors (IGF1 and IGF2) and IGF-binding proteins and insulin resistance in obese adolescents for evaluation of possible contribution of these genes in development of insulin resistance. The expression of IGF1, IGF2, and IGFBPs mRNA was measured in blood of obese adolescents with normal insulin sensitivity and insulin resistance in comparison with the normal (control) individuals. In the blood of obese adolescents with normal insulin sensitivity the expression of IGFBP4, IGFBP5 and HTRA1 genes was down-regulated, but IGFBP2 and IGFBP7 genes up-regulated as compared to control (normal) group. At the same time, no significant changes in IGF1 and IGF2 gene expressions in this group of obese adolescents were found. Insulin resistance in obese adolescents led to up-regulation of IGF2, IGFBP2, and IGFBP7 gene expressions as well as to down-regulation of the expression of IGF1, IGFBP5 and HTRA1 genes in the blood in comparison with the obese patients, which have normal insulin sensitivity. Furthermore, the level of IGFBP4 gene expression was similar in both groups of obese adolescents. Results of this investigation provide evidence that insulin resistance in obese adolescents is associated with gene specific changes in the expression of IGF1, IGF2, IGFBP2, IGFBP5, IGFBP7, and HTRA1 genes and these changes possibly contribute to the development of glucose intolerance and insulin resistance.


Utilization of Arachis hypogaea hull, an agricultural waste for the production of activated carbons to remove phenol from aqueous solutions.
Arachis hypogaea hulls, an agricultural waste, were used to prepare activated carbon by chemical activation with zinc chloride under four different activation atmospheres. The most important parameter in chemical activation was found to be the chemical ratio (activating agent/precursor). Carbonization temperature and time are the other two important variables, which had significant effect on the pore structure of carbon. The maximum Brunquer-Emmett-Teller (BET) surface area and micropore volume of the activated carbon was found to be 418 m(2)/g and 0.28 cm(3)/g, respectively. The activated carbon developed shows substantial capability to adsorb phenol from aqueous solutions. The kinetic data were fitted to the models of intraparticle diffusion, pseudo-second-order, and Lagergren, and followed more closely the pseudo-second-order chemisorption model. The isotherm equilibrium data were well fitted by the Langmuir and Freundlich models. Solution pH has significant effect on adsorption and the maximum uptake of phenol was reported at pH 3.5.


Carbohydrate epitope defined by an antitumor monoclonal antibody detected on glycoproteins and a glycolipid by immunoblotting.
The murine monoclonal antibody (MAb) MOv2 was found to be directed against the carbohydrate moieties of different kinds of molecules expressed on a human ovarian cystoadenocarcinoma. To define further the glycoconjugates carrying the MOv2-defined epitope, different procedures were used to analyze materials from surgical specimens and carcinoma cell lines. SDS-PAGE and immunoblotting showed glycoprotein molecules migrating in the gel as high and intermediate molecular weight components. A low-molecular-weight band, migrating approximately with the dye front, was also immunostained by MOv2. On the other hand, the immunostaining of high-performance thin-layer chromatography (HPTLC) of the total glycolipid extract and its neutral and acid fractions, after DEAE chromatography, showed selective reactivity with a neutral glycolipid. Reanalysis by immunoblotting of this glycolipid band scraped off the HPTLC plate indicated that it corresponds to the low-molecular-weight component. Periodate oxidation and Pronase digestion further demonstrate the saccharide nature of the determinant on both types of glycoconjugates. In conclusion, we report evidence that with a single analytical procedure, i.e., immunoblotting, it is possible to recognize the same carbohydrate determinant carried on both protein and lipid molecules.


Daily Intake of Grape Powder Prevents the Progression of Kidney Disease in Obese Type 2 Diabetic ZSF1 Rats.
Individuals living with metabolic syndrome (MetS) such as diabetes and obesity are at high risk for developing chronic kidney disease (CKD). This study investigated the beneficial effect of whole grape powder (WGP) diet on MetS-associated CKD. Obese diabetic ZSF1 rats, a kidney disease model with MetS, were fed WGP (5%, w/w) diet for six months. Kidney disease was determined using blood and urine chemical analyses, and histology. When compared to Vehicle controls, WGP intake did not change the rat bodyweight, but lowered their kidney, liver and spleen weight, which were in parallel with the lower serum glucose and the higher albumin or albumin/globin ratio. More importantly, WGP intake improved the renal function as urination and proteinuria decreased, or it prevented kidney tissue damage in these diabetic rats. The renal protection of WGP diet was associated with up-regulation of antioxidants (Dhcr24, Gstk1, Prdx2, Sod2, Gpx1 and Gpx4) and downregulation of Txnip (for ROS production) in the kidneys. Furthermore, addition of grape extract reduced H₂O₂-induced cell death of cultured podocytes. In conclusion, daily intake of WGP reduces the progression of kidney disease in obese diabetic rats, suggesting a protective function of antioxidant-rich grape diet against CKD in the setting of MetS.


Cactus Endophytic Fungi and Bioprospecting for their Enzymes and Bioactive Molecules: A Systematic Review.
Endophytic fungi are associated with plant health and represent a remarkable source of potential of enzymes and bioactive compounds, but the diversity of endophytes remains uncertain and poorly explored, especially in Cactaceae, one of the most species-rich families adapted to growing in arid and semi-arid regions. The aim of this study was to conduct a systematic review on the diversity and bioprospecting of endophytic fungi from Cactaceae. We analysed peer-reviewed articles from seven databases using PRISMA guidelines. The results showed that the Cactaceae family is a source of new taxa, but the diversity of endophytic fungi of Cactaceae is little explored, mainly the diversity among tissues and by metagenomics. Bioprospecting studies have shown that these microorganisms can be used in the production of enzymes and larvicidal and antifungal compounds. Our results are relevant as a starting point for researchers to develop studies that expand the knowledge of plant mycobiota in arid and semi-arid ecosystems, as well as comprising a remarkable source of fungal compounds with several biotechnological applications.


