The biology of AIDS.
The biology of AIDS, including a selective review of the immune system, is discussed so that social workers may better understand what happens once the virus becomes activated. Because social workers increasingly will encounter clients who are anxious about possibly developing AIDS or who already have contracted the disease, a thorough understanding of the etiology of AIDS will become essential for practice. An informed social worker can help clients to evaluate rapidly changing medical information and to regain a sense of control through practicing safer behavior and obtaining information about the disease.


The Difficult Path to the Discovery of Novel Treatments in Psychiatric Disorders.
CNS diseases, including psychiatric disorders, represent a significant opportunity for the discovery and development of new drugs and therapeutic treatments with the potential to have a significant impact on human health. CNS diseases, however, present particular challenges to therapeutic discovery efforts, and psychiatric diseases/disorders may be among the most difficult. With specific exceptions such as psychostimulants for ADHD, a large number of psychiatric patients are resistant to existing treatments. In addition, clinicians have no way of knowing which psychiatric patients will respond to which drugs. By definition, psychiatric diagnoses are syndromal in nature; determinations of efficacy are often self-reported, and drug discovery is largely model-based. While such models of psychiatric disease are amenable to screening for new drugs, whether cellular or whole-animal based, they have only modest face validity and, more importantly, predictive validity. Multiple academic, pharmaceutical industry, and government agencies are dedicated to the translation of new findings about the neurobiology of major psychiatric disorders into the discovery and advancement of novel therapies. The collaboration of these agencies provide a pathway for developing new therapeutics. These efforts will be greatly helped by recent advances in understanding the genetic bases of psychiatric disorders, the ongoing search for diagnostic and therapy-responsive biomarkers, and the validation of new animal models.


Biophysical studies on collagen-lipid interaction.
The potential use of liposomes as a delivery system is still limited by the poor understanding of the interaction mechanisms of liposomes underlying with biological media. Interaction between liposomes and protein is important for the structure and function of cells. In the present work, the interaction between collagen and dipalmitoyl phosphatidylcholine (DPPC) liposomes was studied by solubilization using a nonionic detergent, octylglucoside (OG), as well as a monolayer technique. The solubilization of the liposomal membrane was found to proceed in three stages of transition from the vesicular form to the mixed micellar form. Moreover, the amount of detergent needed to completely solubilize the liposomal membrane was increased after the incubation of liposomes with collagen, indicating an increased membrane resistance to the detergent and hence, a change in the natural membrane permeation properties. The addition of collagen in the subphase of different monolayer films induced a considerable shift towards a larger area/molecule in the compression-isotherm curves. This is either due to the insertion of collagen into the monolayer via its hydrophobic residues or to adsorption causing a protein layer to be located parallel to the lipid monolayer. It was concluded that collagen significantly altered the physical state of the liposome membrane, which may be attributed to collagen interaction with the liposomal surface and/or to its incorporation within the bilayer membrane.


Effect of hyperthermia on combination interferon treatment: enhancement of the antiproliferative activity against murine B-16 melanoma.
Previous studies have evaluated the effects of hyperthermia on the antiproliferative activity of interferon. The activities of all three types of interferon have been shown to be synergistically enhanced by hyperthermic conditions. Further, the antiproliferative activity of interferon has been shown to be synergistically enhanced by combinations of gamma-plus alpha- or beta-interferon. The question remained whether combining these two methods of enhancing interferon activity would lead to an even higher level of enhancement of antiproliferative activity or to an antagonism of their separate effects. To address this question, mouse B-16 melanoma cells were cloned at 37.3 degrees C and at 39.4 degrees C in the presence of various combinations of murine alpha/beta- and gamma-interferon. Potentiation of interferon's antiproliferative activity by combination interferon treatment was found to occur at both temperatures. Moreover, the level of potentiation was synergistically enhanced by hyperthermic conditions. The results suggest that a combined treatment regimen of hyperthermia and combination interferon therapy (gamma- plus alpha- or beta-interferon) may provide a highly potent antitumor effect.


Correlations between white blood cell count and metabolic syndrome in middle-age Taiwanese.
Metabolic syndrome was first proposed in 1988 and has been recognized as a powerful predictor for cardiovascular disease and diabetes. At the same time, white blood cell count (WBCC) was proposed to have significant correlation with metabolic syndrome (MS). In this study, we attempted to investigate the relationship between WBCC and components of metabolic syndrome in subjects in Taiwan with normal WBCC, no significant medical disease, and no medications known to affect the components of MS. We enrolled 1185 subjects with age > or = 40 years in 1997. These subjects participated in the annual health examination of the MJ Life Clinic. Subjects with abnormal WBCC (> 10x 10(9) cells/l), history of diabetes, hypertension or hyperlipidemia, or taking medications for these diseases or medications known to affect components of MS, were excluded. Because the menstrual cycle has an effect on the components of MS, we divided the subjects into three groups: male (M group, n = 576), old female (OF group, aged > or = 50 years, n = 307), and young female (YF group: aged < 50 years, n = 302). Each group was further divided into four quartiles according to WBCC (WBCC1 to WBCC4, from the lowest to highest WBCC). The body mass index (BMI) of YF was significantly lower than both M and OF. The diastolic blood pressure (DBP) and triglycerides (TG) were higher in M than YF. High-density lipoprotein cholesterol (HDLC) was lower in M compared to both YF and OF. When evaluating the metabolic components in different quartiles of WBCC in M, only WBCC1 had lower BMI and TG than WBCC4 after adjustment for age and BMI. For OF, the results were similar, the BMI of both WBCC1 and WBCC2 was lower than WBCC3 and TG of WBCC1 was lower than WBCC4. Finally, in YF, none of the BMI, blood pressure, FPG, HDLC, or TG was different in the four WBCC quartiles. The results of multiple regression between the WBCC and components of MS after adjustment for age and BMI were also evaluated. Significant correlations could only be noted in WBCC with BMI and TG in M and OF. In conclusion, in subjects with normal WBCC and no history of significant medical diseases, BMI and TG are significantly related to the levels of WBCC and are the two earliest components of MS to be noted, especially in males and post-menopausal females.


Newly-formed axonal branches of rat sciatic neurons sprouting in the spinal cord after peripheral axotomy.
A retrograde method of nerve tracing using a recombinant adenovirus was applied to experimental regeneration of peripheral nerves to study the sprouting position of the regenerating axon. This enabled us to see the entire length of the axons on a whole-mount neural specimen. The peroneal nerve was transsected and infected with this virus, and the tibial nerve was transsected and sutured in eight Wistar rats. Four to five weeks later, labelled axons appeared in the tibial nerve, some of which could be traced from the tibial nerve to the spinal cord without making a connection with other labelled fibres. Control experiments negated the possibilities of transneuronal immigration or contamination of the virus. When the peroneal and tibial nerves were double-labelled with fluorescent tracers four weeks after their transsection, double-labelled motor neurons appeared. Based on these findings, we conclude that regenerating branches do sprout in the spinal cord after axotomy.


Selective synthesis of (2Z,4E)-dienyl esters by ene-diene cross metathesis.
[reaction: see text] Cross metathesis of terminal alkenes with methyl (2Z,4E)-hexadienoate and related dienyl esters provides substituted (2Z,4E)-dienyl esters in good yields. Small-scale reactions are effectively promoted by the standard second-generation Grubbs-Hoveyda catalyst (GH-II), while a new fluorous GH-II catalyst is used for separation and recovery in gram-scale reactions. The transformation is featured in a rapid synthesis of the bottom fragments of the potent anticancer agents (-)-dictyostatin and 6-epi-dictyostatin.


Spin coupling between cold atoms and the thermal fluctuations of a metal surface.
We describe an experiment in which Bose-Einstein condensates and cold atom clouds are held by a microscopic magnetic trap near a room-temperature metal wire 500 microm in diameter. The lifetime for atoms to remain in the microtrap is measured over a range of distances down to 27 microm from the surface of the metal. We observe the loss of atoms from the microtrap due to spin flips. These are induced by radio-frequency thermal fluctuations of the magnetic field near the surface, as predicted but not previously observed.


Modular instrument mounting system for variable environment in operando X-ray experiments.
In the growing field of in operando and in situ X-ray experiments, there exists a large disparity in the types of environments and equipment to control them. This situation makes it challenging to conduct multiple experiments with a single mechanical interface to the diffractometer. Here, we describe the design and implementation of a modular instrument mounting system that can be installed on a standard six-circle diffractometer (e.g., 5021 Huber GmbH). This new system allows for the rapid changeover of different chambers and sample heaters and permits accurate sample positioning (x, y, z, and azimuthal rotation) without rigid coupling to the chamber body. Isolation of the sample motion from the chamber enclosure is accomplished through a combination of custom rotary seals and bellows. Control of the pressure and temperature has been demonstrated in the ranges of 10(-6)-10(3) Torr and 25°C-900°C, respectively. We have utilized the system with several different modular instruments. As an example, we provide in situ sputtering results, where the growth dynamics of epitaxial LaGaO3 thin films on (001) SrTiO3 substrates were investigated.


