Mechanical properties and neural control of human hand motor units.
Motor units serve both as the mechanical apparatus and the final stage of neural processing through which motor behaviours are enacted. Therefore, knowledge about the contractile properties and organization of the neural inputs to motor units supplying finger muscles is essential for understanding the control strategies underlying the diverse motor functions of the human hand. In this brief review, basic contractile properties of motor units residing in human hand muscles are described. Hand motor units are not readily categorized into the classical physiological types as established in the cat gastrocnemius muscle. In addition, the distribution of descending synaptic inputs to motor nuclei supplying different hand muscles is outlined. Motor neurons innervating intrinsic muscles appear to have relatively independent lines of input from supraspinal centres whereas substantial divergence of descending input is seen across motor nuclei supplying extrinsic hand muscles. The functional significance of such differential organizations of descending inputs for the control of hand movements is discussed.


Effect of human skin explants on the neurite growth of the PC12 cell line.
The skin is a densely innervated organ. After a traumatic injury, such as an amputation, burn or skin graft, nerve growth and the recovery of sensitivity take a long time and are often incomplete. The roles played by growth factors and the process of neuronal growth are crucial. We developed an in vitro model of human skin explants co-cultured with a rat pheochromocytoma cell line differentiated in neuron in presence of nerve growth factor (NGF). This model allowed the study of the influence of skin explants on nerve cells and nerve fibre growth, probably through mediators produced by the explant, in a simplified manner. The neurite length of differentiated PC12 cells co-cultured with skin explants increased after 6 days. These observations demonstrated the influence of trophic factors produced by skin explants on PC12 cells.


Subjective Effects of Thiopental in Young Adults with and without a Family History of Alcoholism.
The development of alcohol use disorders is genetically influenced, and may be mediated through differences in the subjective response to alcohol. There is some evidence to suggest that response differences to alcohol could be conveyed by heritable differences in GABAA receptors. The purpose of this study was to investigate whether individuals with a family history positive (FHP) for alcohol dependence would experience alterations in response to the GABAA receptor agonist thiopental, in comparison to family history negative (FHN) subjects. 73 subjects (24 FHP and 49 FHN) between the ages of 21 and 30 years were administered sub-anesthetic doses of the GABAA receptor agonist thiopental and placebo on two separate test days. Various alcohol-related measures were administered, including those examining subjective effects, coordination, and cognition. Sub-anesthetic doses of thiopental produced alcohol-like subjective effects, as well as alcohol-like impaired coordination and cognition in healthy subjects. While there were no significant main effects in subjective, coordination, or cognitive effects between FHP and FHN individuals, analysis of peak effects suggested FHP had blunted sedative, but not stimulant effects compared to FHN. Thiopental produced alcohol-like effects and perceived similarities to alcohol in healthy individuals. Subtle differences in sedative effects are consistent with reports of blunted FHP response to the negative but not stimulant effects of alcohol. Future studies are needed to better understand how this insight informs our understanding of the heritable risk for alcoholism and the treatment of alcohol use disorders.


Seasonal Toxicity Observed with Amphipods (Eohaustorius estuarius) at Paleta Creek, San Diego Bay, USA.
To assess potential impacts on receiving systems, associated with storm water contaminants, laboratory 10-d amphipod (Eohaustorius estuarius) survival toxicity tests were performed using intact sediment cores collected from Paleta Creek (San Diego Bay, CA, USA) on 5 occasions between 2015 and 2017. The approach included deposition-associated sediment particles collected from sediment traps placed at each of 4 locations during the 2015 to 2016 wet seasons. The bioassays demonstrated wet season toxicity, especially closest to the creek mouth, and greater mortality associated with particles deposited in the wet season compared with dry season samples. Grain size analysis of sediment trap material indicated coarser sediment at the mouth of the creek and finer sediment in the outer depositional areas. Contaminant concentrations of metals (Cd, Cu, Hg, Ni, Pb, and Zn) and organic compounds (polycyclic aromatic hydrocarbons [PAHs], polychlorinated biphenyls [PCBs], and pesticides) were quantified to assess possible causes of toxicity. Contaminant concentrations were determined in the top 5 cm of sediment and porewater (using passive samplers). Whereas metals, PAHs, and PCBs were rarely detected at sufficient concentrations to elicit a response, pyrethroid pesticides were highly correlated with amphipod toxicity. Summing individual pyrethroid constituents using a toxic unit approach suggested that toxicity to E. estuarius could be associated with pyrethroids. This unique test design allowed delineation of spatial and temporal differences in toxicity, suggesting that storm water discharge from Paleta Creek may be the source of seasonal toxicity. Environ Toxicol Chem 2019;39:229-239. © 2019 SETAC.


Evaluation of efficacy, safety and effects on symptoms of androgenization of a generic oral contraceptive containing chlormadinone acetate 2 mg/ethinylestradiol 0.03 mg.
This prospective noninterventional study assessed the contraceptive efficacy, safety and the effects on signs of androgenization of the generic oral contraceptive containing 2 mg chlormadinone acetate/0.03 mg ethinylestradiol (CMA/EE) in a real-world setting. A total of 1440 women were investigated during a six-cycle period by 229 gynecological practices throughout Germany. The adjusted Pearl index was 0.136 (unadjusted: 0.271). Of 463 patients with cycle irregularities at baseline, 83.4% had regular cycles after six cycles. Likewise, 74.1% of 162 patients with spotting or breakthrough bleeding at baseline were free from these symptoms at the end of study. The percentage of patients with dysmenorrhea decreased significantly from baseline (36.5%) to visit 3 after six cycles (12.3%; p=.0001), with a significant reduction in the use of pain medication (p<.0001). Additionally, the number of patients with skin and hair problems was significantly reduced (skin: 56.3% at baseline, 19.6% after six cycles; hair: 45.7% at baseline, 13.4% after six cycles; p=.001). CMA/EE was well tolerated by the patients, and 89.44% of the gynecologists were satisfied with the treatment. Generic CMA/EE exhibits very good contraceptive efficacy, cycle control and dysmenorrhea reduction. Furthermore, treatment with generic CMA/EE led to a favorable reduction of skin and hair problems in our study.


T-cell receptor transgenic analysis of tumor-specific CD8 and CD4 responses in the eradication of solid tumors.
The role of tumor-specific CD8 and CD4 lymphocytes in rejecting solid tumors has been difficult to determine because of the lack of models in which tumor antigen, specific CD8 cells, and specific CD4 cells can be monitored and controlled. To investigate the minimal components required for the induction and maintenance of CTL activity sufficient to reject a solid tumor in vivo, we transfected the influenza hemagglutinin (HA) gene into a nonimmunogenic class I+/class II- murine malignant mesothelioma (MM) tumor line to generate an endogenous tumor antigen and used TCR transgenic mice with class I- or class II-restricted specificities for HA as sources of naive, tumor-specific T cells. The data show that the presence of a strong tumor antigen is not in itself sufficient to induce an effective CTL response, nor does the presence of a high frequency of precursor cells guarantee tumor rejection. We also show that tumor-specific CD4 cells, when CTL numbers are suboptimal, greatly enhance the eradication of tumor, confirming the importance of antigen-presenting cell presentation of tumor antigens to class II-restricted cells. These data confirm that T-cell receptor transgenic cells, combined with nominal tumor antigen transfection, represent powerful tools to analyze tumor-specific T-cell responses.


Enigmatic reticulated filaments in subsurface granite.
In the last few years, geomicrobiologists have focused their researches on the nature and origin of enigmatic reticulated filaments reported in modern and fossil samples from limestone caves and basalt lava tubes. Researchers have posed questions on these filaments concerning their nature, origin, chemistry, morphology, mode of formation and growth. A tentative microbial origin has been elusive since these filaments are found as hollow tubular sheaths and could not be affiliated to any known microorganism. We describe the presence of similar structures in a 16th century granite tunnel in Porto, Northwest Portugal. The reticulated filaments we identify exhibit fine geometry surface ornamentation formed by cross-linked Mn-rich nanofibres, surrounded by a large amount of extracellular polymeric substances. Within these Mn-rich filaments we report for the first time the occurrence of microbial cells.


Stage-sensitivity and dose-response curve of u.v. effect on germ cell formation in embryos of Xenopus laevis.
Ultraviolet light (u.v.) irradiation of the vegetal hemisphere of Xenopus laevis eggs resulted in the elimination of primordial germ cells in tadpoles. Quantitative studies were performed on this phenomenon. The stage sensitivity to u.v. inactivation of germ cell formation was obtained for the early developmental stages ranging from immediately after fertilization to small-cell blastula. It was found that u.v. irradiation at the stage immediately after fertilization was more injurious than irradiation at the beginning of the first cleavage. After deciding optimal conditions for this u.v. irradiation experiment, a dose-response curve of the phenomenon was obtained. It showed a good agreement with the theoretical expectation, which the authors had previously presented.


[A theoretical estimation of the safety of dives culminating in an uninterrupted lifting].
It has been shown using the previously developed model of decompression sickness, which determines the cumulative probability of the development of the symptoms of this illness by the exponential equation whose index is the integral function of cumulative risk of damage to all body tissues by bubbles, Fcum(t) = SigmaFn(t), that underwater dives are practically safe if the function Fcum(t) during its growth will not exceed some small value Fcum-max = SigmaFn-max. Using the hypothetical values of parameters of tissues and functions Fn(t), the curves depth-duration for practically safe non-stop dives on respiration with air and with mixtures of oxygen with helium, neon, and argon have been calculated. The distributions of Fn-max values relative to the half-times of washout of the inert gas from tissues have been obtained, which show that the tissues that experience the largest risks of bubble lesions are different for dives of different duration. A comparison of the curves shows that the short-term dives with air are less dangerous and the long-term dives are more dangerous than the dives with helium-oxygen mixture. It has been shown that the least risk of bubble lesions of tissues arises on dives with neon-oxygen mixture and the greatest risk, on dives with argon-oxygen mixture.