RBM45 associates with nuclear stress bodies and forms nuclear inclusions during chronic cellular stress and in neurodegenerative diseases.
The RNA binding protein (RBP) RBM45 forms nuclear and cytoplasmic inclusions in neurons and glia in amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration with TDP-43 proteinopathy (FTLD-TDP), and Alzheimer's disease (AD). The normal functions of RBM45 are poorly understood, as are the mechanisms by which it forms inclusions in disease. To better understand the normal and pathological functions of RBM45, we evaluated whether the protein functions via association with several membraneless organelles and whether such an association could promote the formation of nuclear RBM45 inclusions. Under basal conditions, RBM45 is diffusely distributed throughout the nucleus and does not localize to membraneless organelles, including nuclear speckles, Cajal bodies, or nuclear gems. During cellular stress, however, nuclear RBM45 undergoes a reversible, RNA-binding dependent incorporation into nuclear stress bodies (NSBs). Chronic stress leads to the persistent association of RBM45 with NSBs and the irreversible accumulation of nuclear RBM45 inclusions. We also quantified the cell type- and disease-specific patterns of RBM45 pathology in ALS, FTLD-TDP, and AD. RBM45 nuclear and cytoplasmic inclusions are found in both neurons and glia in ALS, FTLD-TDP, and AD but are absent in non-neurologic disease controls. Across neurodegenerative diseases, RBM45 nuclear inclusion pathology occurs more frequently than cytoplasmic RBM45 inclusion pathology and exhibits cell type-specific variation. Collectively, our results define new stress-associated functions of RBM45, a mechanism for nuclear RBM45 inclusion formation, a role for NSBs in the pathogenesis of ALS, FTLD-TDP, and AD, and further underscore the importance of protein self-association to both the normal and pathological functions of RBPs in these diseases.


Tough, high conductivity pectin polysaccharide-based hydrogel for strain sensing and real-time information transmission.
Hydrogels from natural polymers are eco-friendly, biocompatible and adjustable for manufacturing wearable sensors. However, it is still challenging to prepare natural polymer hydrogel sensors with excellent properties (e.g., high conductivity). Here, we developed a physically cross-linked, highly conductive and multifunctional hydrogels (named PPTP) to address this challenge. The natural renewable pectin based PPTP hydrogel is synthesized by introducing tannic acid (TA), calcium chloride (CaCl2), and sodium chloride (NaCl) into the pectin/polyvinyl alcohol (PVA) dual network structure. The hydrogel exhibits excellent characteristics, including unique tensile strength (2.6155 MPa), high electrical conductivity (7 S m-1), and high sensitivity (GF = 3.75). It is also recyclable, further enhancing its eco-friendly nature. The PPTP hydrogel can be used for monitoring human joint activities, as flexible electrodes for monitoring electrocardiogram (ECG) signals, and touchable screen pen for electronic skin. Moreover, when combined with Morse code and wireless Bluetooth technology, PPTP hydrogels can be used for underwater and land information encryption, and decryption. Our unique PPTP hydrogel offers promising opportunities for medical monitoring, information transfer, and human-computer interaction.


Low dose of luteolin activates Nrf2 in the liver of mice at start of the active phase but not that of the inactive phase.
A flavone luteolin has various health-promoting activities. Several studies reported that high dose of luteolin activates the Nrf2/ARE pathway in the liver. However, the effect of the low dose of luteolin that can be taken from a dietary meal on the Nrf2 activation remain unclear. It is expected that the flavonoid metabolism possesses a circadian rhythm, since nutritional metabolism processes daily cycle. In this study we investigated whether an administration affects the Nrf2 activation. ICR mice were orally administered 0.01-10 mg/kg body weight of luteolin once a day for 7 days at two time-points: at the start of active phase (ZT12) or at that of inactive phase (ZT0). Luteolin increased the nuclear translocation of Nrf2, resulting in the increases in its target gene products HO-1 and NQO1 at ZT12 but not at ZT0. The expression level of Nrf2 was lower at ZT12 than at ZT0 in the liver. We also found that the level of luteolin aglycon in the plasma is higher at ZT12 than at ZT0. These results suggest that the low dose of luteolin can activate Nrf2 pathway and the aglycon form of luteolin may mainly contribute to activate the Nrf2 pathway at ZT12 in the liver.


[Aging experiences in rural Mexico].
To explore the aging experience among men and women older than 60 years, living in rural areas from the states of Guerrero and Morelos, Mexico. A qualitative study was conducted in poverty-stricken, underserved communities with less than 2,500 inhabitants. Semi-structured interviews were applied to collect data. The aging experience is different according to gender, being more positive for women. Loneliness, together with social networks and the health-illness process, make the difference in the aging experiences. The main fears associated with aging are loneliness, illness, poverty, and loss of independence. Gender identity plays a central role in different aging experiences because the chances for development and accompanying responsibilities foster the inequality between men and women. It is necessary to improve institutional responses tailored to the specific needs of this population.


Suicide and Covid-19 in Mexico: an update to 2021.
To update prior studies on the impact of Covid-19 on suicide in Mexico. We used interrupted time-series analysis to model the national trend in monthly suicides before Covid-19 (January 1, 2010, to March 31, 2020), comparing the expected number of suicides with the observed number for the remainder of the period (April 1, 2020, to December 31, 2021). We observed a 5% increase in suicides, driven by suicides among the younger females ages <44 years and among older males ages 45+. Since in Mexico the impact of Covid-19 on suicide depended on sex and age, tailored public health strategies may be needed to confront the problem.


Predicting Performance in Higher Education Using Proximal Predictors.
We studied the validity of two methods for predicting academic performance and student-program fit that were proximal to important study criteria. Applicants to an undergraduate psychology program participated in a selection procedure containing a trial-studying test based on a work sample approach, and specific skills tests in English and math. Test scores were used to predict academic achievement and progress after the first year, achievement in specific course types, enrollment, and dropout after the first year. All tests showed positive significant correlations with the criteria. The trial-studying test was consistently the best predictor in the admission procedure. We found no significant differences between the predictive validity of the trial-studying test and prior educational performance, and substantial shared explained variance between the two predictors. Only applicants with lower trial-studying scores were significantly less likely to enroll in the program. In conclusion, the trial-studying test yielded predictive validities similar to that of prior educational performance and possibly enabled self-selection. In admissions aimed at student-program fit, or in admissions in which past educational performance is difficult to use, a trial-studying test is a good instrument to predict academic performance.


The fatty acid composition of muscle and adipose tissue of steers offered unwilted or wilted grass silage supplemented with sunflower oil and fishoil.
The effects of the type of grass silage and dietary inclusion of fish oil (FO) on the fatty acid profile of bovine intramuscular and subcutaneous adipose tissue were investigated. Eighty Friesian steers were assigned (n 10) to unwilted or wilted silage, and to one of four rations which contained, per kg, 80 g of sunflower oil and either 0, 10, 20 or 40 g of FO replacing lard. Animals were slaughtered after 108 d and the fatty acid profile of the neutral, polar and total lipid fractions of the M. longissimus dorsi, and the total lipid fraction of the subcutaneous adipose tissue were determined. Wilting of grass prior to ensiling increased the concentration of conjugated linoleic acid (CLA) in intramuscular total lipid (P<0 x 01), but did not affect the n-6:n-3 PUFA ratio. Increasing FO supply linearly increased (P<0 x 05) the concentration of the cis-9, trans-11 and trans-10, cis-12 isomers of CLA and trans-11 18 : 1 predominantly in the neutral lipid fraction of intramuscular total lipid, and linearly decreased the n-6:n-3 PUFA ratio. Wilting of grass prior to ensiling increased the concentration of CLA in subcutaneous adipose tissue (P<0 x 001), while increasing FO supply linearly increased the concentration of cis-9, trans-11 CLA. From a human nutrition perspective, increasing the level of FO in the ration or wilting of grass prior to ensiling appear to modify the fatty acid composition of beef muscle favourably. However, the health implications of associated increases in trans fatty acids remain to be elucidated.