Recent advances in polyubiquitin chain recognition.
Polyubiquitin chains are regulatory signals for a wide array of biological processes. Recent structural studies reveal novel modes of polyubiquitin chain recognition and implicate the diverse repertoire of interactions in providing the specificity of polyubiquitin recognition.


Efficient fiber-coupled single-photon source based on quantum dots in a photonic-crystal waveguide.
Many photonic quantum information processing applications would benefit from a high brightness, fiber-coupled source of triggered single photons. Here, we present a fiber-coupled photonic-crystal waveguide single-photon source relying on evanescent coupling of the light field from a tapered out-coupler to an optical fiber. A two-step approach is taken where the performance of the tapered out-coupler is recorded first on an independent device containing an on-chip reflector. Reflection measurements establish that the chip-to-fiber coupling efficiency exceeds 80 %. The detailed characterization of a high-efficiency photonic-crystal waveguide extended with a tapered out-coupling section is then performed. The corresponding overall single-photon source efficiency is 10.9 % ± 2.3 %, which quantifies the success probability to prepare an exciton in the quantum dot, couple it out as a photon in the waveguide, and subsequently transfer it to the fiber. The applied out-coupling method is robust, stable over time, and broadband over several tens of nanometers, which makes it a highly promising pathway to increase the efficiency and reliability of planar chip-based single-photon sources.


Development of pullulan-based nanocomposite films reinforced with starch nanocrystals for the preservation of fresh beef.
Incorporation of polysaccharide-based nanofillers is an effective strategy to fabricate bio-nanocomposite films with preferable mechanical, barrier, and surface hydrophobicity properties compared to pure biopolymer films. The objective of this research is to investigate the influence of starch nanocrystals obtained from native (NSNC) and waxy rice starch (WSNC) on the physical-chemical properties of pullulan-based nanocomposite films and their preservation performance on fresh beef. Continuous SNCs network structure was observed for pullulan-10% SNCs nanocomposite films, whereas the percolation network of SNCs was destroyed and became no longer continuous with increasing SNCs concentration up to 20% in pullulan films. Among the tested films, pullulan-10% SNCs films showed the highest TS values, lowest WVP and OTR values, due to the formation of percolating SNCs network in pullulan matrix. It is noteworthy that the WVP and OTR values of pullulan-10% WSNC films were significantly lower than that of pullulan-10% NSNC films, probably due to higher hydrophobicity and crystallinity of WSNC compared with NSNC. Beef pieces coated with pullulan-SNCs films had higher L* and a* values, lower TVB-N, TBARS, and TVC values during 7 days' storage at 4 °C compared with samples coated with pullulan films. Pullulan-SNCs nanocomposite films, especially pullulan-WSNC films, could be potentially used as a coating material for fresh beef due to their desirable oxygen and water barrier properties. © 2022 Society of Chemical Industry.


Removal characteristics of microplastics by Fe-based coagulants during drinking water treatment.
Microplastics have caused great concern worldwide recently due to their ubiquitous presence within the marine environment. Up to now, most attention has been paid to their sources, distributions, measurement methods, and especially their eco-toxicological effects. With microplastics being increasingly detected in freshwater, it is urgently necessary to evaluate their behaviors during coagulation and ultrafiltration (UF) processes. Herein, the removal behavior of polyethylene (PE), which is easily suspended in water and is the main component of microplastics, was investigated with commonly used Fe-based salts. Results showed that although higher removal efficiency was induced for smaller PE particles, low PE removal efficiency (below 15%) was observed using the traditional coagulation process, and was little influenced by water characteristics. In comparison to solution pH, PAM addition played a more important role in increasing the removal efficiency, especially anionic PAM at high dosage (with efficiency up to 90.9%). The main reason was ascribed to the dense floc formation and high adsorption ability because of the positively charged Fe-based flocs under neutral conditions. For ultrafiltration, although PE particles could be completely rejected, slight membrane fouling was caused owing to their large particle size. The membrane flux decreased after coagulation; however, the membrane fouling was less severe than that induced by flocs alone due to the heterogeneous nature of the cake layer caused by PE, even at high dosages of Fe-based salts. Based on the behavior exhibited during coagulation and ultrafiltration, we believe these findings will have potential application in drinking water treatment.


Inclusion of persistent organic pollutants in humification processes: direct chemical incorporation of phenanthrene via oxidative coupling.
The participation of phenanthrene in phenol-coupling reactions mediated by horseradish peroxidase was investigated. Aqueous-phase concentrations of phenanthrene were observed to decrease dramatically with phenol as a result of the formation of precipitated products, suggesting a potential means for simultaneous treatment of phenolic contaminants and polycyclic aromatic hydrocarbons (PAHs) using peroxidase-mediated oxidative coupling processes. The studies reveal that phenanthrene removal from the aqueous phase occurs by a combination of sorption by and chemical bonding to precipitated reaction products. In that the oxidative coupling reactions of phenolics comprise an important step in the initiation of humification processes, the results obtained provide insights to potential roles that natural humification may play in the sorption, sequestration, and environmental fate of PAHs and other organic xenobiotics of similar nature.


DNA methylation regulator-mediated modification pattern defines tumor microenvironment immune infiltration landscape in colon cancer.
Emerging evidence implies a non-negligible role of DNA methylation in tumor immunity, however, its comprehensive impact on tumor microenvironment (TME) formation and immune activation remains unclear. In this study, we integrated 24 DNA methylation regulators among 754 colon cancer patients to distinguish different modification patterns via an unsupervised clustering method, and explore their TME immune characteristics. Three DNA methylation modification patterns with distinct prognosis and biological behaviors were identified, consistent with three known phenotypes of immune-inflamed, immune-excluded, and immune-desert. We then determined a DNA methylation gene signature and constructed a DNA methylation score (DMS) to quantify modification patterns individually through principal component analysis algorithms. DMS-low group had characteristics of specific molecular subtypes, including microsatellite instability, CpG island methylator phenotype positive, and mutant BRAF, presented by increased mutation burden, activation of DNA damage repair and immune-related pathways, highly TME immune cells infiltration, and hence, a preferable prognosis. Further, low DMS was also demonstrated to be correlated to better response and prolonged survival of anti-PD-L1 antibody, indicating that DMS could be considered as an effective predictive tool for immunotherapy. In conclusion, our work presented a landscape of different DNA methylation modification patterns, and their vital role in the formation of TME diversity and complexity, which could help to enhance understanding of TME immune infiltration characteristics and more importantly, guide immunotherapy strategies more effectively and personalized.


The chemical syntheses and bioactivities of novel peptide-based endothelin antagonists.
Endothelin antagonists, novel tripeptides containing a series of unnatural amino acids, were synthesized and characterized. A linear peptide BQ-485, perhydroazepin-1-yl-L-leucyl (1)-D-tryptophanyl (2)-D-tryptophan (3), was selected as the parent compound. The introduction of D-Phe derivatives into these peptidic ET antagonists resulted in potent activity against the contraction of rat aortic smooth muscles induced by ET-1 (10 nM) which activated the ET receptors. Among these compounds, 15 tripeptides had high enough antagonistic activity at the level of 10(-7) mol/L (IC50). The activity of three compounds was 10(-6) mol/L (IC50). These HIM-CO-Leu-D-Trp-D-Phe(-R)-OH compounds as ETA antagonists may provide a tool for the development of therapeutic agents in the treatment of putative ET-1-related disorders.