Esmolol pretreatment attenuates heart rate increase and parasympathetic inhibition during rapid increases in desflurane concentration: A preliminary randomized study.
Rapid increases in desflurane concentration can transiently increase the heart rate (HR). Esmolol possesses a high β1-adrenoceptor selectivity and a short duration of action. This preliminary study aimed at investigating the effects of esmolol on the HR and autonomic modulation during a desflurane-induced HR increase. American Society of Anesthesiologists physical status I female subjects, aged 20 to 50 years, who were undergoing minor breast surgery were randomly assigned to 2 groups. Rapid increases in desflurane concentration were commenced after induction of anesthesia. Each subject received either i.v. saline (control group) or esmolol 0.5 mg/kg (esmolol group) before desflurane inhalation. Using time-frequency spectral analysis of HR variability, the HR indices were studied at baseline, postinduction, posttreatment, as well as at minimal alveolar concentrations of desflurane reaching 1.0, 1.3, and 1.5. The low frequency (LF) power is influenced by both the sympathetic and parasympathetic activity, whereas the high frequency (HF) power reflects the parasympathetic activity. The LF/HF ratio is thought to reflect either sympathovagal balance or sympathetic modulation. Electrocardiograms for data analysis were obtained from 8 subjects in each group. Rapid increases in desflurane concentration after induction caused a HR increase. Both the corresponding LF and HF powers were low and the LF/HF ratio remained unchanged. This indicates that the desflurane-induced HR increase may be attributed to parasympathetic inhibition and may be independent of sympathetic activation. Esmolol pretreatment effectively attenuated desflurane-induced HR increase. Moreover, subjects receiving esmolol pretreatment had increased LF and HF powers, but did not have changes in their LF/HF ratios, as compared to those without esmolol. Esmolol pretreatment attenuates HR increase and parasympathetic inhibition during rapid increases in desflurane concentration.


Hepatocellular carcinoma--a clinical study.
Hepatocellular carcinoma afflicts mainly Chinese Singaporeans 75/77 (97.4%), of which 71/77 (92.2%) of the patients are males. It is rare below the 3rd decade of life (1.3%), with the peak incidence occurring in the 5th to 7th decade of life (68.5%). Common presenting features are hepatomegaly (85.7%), jaundice (63.6%), and right hypochondrial pain (51.9%). Liver function tests were abnormal in 98.7%. Alpha-foetoprotein were positive in 61/77 (79.2%) of patients. Hepatitis B surface Antigen were positive in 43.75 (57.3%) of patients. Radiology and ultrasound studies demonstrated that 70.1% had lesions involving both lobes at diagnosis. Only 4/77 (5.1%) had surgical resections of the tumour. 50/65 (76.9%) died within six months of diagnosis, 11/65 (16.9%) survived for one year, 1/65 (1.5%) for 1 1/2 years, 1.65 (1.5%) for 2 years and 2/65 (3.0%) for more than 2 1/2 years; the longest survivor is still alive, at 4 1/2 years after diagnosis.


A specific antagonist of platelet-activating factor suppresses oedema formation in an Arthus reaction but not oedema induced by leukocyte chemoattractants in rabbit skin.
The properties of a novel platelet-activating factor (PAF) antagonist, L-652731, on oedema responses in rabbit skin induced by exogenous inflammatory mediators and by mediators generated endogenously in a reversed passive Arthus reaction have been investigated. Oedema responses in the skin were measured by using the local accumulation of i.v. injected 125I-albumin. The antagonist, mixed with mediators before intradermal injection, caused a dose-dependent suppression of oedema responses to PAF. In contrast, responses induced by other directly acting mediators (bradykinin and histamine) and responses induced by PMN leukocyte-dependent mediators (C5a des Arg, N-formyl-methionyl-leucyl-phenylalanine, and leukotriene B4) were not suppressed. Thus, a secondary release of PAF does not appear to be involved in mediating the actions of these agents. In a reversed passive Arthus reaction, intradermal injection of L-652731 together with antibody resulted in a significant inhibition of the oedema formation measured for 2 hr after i.v. antigen challenge. In contrast, oedema responses induced by intradermal injection of preformed immune complexes were not affected by the antagonist. These results suggest that the endogenous production of PAF, in close proximity to microvascular endothelial cells, appears to be an important step in the development of an Arthus reaction. The cellular source of PAF is unknown, but one possibility is the PMN leukocyte, which releases PAF during phagocytosis of immune complexes.


Radiological characteristics of invasive micropapillary carcinoma of the breast.
To analyse the various imaging features of invasive micropapillary carcinoma (IMPC), a distinct variant of breast cancer, by mammography, ultrasound, and contrast-enhanced mammography. This study included 68 female patients with histopathologically proven invasive micropapillary carcinoma who underwent mammography, ultrasound, and contrast-enhanced mammography examinations. The findings encountered by each imaging tool were analysed using the Breast Imaging Reporting and Data System (BI-RADS) lexicon. In this retrospective study, 64.7% of cases were of the pure form of IMPC. Most of the cases showed an aggressive clinical course, with lymphovascular invasion noted in 76.5% of cases, while 60.3% of cases showed associated pathological lymphadenopathy. The N3 stage was reported in 25% of cases. On analysing the mammographic and ultrasound imaging findings, a significant association between irregular shape and a non-circumscribed margin with IMPC was found. Associated calcification was noted in 47% of cases. Pathological enhancement of moderate or marked conspicuity was noted in cases that underwent contrast-enhanced mammography, with the most commonly encountered finding being enhancing irregular and non-circumscribed masses. The mammographic and ultrasound imaging features of IMPC are indistinguishable from other aggressive types of breast cancer. At contrast-enhanced mammography examination, pathological enhancement of moderate to marked conspicuity was shown in all cases. The observed strong association of IMPC with lymphovascular invasion and lymph node metastasis with higher nodal stage in this study mandate meticulous sonographic examination of the axilla, as well as the infra, and supraclavicular regions if pathological axillary lymphadenopathy was noted.


ABR in eighth-nerve and brain-stem disorders.
Auditory brain-stem response (ABR) results are reported on three cases of acoustic tumors and two cases with brain-stem lesions. These cases highlight several considerations in the clinical use of ABR. The sensitivity of ABR to retrocochlear involvement in light of normal pure-tone hearing and cochlear hearing loss is shown in the first two cases. The third case shows the advantage of "contralateral" ABR testing and a unique effect of stimulus polarity. The use of an intensity function and high presentation rate procedures are shown to be helpful diagnostic procedures in case four. Case five shows bilateral ABR effects which correlate well with the degree of brain-stem involvement. In addition to the ABR data, audiologic, radiologic, and medical findings on these patients are also discussed.


Indian pharmaceutical patent prosecution: The changing role of Section 3(d).
India, like many developing countries, only recently began to grant pharmaceutical product patents. Indian patent law includes a provision, Section 3(d), which tries to limit grant of "secondary" pharmaceutical patents, i.e. patents on new forms of existing molecules and drugs. Previous research suggests the provision was rarely used against secondary applications in the years immediately following its enactment, and where it was, was redundant to other aspects of the patent law, raising concerns that 3(d) was being under-utilized by the Indian Patent Office. This paper uses a novel data source, the patent office's first examination reports, to examine changes in the use of the provision. We find a sharp increase over time in the use of Section 3(d), including on the main claims of patent applications, though it continues to be used in conjunction with other types of objections to patentability. More surprisingly, see a sharp increase in the use of the provision against primary patent applications, contrary to its intent, raising concerns about potential over-utilization.


Nomenclatural changes in Coleus and Plectranthus (Lamiaceae): a tale of more than two genera.
A synopsis of the genera Coleus Lour, Equilabium A.J.Paton, Mwany. & Culham and Plectranthus L'Hér. (Lamiaceae, Tribe Ocimeae, Subtribe Plecranthinae) is presented. Generic delimitation follows a recently published molecular phylogeny which identified Coleus as the sister of the remaining genera of Subtribe Plectranthinae; Plectranthus as sister to Tetradenia Benth. and Thorncroftia N.E.Br., and a separate phylogenetically distinct genus Equilabium comprising species previously placed in Plectranthus. In this treatment, 294 species of Coleus, 42 of Equilabium, and 72 of Plectranthus are recognized. All but one of the combinations in Equilabium are new as only the genus and type species have been previously published. Two-hundred and twelve names are changed to combinations in Coleus from Plectranthus, Pycnostachys Hook. and Anisochilus Benth.


Nanographene with a Nitrogen-Doped Cavity.
Nitrogen-doped cavities are pervasive in graphenic materials, and represent key sites for catalytic and electrochemical activity. However, their structures are generally heterogeneous. In this study, we present the synthesis of a well-defined molecular cutout of graphene featuring N-doped cavity. The graphitization of a macrocyclic pyridinic precursor was achieved through photochemical cyclodehydrochlorination. In comparison to its counterpart with pyridinic nitrogen at the edges, the pyridinic nitrogen atoms in this nanographene cavity exhibit significantly reduced basicity and selective binding to Ag+ ion. Analysis of the protonation and coordination equilibria revealed that the tri-N-doped cavity binds three protons, but only one Ag+ ion. These distinct protonation and coordination behaviors clearly illustrate the space confinement effect imparted by the cavities.


Genome-Wide Identification and Expression Profiles of bZIP Genes in Cannabis sativa L.
Background: The bZIP gene family plays roles in biotic and abiotic stress, secondary metabolism, and other aspects in plants. They have been reported in Arabidopsis thaliana, Oryza sativa, Artemisia annua, and other plants, but their roles in Cannabis sativa have not been determined. Materials and Methods: In this study, we analyzed the genome-wide identification and expression profile of the bZIP gene family in C. sativa. Results: A total of 51 members of the bZIP gene family were identified based on the C. sativa genome and numbered in order from CsbZIP1 to CsbZIP51. Their phylogenetic relationships, cis-elements in promoter region, gene structures and motif compositions, physicochemical properties, chromosome locations, and expression profiles, were analyzed. The results showed that the 51 CsbZIPs were unevenly distributed on 10 chromosomes and could be clustered into 11 subfamilies. Furthermore, CsbZIPs located in the same subfamilies presented similar intron/exon organization and motif composition. The expression levels of CsbZIPs in various tissues (flowers, bracts, vegetative leaves, stems, and seeds) were determined using reverse transcription quantitative polymerase chain reaction. The expression levels of CsbZIPs were higher in flowers and bracts. The 51 CsbZIPs were explored, and their structure, evolution, and expression pattern in different tissues of C. sativa were characterized synthetically. The findings indicated that CsbZIPs are essential for the growth and development of C. sativa. Conclusions: These results provide a theoretical basis for subsequent research on hemp bZIP transcription factors and the cultivation of high-cannabidiol and low-tetrahydrocannabinol high-quality cannabis varieties.