[Remarks on the possibility of the introduction of fractionated dose of the inactivated poliomyelitis vaccine in the Latin American Child Immunization Schedule].
As last notified case of poliomyelitis due to wild poliovirus type 2 was 1999, in 2012, the Strategic Advisory Group of Experts on Immunization (SAGE) of the World Health Organization (WHO) recommended the withdrawal of the type 2 component of oral polio vaccine (OPV) and the introduction of bivalent OPV (bOPV) in all countries by 2016. WHO recommended also that the withdrawal should be preceded by the introduction of at least one dose of inactivated poliovirus vaccine (IPV) in routine immunization schedules. The introduction of IPV prior to the change of the bOPV in 2016 to trivalent OPV (tOPV) was based on the concept of ensuring that a substantial proportion of the population would be protected against type 2 polio after the removal of the type 2 OPV. However, the world's two producers of IPV (Bilthoven Biologicals and Sanofi) have faced problems in the production of this vaccine and therefore reported reduction in IPV global supply. In response to the possible shortage of IPV, the SAGE and Technical Adviser Group (TAG) of the Pan American Health Organization (PAHO), in the meeting of March 10, 2017, has urged that countries in the Latinamerican region should replace the routine administration of the full doses of polio inactivated vaccine (IPV-C) in the immunization schedule (administered by intramuscular route) by the administration of a fraction of the full dose in two shots by intradermal route (IPV-f). The possibility of this strategy was analyzed by leaders of opinions gathered by the call of the Paraguayan Pediatric Society with the support of the Latin American Society of Pediatric Infectious Diseases (SLIPE) and Latin American Association of Pediatrics (ALAPE). The results of the discussion are presented in this document.


Immunotoxin targeting EpCAM effectively inhibits peritoneal tumor growth in experimental models of mucinous peritoneal surface malignancies.
Cytoreductive surgery and intraperitoneal (i.p.) chemotherapy constitute a curative treatment option in mucinous peritoneal surface malignancies of intestinal origin, but treatment outcome is highly variable and the search for novel therapies is warranted. Immunotoxins are attractive candidates for targeted therapy in the peritoneal cavity because of direct cytotoxicity, distinct mechanisms of action and tumor cell selectivity. The MOC31PE immunotoxin targets the tumor-associated adhesion protein EpCAM (Epithelial Cell Adhesion Molecule), and has been administered safely in early clinical trials. In our work, the efficacy of i.p. administration of MOC31PE alone and together with mitomycin C (MMC) was investigated in unique animal models of human mucinous peritoneal surface malignancies. In initial model validation experiments, clear differences in efficacy were demonstrated between MMC and oxaliplatin, favoring MMC in five investigated tumor models. Subsequently, MOC31PE and MMC were given as single i.p. injections alone and in combination. In the PMCA-2 model, moderate growth inhibition was obtained with both drugs, while the combination resulted in at least additive effects; whereas the PMP-2 model was highly sensitive to both drugs separately and in combination and intermediate sensitivity was found for the PMCA-3 model. Furthermore, results from ex vivo experiments on freshly obtained mucinous tumor tissue from animals and patients suggested that classic mechanisms of immunotoxin activity were involved, i.e., inhibition of protein synthesis and induction of apoptosis. The present results suggest that adding MOC31PE to MMC-based i.p. chemotherapy should be further explored for EpCAM-expressing peritoneal surface malignancies, and a phase I trial is in preparation.


Interpreting subtle inconsistency: a developmental-clinical perspective.
The meaning attributed to subtle inconsistent messages by outpatient clinical and nonclinical adolescents was studied. The verbal and nonverbal cues used to attribute this meaning were also studied. Both groups attributed meaning to consistent messages accurately and without hesitation and attributed meaning to subtle inconsistent messages with much less consensus and clarity. The clinical group used a verbal focus at times and a nonverbal one at other times to interpret consistent and inconsistent messages that were indicative of a developmentally transitional phase. Nonclinical adolescents always used a nonverbal focus to interpret consistent and inconsistent messages in a developmentally age-appropriate manner.


Effect of type and concentration of ballasting particles on sinking rate of marine snow produced by the appendicularian Oikopleura dioica.
Ballast material (organic, opal, calcite, lithogenic) is suggested to affect sinking speed of aggregates in the ocean. Here, we tested this hypothesis by incubating appendicularians in suspensions of different algae or Saharan dust, and observing the sinking speed of the marine snow formed by their discarded houses. We show that calcite increases the sinking speeds of aggregates by ~100% and lithogenic material by ~150% while opal only has a minor effect. Furthermore the effect of ballast particle concentration was causing a 33 m d(-1) increase in sinking speed for a 5×10(5) µm(3) ml(-1) increase in particle concentration, near independent on ballast type. We finally compare our observations to the literature and stress the need to generate aggregates similar to those in nature in order to get realistic estimates of the impact of ballast particles on sinking speeds.


Modulation of Rumen Microbes Through Extracellular Vesicle Released by the Rumen Fluke Calicophoron daubneyi.
Parasite derived extracellular vesicles (EVs) have been proposed to play key roles in the establishment and maintenance of infection. Calicophoron daubneyi is a newly emerging parasite of livestock with many aspects of its underpinning biology yet to be resolved. This research is the first in-depth investigation of EVs released by adult C. daubneyi. EVs were successfully isolated using both differential centrifugation and size exclusion chromatography (SEC), and morphologically characterized though transmission electron microscopy (TEM). EV protein components were characterized using a GeLC approach allowing the elucidation of comprehensive proteomic profiles for both their soluble protein cargo and surface membrane bound proteins yielding a total of 378 soluble proteins identified. Notably, EVs contained Sigma-class GST and cathepsin L and B proteases, which have previously been described in immune modulation and successful establishment of parasitic flatworm infections. SEC purified C. daubneyi EVs were observed to modulate rumen bacterial populations by likely increasing microbial species diversity via antimicrobial activity. This data indicates EVs released from adult C. daubneyi have a role in establishment within the rumen through the regulation of microbial populations offering new routes to control rumen fluke infection and to develop molecular strategies to improve rumen efficiency.