Cyclolinear Oligo- and Poly(iminoborane)s: The Missing Link in Inorganic Main-Group Macromolecular Chemistry.
The reaction of n-C8 H17 B[N(Me)SiMe3 ]2 (1) with n-C8 H17 BCl2 (2 a) yielded, instead of a linear poly(iminoborane), the aminoborane n-C8 H17 B(Cl)N(Me)SiMe3 (4) and after cyclotrimerization the borazine cyclo-(n-C8 H17 BNMe)3 (6). Side reactions that result in borazine formation were effectively suppressed if 1,3-bis(trimethylsilyl)-1,3,2-diazaborolidines 7 were employed as co-monomers in combination with dichloro- or dibromoboranes 2 or 8, respectively. Silicon/boron exchange polycondensation led to oligo(iminoborane)s 11 a,b,ac,d. Alternative synthetic routes to such species involve Sn/B exchange of 1,3-bis(trimethylstannyl)-2-n-octyl-1,3,2-diazaborolidine (16) and n-C8 H17 BBr2 (8 a), and the initiated polycondensation of the dormant monomer 14 in the presence of a Brønsted acid (HCl, HOTf, or HNTf2 ; Tf=trifluoromethylsulfonyl). Although an attempt to obtain an oligo-/poly(iminoborane) with phenyl side groups yielded only insoluble material, the incorporation of aryl groups was proven for a derivative with both phenyl and n-octyl boron substituents (11 ac), as well as for a derivative with 4-n-butylphenyl side groups (11 d). The highest-molecular-weight sample obtained was 11 ac. Featuring about 18 catenated BN units, on average, this is the closest approach to a poly(iminoborane) known.


Frequent downregulation of BTB and CNC homology 2 expression in Epstein-Barr virus-positive diffuse large B-cell lymphoma.
Diffuse large B-cell lymphoma (DLBCL) is the most common B-cell lymphoma subtype, and the Epstein-Barr virus (EBV)-positive subtype of DLBCL is known to show a more aggressive clinical behavior than the EBV-negative one. BTB and CNC homology 2 (BACH2) has been highlighted as a tumor suppressor in hematopoietic malignancies; however, the role of BACH2 in EBV-positive DLBCL is unclear. In the present study, BACH2 expression and its significance were studied in 23 EBV-positive and 43 EBV-negative patient samples. Immunohistochemistry revealed BACH2 downregulation in EBV-positive cases (P < 0.0001), although biallelic deletion of BACH2 was not detected by FISH. Next, we analyzed the contribution of BACH2 negativity to aggressiveness in EBV-positive B-cell lymphomas using FL-18 (EBV-negative) and FL-18-EB cells (FL-18 sister cell line, EBV-positive). In BACH2-transfected FL-18-EB cells, downregulation of phosphorylated transforming growth factor-β-activated kinase 1 (pTAK1) and suppression in p65 nuclear fractions were observed by Western blot analysis contrary to non-transfected FL-18-EB cells. In patient samples, pTAK1 expression and significant nuclear p65, p50, and p52 localization were detected immunohistochemically in BACH2-negative DLBCL (P < 0.0001, P = 0.006, and P = 0.001, respectively), suggesting that BACH2 downregulation contributes to constitutive activation of the nuclear factor-κB pathway through TAK1 phosphorylation in BACH2-negative DLBCL (most EBV-positive cases). Although further molecular and pathological studies are warranted to clarify the detailed mechanisms, downregulation of BACH2 may contribute to constitutive activation of the nuclear factor-κB pathway through TAK1 activation.


Is the shape of the density-growth relationship for stream salmonids evidence for exploitative rather than interference competition?
1. Empirical studies show that average growth of stream-dwelling salmon and trout often declines with increasing density in a characteristic concave relationship. However, the mechanisms that generate negative density-growth relationships in populations in natural streams are not certain. 2. In a recent study, Imre, Grant & Cunjak (2005; Journal of Animal Ecology, 74, 508-516) argue that density-dependent growth due to exploitative competition for prey causes the negative density-growth relationships for stream salmonids. They argue that the concave shape of empirical density-growth relationships is consistent with a simple model of exploitative competition and not consistent with interference competition for space. 3. We use a simple model to show that competition for space can yield concave density-growth relationships consistent with the empirical pattern when individuals compete for foraging sites that vary spatially in quality and lower-quality sites predominate. Thus, the predictions of the exploitative competition and spatial competition models overlap. 4. The shape of the density-growth relationship does not differentiate between candidate mechanisms underlying density-dependent growth for stream salmonids. Our results highlight the general problem with determining the mechanism driving an ecological process from patterns in observational data within the context of linking population demographics to habitat structure and animal behaviour.


Challenging Implantation of Hip Prosthesis in a 32-year-old Patient with Kniest Syndrome.
Kniest dysplasia is associated with short body stature (dwarfism) and impairment of the musculoskeletal system due to a mutation in the COL2A1 gene coding for a protein that forms type II collagen. Hip endoprosthesis for patients with Kniest system requires a specific femoral shaft design since the medullar space is limited due to the underlying dysplasia. The Wagner cone stem has shown excellent results. It is especially suitable for patients with small or dysplasic femur. However, no data exist regarding hip endoprosthesis in a patient with Kniest syndrome. A 32-year-old female patient with Kniest syndrome presented at our department with a painful pseudarthrosis after femoral valgisation osteotomy 8 years ago. A Wagner cone stem and acetabular roof cup with a cemented Ecofit cup 2M (dual-articulation acetabular cup system) were implanted due to a dysplastic femur with a small medullary space. The Ecofit cup itself is associated with a reduced risk of dislocation. The patient was satisfied with the range of motion after hip endoprosthesis and reported a significant increase in quality of life. The patient is still comfortable with the hip prosthesis at the most recent follow-up 4 years after implantation. Follow-up radiographs over 4 years have not revealed any signs of loosening or migration, and no Trendelenburg sign was reported for the affected side. The Wagner cone stem provides a good solution in challenging femora caused by previous osteotomies, fractures, or dysplasia. Additional stability of hip prosthesis can be achieved using a dual articulation acetabular cup system. Furthermore, we applied an attachment tube based on the concept of tumorprosthesis where the abductor muscle group got reattached.


Nucleic Acid Amplification-Free Bioluminescent Detection of MicroRNAs with High Sensitivity and Accuracy Based on Controlled Target Degradation.
Accurate and sensitive detection of microRNAs is crucial to clinical diagnosis and therapy. Most of microRNA assays require target conversion in combination with nucleic acid amplification to improve the detection sensitivity, which may compromise the assay accuracy and specificity. Herein we report a sensitive bioluminescent method for microRNA assay on the basis of controlled target degradation without target conversion and nucleic acid amplification. In this assay, the target microRNA can be specifically degraded by exonuclease III after hybridization to its complementary probe, releasing adenosine monophosphate (AMP) from microRNA itself. The AMP then triggers an efficient bioluminescence generation system to produce a strong bioluminescence signal. This assay is highly sensitive with zero-background signal and a detection limit of 7.6 fM even without target amplification, and it can discriminate the single-nucleotide difference among microRNA family members with extremely high discrimination ratio. With the assistance of magnetic separation to eliminate the interference of endogenous ATP, ADP, and AMP in sample matrix, this assay can be further applied to absolute quantification of microRNAs in cancer cells and tissues from lung cancer patients, holding great potential in biomedical research and clinical diagnosis.


[Electroencephalograms (EEG) in 250 patients with epilepsy in a cysticercosis endemic area in Burundi].
This work aimed at describing EEG abnormalities in epileptic patients living in areas endemic for cysticercosis, underlining the electroclinical correlations and discussing the interest of EEG examination in this context. During a case-control study, 250 EEGs from patients with epilepsy were recorded with a portable system. Types of seizures were assessed clinically and from information obtained through a standardised questionnaire, and along with EEG were related to the results of cysticercosis serological tests. Among the 249 EEGs, 48% were normal, 5.2% had epileptic abnormalities, 6.8% showed an association between epileptic abnormalities and slow alterations. Slow theta and delta abnormalities were found in 21.8% of cases, and isolated deterioration of basic rhythms was observed in 17.3% of cases. Most seizures were generalized, and 61% of the patients had positive serology. One EEG was uninterpretable and another showed isolated spikes. Electroclinical agreement was considered to be satisfactory in 33 patients, and was better with the epileptic than with slow abnormalities. The existence of epileptiform EEG abnormalities confirmed clinically diagnosed epilepsy, but did not allow etiological diagnosis. Electroserological agreement was good in 24 patients. A significant association (Chi2, p = 0.03) existed between slow focal abnormalities and positive cysticercosis serology. Conversely, no significant association was detected between epileptic patterns and serology results. While the EEG alone clearly does not allow aetiological diagnosis, its joint use with clinical and biological results was a key element of the etiological and therapeutic discussion. When it shows focal abnormalities in a patient with epilepsy living in a high prevalence cysticercosis area, it confirms the clinical suspicion of neurocysticercosis. Morphological imagery alone can provide etiological information on the seizures by showing the nature and localization of the parenchymal lesions.