Analysis of core promoter sequences located downstream from the TATA element in the hsp70 promoter from Drosophila melanogaster.
TFIID recognizes multiple sequence elements in the hsp70 promoter of Drosophila. Here, we investigate the function of sequences downstream from the TATA element. A mutation in the initiator was identified that caused an eightfold reduction in binding of TFIID and a fourfold reduction in transcription in vitro. Another mutation in the +24 to +29 region was somewhat less inhibitory, but a mutation in the +14 to +19 region had essentially no effect. The normal promoter and the mutants in the initiator and the +24 to +29 region were transformed into flies by P element-mediated transformation. The initiator mutation reduced expression an average of twofold in adult flies, whereas the mutation in the +24 to +29 region had essentially no effect. In contrast, a promoter combining the two mutations was expressed an average of sixfold less than the wild type. The results suggest that the initiator and the +24 to +29 region could serve overlapping functions in vivo. Protein-DNA cross-linking was used to identify which subunits of TFIID contact the +24 to +29 region and the initiator. No specific subunits were found to cross-link to the +24 to +29 region. In contrast, the initiator cross-linked exclusively to dTAF230. Remarkably, dTAF230 cross-links approximately 10 times more efficiently to the nontranscribed strand than to the transcribed strand at the initiator.


School-screening for scoliosis. A prospective epidemiological study in northwestern and central Greece.
A two-year prospective study was done to assess the prevalence and distribution of various parameters associated with scoliosis in schoolchildren in northwestern and central Greece. A total of 82,901 children (41,939 boys and 40,962 girls) who were nine to fourteen years old were screened for scoliosis. Five thousand eight hundred and three children had clinical signs of scoliosis and, of these, 4185 were referred for posteroanterior radiographs (to be made with the patient standing) because they had a positive result on the forward-bending test (a difference of more than five millimeters between the two sides of the torso as measured in the thoracic or thoracolumbar region with use of a ruler and a level plane) at the time of a second screening. The prevalence of scoliosis (defined as a curve of 10 degrees or more) was 1.7 per cent (1436 of 82,901 children), and most of the curves (1255; prevalence, 1.5 per cent) were small (10 to 19 degrees). The ratio of boys to girls was 1:2.1 over-all but varied according to the magnitude of the curve (1:1.5 for curves of less than 10 degrees, 1:2.7 for curves of 10 to 19 degrees, 1:7.5 for curves of 20 to 29 degrees, 1:5.5 for curves of 30 to 39 degrees, and 1:1.2 for curves of 40 degrees or more). Thoracolumbar curves were the most common type of curve identified, followed by lumbar curves; specifically, of the 1436 children who had a curve of at least 10 degrees, 493 (34.3 per cent) had a thoracolumbar curve, 475 (33.1 per cent) had a lumbar curve, 261 (18.2 per cent) had a thoracic curve, and 207 (14.4 per cent) had a double curve. Although most (753) of these curves were to the left, the left:right ratio varied according to the location of the apex of the curve (1:3.1 for thoracic curves, 2.0:1 for thoracolumbar curves, and 3.2:1 for lumbar curves). The cost of the screening process was negligible (estimated at thirty cents per child); however, the decreased number of operative procedures performed in children from the geographical area of our University Hospital, the identification of a large number of previously undiagnosed curves (eleven of which were treated operatively and 170 of which were treated with a brace), and the identification of children who were at high risk for progression were considered important benefits of the school-screening program.


Expression of Campylobacter hyoilei lipo-oligosaccharide (LOS) antigens in Escherichia coli.
Campylobacter spp. are well recognized as primary pathogens in animals and in people. To isolate and define the genetic regions encoding major surface antigens of Campylobacter hyoilei, genomic DNA of the type strain of the species, RMIT-32A, was cloned into a cosmid vector, pLA2917, in Escherichia coli and the resulting genomic library was screened using antiserum raised to the parent C. hyoilei strain. Six cosmid clones were found to express a series of immunoreactive bands in the 15-25 kDa range. These bands were proteinase K-resistant and were found in the LPS fraction of the cells, suggesting that the recombinant cosmids expressed C. hyoilei lipo-oligosaccharide (LOS) antigen(s). The minimum DNA insert size required for expression of C. hyoilei LOS antigen(s) in E. coli was 11.8 kb. This region was subcloned into the plasmid vector pBR322. The partial sequencing of the 11.8 kb region showed that it contains two ORFs, designated rfbF and rfbP, showing homology with the rfbF gene from Serratia marcescens and the rfbP gene from Salmonella typhimurium. Both genes are involved in LPS synthesis. The region also contained a sequence homologous to the rfaC gene of E. coli and Sal. typhimurium which is involved in core oligosaccharide synthesis.


Predicting renal failure after liver transplantation from measured glomerular filtration rate: review of up to 15 years of follow-up.
The immunosuppressive medications that have contributed greatly to the success of liver transplantation are also associated with posttransplant renal dysfunction. We reviewed measured glomerular filtration rate (GFR) data from patients who underwent transplantation more than 10 years ago to assess whether results from specific time points can predict renal failure. The GFR data were obtained at initial evaluation (IE), at month 3, and at years 1, 2, 5, 10, and 15. Two groupings were compared, one based on GFR at IE and the other at month 3. Patients were further stratified into three GFR (mL/min/1.73 m2) groups: G1, GFR more than 80; G2, GFR 60 to 80; and G3, GFR less than 60. A total of 592 liver transplant recipients met the inclusion criteria; 114 had paired GFR data from IE to year 15. Analysis of paired and censored data based on IE GFR showed that 62.2% of G3 patients developed renal failure by year 5; another 6.7% did so by year 10 (P=0.027). The month 3 GFR data showed that 56.3% of G3 patients developed renal failure by year 5; another 15.6% did so by year 10. Surprisingly, 37.0% of G2 patients experienced renal failure by year 5; another 11.1% did so by year 10 (P=0.0024). The month 3 data indicate a slow but steady decline in GFR over years. The lower the initial GFR is after transplant, the sooner renal failure develops. Patients with GFR less than 60 mL/min per 1.73 m2 at month 3 have a higher risk of renal failure; however, those who avoid renal failure seem to maintain renal function long term.


Process-oriented integration and coordination of healthcare services across organizational boundaries.
The paper presents a methodology that follows a top-down approach based on a Model-Driven Architecture for integrating and coordinating healthcare services through cross-organizational processes to enable organizations providing high quality healthcare services and continuous process improvements. The methodology provides a modeling language that enables organizations conceptualizing an integration agreement, and identifying and designing cross-organizational process models. These models are used for the automatic generation of: the private view of processes each organization should perform to fulfill its role in cross-organizational processes, and Colored Petri Net specifications to implement these processes. A multi-agent system platform provides agents able to interpret Colored Petri-Nets to enable the communication between the Healthcare Information Systems for executing the cross-organizational processes. Clinical documents are defined using the HL7 Clinical Document Architecture. This methodology guarantees that important requirements for healthcare services integration and coordination are fulfilled: interoperability between heterogeneous Healthcare Information Systems; ability to cope with changes in cross-organizational processes; guarantee of alignment between the integrated healthcare service solution defined at the organizational level and the solution defined at technological level; and the distributed execution of cross-organizational processes keeping the organizations autonomy.


[Effect of thymocyte autotransplantation on postradiation regeneration of hematopoiesis].
Experiments were conducted on Wistar rats irradiated in a dose of 400 R; a study was made of the effect of thymocyte autotransplantation (4-10(8)--8-10(8)) on the restoration of cell number of the bone marrow and the spleen. There was revealed a significant stimulating effect of autotransplantation of thymocytes on the erythroid and granulocytic series in the bone marrow and on the lymphoid one in the spleen during the restoration (the 5 th-- 7 th days) after the irradiation. Irradiation of the thymocyte suspension with gamma-rays in a dose of 10 000 R failed to prevent the effect of autotransplantation on the bone marrow, but decreased its stimulating effect. A conclusion was drawn on the interaction of the administered thymocytes with the stem hemopoietic cell.


Acute zonal occult outer retinopathy: a classification based on multimodal imaging.
We describe the multimodal imaging in a group of patients showing a distinct clinical entity that best represents acute zonal occult outer retinopathy (AZOOR). To propose a classification of AZOOR based on clinical fundus and multimodal imaging. A retrospective review of patients diagnosed as having AZOOR at 2 centers. After reviewing more than 400 cases diagnosed or referred to us as AZOOR or AZOOR complex, we assembled 30 cases that fit our current definition; (48 eyes) with a median age at diagnosis of 47 years (age range, 17-86 years) and a mean follow-up period of 39 months. Twenty patients were female. Eighteen patients had initially been seen with bilateral lesions, mostly asymmetric (4 cases were symmetric). Most patients had no remarkable medical or ocular history. The median visual acuity at the time of presentation was 20/25 (range, 20/20 to 20/400). Multimodal imaging, including fundus photography, fluorescein and indocyanine green angiography, fundus autofluorescence imaging, and corresponding eye-tracked spectral-domain coherence tomography imaging. Each patient was initially seen with visual symptoms of photopsia and scotoma, and most had a detectable lesion in the fundus evident clinically or detected on multimodal imaging. The clinical appearance of the AZOOR lesions varied depending on their duration and location, but some features were characteristic, including a demarcating line of the progression at the level of the outer retina and a trizonal pattern of sequential involvement of the outer retina, retinal pigment epithelium, and choroid, as well as frequent zonal progression. Advanced cases of AZOOR demonstrated disruption of the inner and outer retina and severe damage or loss of the retinal pigment epithelium and the choroid. A specific definition of AZOOR based on multimodal imaging is proposed to help physicians distinguish it from other diseases of the posterior fundus, including white spot syndromes and autoimmune, hereditary, paraneoplastic, toxic, and other inflammatory retinopathies.