Intraluminal Brachytherapy in Unresectable Extrahepatic Biliary Duct Cancer: An Italian Pooled Analysis.
To evaluate the outcome of patients with unresectable extrahepatic cholangiocarcinoma (CC) treated with external-beam radiotherapy (EBRT) and concurrent chemotherapy (CT) with or without intraluminal brachytherapy (ILBT) boost or with definitive ILBT. A pooled analysis of patients with non-metastatic unresectable CC was performed. They were treated in three different institution with EBRT plus CT with or without an ILBT boost. Some patients received only ILBT with curative dose. Seventy-three patients were included in the analysis. Thirty-nine patients (53%) received EBRT treatment with ILBT boost (18 patients with CT during EBRT), while 28 patients (38%) were treated with EBRT (CT in 26 patients) and 6 patients (8.2%) with definitive ILBT (2 patients with CT). CT was administered including either the use of gemcitabine or 5-fluorouracil. With a median follow-up of 16 month (range=1-94 months), median overall survival (OS) was 16 months. Overall median LC was 16 months and patients who underwent ILBT had a better local control (LC) (p=0.018). The role of ILBT in unresectable CC is not yet supported by robust evidence in the literature. However, within this limit, preliminary results seem to suggest an improved local control in patients treated with ILBT, almost comparable to the ones of standard chemo-radiotherapy (CRT).


Synthesis, Regulation and Degradation of Carotenoids Under Low Level UV-B Radiation in the Filamentous Cyanobacterium Chlorogloeopsis fritschii PCC 6912.
Carotenoids in cyanobacteria play an important role in protecting against and in repairing damage against low level UV-B radiation. Here we use transcriptomics and metabolomic HPLC pigment analysis to compare carotenoid pathway regulation in the filamentous cyanobacterium Chlorogloeopsis fritschii PCC 6912 exposed to white light and to white light supplemented with low level UV-B. Under UV-B changes in carotenoid transcription regulation were found associated with carotenogenesis (carotenoid synthesis), photoprotection and carotenoid cleavage. Transcriptional regulation was reflected in corresponding pigment signatures. All carotenogenesis pathway genes from geranylgeranyl-diphosphate to lycopene were upregulated. There were significant increases in expression of gene homologs (crtW, crtR, cruF, and cruG) associated with routes to ketolation to produce significant increases in echinenone and canthaxanthin concentrations. There were gene homologs for four β-carotene-ketolases (crtO and crtW) present but only one crtW was upregulated. Putative genes encoding enzymes (CruF, CrtR, and CruG) for the conversion of γ-carotene to myxol 2'-methylpentoside were upregulated. The hydroxylation pathway to nostaxanthin via zeaxanthin and caloxanthin (gene homologs for CrtR and CrtG) were not upregulated, reflected in the unchanged corresponding pigment concentrations in zeaxanthin, caloxanthin and nostaxanthin, Transcripts for the non-photochemical quenching related Orange-Carotenoid-Protein (OCP) and associated Fluoresence-Recovery-Protein (FRP) associated with photoprotection were upregulated, and one carotenoid binding Helical-Carotenoid-Protein (HCP) gene homolog was downregulated. Multiple copies of genes encoding putative apocarotenoid related carotenoid oxygenases responsible for carotenoid cleavage were identified, including an upregulated apo-β-carotenal-oxygenase gene homologous to a retinal producing enzyme. Our study provides holistic insight into the photoregulatory processes that modulate the synthesis, photoprotection and cleavage of carotenoids in cyanobacterial cells exposed to low level UV-B. This is important to understanding how regulation of metabolism responds to a changing environment and how metabolism can be modulated for biotechnological purposes.


[Retroperitoneal Dedifferentiated Liposarcoma which Could Be Diagnosed Using Dual Color in Situ Hybridization : A Case Report].
Ten years ago, a seventy-year-old female underwent extirpation of a left retroperitoneal tumor that was 58×36 mm in size. The pathological diagnosis was malignant peripheral nerve sheath tumor (MPNST) at that time. The patients visited our hospital with the chief complaint of back pain at ten years after surgery. Computer tomography (CT) showed recurrent tumors at the pancreas and the left kidney. Fine-needle aspiration biopsy was performed because of the possibility of pancreatic tumor. The pathological diagnosis was the recurrence of MPNST. The patient underwent extirpation of the recurrent tumors along with the pancreatic body and tail, transverse colon, spleen and left kidney. The definitive diagnosis was dedifferentiated liposarcoma with murine double minute 2 (MDM2) gene amplification and positive of p16Ink4 (p16). The previously resected tumor also revealed MDM2 gene amplification and positive of p16. Based on these results, our diagnosis in this case was recurrence of dedifferentiated liposarcoma. At 6 months after surgery, the patient had no local recurrence or distant metastases.


Permselective dysfunction of podocyte-podocyte contact upon angiotensin II unravels the molecular target for renoprotective intervention.
Ameliorating the function of the glomerular barrier to circulating proteins by blocking angiotensin II (Ang II) translates into less risk of progression toward end-stage renal failure in diabetic and nondiabetic nephropathies. However, the mechanisms underlying this barrier protection are not clear. Specialized contacts between adjacent podocytes are major candidate targets, and the actin cytoskeleton is emerging as a regulatory element. Here, we present data demonstrating that Ang II induced reorganization of F-actin fibers and redistribution of zonula occludens-1 (ZO-1) that is physically associated with actin in murine podocytes. These effects were paralleled by increased albumin permeability across podocyte monolayers. The F-actin stabilizer jasplakinolide prevented both ZO-1 redistribution and albumin leakage, suggesting that actin cytoskeleton rearrangement is instrumental to podocyte permselective dysfunction induced by Ang II. Changes in both F-actin and ZO-1 patterns were confirmed in glomeruli of rat isolated perfused kidneys on short infusion of Ang II, leading to increased protein excretion. Podocyte dysfunction was mediated by Ang II type 1 receptor and was partly dependent on Src kinase-phospholipase C activation. These data demonstrate that strategies aimed at stabilizing podocyte-podocyte contacts and targeting the relevant intracellular signal transduction are crucial to renoprotection.


Reasons parents exempt children from receiving immunizations.
School nurses are on the front lines of educational efforts to promote childhood vaccinations. However, some parents still choose to exempt their children from receiving vaccinations for personal reasons. Studying the beliefs of parents who exempt vaccinations allows health care workers, including school nurses, to better understand parental concerns which may, in turn, help prepare school nurses for effective communication with these parents. The objective of the study was to explore personal beliefs of parents living in Utah, who exempted their children from receiving vaccinations. A cross-sectional, descriptive design was implemented. Data were collected from a convenience sample of 287 parents responding to an open-ended question about why they exempted their children from receiving at least one vaccination. The qualitative data included parental comments, concerns, or suggestions regarding childhood vaccinations. Five categories were identified regarding reasons for personal exemptions: parental perceptions, health care systems issues, chronic disease concerns, immune system concerns, adverse reaction concerns and other reasons not classified. The number of parents refusing childhood vaccinations remains relatively low; however, despite public health efforts, the percentage increases each year.