Point-of-care ultrasound training for respiratory therapists: A scoping review.
Point-of-care ultrasound (POCUS), although commonly used in clinical practice, is not currently included in training programs for respiratory therapists (RTs). In fact, given its ubiquity and clinical utility, RTs in Ontario, Canada, are changing their mandate to incorporate POCUS into their daily patient assessment. Therefore, we conducted a scoping review of the literature, aiming to describe the current evidence of POCUS training and methods of curriculum delivery for RTs to inform an evidence-based program design. We systematically searched MEDLINE, EMBASE, CINAHL, and Web of Science from inception to 8 July 2020. We included all studies reporting on RT training in POCUS. Documents included English language, full-text reports of all study designs. Title and abstract screening, full-text review, and data abstraction were done independently and in duplicate. Seven studies met our inclusion criteria, including four full texts and three abstracts; all were prospective and single-center studies, except one multicenter study. Reports were from nine different countries. Studies described cardiac, lung, and procedural ultrasonography use. The majority used a combination of educational methods; didactic talks, hands-on sessions, and practical assessments being the most common methods. There was a median of 11 participants enrolled in a training session. The instructors were physicians from various specialties such as critical care, pulmonology, and radiology. This scoping review identified seven papers that explored different methods of a POCUS curriculum delivery for RTs. From the interventions outlined, teaching POCUS skills to RTs seems feasible. However, further work needs to be done to solidify a POCUS curriculum specific to RTs and examine the impact on patient-related outcomes.


Infants' perception of melodies: the role of melodic contour.
Infants 8-11 months of age were exposed to repetitions of a 6-tone sequence or melody, then tested for their discrimination of transpositions of that sequence as well as other melodic transformations previously used by Massaro, Kallman, and Kelly with adults. In experiment 1, infants showed evidence of discriminating all transformations from the original melody. In Experiment 2, the task was made more difficult, and infants failed to discriminate transpositions of the original melody as well as transformations that preserved the melodic contour and approximate frequency range of the original melody. By contrast, infants showed evidence of discriminating transformations that violated the contour of the original melody or that included changes in the octaves from which component tones were drawn. This global processing strategy parallels that used by adults with atonal or unfamiliar tonal melodies.


Polyomavirus allograft nephropathy: sequential assessment of histologic viral load, tubulitis, and graft function following changes in immunosuppression.
Our initial cases of polyoma virus allograft nephropathy (PVAN) received pulse steroids due to anxiety about concomitant acute rejection triggered by the presence of tubulitis. However, our current policy is to reduce immunosuppression in all cases. The aim of this study was to determine whether clinical follow-up in these patient categories shows any differences in: (a) histologic viral load, (b) grade of tubulitis, and (c) graft function. Reduced viral load assessed within 8 weeks was seen in 4/20 (20.0%) biopsies treated initially by increased immunosuppression, compared to 15/19 (83.3%) biopsies treated with reduced immunosuppression (p = 0.001, Fisher's exact test). Yet, >70% reversal of the rise in serum creatinine occurred in only 3/19 (15.8%) and 1/19 (5.3%) patients, respectively, in these two groups. Improved tubulitis was seen in 11/20 (55%) of biopsies treated with steroids, despite the lack of beneficial effect on serum creatinine in 12/19 (63.1%) instances. In biopsies not treated with any change in immunosuppression, the serum creatinine remained stable in 1/5 (20%) and worsened in 4/5 (80%) biopsies. These data demonstrate that in biopsies with PVAN and tubulitis, reduced immunosuppression is more effective in lowering viral load than steroid therapy. Lack of parallelism between viral load, tubulitis grade, and serum creatinine illustrates a complex interplay of viral and alloimmune factors leading to graft injury.


Treatment of Nonalcoholic Fatty Liver Disease with Total Alkaloids in Rubus aleaefolius Poir through Regulation of Fat Metabolism.
Total alkaloids in Rubus aleaefolius Poir (TARAP) is a folk medicinal herb that has been used clinically in China to treat nonalcoholic fatty liver disease (NAFLD) for many years. However, the mechanism of its anti-NAFLD effect is largely unknown. In this study, we developed a NAFLD rat model by supplying a modified high-fat diet (mHFD) ad libitum for 8 weeks and evaluated the therapeutic effect of TARAP in NAFLD rats as well as the underlying molecular mechanism. We found that TARAP could reduce the serum triglycerides (TG), total cholesterol (TC), and low-density lipoprotein (LDL-C) levels and increase the serum high-density lipoprotein (HDL-C) level in NAFLD rats. In addition, TARAP treatment reduced expression of fatty acid synthetase (FAS), and acetyl-CoA carboxylase (ACC) and upregulated the expression of carnitine palmitoyltransferase (CPT). Our results suggest that regulation of lipid metabolism may be a mechanism by which TARAP treats NAFLD.


Broad adsorption of sepsis-related PAMP and DAMP molecules, mycotoxins, and cytokines from whole blood using CytoSorb® sorbent porous polymer beads.
Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. In sepsis and septic shock, pathogen-associated molecular pattern molecules (PAMPS), such as bacterial exotoxins, cause direct cellular damage and/or trigger an immune response in the host often leading to excessive cytokine production, a maladaptive systemic inflammatory response syndrome response (SIRS), and tissue damage that releases DAMPs, such as activated complement and HMGB-1, into the bloodstream causing further organ injury. Cytokine reduction using extracorporeal blood filtration has been correlated with improvement in survival and clinical outcomes in experimental studies and clinical reports, but the ability of this technology to reduce a broader range of inflammatory mediators has not been well-described. This study quantifies the size-selective adsorption of a wide range of sepsis-related inflammatory bacterial and fungal PAMPs, DAMPs and cytokines, in a single compartment, in vitro whole blood recirculation system. Purified proteins were added to whole blood at clinically relevant concentrations and recirculated through a device filled with CytoSorb® hemoadsorbent polymer beads (CytoSorbents Corporation, USA) or control (no bead) device in vitro. Except for the TNF-α trimer, hemoadsorption through porous polymer bead devices reduced the levels of a broad spectrum of cytokines, DAMPS, PAMPS and mycotoxins by more than 50 percent. This study demonstrates that CytoSorb® hemoadsorbent polymer beads efficiently remove a broad spectrum of toxic PAMPS and DAMPS from blood providing an additional means of reducing the uncontrolled inflammatory cascade that contributes to a maladaptive SIRS response, organ dysfunction and death in patients with a broad range of life-threatening inflammatory conditions such as sepsis, toxic shock syndrome, necrotizing fasciitis, and other severe inflammatory conditions.


Effects of heat stress and insulin sensitizers on pig adipose tissue.
Heat stress (HS) negatively impacts several swine production variables, including carcass fat quality and quantity. Pigs reared in HS have more adipose tissue than energetically predicted, explainable, in part, by HS-induced hyperinsulinemia. Study objectives were to evaluate insulin's role in altering fat characteristics during HS via feeding insulin-sensitizing compounds. Forty crossbred barrows (113 ± 9 kg BW) were randomly assigned to one of five environment by diet treatments: 1) thermoneutral (TN) fed ad libitum (TNAL), 2) TN and pair-fed (TNPF), 3) HS fed ad libitum (HSAL), 4) HS fed ad libitum with sterculic oil (SO) supplementation (HSSO; 13 g/d), and 5) HS fed ad libitum with dietary chromium (Cr) supplementation (HSCr; 0.5 mg/d; Kemin Industries, Des Moines, IA). The study consisted of three experimental periods (P). During P0 (2 d), all pigs were exposed to TN conditions (23 ± 3 °C, 68 ± 10% RH) and fed ad libitum. During P1 (7 d), all pigs received their respective dietary supplements, were maintained in TN conditions, and fed ad libitum. During P2 (21 d), HSAL, HSSO, and HSCr pigs were fed ad libitum and exposed to cyclical HS conditions (28 to 33 °C, 58 ± 10% RH). The TNAL and TNPF pigs remained in TN conditions and were fed ad libitum or pair-fed to their HSAL counterparts. Rectal temperature (TR), respiration rate (RR), and skin temperature (TS) were obtained daily at 0600 and 1800 h. At 1800 h, HS exposed pigs had increased TR, RR, and TS relative to TNAL controls (1.13 °C, 48 bpm, and 3.51 °C, respectively; P < 0.01). During wk 2 and 3 of P2, HSSO pigs had increased 1800 h TR relative to HSAL and HSCr (~0.40 and ~0.42 °C, respectively; P ≤ 0.05). Heat stress decreased ADFI and ADG compared to TNAL pigs (2.24 vs. 3.28 and 0.63 vs. 1.09 kg/d, respectively; P < 0.01) and neither variable was affected by SO or Cr supplementation. Heat stress increased or tended to increase moisture content of abdominal (7.7 vs. 5.9%; P = 0.07) and inner s.c. (11.4 vs. 9.8%; P < 0.05) adipose depots compared to TNAL controls. Interestingly, TNPF pigs also had increased adipose tissue moisture content and this was most pronounced in the outer s.c. depot (15.0 vs. 12.2%; P < 0.01) compared to TNAL pigs. Heat stress had little or no effect on fatty acid composition of abdominal, inner, and outer s.c. adipose tissue depots. In summary, the negative effects of HS on fat quality do not appear to be fatty acid composition related, but may be explained by increased adipose tissue moisture content.