Investigation of vascular endothelial growth factor receptor-dependent neuroplasticity on rat nucleus tractus solitarius and phrenic nerve after chronic sustained hypoxia.
The neuronal system that controls respiration creates plasticity in response to physiological changes. Chronic sustained hypoxia causes neuroplasticity that contributes to ventilatory acclimatization to hypoxia (VAH). The purpose of this study is to explain the potential roles of the VAH mechanism developing because of chronic sustained hypoxia on respiratory neuroplasticity of vascular endothelial growth factor (VEGF) receptor activation on the nucleus tractus solitarius (NTS) and phrenic nerve. In this study 24 adult male Sprague-Dawley rats were used. Subjects were separated into four groups, a moderate-sham (mSHAM), severed-sham (sSHAM), moderate chronic sustained hypoxia (mCSH), and severed chronic sustained hypoxia (sCSH). Normoxic group (mSHAM and sSHAM) rats were exposed to 21% O₂ level (7 days) in the normobaric room while hypoxia group (mCSH and sCSH) rats were exposed to 13% and 10% O₂ level (7 days). Different protocols were applied for normoxic and hypoxia groups and ventilation, respiratory frequency, and tidal volume measurements were made with whole-body plethysmography. After the test HIF-1α, erythropoietin (EPO), and VEGFR-2 expressions on the NTS region in the medulla oblongata and phrenic nerve motor neurons in spinal cord tissue were analyzed using the immunohistochemical stain method. Examinations on the medulla oblongata and spinal cord tissues revealed that HIF-1α, EPO, and VEGFR-2 expressions increased in hypoxia groups compared to normoxic groups while a similar increase was also seen when respiratory parameters were assessed. Consequently, learning about VAH-related neuroplasticity mechanisms developed as a result of chronic continuous hypoxia will contribute to developing new therapeutical approaches to various diseases causing respiratory failure using brain plasticity without recourse to medicines.


Wheat pre-anthesis development as affected by photoperiod sensitivity genes (Ppd-1) under contrasting photoperiods.
Fine tuning wheat phenology is of paramount importance for adaptation. A better understanding of how genetic constitution modulates the developmental responses during pre-anthesis phases would help to maintain or even increase yield potential as temperature increases due to climate change. The photoperiod-sensitive cultivar Paragon, and four near isogenic lines with different combinations of insensitivity alleles (Ppd-A1a, Ppd-B1a, Ppd-D1a or their triple stack) were evaluated under short (12h) and long (16h) photoperiods. Insensitivity alleles decreased time to anthesis and duration of the three pre-anthesis phases (vegetative, early reproductive and late reproductive), following the Ppd-D1a > Ppd-A1a > Ppd-B1a ranking of strength. Stacking them intensified the insensitivity, but had no additive effect over that of Ppd-D1a. The late reproductive phase was the most responsive, even exhibiting a qualitative response. Leaf plastochron was not affected but spikelet plastochron increased according to Ppd-1a ranking of strength. Earlier anthesis resulted from less leaves differentiated and a fine tuning effect of accelerated rate of leaf appearance. None of the alleles affected development exclusively during any particular pre-anthesis phase, which would be ideal for tailoring time to anthesis with specific partitioning of developmental time into particular phases. Other allelic variants should be further tested to this purpose.


From genomics to metabolomics: Deciphering sanguinarine biosynthesis in Dicranostigma leptopodum.
Dicranostigma leptopodum (Maxim) Fedde (DLF) is a renowned medicinal plant in China, known to be rich in alkaloids. However, the unavailability of a reference genome has impeded investigation into its plant metabolism and genetic breeding potential. Here we present a high-quality chromosomal-level genome assembly for DLF, derived using a combination of Nanopore long-read sequencing, Illumina short-read sequencing and Hi-C technologies. Our assembly genome spans a size of 621.81 Mb with an impressive contig N50 of 93.04 Mb. We show that the species-specific whole-genome duplication (WGD) of DLF and Papaver somniferum corresponded to two rounds of WGDs of Papaver setigerum. Furthermore, we integrated comprehensive homology searching, gene family analyses and construction of a gene-to-metabolite network. These efforts led to the discovery of co-expressed transcription factors, including NAC and bZIP, alongside sanguinarine (SAN) pathway genes CYP719 (CFS and SPS). Notably, we identified P6H as a promising gene for enhancing SAN production. By providing the first reference genome for Dicranostigma, our study confirms the genomic underpinning of SAN biosynthesis and establishes a foundation for advancing functional genomic research on Papaveraceae species. Our findings underscore the pivotal role of high-quality genome assemblies in elucidating genetic variations underlying the evolutionary origin of secondary metabolites.


Ochratoxin A mediates cytotoxicity through the MAPK signaling pathway and alters intracellular homeostasis in bovine mammary epithelial cells.
Ochratoxin A (OTA), a secondary metabolite of the genera Penicillium and Aspergillus, contaminates many types of food and causes apoptosis as well as immunosuppression in many animal species. However, a mechanistic analysis of OTA-mediated cytotoxicity in bovine mammary epithelial cells has not yet been performed. Hence, we investigated the effects of OTA on bovine mammary epithelial (MAC-T) cells using several mechanistic analyses. We report that OTA may induce cell cycle arrest and apoptosis via MAPK and JNK signaling pathways in MAC-T cells. Moreover, homeostasis of cellular components, such as that of the mitochondrial membrane, was disrupted by OTA, leading to a decrease in mitochondrial and cytosolic Ca2+ in MAC-T cells. In addition, we evaluated the effects of OTA on inflammatory responses and major tight junction regulators, such as occludin and claudin 3. In summation, we suggest that OTA contamination may adversely affect bovine mammary epithelial cells, leading to improper lactation and decreased milk quality. This article aims to improve the understanding of physiological mechanisms involved in lactation, in addition to providing a guideline for the stabilization of industrial milk production by countering exogenous contaminants in livestock.


Interaction of prolactin with adrenal hormones in blood pressure regulation in rats.
This study examined the role of the adrenals in the systolic blood pressure (BP) response to ovine prolactin (oPRL) administration as well as the interaction of oPRL with epinephrine (EPI), norepinephrine (NOR), and corticosterone (CORT) on BP in the rat. After intraperitoneal implantation of 7-day osmotic minipumps releasing 0.6 micrograms oPRL/h in 0.9% NaCl on day 1, BP was measured via tail cuff on days 1, 4, and 7 in adrenalectomized (ADX) and sham-ADX male rats (n = 8/group). BP was also measured in ADX rats receiving CORT (27.0 micrograms/h), EPI (1.7 micrograms/h), NOR (5.0 micrograms/h), CORT + oPRL, EPI + oPRL, and NOR + oPRL by osmotic pump (n = 8/group). All ADX rats not receiving CORT were given 1.0% NaCl replacement for drinking water. oPRL increased BP over 17 days in sham-ADX rats (P less than 0.01) but had no effect in ADX rats. BP also increased over 7 days in ADX animals receiving CORT, EPI (P less than 0.01), and NOR (P less than 0.01). BP responses to CORT + oPRL and EPI + oPRL were similar to those of CORT and EPI alone, respectively. However, the BP response to NOR + oPRL on day 4 was 250% (P less than 0.01) that to NOR alone and similar to NOR alone on day 7. Replacement of CORT + NOR + oPRL did not prolong the oPRL-induced sensitization to NOR. In no instance did oPRL, by itself, alter heart rate. These data suggest that the pressor response to oPRL requires the presence of the adrenal glands and that oPRL transiently potentiates the pressor response to NOR in vivo.


Performance of a 70-mer oligonucleotide microarray for genotyping of Campylobacter jejuni.
Campylobacter jejuni is widespread in the environment and is the major cause of bacterial gastroenteritis in humans. In the present study we use microarray-based comparative genomic hybridizations (CGH), pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) to analyze closely related C. jejuni isolates from chicken and human infection. With the exception of one isolate, the microarray data clusters the isolates according to the five groups determined by PFGE. In contrast, MLST defines only three genotypes among the isolates, indicating a lower resolution. All methods show that there is no inherit difference between isolates infecting humans and chicken, suggesting a common underlying population of C. jejuni. We further identify regions that frequently differ between isolates, including both previously described and novel regions. Finally, we show that genes that belong to certain functional groups differ between isolates more often than expected by chance. In this study we demonstrated the utility of 70-mer oligonucleotide microarrays for genotyping of Campylobacter jejuni isolates, with resolution outperforming MLST.


GATA Transcription Factors in Pregnancy.
GATA transcription factors are Zinc finger members which perform a variety of important functions within the 3-germ layers as well as in extra embryonic endoderm during embryonic development. Distinct roles for GATA transcription factors have previously been identified in hematopoietic, the cardiac vascular system, the central neural system, as well as respiratory and intestinal systems. However, the role of GATA transcription factors in trophoblast lineage and placental development is far more complete. This review focuses on the roles of GATA transcription factors during pregnancy: the establishment of trophoblast lineage, trophoectoderm maintenance, trophoblast differentiation and the pathogenesis of placenta-related diseases of pregnancy.


Analysis of Reasons for Orthopaedic Walkouts from the Emergency Department in a Private Tertiary Care Centre.
A small proportion of patients presenting to the Emergency department (ED) of any hospital tend to take discharge against medical advice (DAMA) due to several patient related or hospital/service related reasons. Amongst these, orthopaedic patients are a special group due to their inability to mobilise independently due to injuries and have treatment needs which involve higher costs. The aim of the current study was to ascertain and analyse the reasons for orthopaedic walkouts at a tertiary care new private hospital. This retrospective telephonic structured interview-based study was carried out on all orthopaedic patients taking DAMA during a one-year period from July 2016 to June 2017. They were telephonically interviewed with a structured questionnaire. Hospital and ED records were analysed for demographic as well as temporal characteristics. A total of 68 orthopaedic patients walked out of casualty against medical advice out of a total 775 (8.77%) orthopaedic patients presenting during the period as against 6.4% overall rate of DAMA for all specialties. The main reasons for DAMA were financial unaffordability of treatment (36.7%), preference for another orthopaedic surgeon (22%) and on advice of the patient's General Practitioner (16.1%). Unaffordability of treatment is a significant cause for walkouts amongst orthopaedic patients. Private hospitals need to recognise and implement processes by which these patients can be treated at affordable costs and with coverage either by medical insurance or robust charity programs. Patient education and awareness are important to encourage them to have insurance coverage.


Adherence to Mediterranean Diet and Metabolic Syndrome in BRCA Mutation Carriers.
Insulin resistance is associated with higher breast cancer (BC) penetrance in BRCA mutation carriers. Metabolic syndrome (MetS), an insulin resistance syndrome, can be reversed by adhering to the Mediterranean diet (MedDiet). In a dietary intervention trial on BRCA mutation carriers, we evaluated adherence to the MedDiet, and the association with the MetS, by analyzing data from the Mediterranean Diet Adherence Screener (MEDAS). BRCA mutation carriers, with or without BC, aged 18 to 70 years, were eligible for the trial. After the baseline examinations, women were randomized to a dietary intervention or to a control group. Both groups completed the MEDAS at baseline and at the end of the dietary intervention. A total of 163 women completed the 6 months of dietary intervention. Compared with controls, the women in the intervention group significantly reduced their consumption of red meat ( P < .01) and commercial sweets ( P < .01) and their MEDAS score rose significantly (+1.3 vs +0.55, P = .02). The number of MetS parameters decreased with increasing points of adherence to the MEDAS score ( P = .01). In the intervention group, there was a significant association with the greater reduction of MetS. BRCA mutation carriers in the intervention group experienced greater improvement in their MedDiet and MetS parameters.