RNA sequence and secondary structure participate in high-affinity CsrA-RNA interaction.
The global Csr regulatory system controls bacterial gene expression post-transcriptionally. CsrA of Escherichia coli is an RNA binding protein that plays a central role in repressing several stationary phase processes and activating certain exponential phase functions. CsrA regulates translation initiation of several genes by binding to the mRNA leaders and blocking ribosome binding. CsrB and CsrC are noncoding regulatory RNAs that are capable of sequestering CsrA and antagonizing its activity. Each of the known target transcripts contains multiple CsrA binding sites, although considerable sequence variation exists among these RNA targets, with GGA being the most highly conserved element. High-affinity RNA ligands containing single CsrA binding sites were identified from a combinatorial library using systematic evolution of ligands by exponential enrichment (SELEX). The SELEX-derived consensus was determined as RUACARGGAUGU, with the ACA and GGA motifs being 100% conserved and the GU sequence being present in all but one ligand. The majority (51/55) of the RNAs contained GGA in the loop of a hairpin within the most stable predicted structure, an arrangement similar to several natural CsrA binding sites. Strikingly, the identity of several nucleotides that were predicted to form base pairs in each stem were 100% conserved, suggesting that primary sequence information was embedded within the base-paired region. The affinity of CsrA for several selected ligands was measured using quantitative gel mobility shift assays. A mutational analysis of one selected ligand confirmed that the conserved ACA, GGA, and GU residues were critical for CsrA binding and that RNA secondary structure participates in CsrA-RNA recognition.


Effort-related decision making and cannabis use among college students.
Cannabis exerts an indirect effect on dopamine (DA) output in the mesolimbic projection, a circuit implicated in reward processing and effort expenditure, and thus may be associated with aberrant effort-based decision making. The "amotivation syndrome" hypothesis suggests that regular cannabis use results in impaired capacity for goal-directed behavior. However, investigations of this hypothesis have used divergent methodology and have not controlled for key confounding variables. The present study extends these findings by examining the relation between cannabis use and effort-related decision making in a sample of college students. Cannabis using (n = 25; 68% meeting criteria for Cannabis Use Disorder) and noncannabis using (n = 22) students completed the Effort Expenditure for Rewards Task (EEfRT). In generalized estimating equation models, reward magnitude, reward probability, and expected value predicted greater likelihood of selecting a high-effort trial. Furthermore, past-month cannabis days and cannabis use disorder symptoms predicted the likelihood of selecting a high-effort trial, such that greater levels of both cannabis use days and symptoms were associated with an increased likelihood after controlling for Attention Deficit/Hyperactivity Disorder (ADHD) symptoms, distress tolerance, income, and delay discounting. The results provide preliminary evidence suggesting that college students who use cannabis are more likely to expend effort to obtain reward, even after controlling for the magnitude of the reward and the probability of reward receipt. Thus, these results do not support the amotivational syndrome hypothesis. Future research with a larger sample is required to evaluate possible associations between cannabis use and patterns of real-world effortful behavior over time. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Histamine gustatory aversion in Drosophila melanogaster.
Many foods and drinks contain histamine; however, the mechanisms that drive histamine taste perception have not yet been investigated. Here, we use a simple model organism, Drosophila melanogaster, to dissect the molecular sensors required to taste histamine. We first investigated histidine and histamine taste perception by performing a binary food choice assay and electrophysiology to identify essential sensilla for histamine sensing in the labellum. Histamine was found to activate S-type sensilla, which harbor bitter-sensing gustatory receptor neurons. Moreover, unbiased genetic screening for chemoreceptors revealed that a gustatory receptor, GR22e and an ionotropic receptor, IR76b are required for histamine sensing. Ectopic expression of GR22e was sufficient to induce a response in I-type sensilla, which normally do not respond to histamine. Taken together, our findings provide new insights into the mechanisms by which insects discriminate between the toxic histamine and beneficial histidine via their taste receptors.


Imaging the secretory compartments involved in the intracellular traffic of CHS-4, a class IV chitin synthase, in Neurospora crassa.
In Neurospora crassa hyphae the localization of all seven chitin synthases (CHSs) at the Spitzenkörper (SPK) and at developing septa has been well analyzed. Hitherto, the mechanisms of CHSs traffic and sorting from synthesis to delivery sites remain largely unexplored. In Saccharomyces cerevisiae exit of Chs3p from the endoplasmic reticulum (ER) requires chaperone Chs7p. Here, we analyzed the role of CSE-7, N. crassa Chs7p orthologue, in the biogenesis of CHS-4 (orthologue of Chs3p). In a N. crassa Δcse-7 mutant, CHS-4-GFP no longer accumulated at the SPK and septa. Instead, fluorescence was retained in hyphal subapical regions in an extensive network of elongated cisternae (NEC) referred to previously as tubular vacuoles. In a complemented strain expressing a copy of cse-7 the localization of CHS-4-GFP at the SPK and septa was restored, providing evidence that CSE-7 is necessary for the localization of CHS-4 at hyphal tips and septa. CSE-7 was revealed at delimited regions of the ER at the immediacies of nuclei, at the NEC, and remarkably also at septa and the SPK. The organization of the NEC was dependent on the cytoskeleton. SEC-63, an extensively used ER marker, and NCA-1, a SERCA-type ATPase previously localized at the nuclear envelope, were used as markers to discern the nature of the membranes containing CSE-7. Both SEC-63 and NCA-1 were found at the nuclear envelope, but also at regions of the NEC. However, at the NEC only NCA-1 co-localized extensively with CSE-7. Observations by transmission electron microscopy revealed abundant rough ER sheets and distinct electron translucent smooth flattened cisternae, which could correspond collectively to the NEC, thorough the subapical cytoplasm. This study identifies CSE-7 as the putative ER receptor for its cognate cargo, the polytopic membrane protein CHS-4, and elucidates the complexity of the ER system in filamentous fungi.


GISTs' classifications in predicting aggressive behavior: a single institution experience.
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract. When making treatment plan it is very important to make proper tumor aggressiveness estimation. Traditionally, the best prognostic factors are tumor size and number of mitoses. The aim of this study was to define which GIST classification (Amin's or Newman's classification or Fletcher's Consensus Criteria) is the most significant determining prognosis and has the strongest impact on survival. This study included 63 GIST patients whose tumor specimens were evaluated by standard histopathological methods and classified based on histological assessment of malignant behavior to the three different systems. Comparison of those classification systems was done and none of them was proven to be statistically significantly better in predicting overall survival and probability of lethal outcome. We conclude that all three classifications are comparable in prediction of malignant behavior. The worst prognostic factor is existence of metastases at the time of disease diagnosis.