Epidermal growth factor activation of NF-kappaB is mediated through IkappaBalpha degradation and intracellular free calcium.
The transcription factor NF-kappa-B is normally sequestered in the cytoplasm by its inhibitory subunit IkappaB. Most extracellular signals activate NF-kappa-B through a mechanism involving the phosphorylation and proteasome-dependent degradation of IkappaB. EGF activates NF-kappaB in A-431 carcinoma cells, which overexpress EGF receptors and in mouse embryo fibroblasts, which have a normal complement of receptors. Supershift experiments indicate that the NF-kappa-B complexes induced by EGF are composed of p50/p50 homodimers and p65/p50 heterodimers, but not c-rel. EGF stimulation enhances the degradation of IkappaBalpha, but not IkappaBbeta nor an N-terminal deletion mutant of IkappaBalpha. Treatment of cells with a proteasome inhibitor, such as ALLN or MG132, blocks EGF-mediated NF-kappaB activation, indicating that EGF-induced NF-kappa-B activation requires proteasome-dependent IkappaB degradation. Also, Bapta A/M (a cell-permeable chelator of intracellular calcium) blocks EGF-induced NF-kappa-B activation and IkappaBalpha degradation, suggesting a requirement of intracellular free Ca2+ for this growth factor response. Protein kinase C inhibition, in contrast, did not influence EGF activation of NF-kappaB.


Drug-induced depression and attempted suicide.
Sixty-eight patients who had attempted suicide were matched with non-suicidal patients with similar diagnoses to assess the extent to which excessive drug ingestion by the suicidal group might have contributed to their behaviour. It was found that the suicidal patients were consuming more drugs, particularly those of a potentially depressing kind. The implications of this finding are discussed.


Resting Energy Expenditure during Breastfeeding: Body Composition Analysis vs. Predictive Equations Based on Anthropometric Parameters.
Accurate estimation of energy expenditure in a breastfeeding woman is crucial for maintaining the proper nutritional status of the woman and healthy development of the infant. The current literature does not contain data regarding resting energy expenditure (REE) in breastfeeding women. Using mathematical equations is the most common method of REE assessment. However, due to changes in metabolism and body composition during pregnancy and lactation, the mathematical equations used among the general population may not apply. The aim of this study was to evaluate the resting energy expenditure of exclusively breastfeeding women by using body composition analysis - estimated REE (eREE) and to provide the most appropriate predictive equations - predicted REE (pREE) based on anthropometric parameters to estimate it. This was a pilot study with 40 exclusively breastfeeding women. Height and weight were measured and body composition analysis was performed. We predicted REE using fourteen self-selected equations, based on anthropometric parameters and/or age, and/or sex. The median eREE was 1515.0 ± 68.4 kcal (95% Cl, 1477-1582 kcal) and the pREE ranged from 1149.7 kcal (95% Cl, 1088.7-1215.0) by Bernstein et al., to 1576.8 kcal (95% Cl, 1479.9-1683.4), by Müller et al. Significant differences between eREE and all pREE were observed (p < 0.001, except Korth et al. equations). The Müller et al. equation was the most accurate with the smallest individual variation. All predictive equations showed low agreement, and in most cases, the results were underestimated. These findings indicate the need for further studies to propose more suitable methods to determine the energy requirements for breastfeeding women.


1,25-Dihydroxyvitamin D promotes negative feedback regulation of TLR signaling via targeting microRNA-155-SOCS1 in macrophages.
The negative feedback mechanism is essential to maintain effective immunity and tissue homeostasis. 1,25-dihydroxyvitamin D (1,25[OH]2D3) modulates innate immune response, but the mechanism remains poorly understood. In this article, we report that vitamin D receptor signaling attenuates TLR-mediated inflammation by enhancing the negative feedback inhibition. Vitamin D receptor inactivation leads to hyperinflammatory response in mice and macrophage cultures when challenged with LPS, because of microRNA-155 (miR-155) overproduction that excessively suppresses suppressor of cytokine signaling 1, a key regulator that enhances the negative feedback loop. Deletion of miR-155 attenuates vitamin D suppression of LPS-induced inflammation, confirming that 1,25(OH)2D3 stimulates suppressor of cytokine signaling 1 by downregulating miR-155. 1,25(OH)2D3 downregulates bic transcription by inhibiting NF-κB activation, which is mediated by a κB cis-DNA element located within the first intron of the bic gene. Together, these data identify a novel regulatory mechanism for vitamin D to control innate immunity.


Effect of fragile histidine triad gene transduction on proliferation and apoptosis of human hepatocellular carcinoma cells.
To evaluate the inhibitory effects of human fragile histidine triad (FHIT) gene on cell proliferation and apoptosis in human hepatocellular carcinoma line Hep3B in vitro. A recombinant pcDNA3.1 (+)/FHIT including the functional region of FHIT gene was constructed and transferred into human hepatocellular carcinoma cells in vitro. mRNA and protein expression of the FHIT gene in the transfected cells was detected by RT-PCR and Western blot, respectively. The effect of FHIT on proliferation was detected by MTT assay. Changes in cell cycle and apoptosis were assayed by flow cytometry. Five mice received subcutaneous transplantation of Hep3B-FHIT; 5 mice received subcutaneous transplantation of normal Hep3B and Hep3B-C as controls. The body weight of nude mice and tumor growth were measured. RT-PCR and Western blot analysis showed that the expression level of FHIT-mRNA and FHIT protein was higher in Hep3B cells after infection with pcDNA3.1 (+)/FHIT. The growth of Hep3B cells treated with pcDNA3.1 (+)/FHIT was significantly inhibited. The pcDNA3.1 (+)/FHIT-transfected Hep3B cells showed a significantly higher cell rate at G(0)-G(1) phase and increased apoptosis in comparison with controls (P < 0.05). The growth of transplanted tumor was inhibited markedly by FHIT. Tumors arising from the Hep3B-FHIT cells occurred much later than those arising from the Hep3B and Hep3B-C cells. The growth of Hep3B-FHIT cells was slow and the tumor volume was low. Transduction of FHIT gene inhibits the growth of human hepatocellular carcinoma cells and induces cell apoptosis in vivo and in vitro.


DNA damage and cell cycle regulation of ribonucleotide reductase.
Ribonucleotide reductase (RNR) catalyzes the rate limiting step in the production of deoxyribonucleotides needed for DNA synthesis. In addition to the well documented allosteric regulation, the synthesis of the enzyme is also tightly regulated at the level of transcription. mRNAs for both subunits are cell cycle regulated and inducible by DNA damage in all organisms examined, including E. coli, S. cerevisiae and H. sapiens. This DNA damage regulation is thought to provide a metabolic state that facilitates DNA replicational repair processes. S. cerevisiae also encodes a second large subunit gene, RNR3, that is expressed only in the presence of DNA damage. Genetic analysis of the DNA damage response in S. cerevisiae has shown that RNR expression is under both positive and negative control. Among mutants constitutive for RNR expression are the general transcriptional repression genes, SSN6 and TUP1. Mutations in POL1 and POL3 also activate RNR expression, indicating that the DNA damage sensory network may respond directly to blocks in DNA synthesis. A protein kinase, Dun1, has been identified that controls inducibility of RNR1, RNR2 and RNR3 in response to DNA damage and replication blocks. This result suggests that the RNR genes in S. cerevisiae form a regulon that is coordinately regulated by protein phosphorylation in response to DNA damage.


EGF- and TGF-alpha-like peptides in human fetal gut.
The presence of epidermal growth factor (EGF) and transforming growth factor-alpha (TGF alpha) immunoreactivities in fetal human tissues was studied immunohistochemically at different gestational ages. EGF and TGF alpha immunoreactivities were detected from the 20th gestational wk. EGF immunoreactivity was limited to the small intestine, but TGF alpha immunoreactive cells were present in the colon also. According to radioreceptor assay, the intestine of a 19-wk-old human fetus contained 10 times more EGF receptor-binding substance than EGF, as measured by immunofluorometric assay. Chromatographic analysis suggests that TGF alpha-like peptides account for at least part of this activity, as so argues in favor of the presence of TGF alpha- and EGF-like peptides in the human fetal gut. Whether they are synthesized in the fetus is yet unknown.