Regulation of tyrosinase by tetrahydropteridines and H2O2.
Recently two alternative mechanisms have been put forward for the inhibition of tyrosinase by 6R-l-erythro 5,6,7,8-tetrahydrobiopterin (6BH(4)). Initially allosteric uncompetitive inhibition was demonstrated due to 1:1 binding of 10(-6)M 6BH(4) to a specific domain 28 amino acids away from the Cu(A) active site of the enzyme. Alternatively it was then shown that 10(-3)M 6BH(4) inhibit the reaction by the reduction of the product dopaquinone back to l-dopa. In the study presented herein we have used two structural analogues of 6BH(4) (i.e., 6,7-(R,S)-dimethyl tetrahydrobiopterin and 6-(R,S)-tetrahydromonapterin) confirming classical uncompetitive inhibition due to specific binding of the pyrimidine ring of the pterin moiety to the regulatory domain on tyrosinase. Under these conditions there was no reduction of l-dopaquinone back to l-dopa by both cofactor analogues. Inhibition of tyrosinase by 6BH(4) occurs in the concentration range of 10(-6)M after preactivation with l-tyrosine and this mechanism uncouples the enzyme reaction producing H(2)O(2) from O(2). Moreover, a direct oxidation of 6BH(4) to 7,8-dihydrobiopterin by tyrosinase in the absence of the substrate l-tyrosine was demonstrated. The enzyme was activated by low concentrations of H(2)O(2) (<0.3 x 10(-3)M), but deactivated at concentrations in the range 0.5-5.0 x 10(-3)M. In summary, our results confirm a major role for 6BH(4) in the regulation of human pigmentation.


How to Diagnose and Manage Angina Without Obstructive Coronary Artery Disease: Lessons from the British Heart Foundation CorMicA Trial.
Patients with symptoms and/or signs of ischaemia but no obstructive coronary artery disease (INOCA) present a diagnostic and therapeutic challenge. Microvascular and/or vasospastic angina are the two most common causes of INOCA; however, invasive coronary angiography lacks the sensitivity to diagnose these functional coronary disorders. In this article, the authors summarise the rationale for invasive testing in the absence of obstructive coronary disease, namely that correct treatment for angina patients starts with the correct diagnosis. They provide insights from the CORonary MICrovascular Angina (CorMicA) study, where an interventional diagnostic procedure was performed with linked medical therapy to improve patient health. Identification of these distinct disorders (microvascular angina, vasospastic angina or non-cardiac chest pain) is key for stratifying INOCA patients, allowing prognostic insights and better patient care with linked therapy based on contemporary guidelines. Finally, they propose a framework to diagnose and manage patients in this common clinical scenario.


[Post-transfusion hemolytic reactions in regions endemic for the hereditary glucose-6-phosphate dehydrogenase deficiency].
This paper deals with the problem of hemocomponent therapy in the use of blood components from donors with hereditary glucose-6-phosphate dehydrogenase (G-6-PD) deficiency and with the matters of family donation in this blood anomaly. Posttransfusion hemolytic reactions during transfusions of packed red blood cells from donors with hereditary blood anomaly are retrospectively analyzed. Recommendations are formulated for recipients who have undergone transfusions of blood components from donors with G-6-PD deficiency.


Assessment of Hydroxyethyl Starch (6% HES 130/0.4) Kidney Storage in Critically Ill Dogs: A Post-mortem Prospective Study.
Objective: Intravenous hydroxyethyl starch (HES) solutions are potentially nephrotoxic due to rapid renal tissue uptake, subsequent osmotic nephrosis, and long-lasting intracellular storage. This study aimed to investigate the severity of intracellular storage of HES in renal tissue samples from critically ill dogs receiving 6% HES 130/0.4. Materials and Methods: Fresh, post-mortem (<2 h after death) renal tissue samples were analyzed through histology, immunohistochemistry (HES 130/0.4-specific antibodies), and electron microscopy for the severity of renal tubular vacuolization (VAC), intravacuolar HES accumulation (ACC), and ultra-structure impairment. Moreover, we investigated the relationship between VAC or ACC grade and HES dose (mL/kg), duration of HES administration (h), and pre-HES plasma creatinine concentrations. Results: Histology revealed that 2/20 dogs (10%) had no, 11/20 dogs (55%) had mild, 5/20 dogs (25%) had moderate, and 2/20 dogs (10%) had severe VAC. Immunohistochemistry revealed that 5/20 dogs (25%) had no, 6/20 dogs (30%) had mild, 7/20 dogs (35%) had moderate, and 2/20 dogs (10%) had severe ACC. Both changes were predominantly found in the distal tubular epithelium of mild and moderate cases, and all tubular segments were affected in severe cases. Seven of 20 dogs (35%) had osmotic nephrosis (ON). On electron microscopy, large granules with an electron-dense content were repeatedly detected in individual cells, mainly in the distal tubules. No correlation was found between cumulative HES dose or duration of HES administration and VAC grade, ACC grade, or presence/absence of ON. Conclusion: A high percentage of dogs had renal tubular HES storage and one-third of dogs showed HES-induced ON. Short-term HES administration caused VAC and ACC, regardless of the dose or duration of administration. In contrast to previous studies, HES 130/0.4 deposits were mainly located in the renal distal tubule.


The chemokine receptor cxcr5 regulates the regenerative neurogenesis response in the adult zebrafish brain.
Unlike mammals, zebrafish exhibits extensive neural regeneration after injury in adult stages of its lifetime due to the neurogenic activity of the radial glial cells. However, the genes involved in the regenerative neurogenesis response of the zebrafish brain are largely unknown. Thus, understanding the underlying principles of this regeneration capacity of the zebrafish brain is an interesting research realm that may offer vast clinical ramifications. In this paper, we characterized the expression pattern of cxcr5 and analyzed the function of this gene during adult neurogenesis and regeneration of the zebrafish telencephalon. We found that cxcr5 was upregulated transiently in the RGCs and neurons, and the expression in the immune cells such as leukocytes was negligible during both adult neurogenesis and regeneration. We observed that the transgenic misexpression of cxcr5 in the ventricular cells using dominant negative and full-length variants of the gene resulted in altered proliferation and neurogenesis response of the RGCs. When we knocked down cxcr5 using antisense morpholinos and cerebroventricular microinjection, we observed outcomes similar to the overexpression of the dominant negative cxcr5 variant. Thus, based on our results, we propose that cxcr5 imposes a proliferative permissiveness to the radial glial cells and is required for differentiation of the RGCs to neurons, highlighting novel roles of cxcr5 in the nervous system of vertebrates. We therefore suggest that cxcr5 is an important cue for ventricular cell proliferation and regenerative neurogenesis in the adult zebrafish telencephalon. Further studies on the role of cxcr5 in mediating neuronal replenishment have the potential to produce clinical ramifications in efforts for regenerative therapeutic applications for human neurological disorders or acute injuries.


Altered response to and production of TGF-beta by B cells from autoimmune NZB mice.
New Zealand Black (NZB) mice spontaneously develop immune dysfunction manifested as autoimmune hemolytic anemia and systemic lupus erythematosus. In later life, a subset of these mice develop clonal CD5+ B cell tumors analogous to human chronic lymphocytic leukemia (CLL). NZB disease is marked by B cell hyperactivity characterized by spontaneous immunoglobulin secretion and proliferation. Elimination of autoreactive lymphocytes by apoptosis is a vital mechanism to prevent expansion of self-reactive lymphocyte population. TGF-beta appears to be an important factor in normal and abnormal immune regulation and this cytokine may play a role in the development of chronic human B cell tumors. We asked whether the response to or production of TGF-beta by NZB B cells was aberrant and could contribute to disease development. In this study, we demonstrated that the apoptotic response to TGF-beta was increased in B cells from NZB mice compared to B cells from normal BALB/c mice. The increased apoptosis was related to endogenous activation and was possibly mediated through increased expression of the TGF-beta Type II receptor. Despite functional differences between CD5-negative B cells and CD5-positive B cells, TGF-beta induced apoptosis in both populations to a similar extent. NZB B cells also secrete increased active TGF-beta compared to BALB/c B cells. We suggest that the aberrant secretion of active TGF-beta and the increased response to the apoptotic effects of TGF-beta by NZB B cells may play a role in the disease process of these mice, perhaps attempting to limit the autoimmune phenomena, but possibly also contributing to generalized immunosuppression. We also suggest that the CD5(+) tumors in the NZB mouse may not be a fully appropriate model of human CLL, since CLL B cells are abnormally resistant to the apoptotic effects of TGF-beta.


A comparison of single-photon emission CT lung scintigraphy and CT pulmonary angiography for the diagnosis of pulmonary embolism.
This study compared single-photon emission CT (SPECT) ventilation/perfusion (V/Q) scintigraphy with multislice CT pulmonary angiography (CTPA). In a prospective, observational study, 100 patients who were >or= 50 years of age were recruited. Seventy-nine patients underwent both diagnostic 16-detector CTPA, and planar and SPECT V/Q scintigraphy. The agreement between the CTPA and the SPECT V/Q scintigraphy for the diagnosis of pulmonary embolism (PE) was calculated. The sensitivity and specificity of blinded SPECT scintigraphy reporting was calculated against a reference diagnosis made by a panel of respiratory physicians that was provided with CTPA and planar V/Q scintigraphy reports, clinical information, and 3-month follow-up data. The observed percentage of agreement between SPECT V/Q scintigraphy and CTPA data for the diagnosis of PE was 95%. When calculated against the respiratory physicians' reference diagnosis, SPECT V/Q scintigraphy had a sensitivity of 83% and a specificity of 98%. This study indicates that SPECT V/Q scintigraphy is a viable alternative to CTPA for the diagnosis of PE and has potential advantages in that it was feasible in more patients and had fewer contraindications; lower radiation dose; and, arguably, fewer nondiagnostic findings than CTPA. Australian New Zealand Clinical Trials Registry Registration Number: ACTRN12609000089235.