Efficacy and safety of switching between biologics in chronic rhinosinusitis with nasal polyps or N-ERD.
The effectiveness of biologics in chronic rhinosinusitis with nasal polyps (CRSwNP) is well-established. However, real-world experience on the effectiveness of transitioning between two monoclonal antibodies is scarce. Therefore, we aimed to analyze the safety and efficacy of antibody switching in treatment of chronic rhinosinusitis. All patients with CRSwNP or nonsteroidal anti-inflammatory drugs-exacerbated respiratory disease (N-ERD) requiring a switch between biologics were retrospectively studied. Analysis included changes in polyp size, quality of life parameters, asthma control, and side effects. Out of 195 patients treated with biologics for CRSwNP or N-ERD in our center, 23 (11.8%) required transition to a different monoclonal antibody. The majority switched from omalizumab to dupilumab (17/23, 73.9%), mostly due to inadequate symptom control. Nine out of these 17 patients (52.9%) were switched without a washout period. All patients showed significant improvement in nasal polyp score, asthma control test and sino-nasal outcome test-22 after changing to dupilumab. Keratoconjunctivitis sicca was the side-effect (4.3%) reported after the switch from omalizumab to dupilumab, which lead to termination of therapy in one patient. Due to limited sample size, other antibody transitions were reported in a descriptive manner. The transition to dupilumab is an effective option in patients with inadequate treatment response or side-effects of omalizumab in nasal polyposis. Our preliminary results indicate that a wash-out period may not be necessary when switching between biologics, however, these findings require further investigations. Other monoclonal antibody transitions also show promising results, but warrant validations in larger cohorts due to small patient samples in our study.


[Effect of immunomodulator cycloferon on quality of life and psychoemotional state of patients with chronic active brucellosis subjected to complex pharmacotherapy].
Indices of the quality of life and parameters of the psychofunctional status of patients with chronic active brucellosis are presented and the clinical efficiency of immunomodulator cycloferon in a complex therapy of this disease is estimated for a group of 40 patients. Cycloferon was administered to 20 patients, while the control group of 20 other patients received only a traditional therapy. It is established that the chronic active brucellosis is accompanied by a considerable decrease in parameters of the quality of life. The administration of cycloferon on the background of a base therapy leads to improvement of the quality of life and the parameters of the psychoemotional status in comparison to those achieved with the traditional methods of therapy.


Collisional model of energy dissipation in three-dimensional granular impact.
We study the dynamic process occurring when a granular assembly is displaced by a solid impactor. The momentum transfer from the impactor to the target is shown to occur through sporadic, normal collisions of high force carrying grains at the intruder surface. We therefore describe the stopping force of the impact through a collisional-based model. To verify the model in impact experiments, we determine the forces acting on an intruder decelerating through a dense granular medium by using high-speed imaging of its trajectory. By varying the intruder shape and granular target, intruder-grain interactions are inferred from the consequent path. As a result, we connect the drag to the effect of intruder shape and grain density based on a proposed collisional model.


Role of Mitomycin C in Preventing Capsular Contracture in Implant-Based Reconstructive Breast Surgery: A Randomized Controlled Trial.
Capsular contracture represents the most frequent complication after implant-based breast reconstruction. An experimental study on mice demonstrated that capsule formation around breast implants is considerably diminished after topical application of mitomycin C. The authors conducted a randomized controlled clinical trial investigating the efficacy of mitomycin C in reducing capsular contracture rates following implant-based breast reconstruction after mastectomy for breast cancer. The authors randomized all women older than 18 years scheduled for the second stage of an implant-based breast reconstruction after mastectomy for breast cancer at the National Cancer Institute in Milan from October of 2005 to February of 2010 to receive or not receive the topical application of mitomycin C during surgery. The authors assessed capsular contracture, major postoperative complications, and aesthetic outcome. The authors randomized 322 patients to receive mitomycin C or not at the second stage of implant-based breast reconstruction. One hundred sixty-two patients were allocated to the mitomycin C group and 160 patients were allocated to the control group. The relative risk of capsular contracture in the mitomycin C group was 0.92 (95 percent CI, 0.60 to 1.41). Major complications leading to reintervention, oncologic outcomes, and aesthetic outcomes were comparable between the two groups. This is the first trial reporting data about the use of mitomycin C in breast reconstructive surgery in a clinical setting. Mitomycin C seems not to significantly affect capsular contracture rate and severity following implant-based reconstructive breast surgery at the tested doses. Therapeutic, I.


Effect of antifibrinolytic therapy with tranexamic acid on abdominal aortic aneurysm shrinkage after endovascular repair.
The long-term outcomes of endovascular abdominal aortic aneurysm repair (EVAR) remain to be determined, but patients with aneurysm shrinkage after EVAR appear to have a good prognosis. We previously observed that antiplatelet therapy is a risk factor for lack of aneurysm shrinkage, a finding suggesting that coagulation and fibrinolysis play roles in shrinkage. We therefore studied the effect of antifibrinolytic therapy with tranexamic acid (TXA) on aneurysm shrinkage after EVAR. From May 2007 to May 2012, EVAR was performed in 187 patients, 165 of whom had an enhanced computed tomographic evaluation 6 months after their procedure. Six of the 165 patients were excluded from the study because they had a type Ia endoleak or coil embolization to treat a type II endoleak ≤ 6 months after EVAR. Of the remaining 159 patients, 110 underwent EVAR before we started to use TXA in our centers. TXA therapy (1500 mg/d for 6 months) began in January 2011, and 48 patients completed the treatment regimen. Patients not treated with TXA were compared with those given TXA. Analyses to identify risk factors for lack of aneurysm shrinkage were performed. No patient had a thromboembolic event. There were no significant differences between the no-TXA and TXA groups in demographics, aneurysm characteristics, prosthesis implanted, type II endoleak occurrence during EVAR or 1 or 6 months afterward, or aneurysm shrinkage at 1 month. However, at 6 months after EVAR, the TXA group had significantly greater aneurysm shrinkage (P = .035) and a significantly higher percentage of patients with >4 mm in shrinkage (P = .010). Multiple regression analysis showed aneurysm diameter, type II endoleak 6 months after EVAR, and TXA treatment were independently associated with aneurysm shrinkage or lack of shrinkage. Antifibrinolytic therapy with TXA was associated with aneurysm shrinkage after EVAR. Studies to identify the dosage of TXA that is optimally safe and effective in this application, as well as investigations of the best timing and route (parenteral vs oral) for TXA administration, are warranted.