B vitamins related to homocysteine metabolism in adults celiac disease patients: a cross-sectional study.
The only treatment for celiac disease is the gluten-free diet. Few studies have assessed the nutritional adequacy of this diet, especially of B vitamins related to homocysteine metabolism. The aim of this study was to assess the nutritional status and serum concentrations of B vitamins involved in homocysteine metabolism, and to determine whether the dietary intake of these vitamins are meeting Dietary Reference Intakes in celiac patients. A cross-sectional study enrolled a total of 20 celiac patients (36.3 ± 13.7 years old; 65% women), following strict gluten-free diet (GFD) and 39 healthy controls matched by sex and age. The dietary intake was assessed by 3-day food records, and serum concentrations of homocysteine and vitamins B6, B12, and folate were determined after overnight fasting. Comparisons between the two groups were performed by Student's t test or Mann-Whitney U-test, for continuous variables. Pearson's chi-square test or Fisher's exact test was used for categorical variables. An alpha level of 5% were considered significant. Celiac patients had lower serum folate concentrations (7.7 ± 3.5 ng/mL, P < 0.05) than controls. All celiac patients had folate intake below the Estimated Average Requirement (EAR) (130.8 ± 53.6 μg/d). However, only a small proportion of celiac patients had hyperhomocysteinemia. Celiac patients treated with GFD presented inadequacy of dietary folate intake and low-serum concentrations of folate, suggesting that more attention should be given to the quality of the nutrients offered by the GFD, as it constitutes a lifelong treatment.


Insights from specimen data for two economic Chrysobothris species (Coleoptera: Buprestidae) in the western United States.
Chrysobothris mali Horn and Chrysobothris femorata (Olivier) (Coleoptera: Buprestidae) are wood-boring beetles native to western North America. Both species are highly polyphagous, feeding on a wide range of deciduous trees and shrubs, including fruit and nut trees as well as shade trees grown as nursery stock. Chrysobothris femorata is widely distributed across North America, while C. mali occurs west of the Rocky Mountains. There is a notable lack of basic biological information regarding both species' phenology and distributions in the Pacific Northwest. To better understand the biology of these economically important insects, seasonal adult collection information, host plant association data, and morphological measurements were collected from preserved specimens residing in 5 major regional arthropod collections. Label information was collected from 661 C. mali and 165 C. femorata specimens. Collection location data were used to create a map of C. femorata and C. mali distributions in the western United States, indicating that C. femorata is significantly less abundant in California, Oregon, and Washington than C. mali. Of the 50 associated plant taxa noted on specimen labels, only 4 associations were shared between the species, potentially indicating host specialization. New reproductive hosts are recorded for C. femorata (2 hosts) and C. mali (3 hosts). Tree species commonly damaged by flatheaded borers in commercial orchards and nurseries were not present in the historical records. The insights gleaned from specimen data allow researchers to better understand the biology and ecology of these understudied, yet economically impactful insects in the western United States.


Synergy of low-energy {101} and high-energy {001} TiO₂ crystal facets for enhanced photocatalysis.
Controlled crystal growth determines the shape, size, and exposed facets of a crystal, which usually has different surface physicochemical properties. Herein we report the size and facet control synthesis of anatase TiO2 nanocrystals (NCs). The exposed facets are found to play a crucial role in the photocatalytic activity of TiO2 NCs. This is due to the known preferential flow of photogenerated carriers to the specific facets. Although, in recent years, the main focus has been on increasing the surface area of high-energy exposed facets such as {001} and {100} to improve the photocatalytic activity, here we demonstrate that the presence of both the high-energy {001} oxidative and low-energy {101} reductive facets in an optimum ratio is necessary to reduce the charge recombination and thereby enhance photocatalytic activity of TiO2 NCs.


Phenolic acids analysis in ligusticum chuanxiong using HPLC.
A reversed-phase high-performance liquid chromatographic method with diode array UV detection is developed for the determination of five kinds of phenolic acids common in herbal medicines. Based on this method, ferulic acid and caffeic acid are found to be two main phenolic acids in Chuanxiong (one of the important crude drugs in traditional Chinese medicine). More important, ferulic acid is found to exist in free form, and caffeic acid--a previously unreported component--is found to exist in esterified or insoluble-bound form.


Serum cytokine profile contributes to discriminating M. pneumoniae pneumonia in children.
To evaluate the role of serum cytokines in discriminating M. pneumoniae infection in children with community-acquired pneumonia (CAP). A prospective observational study was conducted. 385 hospitalized patients with CAP had only M. pneumoniae (MP group) infection; 321 hospitalized patients with CAP had no M. pneumoniae and other specific pathogen (control group) infections. Serum interleukin-2 (IL-2), IL-4, IL-6, IL-10, tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ) were detected by flow cytometry. In children younger than 5years, serum IL-6, TNF-α, and IFN-γ levels from MP group were significantly higher than those from control group. However in children 5-15years, serum IL-6, IL-10, and IFN-γ levels from MP group were significantly higher than those from control group. In the final multivariate logistic regression model for serum cytokine, moderately elevated IL-6, IL-10, and IFN-γ shows a higher prediction of development of M. pneumoniae pneumonia among CAP patients. A specific cytokine pattern showed a higher prediction of M. pneumoniae pneumonia among CAP patients, further suggesting that serum cytokine pattern might be useful in differentiating infectious causative agents in children.


Acute toxicity and biodistribution of different sized titanium dioxide particles in mice after oral administration.
In order to evaluate the toxicity of TiO(2) particles, the acute toxicity of nano-sized TiO(2) particles (25 and 80nm) on adult mice was investigated compared with fine TiO(2) particles (155nm). Due to the low toxicity, a fixed large dose of 5g/kg body weight of TiO(2) suspensions was administrated by a single oral gavage according to the OECD procedure. In 2 weeks, TiO(2) particles showed no obvious acute toxicity. However, the female mice showed high coefficients of liver in the nano-sized (25 and 80nm) groups. The changes of serum biochemical parameters (ALT/AST, LDH) and pathology (hydropic degeneration around the central vein and the spotty necrosis of hepatocytes) of liver indicated that the hepatic injury was induced after exposure to mass different-sized TiO(2) particles. In addition, the nephrotoxicity like increased BUN level and pathology change of kidneys was also observed in the experimental groups. The significant change of serum LDH and alpha-HBDH in 25 and 80nm groups showed the myocardial damage compared with the control group. However, there are no abnormal pathology changes in the heart, lung, testicle (ovary), and spleen tissues. Biodistribution experiment showed that TiO(2) mainly retained in the liver, spleen, kidneys, and lung tissues, which indicated that TiO(2) particles could be transported to other tissues and organs after uptake by gastrointestinal tract.


[Investigation of HTLV-I/II Seroprevalance of Patients with HIV Positivity being Monitored by Real-Time RT-PCR].
Human T-lymphotropic virus-I/II (HTLV-I/II) and human immun viruses (HIVs), that have similar genomic characteristics also share the same transmission routes and infect T lymphocytes. Regarding this epidemiological similarity, HIV and HTLV infections can be seen together. HIV and HTLV-I/II coinfection occurs with variable frequencies in different populations and geographic regions. There are not any population-based studies carried out defining the number of individuals coinfected with HIV and HTLV-I/II in Turkey. The aim of this study was to determine the seropositivity rates of HTLV-I/II in patients whose HIV viral load was monitored in Gazi University Faculty of Medicine Medical Virology Laboratory Forty-seven HIV positive cases followed-up in Medical Virology Laboratory for HIV viral load monitoring between May 2017-January 2019 were included in the study. HIV seropositivity of the samples was confirmed by the chemiluminescence microparticle immunoassay method. HIV viral load values of the samples were evaluated by real-time reverse transcriptase polymerase chain reaction. The samples were screened for antibodies against HTLV-I/II using chemiluminescent microparticle immunoassay. The study population range was between 19 to 60 years of age. Among the study population, 39 (83%) patients were male and 8 (17%) patients were female. Of 47 samples, 18 samples (38.3%) had viral load of <1000 copies/ml, 10 samples (21.3%) had viral load of 1000-10000 copies/ml, 19 samples (40.4%) had viral load of ≥10000 copies/ml. HTLV serology was negative in all samples included in the study. CD4+ results were available for 42 patients and the CD4+ results of five patients could not be studied. Co-infection with different retroviruses is a well-known fact which should be thoroughly examined. HTLV-I co-infection leads to faster progression of the disease in HIV-1 positive patients. Although it is known that the co-infection has a significant effect on the progression of the disease, there are very few centers in the world and in our country that routinely perform HTLV testing in HIV-positive patients. We think that in order to evaluate the clinical and microbiological importance of the coinfection of retroviruses with each other and to determine the frequency of these infections together, there is a need for studies involving a larger number of patients, including detailed clinical backgrounds of individuals, and that the importance of this issue should be realized at the same time.