Human papillomavirus testing for primary screening of cervical cancer precursors.
Our objective was to determine whether the addition of human papillomavirus (HPV) testing to screening cytology improves the detection of cervical cancer precursors. Women of ages 18-69 years underwent conventional Pap cytology and HPV DNA testing in a multicenter study in Newfoundland, Canada. Those with positive cytology and/or HPV and a random sample of those with dual negative results were referred for colposcopy. The study enrolled 2098 women. The relative sensitivity of HPV testing was significantly higher than cytology for all-grade squamous intraepithelial lesions [SILs; 73%; 95% confidence interval (CI), 62-82] and high grade SILs (HSILs; 90%; 95% CI, 74-97) but had lower relative specificity (62% for all-grade SILs and 51% for HSILs) than most cytological cutpoints. The rate of combined correct results for all-grade lesions was higher for HPV testing (68.8%) than for any cytological cutpoint (equivocal, 52.3%; LSILs, 51.6%; HSILs, 44.5%). The combination of HPV and an LSIL cutpoint had a negative predictive value of 68% (95% CI, 52-80) for all SILs and 100% (95% CI, 91-100) for HSILs, while referring for colposcopy only 12% of the women. We concluded that HPV testing in conjunction with cytology improved the screening efficacy of cytology alone and may allow for a more effective and safe primary screening program with increased screening intervals.


High-sensitivity immunofluorescence/flow cytometry: detection of cytokine receptors and other low-abundance membrane molecules.
Cell marker identification by traditional phenotyping techniques is now considered straight-forward and relatively uncomplicated. In immunofluorescence/flow cytometry, the sensitivity, or detection limit, depends on the reagents, staining, and instrument parameters. The sensitivity of the most commonly used procedures, based on fluorescein-conjugated antibodies, approximately 2000 molecules of target antigen per cell, which is adequate for most of the widely used leukocyte markers. However, measuring target antigens of low density has proven very difficult indeed. Flow cytometric immunofluorescence is capable of detecting 100 molecules of target antigen per cell in practical applications, provided that every step of the staining and analysis procedure is optimized for sensitivity. This level of sensitivity reveals staining not seen using conventional analytical procedures. This unit discusses the underlying principles of high-sensitivity immunofluorescence and provides an excellent series of protocols for the practical detection of as few as 100 target antigen molecules per cell.


Interplay between ER Ca2+ uptake and release fluxes in neurons and its impact on [Ca2+] dynamics.
In neurons, depolarizing stimuli open voltage-gated Ca2+ channels, leading to Ca2+ entry and a rise in the cytoplasmic free Ca2+ concentration ([Ca2+]i). While such [Ca2+]i elevations are initiated by Ca2+ entry, they are also influenced by Ca2+ transporting organelles such as mitochondria and the endoplasmic reticulum (ER). This review summarizes contributions from the ER to depolarization-evoked [Ca2+]i responses in sympathetic neurons. As in other neurons, ER Ca2+ uptake depends on SERCAs, while passive Ca2+ release depends on ryanodine receptors (RyRs). RyRs are Ca2+ permeable channels that open in response to increases in [Ca2+]i, thereby permitting [Ca2+]i elevations to trigger Ca2+ release through Ca(2+)-induced Ca2+ release (CICR). However, whether this leads to net Ca2+ release from the ER critically depends upon the relative rates of Ca2+ uptake and release. We found that when RyRs are sensitized with caffeine, small evoked [Ca2+]i elevations do trigger net Ca2+ release, but in the absence of caffeine, net Ca2+ uptake occurs, indicating that Ca2+ uptake is stronger than Ca2+ release under these conditions. Nevertheless, by increasing ER Ca2+ permeability, RyRs reduce the strength of Ca2+ buffering by the ER in a [Ca2+](I)-dependent manner, providing a novel mechanism for [Ca2+]i response acceleration. Analysis of the underlying Ca2+ fluxes provides an explanation of this and two other modes of CICR that are revealed as [Ca2+]i elevations become progressively larger.


Optical-vortex laser ablation.
Laser ablation of Ta plates using nanosecond optical vortex pulses was carried out, for the first time. It was suggested that owing to orbital angular momentum of optical vortex, clearer and smoother processed surfaces were obtained with less ablation threshold fluence, in comparison with the ablation by a nonvortex annular beam modified from a spatially Gaussian beam.


Employing Participatory Citizen Science Methods to Promote Age-Friendly Environments Worldwide.
The trajectory of aging is profoundly impacted by the physical and social environmental contexts in which we live. While "top-down" policy activities can have potentially wide impacts on such contexts, they often take time, resources, and political will, and therefore can be less accessible to underserved communities. This article describes a "bottom-up", resident-engaged method to advance local environmental and policy change, called Our Voice, that can complement policy-level strategies for improving the health, function, and well-being of older adults. Using the World Health Organization's age-friendly cities global strategy, we describe the Our Voice citizen science program of research that has specifically targeted older adults as environmental change agents to improve their own health and well-being as well as that of their communities. Results from 14 Our Voice studies that have occurred across five continents demonstrate that older adults can learn to use mobile technology to systematically capture and collectively analyze their own data. They can then successfully build consensus around high-priority issues that can be realistically changed and work effectively with local stakeholders to enact meaningful environmental and policy changes that can help to promote healthy aging. The article ends with recommended next steps for growing the resident-engaged citizen science field to advance the health and welfare of all older adults.


Selective changes to phosphatidylcholine and phosphatidylethanolamine molecular species in the developing fetal guinea pig liver and plasma.
The molecular species composition of membrane phospholipids influences the activities of integral proteins and cell signalling pathways. We determined the effect of increasing gestational age on fetal guinea pig liver phosphatidylcholine (PC) and phosphatidylethanolamine (PE), and plasma PC molecular species composition. The livers were collected from fetuses (n = 5/time point) at 5 day intervals between 40 and 65 days of gestation, and at term (68 days). Hepatic PC and PE molecular species composition was determined by electrospray ionisation mass spectrometry. An increasing gestational age was accompanied by selective changes in individual molecular species. The proportion of the sn-1 18:0 species increased relative to the sn-1 16:0 species in liver PC, but not PE, with an increasing gestational age. 1-O-alkyl-2-acyl PC species concentrations decreased significantly between 40 and 45 days of gestation (40%), and 65 and 68 days (54%). Total 1-O-alkenyl-2-acyl PE species concentration increased between days 60 and 65, due to a rise in 1-O-16:0 alkyl/20:4 content, and then decreased until term. Between day 40 and term, PC and PE sn-2 18:2n-6 species concentrations increased 3-fold. PC16:0/18:2 increased gradually throughout gestation, while PC18:0/18:2 content only increased after day 65. The overall increase in PE18:2n-6 content was due to PE18:0/18:2 alone. The composition of plasma PC essentially reflected hepatic PC. Overall, these data suggest differential regulation of hepatic PC and PE molecular species composition during development which is essentially independent of the maternal fatty acid supply.


Parenteral antibiotics and carbohydrate intolerance in term neonates.
To evaluate the effects of parenteral antibiotics on carbohydrate tolerance, fecal reducing substances, stool frequency, and dietary manipulation were monitored in two groups of term neonates. The first group (n = 25) consisted of neonates receiving parenteral ampicillin sodium and gentamicin sulfate. A second group (n = 25) of matched neonates not receiving antibiotics served as controls. Most of the neonates were fed a standard lactose-containing formula and the remainder were breast-fed. Stool frequency, presence of fecal reducing substances, and requirement for dietary manipulation were significantly greater in neonates receiving antibiotics compared with controls. Infants manifesting symptomatic carbohydrate intolerance while receiving parenteral antibiotics may benefit either from receiving lactose-free formula or from decreasing the intake of lactose for the duration of antibiotic therapy.


"Diabetes Just Tends to Take Over Everything": Experiences of Support and Barriers to Diabetes Management for Pregnancy in Women With Type 1 Diabetes.
To optimize clinical outcomes, women with type 1 diabetes are advised to consistently achieve blood glucose levels in their target range before becoming pregnant. However, following this recommendation can be clinically and psychologically challenging for patients. We explored women's experiences of pregnancy-related diabetes management and any barriers and support systems affecting their self-management. Fifteen semi-structured telephone interviews were conducted with a nationwide sample. Interviews focused on women's perceptions of barriers hindering pregnancy-related diabetes management and support systems facilitating their self-management. Audio recordings were analyzed using inductive thematic analysis. Results indicated significant impairment of psychological health and overall quality of life in women with type 1 diabetes who were pregnant or planning pregnancy. Most participants reported a lack of support and empathetic engagement from their health care team, which affected their clinical management. Guilt and concerns about high blood glucose levels, constant pressure to meet glucose targets, and difficult interactions with health care professionals were a few of the primary themes with regard to barriers to optimal management. Patient-centered programs that provide effective clinical and psychosocial support for women who are preparing for pregnancy with preexisting diabetes are urgently needed so that these women feel adequately supported and empowered to undertake pregnancy.


Cytologic and histologic examination of transbronchial lung biopsy.
Transbronchial lung biopsy via the fiberoptic bronchoscope has been proposed for the diagnosis of diffuse lung diseases, particularly sarcoidosis. This study reports results in 167 patients. Lung parenchyma was obtained i 143 patients (85.6%). A cytologic or histologic picture compatible with the clinical presentation was found in 62.3% of all cases. Percentage of positive results was related to the study groups under consideration: 75.6% for diffuse interstitial infiltrates, 50.0% for chronic localized infiltrates, 52.0% fro solitary nodules, 73.5% for sarcoidosis (69.8% at stages 0 and I, 83.0% at stage II, 75.0% at stage III); and 54.4% for infectious pneumonitis. Complications included pneumothorax and bronchial hemorrhage, but were rare (4%) and minor. Because of its low morbidity and high diagnostic yield, fiberoptic transbronchial lung biopsy is the diagnostic tool of choice in various respiratory diseases, whether diffuse or localized.


Direct oral anticoagulant concentrations and adherence in stroke patients.
No therapeutic ranges linking drug concentrations of apixaban and rivaroxaban to clinical outcomes have been defined. We investigated whether direct oral anticoagulant (DOAC) concentrations among patients admitted to hospital with symptoms of stroke differed between those later verified to suffer an ischaemic cerebrovascular event (stroke or transient ischaemic attack) and those having other diagnoses (control group). Serum concentrations in 102 patients on DOAC for atrial fibrillation (84%) and thromboembolic disease (16%) were measured within 24 h of the acute event, employing ultra-high performance liquid chromatography with tandem mass spectrometry. We converted all concentrations to standardized trough levels. DOAC concentrations were lower in the 64 patients with verified ischaemic cerebrovascular event than in the 30 controls, 255 ± 155 versus 329 ± 144 nmol/L (p = 0.029), despite no statistically significant difference in self-reported adherence and daily dosages. Calculated concentrations were 5.4-596 nmol/L (median = 229 nmol/L) in the ischaemic stroke group and 41-602 nmol/L (median = 316 nmol/L) in controls. CHA2 DS2 -VASc score was significantly higher in the ischaemic stroke group than in controls (4.9 ± 1.6 versus 4.1 ± 1.7; p = 0.007). These results may suggest that patients with high cerebrovascular risk might benefit from higher DOAC levels than those with a lower risk.