The human enamel protein gene amelogenin is expressed from both the X and the Y chromosomes.
Amelogenins, a family of extracellular matrix proteins of the dental enamel, are transiently but abundantly expressed by ameloblasts during tooth development. Amelogenins seem to regulate the formation of crystallites during the secretory stage of enamel development, while they are specifically degraded during tooth-bud maturation. In this paper we report the characterization of the AMGX and AMGY genes on the short arms of the human X and Y chromosomes which encode the amelogenins. Our studies on the expression of the amelogenin genes in male developing tooth buds showed that both the AMGX and AMGY genes are transcriptionally active and encode potentially functional proteins. We have isolated genomic and cDNA clones from both the AMGX and AMGY loci and have studied the sequence organization of these two genes. Reverse transcriptase (RT)PCR amplification of the 5' portion of the amelogenin transcripts revealed several alternatively spliced products. The splicing pattern observed in the Y-derived mRNA varies from that of the X-derived mRNA. The promoter regions from both genes and the predicted amelogenin protein sequences are presented. This information will be useful for studying the molecular basis of X-linked amelogenesis imperfecta, for understanding the evolution and regulation of gene expression on the mammalian sex chromosomes, and for investigating the role of amelogenin genes during tooth development.


Histidase and histidinemia. Clinical and molecular considerations.
Histidase (histidine ammonia-lyase, EC 126.96.36.199) catalyzes the deamination of L-histidine to trans-urocanic acid in the liver and skin of mammals. Histidase deficiency results in increased histidine and histamine in blood, and decreased urocanic acid in blood and skin. In this review we discuss current research on: (1) the mechanism of formation of an unusual residue, dehydroalanine, at the active site of histidase; and (2) the role of urocanic acid as an ultraviolet light-induced immunoregulator in the skin, and the implications of urocanic acid deficiency for human histidinemia. Genetic mechanisms that may account for the 1% of histidinemic patients with neurological impairments are considered briefly.


A 10-hours workshop improves physical activity prescription for mental illness knowledge and confidence in health care professionals: a nation-wide multicentre study from Uganda.
Lack of knowledge about and confidence in physical activity (PA) prescription for people with mental illness are important barriers for clinical practice in low-income countries. The aim of this study was to evaluate whether a 10-hour workshop improved the knowledge and confidence in PA prescription among health care professionals in 13 regional referral hospitals across Uganda. 260 health care professionals (age = 40.4 ± 10.8 years; 48% women; 63.8% nurses, 10% social workers, 8.1% psychologists, 7.3% medical doctors, 5.8% psychiatrists, 5% physical or occupational therapists) completed the Exercise in Mental Illness Questionnaire - Health Professionals Version (EMIQ-HP) pre- and post-workshop. The EMIQ-HP PA knowledge score (3.1 ± 0.7 versus 1.3 ± 1.3, p < 0.001, Cohen's d = 1.28, 95% confidence interval, CI = 1.04-1.52, i.e., large effect) and EMIQ-HP confidence in PA prescription score (3.0 ± 0.8 versus 1.2 ± 1.2, p < 0.001, Cohen's d = 1.14, 95% CI = 0.91-1.36, i.e., large effect) improved significantly following training. Significantly more benefits and fewer barriers to prescribing PA in busy low-resourced settings were reported. Training in PA counselling improved the knowledge and confidence in PA prescription in Ugandan health care professionals. Future research should investigate whether PA uptake in people with mental illness can be improved via additional training of health care professionals.IMPLICATIONS FOR REHABILITATIONThe majority of mental health professionals never recommend physical activity to their patients in low-resourced settings and increased awareness is needed to improve rehabilitation programs.Training in prescribing physical activity using the 5A framework improves knowledge about physical activity prescription in mental health professionals at all levels of care.Training in prescribing physical activity using motivational interviewing improves confidence in physical activity prescription in rehabilitation programs.Training in prescribing physical activity reduces perceived barriers for prescribing in rehabilitation programs in low-resourced settings.


Burst fracture in the metastatically involved spine: development, validation, and parametric analysis of a three-dimensional poroelastic finite-element model.
A finite-element study and in vitro experimental validation was performed for a parametric investigation of features that contribute to burst fracture risk in the metastatically involved spine. To develop and validate a three-dimensional poroelastic model of a metastatically compromised vertebral segment, to evaluate the effect of lytic lesions on vertebral strains and pressures, and to determine the influence of loading and motion segment status (bone density, pedicle involvement, disc degeneration, and tumor size) on the relative risk of burst fracture initiation. Finite-element analysis has been used successfully to predict failure loads and fracture patterns for bone. Although models for vertebra affected with tumors have been presented, these have not been thoroughly validated experimentally. Consequently, their predictive capabilities remain uncertain. A three-dimensional poroelastic finite-element model of the first lumbar vertebra and adjacent intervertebral discs, including a tumor of variable size, was developed. To validate the model, 12 cadaver spinal motion segments were tested in axial compression, in intact condition, and with simulated osteolytic defects. Features of the validated model were parametrically varied to investigate the effects of tumor size, trabecular bone density, pedicle involvement, applied loads, loading rates, and disc degeneration using outcome variables of vertebral bulge and vertebral axial deformation. Consistent trends between the experimental data and model predictions were observed. Overall, the model results suggest that tumor size contributes most toward the risk of initiating burst fracture, followed by the applied load magnitude and bone density. The parametric analysis suggests that the principal factors affecting the initiation of burst fracture in metastatically affected vertebrae are tumor size, magnitude of spinal loading, and bone density. Consequently, patient-specific measures of these factors should be factored into decisions regarding clinical prophylaxis. Pedicle involvement or disc degeneration was less important according to the outcome measures in this study.


The effect of apolipoprotein E isoform difference on postprandial lipoprotein in patients matched for triglycerides, LDL-cholesterol, and HDL-cholesterol.
The postprandial response to three test meals provided during a single day was investigated in subjects with either the apo E3/3 phenotype (n = 8), or the apo E4/3 phenotype (n = 4), who had LDL-C greater than 160 mg/dl. Vitamin A (60,000 U/m2) was ingested with the first meal and retinyl palmitate determined four hours later. Triglyceride and total cholesterol concentration were determined on whole plasma and total cholesterol and free cholesterol determined following single spin ultracentrifugation (d less than 1.006 g/ml) and dextran precipitation of the d greater than 1.006 fraction to separate apoprotein-B containing lipoproteins. Fasting values revealed significantly lower HDL-cholesterol ester (p less than 0.03) and HDL3-cholesterol ester (p less than 0.03) and significantly greater HDL-free cholesterol (p less than 0.03) and HDL3-free cholesterol (p less than 0.02) in subjects with the E4/3 phenotype. Four hour postprandial HDL and HDL3 cholesterol ester increased significantly more (p less than 0.05) in E4/3 patients and HDL and HDL3 free cholesterol decreased significantly more (p less than 0.05) in E4/3 subjects. Eight-hour postprandial change values maintained the significant HDL3-cholesterol ester and free cholesterol difference, and, revealed a significantly greater triglyceride rich lipoprotein cholesterol ester reduction (p less than 0.01) in the E4/3 group. Individuals with the apolipoprotein E4/3 phenotype reveal significant differences in postprandial lipemia compared to individuals with the E3/3 phenotype, and, postprandial lipemia following multiple meals reveals differences not apparent from responses to a single meal.