Self-Assembly of Solvent-Stabilized Au Nanocluster as Efficient Förster Resonance Energy-Transfer Initiator for White Light Generation.
Aggregation-induced enhancement (AIE) in the photoluminescence quantum yield (PLQY) from 12.5 to 51% in the N,N-dimethylformamide (DMF)-stabilized Au nanocluster (AuNC) system is reported here. The self-assembling of AuNC has been achieved via hydrogen bonding interaction, which is further utilized in designing the AuNC_DCM system for realizing a Förster resonance energy transfer (FRET)-based white LED (WLED), having CIE coordinates of (0.35, 0.29). The solution-processed fabrication strategy used, has given us the liberty to optimize its components for optimal full-spectrum light output. The CIE coordinates of the designed WLED have been improved further to (0.33, 0.32), with a high color rendering index of 93 and correlated color temperature of 5620 K by incorporating a green emitter, namely nitrogen-doped graphene quantum dots (NGQD), in the AuNC_DCM system. The excellent spectral quality of the as-designed WLED and the repeatability of the proposed fabrication method will make the developed AuNCs_DCM FRET conjugate useful in practical photonic applications.


Ascorbic acid increases the number of dopamine neurons in vitro and in transplants to the 6-OHDA-lesioned rat brain.
The inadequate survival of dopamine neurons following intracerebral transplantation is in part attributed to the generation of reactive oxygen species and subsequent oxidative stress. To address this, we investigated whether the antioxidant ascorbic acid (vitamin C) had any effect on the yields of dopamine neurons derived from E14 rat ventral mesencephalic cells in vitro and in grafts. Following in vitro differentiation in medium containing ascorbic acid at concentrations ranging from 20 to 100 microM, significantly more neurons were immunopositive for the marker of mesencephalic dopamine neurons, tyrosine hydroxylase (TH), when compared to standard differentiation conditions containing no ascorbic acid. Mesencephalic cell suspensions supplemented with 100 microM ascorbic acid were also transplanted into unilateral 6-OHDA-lesioned rats and behavioral rotation was assessed at 2, 4, and 6 weeks posttransplantation. Grafts pretreated with ascorbic acid contained significantly more surviving dopamine neurons compared to nontreated grafts. However, no significant difference in rotation score was observed, with both groups showing a reversal and overcompensation of rotational bias. In addition, no evidence of neurogenesis of nigral dopamine neurons was observed in transplant groups. While the increased number of dopamine neurons observed in our study following ascorbic acid treatment may reflect a selective survival effect, our in vitro results suggest that ascorbic acid may act to increase the number dopamine neurons, both in culture and following transplantation, by stimulating dopaminergic differentiation of neural precursors from the fetal ventral mesencephalon.


[Acquired isolated factor VII deficiency and bronchogenic carcinoma. A case report].
An acquired factor VII deficiency was identified in a 63-year-old man with bronchogenic carcinoma. Initial studies indicated a normal activated partial thromboplastin time and a prolonged prothrombin time. The factor VII level was 6%. No evidence of a factor VII inhibitor or inactivator was demonstrable. However, on account of the initial normal laboratory test of emostases, the partial correction of the prothrombin time with 50% normal plasma in vitro and the family history, the congenital deficiency in factor VII was ruled out. Whatever the mechanism involved, this factor VII deficiency was related to malignancy.


Effects of M274773, a neurokinin-2 receptor antagonist, on bladder function in chronically spinalized rats.
Increased afferent nerve activity may have an important role in the pathogenesis of neurogenic detrusor overactivity. We tested the efficacy of the neuokinin-2 receptor antagonist M274773 ((S)-N-[2-(3,4-Dichlorophenyl)-4-[4-(2-oxoperhydro-pyrimidin-l-yl) piperidino]butyl]-N-methylbenzamide dihydrochloride) on neurogenic detrusor overactivity after spinal cord injury in rats. Included in this study were 48 adult Sprague-Dawley rats (Charles River, Montreal, Quebec, Canada). Six animals served as normal controls, while 32 underwent spinal cord transection at the 10th thoracic vertebra. Two weeks after spinal cord injury 6 animals underwent filling cystometrography to confirm neurogenic detrusor overactivity, while another 12 served as paraplegic controls. The remaining 24 paraplegic animals were used to test the drug and they were divided into 2 equal groups of 12. Group 1 received the drug at a dose of 0.3 mg/kg daily, while group 2 received a dose of 0.6 mg/kg daily. Each paraplegic control and treatment group was further subdivided into 2 subgroups of 6 rats each. In subgroup 1 filling cystometrography was done 3 weeks after spinal cord injury, while in subgroup 2 it was done 4 weeks after spinal cord injury. Three weeks after spinal cord injury neurogenic detrusor overactivity developed in all paraplegic control animals with a mean bladder capacity +/- SD of 0.7 +/- 0.2 ml and a mean voiding pressure of 59 +/- 14.2 cm H2O. Neurogenic detrusor overactivity resolved in 50% and 83% of the animals that received M274773 for 1 week at doses of 0.3 and 0.6 mg/kg daily, respectively. Mean cystometric bladder capacity was 1.2 +/- 0.5 vs 1.3 +/- 0.4 ml and mean voiding pressure was 46.1 +/- 10.8 vs 40 +/- 9.9 cm H2O in animals that received 0.3 vs 0.6 mg/kg daily, respectively. The drug produced better urodynamic results when given for 2 weeks rather than 1 week. M274773 is effective for neurogenic detrusor overactivity after spinal cord injury in the rat. It may provide an alternative clinical treatment option for neurogenic detrusor overactivity and urgency/frequency syndrome. This new neurokinin-2 selective antagonist has time and dose response effects, which further suggests the potential for clinical application.


Laboratory medicine: a view to the future of diagnostics and training.
Laboratory Medicine is poised to undergo quantal changes over the next decade. These are pregnant with opportunities to impact medical care in new ways as well as being fraught with dangers to our management of diagnostic modalities. New knowledge brought about by the human genome and functional genomics endeavors have led to new biomarkers, many of which are prognostic or theragnostic rather than simply diagnostic, thus introducing new testing modalities, such as deep sequencing and proteomics. Computer algorithms can derive associations and implications based on changes in a multitude of 'weak' biomarkers, necessitating the assessment of large panels of targets rather than discrete biomarkers. The linkage of genomics and proteomics to morphometric aspects blurs the lines between Laboratory Medicine and Anatomic/Surgical Pathology or Radiologic imaging. The utility of these diagnostics is being push closer to the patient to speed implementation as cost issues drive the need for rapid decision making. Despite the resource pressures on all of medical care, laboratory diagnostics remain the most cost-efficient aspect and thus will be even more in demand as practice is shifted towards rapid laboratory medicine. These great opportunities for a new golden age in Laboratory Medicine will depend to a great extent on our ability to train the next generation not only in these new technologies and knowledge bases but also in this new mode of information delivery and direct interactions with patient-care physicians and patients themselves.


A GH Secretagogue Receptor Agonist (LUM-201) Elicits Greater GH Responses than Standard GH Secretagogues in Subjects of a Pediatric GH Deficiency Trial.
LUM-201 (ibutamoren, formerly MK-0677) is an orally administered GH secretagogue receptor agonist under development for treatment of pediatric growth hormone deficiency (PGHD). The GH response to a single dose of LUM-201 and to other GH secretagogues used for diagnosis of PGHD were compared in 68 pediatric subjects participating in a trial for growth hormone deficiency. LUM-201 elicited greater GH responses than observed in GHD diagnostic tests with arginine, glucagon, clonidine, L-dopa, and insulin-induced hypoglycemia [median and interquartile ranges 15.0 ng/mL (3.5, 49) vs. 5.5 ng/mL (1.8, 7.6) (p < 0.0001)]. The difference between responses was greatest in subjects with higher baseline IGF-I concentrations and higher GH responses to standard GH stimuli. LUM-201 elicits greater GH responses than standard stimuli in subjects with higher peak GH in response to conventional testing and is potentially an orally administered treatment alternative to injectable rhGH in a subset of patients with adequate responses to an acute dose of LUM-201.