[Problems and prospects anesthesiology].
Anesthesiology is one of the most progressive medical science. Today's anesthesiologist is not only specialist in anesthetic management, he is also involved in pre- and postoperative treatment. The majority of urgent situations in hospital requires anesthesiologic assistance. But absence of prestige and low salary lead to low receipt of new specialists. The article also reviews the problems of training specialists, management, future prospects of modern anesthesiology.


The evolution of sex roles in birds is related to adult sex ratio.
Sex-role reversal represents a formidable challenge for evolutionary biologists, since it is not clear which ecological, life-history or social factors facilitated conventional sex roles (female care and male-male competition for mates) to be reversed (male care and female-female competition). Classic theories suggested ecological or life-history predictors of role reversal, but most studies failed to support these hypotheses. Recent theory however predicts that sex-role reversal should be driven by male-biased adult sex ratio (ASR). Here we test this prediction for the first time using phylogenetic comparative analyses. Consistent with theory, both mating system and parental care are strongly related to ASR in shorebirds: conventional sex roles are exhibited by species with female-biased ASR, whereas sex-role reversal is associated with male-biased ASR. These results suggest that social environment has a strong influence on breeding systems and therefore revealing the causes of ASR variation in wild populations is essential for understanding sex role evolution.


Utility and safety of temporary pacing using active fixation leads and externalized re-usable permanent pacemakers after lead extraction.
After extraction of an infected cardiac implantable electronic device (CIED) in a pacemaker-dependent patient, a temporary pacemaker wire may be required for long periods during antibiotic treatment. Loss of capture and under sensing are commonly observed over time with temporary pacemaker wires, and patient mobility is restricted. The use of an externalized permanent active-fixation pacemaker lead connected to a permanent pacemaker generator for temporary pacing may be beneficial because of improved lead stability, and greater patient mobility and comfort. The aim of this study was to investigate the efficacy and safety of a temporary permanent pacemaker (TPPM) system in patients undergoing transvenous lead extraction due to CIED infection. Of 47 patients who underwent lead extraction due to CIED infection over a 2-year period at our centre, 23 were pacemaker dependent and underwent TPPM implantation. A permanent pacemaker lead was implanted in the right ventricle via the internal jugular vein and connected to a TPPM generator, which was secured externally at the base of the neck. The TPPM was used for a mean of 19.4 ± 11.9 days (median 18 days, range 3-45 days), without loss of capture or sensing failure in any patient. Twelve of 23 patients were discharged home or to a nursing facility with the TPPM until completion of antibiotic treatment and re-implantation of a new permanent pacemaker. External TPPMs are safe and effective in patients requiring long-term pacing after infected CIED removal.


Self-Extinguishing Resin Transfer Molding Composites Using Non-Fire-Retardant Epoxy Resin.
Introducing fire-retardant additives or building blocks into resins is a widely adopted method used for improving the fire retardancy of epoxy composites. However, the increase in viscosity and the presence of insoluble additives accompanied by resin modification remain challenges for resin transfer molding (RTM) processing. We developed a robust approach for fabricating self-extinguishing RTM composites using unmodified and flammable resins. To avoid the effects on resin fluidity and processing, we loaded the flame retardant into tackifiers instead of resins. We found that the halogen-free flame retardant, a microencapsulated red phosphorus (MRP) additive, was enriched on fabric surfaces, which endowed the composites with excellent fire retardancy. The composites showed a 79.2% increase in the limiting oxygen index, a 29.2% reduction in heat release during combustion, and could self-extinguish within two seconds after ignition. Almost no effect on the mechanical properties was observed. This approach is simple, inexpensive, and basically applicable to all resins for fabricating RTM composites. This approach adapts insoluble flame retardants to RTM processing. We envision that this approach could be extended to load other functions (radar absorbing, conductivity, etc.) into RTM composites, broadening the application of RTM processing in the field of advanced functional materials.


Total hip arthroplasty using the direct anterior approach and intraoperative neurophysiological monitoring for Crowe III hip dysplasia : surgical technique and case series.
Developmental dysplasia of the hip with a high dislocation may lead to severe hip pain and a marked shortening. Nerve palsy rates following THA in dysplastic hips have been reported as being higher by ten times or more compared to the general population. We report a new technique to perform THA in high congenital dislocations. Between 2013 and 2015, 3 consecutive patients (4 hips) with severe hip pain and Crowe III hip dysplasia were treated. Surgeries were performed on a standard table using the DAA and intraoperative neurophysiological monitoring. At final follow-up (mean 24 months, range 15-43), all 3 patients reported excellent pain relief and significant improvement in activities of daily living. Radiographs showed the components to be solidly fixed in satisfactory position. Average postoperative leg lengthening was 24 mm (range 20-36). None of the patients experienced an acute or delayed neurologic deficit. Total hip arthroplasty for high congenital dislocations can be safely performed using the direct anterior approach and neuromonitoring. Significant lengthening could be obtained without neurological complications.


Age-Related Reversals in Neural Recruitment across Memory Retrieval Phases.
Over the last several decades, neuroimaging research has identified age-related neural changes that occur during cognitive tasks. These changes are used to help researchers identify functional changes that contribute to age-related impairments in cognitive performance. One commonly reported example of such a change is an age-related decrease in the recruitment of posterior sensory regions coupled with an increased recruitment of prefrontal regions across multiple cognitive tasks. This shift is often described as a compensatory recruitment of prefrontal regions due to age-related sensory-processing deficits in posterior regions. However, age is not only associated with spatial shifts in recruitment, but also with temporal shifts, in which younger and older adults recruit the same neural region at different points in a task trial. The current study examines the possible contribution of temporal modifications in the often-reported posterior-anterior shift. Participants, ages 19-85, took part in a memory retrieval task with a protracted retrieval trial consisting of an initial memory search phase and a subsequent detail elaboration phase. Age-related neural patterns during search replicated prior reports of age-related decreases in posterior recruitment and increases in prefrontal recruitment. However, during the later elaboration phase, the same posterior regions were associated with age-related increases in activation. Further, ROI and functional connectivity results suggest that these posterior regions function similarly during search and elaboration. These results suggest that the often-reported posterior-anterior shift may not reflect the inability of older adults to engage in sensory processing, but rather a change in when they recruit this processing.SIGNIFICANCE STATEMENT The current study provides evidence that the often-reported posterior-anterior shift in aging may not reflect a global sensory-processing deficit, as has often been reported, but rather a temporal modification in this processing in which older adults engage the same neural regions during a detail elaboration phase that younger adults engage during memory search. In other words, older adults may ultimately be able to engage the same processes as younger adults during some cognitive tasks when given the time to do so. Future research should examine the generalizability of this effect and the importance of encouraging older adults to engage in these processes through task instruction or questions.


The mitochondrial genomes of Ancylostoma caninum and Bunostomum phlebotomum--two hookworms of animal health and zoonotic importance.
Hookworms are blood-feeding nematodes that parasitize the small intestines of many mammals, including humans and cattle. These nematodes are of major socioeconomic importance and cause disease, mainly as a consequence of anaemia (particularly in children or young animals), resulting in impaired development and sometimes deaths. Studying genetic variability within and among hookworm populations is central to addressing epidemiological and ecological questions, thus assisting in the control of hookworm disease. Mitochondrial (mt) genes are known to provide useful population markers for hookworms, but mt genome sequence data are scant. The present study characterizes the complete mt genomes of two species of hookworm, Ancylostoma caninum (from dogs) and Bunostomum phlebotomum (from cattle), each sequenced (by 454 technology or primer-walking), following long-PCR amplification from genomic DNA (approximately 20-40 ng) isolated from individual adult worms. These mt genomes were 13717 bp and 13790 bp in size, respectively, and each contained 12 protein coding, 22 transfer RNA and 2 ribosomal RNA genes, typical for other secernentean nematodes. In addition, phylogenetic analysis (by Bayesian inference and maximum likelihood) of concatenated mt protein sequence data sets for 12 nematodes (including Ancylostoma caninum and Bunostomum phlebotomum), representing the Ascaridida, Spirurida and Strongylida, was conducted. The analysis yielded maximum statistical support for the formation of monophyletic clades for each recognized nematode order assessed, except for the Rhabditida. The mt genomes characterized herein represent a rich source of population genetic markers for epidemiological and ecological studies. The strong statistical support for the construction of phylogenetic clades and consistency between the two different tree-building methods employed indicate the value of using whole mt genome data sets for systematic studies of nematodes. The grouping of the Spirurida and Ascaridida to the exclusion of the Strongylida was not supported in the present analysis, a finding which conflicts with the current evolutionary hypothesis for the Nematoda based on nuclear ribosomal gene data.


Interleukin (IL) 1beta and IL-10 gene polymorphism in chronic hepatitis C patients with normal or elevated alanine aminotransferase levels.
To evaluate the frequency of cytokine gene single nucleotide polymorphisms (SNP) of IL-1beta and IL-10 at promoter sites -115 and -1082 respectively and their association with hepatocellular injury as suggested by alanine aminotransferase (ALT) level. Fifty six patients (31 males, 25 females) positive for HCV antibody were studied. Their mean age was 37.5 +/- 12.0 years (range 16-62). Fifty one were HCV RNA positive; 14 had normal and 37 elevated ALT levels. Type 3 was the predominant genotype. For cytokine polymorphism DNA was extracted from the whole blood. After amplification with polymerase chain reaction, biallelic polymorphisms of IL-1beta at -115 and IL-10 at -1082 promotor site were determined using sequence specific oligonucleotide primers. IL-1beta-15 C allele was present in 49 (87.5%) and -115 T in 30 (53.6%) patients. Genotype CC was present in 26 (46%), TC 23 in (42%), and TT in 07 (12%). IL-10 -1082 A allele was seen in 50 (89.3%) and -1082 G in 35 (62.5%). Genotype AG in 29 (52%), AA in 21(37%), and GG in 06 (11%). Though greater number of HCV RNA positive patients with normal ALT had IL-10 -1082 AG genotype (10 out of 14), no statistically significant difference could be found in the genotype profile of the above promoter sites of IL-1beta and IL-10 in patients with normal or elevated ALT. IL-1beta-115 C and IL-10 -1082A are the more frequent alleles in our patients. Genotypes L-1beta -115 CC and TC, and IL-10 -1082AG and AA are common while -115 TT and -1082 GG are less common. Any effect of IL-1beta and IL-10 gene polymorphism on the degree of hepatocellular injury may not be apparent by the ALT levels.