Research progress of TiO2-based photocatalytic degradation of wastewater: bibliometric analysis.
The pollution caused by modernization and industrialization has caused serious harm to the biodiversity of the earth. TiO2-based photocatalyst has been widely studied as an effective and sustainable water environment remediation material. In this study, we analyzed the status and research trends of TiO2-based photocatalytic degradation of wastewater in depression from 2003 to 2023 to provide a reference for further research. "Doping", "Modification" and "Heterojunction" were used as keywords, and 817 related academic literatures were screened out by using Web of Science database. Through the visualization software VOSviewer and CiteSpace, the authors, institutions and literature keywords were clustered. The results show that since 2008, the annual number of published papers on TiO2-based photocatalytic degradation of wastewater has increased from 9 to 114. Among them, China has published 432 articles and made great contributions, and there are many representative research teams. Chinese universities are the main body to study TiO2-based photocatalytic degradation of wastewater, but the cooperation between universities is not as close as that abroad. This paper comprehensively analyzes the research hotspots of TiO2-based photocatalytic degradation of wastewater, such as the doping of TiO2 and the construction of different types of heterojunctions of TiO2. It is expected that these analysis results will provide new research ideas for researchers to carry out future research on related topics and let researchers know in-depth research institutions and possible collaborators to conduct academic exchanges and discussions with active institutions.


Viral vaccines for farmed finfish.
Over the past decade, aquaculture has grown at an average annual growth rate of approximately 6 % worldwide despite many challenges. Viral diseases are one of the major challenges that are threatening a sustainable growth of finfish farming globally. Vaccination of farmed fish plays an important role in commercial fish farming to mitigate viral diseases. In this review, we summarized the major viral diseases that have caused serious economic losses, and emerging diseases that pose a potential threat to aquaculture. The current status of viral vaccines in farmed fish are discussed, particularly the different types of vaccines that were licensed in recent years and are now commercially available, and the routes of delivery of those vaccines including the merits and demerits of each of these delivery method. Furthermore, the article provides an overview of different experimental vaccines that have been reported in the literatures in recent years besides highlighting the future need for developing cost-effective, oral vaccines that can be easily applicable at farm level.


Streptolysin O: sedimentation coefficient and molecular weight determinations.
The sedimentation coefficient of streptolysin O as determined by sucrose density gradient ultracentrifugation is 3.7S. An approximate molecular weight of 60,500 was calculated from the sedimentation velocity, and a similar value was obtained by Sephadex gel filtration. There was no measurable difference in the sedimentation coefficient of streptolysin O in either the active or reversibly inactive forms, indicating that there were at most only minor conformational differences between the two forms.


Refocusing acute psychiatry, performance management, standards and accountability, a new context for mental health nursing.
The term 'performance management' has an aversive 'managerial' aspect, is unappealing to many public sector staff and has an 'image problem'. Perhaps as a consequence, it has failed to make a significant impact on Irish public sector workers, notably mental health nurses. In this paper, performance management is introduced and examined within an Irish healthcare context and with reference to its use in other countries. Some of the challenges faced by Irish mental health nurses and the potential benefits of working within a performance managed workplace are discussed. The paper concludes that performance management is likely to increasingly affect nurses, either as active agents or as passive recipients of a change that is thrust on them. The authors anticipate that the performance management 'image problem' will give way to recognition that this is a fundamental change which has the potential to enable health services to change. This change will bring high standards of transparency, worker involvement in decision making, an explicit value base for health services and individual teams. It provides the potential for clear practice standards and high standards of transparency as well as worker welfare in all aspects, including supporting employment and career progression.


Asexual sporulation in coprinus cinereus: structure and development of oidiophores and oidia in an amut bmut homokaryon
Polak, E., Hermann, R., Kues, U., and Aebi, M. 1997. Asexual sporulation in Coprinus cinereus: Structure and development of oidiophores and oidia in an Amut Bmut homokaryon. 22, 112-126. Coprinus cinereus strain AmutBmut is a homokaryon with mutations in both mating type loci. It produces asexual spores (oidia) in sticky liquid droplets on specialized aerial structures (oidiophores). These oidiophores have uninucleate cells and are organized as those of the monokaryon 5026 from which the strain derived. However, unlike in the monokaryon, oidiophores in strain AmutBmut are induced by light. Young oidiophores are easily detected upon light induction and the process of oidiophore development is readily followed in this strain. Fully grown oidiophores consecutively give rise to short branches (oidial hyphae) that break up into two or occasionally three uninucleate oidia (arthroconidia) until up to 200 oidia are collected at the tip of the oidiophore. Mature spores are enclosed by a mucilage and a double-layered primary cell wall with hair-like structures except for the sides of former cell attachments. In a summary of our microscopic observations on developing oidiophores and nuclear stainings we present a model showing the successive steps of oidiophore and spore development.


Coronary microvascular endothelial stunning after acute pressure overload in the conscious dog is caused by oxidant processes: the role of angiotensin II type 1 receptor and NAD(P)H oxidase.
Few studies have examined the effect of acute pressure overload on endothelial function in the coronary microcirculation. In instrumented conscious dogs with heart rate held constant, veratrine caused a cholinergic nitric oxide (NO)-dependent increase in coronary blood flow by 23+/-3 mL/min (Bezold-Jarisch reflex). Ten minutes after release of constriction of the ascending aorta to increase left ventricular (LV) systolic pressure to 214+/-5 mm Hg for 30 minutes, the veratrine-induced increase in coronary blood flow (7+/-1 mL/min) was reduced by 66% and remained depressed for 2 hours (ie, endothelial stunning [ES]). Nitrite production from isolated coronary microvessels during ES was not different from normal. Ascorbic acid (AA), losartan, or apocynin prevented ES. Myocardial oxygen consumption (MVO2) of LV tissue was measured in vitro in response to bradykinin with preincubation of angiotensin II for 30 minutes. Bradykinin (10(-4) mol/L)-induced reduction in MVO2 was reversed in a concentration-dependent manner by angiotensin II (38+/-1% versus 19+/-2% at 10(-8) mol/L) and restored by coincubation of AA (37+/-2%), tempol (33+/-2%), losartan (34+/-2%), or apocynin (36+/-1%). Exogenous NO-induced reduction in MVO2 was not altered by angiotensin II. Angiotensin II increased lucigenin-detectable superoxide anion in LV tissue in a manner that was inhibited by bradykinin, AA, tempol, losartan, or apocynin. Endothelial stunning is caused by oxidant processes inhibited by ascorbate, and the activation of NAD(P)H oxidase by increased angiotensin II plays an important role in this process.