Depression and endocrine disorders: focus on the thyroid and adrenal system.
Of the various hypothalamic-pituitary-end organ axes, the thyroid and adrenal systems have been implicated most often in affective disorders. Patients with primary thyroid disease have high rates of depression, and patients with Addison's disease or Cushing's syndrome have relatively high rates of affective and anxiety symptoms. However, the major support for these endocrine axes in the pathophysiology of mood disorders comes from studies in which alterations in components of the hypothalamic-pituitary-thyroid (HPT) and the hypothalamic-pituitary-adrenal (HPA) axes have been documented in patients with primary depression. Concerning the HPT axis, depressed patients have been reported to have: (a) alterations in thyroid-stimulating hormone response to thyrotropin-releasing hormone (TRH); (b) an abnormally high rate of antithyroid antibodies; and (c) elevated cerebrospinal fluid (CSF) TRH concentrations. Moreover, tri-iodothyronine has been shown conclusively to augment the efficacy of various antidepressants. Concerning the HPA axis, depressed patients have been reported to exhibit: (a) adrenocorticoid hypersecretion; (b) enlarged pituitary and adrenal gland size; and (c) elevated CSF corticotropin-releasing factor concentrations. All of the HPA axis alterations in depression studied thus far are state-dependent, whereas the HPT axis alterations may be partially trait and partially state markers.


Fractures and the gut microbiome.
The role of the gut microbiome in the pathogenesis of several inflammatory, non-AIDS comorbidities, such as cardiovascular disease, cognitive impairment and liver disease has become a focus of recent research. Low bone mineral density (BMD) and increased fracture incidence in people living with HIV (PLWH) is also widely reported, however, the relationship between alterations in the gut microbiome and bone disease in PLWH has not been previously reviewed. Murine models that manipulate the gut microbiome, either through breeding of 'germ-free' mice or antibiotic-depleted gut microbiome, show differences in bone mineral density and bone mass in those with altered gut microbiome. This effect is reported to be driven via changes in the gut-immune-skeletal axis, with changes favouring bone resorption. Several inflammatory conditions wherever bone loss is a prominent feature, such as rheumatoid arthritis and inflammatory bowel disease, have also reported alterations in the gut microbiome, which are associated with bone loss, again through changes in the gut-immune-skeletal axis. The interplay between the gut microbiome and the immune-skeletal axis in HIV represents a complex relationship. Alterations in the gut microbiome, which induce an activated immune phenotype and inflammatory milieu are associated with non-AIDS comorbidities in PLWH and bone loss in several other conditions characterized by chronic immune activation and inflammation. It is, therefore, likely that there are comparable effects between altered gut microbiome and bone loss in HIV, however, further research is required to better define this relationship in populations of PLWH.


My Brain Needs a Break: Kindergarteners' Willpower Theories Are Related to Behavioral Self-Regulation.
Is the way that kindergarteners view their willpower - as a limited or as a non-limited resource - related to their motivation and behavioral self-regulation? This study is the first to examine the structure of beliefs about willpower in relation to behavioral self-regulation by interviewing 147 kindergarteners (52% girls) aged 5 to 7 years (M = 6.47, SD = 0.39). A new instrument was developed to assess implicit theories about willpower for this specific age group. Results indicated that kindergarteners who think of their willpower as a non-limited resource showed better behavioral self-regulation than children who adopted a more limited theory, even when controlling for age and gender. This relation was especially pronounced in low achieving children. Mediation and moderation analyses showed that this relation was partly mediated through the children's willingness to invest effort to reach a learning goal. Findings suggest that fostering metacognitive beliefs in children, such as the belief that willpower is a non-limited resource, may increase behavioral self-regulation for successful adjustment to the demands of kindergarten and school.


Characteristics of Post-hoc Subgroup Analyses of Oncology Clinical Trials: A Systematic Review.
Subgroup analyses in clinical trials assess intervention effects on specific patient subgroups, ensuring generalizability. However, they are usually only able to generate hypotheses rather than definitive conclusions. This study examined the prevalence and characteristics of subgroup analysis. We systematically reviewed published subgroup analyses from 2000-2022. We included articles presenting secondary, post-hoc, or subgroup analyses of interventional clinical trials in oncology, cancer survivorship, or cancer screening, published separately to the original clinical trial publication. We collected cancer type, year of publication, where and how subgroup analysis was reported, and funding. Out of 16,487-screened publications, 1,612 studies were included; primarily subgroup analyses of treatment trials for solid tumors (82%). Medical writers contributed to 31% of articles, and 58% of articles reported conflicts of interest. Subgroup analyses increased significantly over time, with 695 published between 2019-2022, compared to 384 from 2000-2014. Gastrointestinal tumors (25%) and lymphoid lineage tumors (39%) were the most frequently studied solid and hematological malignancies, respectively. Industry funding and reporting of conflicts of interest increased over time. Subgroup analyses often neglected to indicate their secondary nature in the title. Most authors were from high-income countries, most commonly North America (45%). This study demonstrates the rapidly growing use of subgroup analysis of oncology clinical trials, revealing that the majority are supported by pharmaceutical companies, and they frequently fail to indicate their secondary nature in the title. Given the known methodological limitations of subgroup analyses, caution is recommended among authors, readers, and reviewers when conducting and interpreting these studies.


Nonenzymatic glycation at the N terminus of pathogenic prion protein in transmissible spongiform encephalopathies.
Transmissible spongiform encephalopathies (TSEs) are transmissible neurodegenerative diseases characterized by the accumulation of an abnormally folded prion protein, termed PrPSc, and the development of pathological features of astrogliosis, vacuolation, neuronal cell loss, and in some cases amyloid plaques. Although considerable structural characterization of prion protein has been reported, neither the method of conversion of cellular prion protein, PrPC, into the pathogenic isoform nor the post-translational modification processes involved is known. We report that in animal and human TSEs, one or more lysines at residues 23, 24, and 27 of PrPSc are covalently modified with advanced glycosylation end products (AGEs), which may be carboxymethyl-lysine (CML), one of the structural varieties of AGEs. The arginine residue at position 37 may also be modified with AGE, but not the arginine residue at position 25. This result suggests that nonenzymatic glycation is one of the post-translational modifications of PrP(Sc). Furthermore, immunostaining studies indicate that, at least in clinically affected hamsters, astrocytes are the first site of this glycation process.


Photocatalytic activity of semiconductor sulfide heterostructures.
This paper reports a theoretical and experimental study of the heterostructure photocatalytic activity in a CdS or ZnS and CdS@ZnS decorated system prepared by a microwave assisted solvothermal (MAS) method. A theoretical model of the decorated system was created in order to analyze the electronic transition mainly in their interface. The results show that CdS and ZnS interfaces produce an electron charge transfer from the CdS electron-populated clusters to the ZnS hole-populated clusters which helps to enhance the photocatalytic activity of the CdS@ZnS decorated system.


Track-Density Ratio Mapping With Fiber Types in the Cerebral Cortex Using Diffusion-Weighted MRI.
The nerve fibers are divided into three categories: projection, commissural, and association fibers. This study demonstrated a novel cortical mapping method based on these three fiber categories using MR tractography data. The MR fiber-track data were extracted using the diffusion-weighted 3T-MRI data from 19 individuals' Human Connectome Project dataset. Anatomical MR images in each dataset were parcellated using FreeSurfer software and Brainnetome atlas. The 5 million extracted tracks per subject by MRtrix software were classified based on the basic cortical structure (cortical area in the left and right hemisphere, subcortical area), after the tracks validation procedure. The number of terminals for each categorized track per unit-sized cortical area (1 mm3) was defined as the track-density in that cortical area. Track-density ratio mapping with fiber types was achieved by mapping the density-dependent color intensity for each categorized tracks with a different primary color. The mapping results showed a highly localized, unique density ratio map determined by fiber types. Furthermore, the quantitative group data analysis based on the parcellation information revealed that the majority of nerve fibers in the brain are association fibers, particularly in temporal, inferior parietal, and occipital lobes, while the projection and commissural fibers were mainly located in the superior part of the brain. Hemispheric asymmetries in the fiber density were also observed, such as long association fiber in the Broca's and Wernicke's areas. We believe this new dimensional brain mapping information allows us to further understand brain anatomy, function.


Six Weeks of Polarized Versus Moderate Intensity Distribution: A Pilot Intervention Study.
Previous research indicates that polarized training-intensity-distribution (TID) programs could enhance endurance performance. Short-distance triathletes, however, perform most of their competition-specific training around moderate-intensity intervals. There is still a lack of evidence as to which program is more beneficial during triathlete training. This pilot study examined 6 weeks of training-macrocycle using polarized intensity distribution compared to moderate TID and it's effects on sub-maximal and maximal performance indices during running and cycling. Fifteen moderately trained triathletes were either assigned to an intervention group (INT, n = 7, 2 females/5 males, Age: 29.1 ± 7.6) or a control group (CON, n = 8, 2 females/6 males, Age: 30.3 ± 6.1). We used the minimization method (Strata: gender, age competition times, training volumes) to allocate the groups. The participants underwent incremental cycling and running testings before and after the intervention period to assess performance indices until objective exhaustion. CON employed a moderate TID with either medium-intensity (MIT) or low-intensity training (LIT). INT used polarized training intensity distribution (TID), with either LIT or high-intensity training (HIT). Average training hours and anthropometric data did not indicate any differences between CON and INT during the study period. We applied the polarization index of >2 in INT (2.1 ± 0.4) and <1 in CON (0.9 ± 0.3). Both groups notably improved their lactate threshold 2 (+2.8 ± 5.1 %, p = 0.026) and peak (+5.4 ± 6.2 %, p = 0.002) running performance. We did not observe statistically significant time × group interaction effects in any of the performance outcomes between both groups. Polarized TID in moderately trained triathletes did not prove to be superior compared to a more moderate TID. However, more studies in larger and more highly trained subjects are needed.