A coordinate-free approach to the analysis of growth patterns: models and theoretical considerations.
Developmental biology holds keys to our understanding of morphological pattern formation whether these patterns are expressed in the fossil record or among extant species. Though much is known about osseous growth at the cellular level (e.g. Hall, 1991), we have minimal understanding of the coordinated processes that combine to produce a complex, three-dimensional form. We have proposed a framework for the coordinate-free representation of form, a statistical method for comparing and modelling growth trajectories for complex morphologies, and a means for the eventual elucidation of the role of growth in the evolution of morphology. Our method uses the coordinate locations of biological landmarks to represent form as a matrix of all possible linear distances between landmarks, the form matrix. When two forms are expressed in this way, comparison of these forms is accomplished by computing the ratios of like linear distances, the form difference matrix. When the forms being compared are from a growth series, the matrix of ratios is called a growth matrix. Patterns of growth for two groups can be compared by computing the growth difference matrix. We applied growth difference matrix analysis to the study of sexual dimorphism of ontogeny in the M. fascicularis craniofacial skeleton. Growth matrices describing growth in male and female M. fascicularis were presented along with the growth difference matrix that describes sexual dimorphism of growth to underscore the detailed information available from this analytical technique. The method is quite general and can be applied to two- or three-dimensional data sets of landmark coordinates (cross-sectional or longitudinal) collected from almost any developing structure. The methods that we propose enable us to go beyond a mathematical summary of the comparison of forms and the comparison of growth patterns. We provide examples of how growth patterns might be used in the study of phylogenetic relationships. Our plans for use of this method in the study of evolutionary change assumes that morphological change in the craniofacial skeleton results from evolutionary change in developmental units (as defined by Atchley & Hall, 1991) that underlie morphological structure. We believe we have the basic tools to ultimately propose informed phylogenies based solely on developmental data. This task requires the identification of 'growth features' and the polarization of these features as primitive or derived. It is also advisable to determine a set of primitive growth features for the groups of interest. This will necessitate the inclusion of outgroups in our growth analysis.(ABSTRACT TRUNCATED AT 400 WORDS)


Microbial community structure of leaf-cutter ant fungus gardens and refuse dumps.
Leaf-cutter ants use fresh plant material to grow a mutualistic fungus that serves as the ants' primary food source. Within fungus gardens, various plant compounds are metabolized and transformed into nutrients suitable for ant consumption. This symbiotic association produces a large amount of refuse consisting primarily of partly degraded plant material. A leaf-cutter ant colony is thus divided into two spatially and chemically distinct environments that together represent a plant biomass degradation gradient. Little is known about the microbial community structure in gardens and dumps or variation between lab and field colonies. Using microbial membrane lipid analysis and a variety of community metrics, we assessed and compared the microbiota of fungus gardens and refuse dumps from both laboratory-maintained and field-collected colonies. We found that gardens contained a diverse and consistent community of microbes, dominated by Gram-negative bacteria, particularly gamma-Proteobacteria and Bacteroidetes. These findings were consistent across lab and field gardens, as well as host ant taxa. In contrast, dumps were enriched for Gram-positive and anaerobic bacteria. Broad-scale clustering analyses revealed that community relatedness between samples reflected system component (gardens/dumps) rather than colony source (lab/field). At finer scales samples clustered according to colony source. Here we report the first comparative analysis of the microbiota from leaf-cutter ant colonies. Our work reveals the presence of two distinct communities: one in the fungus garden and the other in the refuse dump. Though we find some effect of colony source on community structure, our data indicate the presence of consistently associated microbes within gardens and dumps. Substrate composition and system component appear to be the most important factor in structuring the microbial communities. These results thus suggest that resident communities are shaped by the plant degradation gradient created by ant behavior, specifically their fungiculture and waste management.


Ambulatory teaching "lite": less clinic time, more educationally fulfilling.
Typically, the primary instructional method for ambulatory care education is direct interaction between a preceptor and a learner during a patient encounter. This paper describes instructional strategies teachers and learners can use in ambulatory care training that can occur before or after scheduled clinic hours, thus providing instruction without disrupting a preceptor's busy clinic. First, they describe how preceptors and clerkship or residency-program directors can orient learners prior to their arrival at assigned sites, so that learners are better prepared to assume their patient-care responsibilities. Then they discuss strategies for making use of various types of conferences and independent learning activities to enhance learners' clinical experiences. Conferences and independent study projects that occur before clinic hours can help learners bring a higher level of thinking and clinical sophistication to their role in the ambulatory care site; conferences and independent study activities that occur after clinic hours give learners an opportunity to reinforce and expand on what they have learned during clinic. In this way, learners' educational experiences are enhanced, the best use is made of preceptors' time and expertise, and clinic efficiency is not disrupted.


Iduna contributes to the therapeutic effect of DHA in a cell and mouse model of traumatic brain injury via Wnt/MDM2 pathway.
Traumatic brain injury (TBI) is a severe condition that leads to brain damage and affects brain function. Importantly, TBI incurs public health costs due to its high mortality, and effective treatment for TBI is still lacking. Docosahexaenoic acid (DHA) has a neuroprotective effect that can reduce oxidative, apoptosis, and inflammatory processes. Administration of DHA after TBI attenuates oxidative stress and protein accumulation and is regarded as a potential therapeutic. Iduna is a regulator of parthanatos, and upregulation of Iduna reduces cellular damage and mitochondrial dysfunction. Thus, we speculated that overexpression of Iduna might promote DHA therapy in the treatment of TBI. Here, we found that after combination overexpression of Iduna and DHA in a mouse model of TBI, the expression of inflammatory factors was reduced, while the secretion of neuroprotective factors was increased. In addition, we found that these effects might be mediated by the Wnt/MDM2 pathway, and Iduna might be a therapeutic target for TBI.


Micro RNA-363 inhibits esophageal squamous cell carcinoma progression by directly targeting sperm-associated antigen 5.
Micro RNA (miR)-363 has many important biological functions in cancers, but its roles in esophageal squamous cell carcinoma (ESCC) remain unclear. We used reverse transcription PCR to quantify the expression of miR-363 in 80 ESCC tissues and analyzed its relationship with clinicopathological factors and overall survival. The effects of miR-363 on cell proliferation, apoptosis, and invasion were detected using the MTT assay, flow cytometry, and Transwell invasion assays, respectively. Further, we investigated the post-transcriptional regulation of sperm-associated antigen 5 (SPAG5) expression by miR-363 using luciferase reporter assays. Finally, the effects of SPAG5 on miR-363 were studied by SPAG5 overexpression. miR-363 expression was decreased in both ESCC specimens and cell lines, compared with controls, and correlated with lymph node metastasis and tumor differentiation. Low miR-363 expression was identified as an independent prognostic factor for ESCC. miR-363 overexpression decreased ESCC cell proliferation and invasion and increased apoptosis, while the opposite was seen after miR-363 inhibition. Moreover, SPAG5 was identified as a direct target of miR-363, and the reintroduction of SPAG5 restored miR-363-induced effects. miR-363 acts as a tumor suppressor by post-transcriptionally regulating SPAG5 expression, suggesting its potential as a diagnostic biomarker and therapeutic target for ESCC.


Repair of aortic coarctation using temporary ascending to descending aortic bypass in children with poor collateral circulation.
Aortic coarctation can now be repaired surgically with excellent results. Even though rare, injury to the spinal cord resulting in paraplegia remains a major concern. Preoperative evaluation showing the absence of collateral circulation is valuable in order to introduce protective actions. This report describes our experience using a temporary bypass from the ascending to the descending aorta bypass in children undergoing surgical correction of aortic coarctation in the setting of poorly developed collateral circulation. Between 1990 and 2002, we undertook direct surgical repair in 56 patients with isolated aortic coarctation, 20 as neonates, 11 as infants, and 25 during childhood. From 1998 onwards, we introduced preoperative evaluation of the collateral circulation with magnetic resonance imaging. From that time, we placed a temporary bypass from the ascending to the descending aorta, using a polytetrafluoroethylene tube of 4 to 8 mm diameter, whenever distal pressures were shown to be 25 mmHg or less after test clamping, or when magnetic resonance imaging revealed absence of collateral circulation. We found excellent correlations between the direct intra-operative measurements of distal pressure and the findings at magnetic resonance imaging. Following introduction of the temporary bypass, we observed no neurological complications, nor were there any complications related to bypass. Freedom from restenosis was 96%. Preoperative magnetic resonance imaging, therefore, can accurately visualize poor collateral circulation in children with aortic coarctation. The use of a temporary bypass can possibly eliminate the risk of neurological sequels following direct repair of coarctation in children with poorly developed collateral circulation. The temporary bypass is both easy to apply and safe.


A manual corpus of annotated main findings of clinical case reports.
Clinical case reports are the `eyewitness reports' of medicine and provide a valuable, unique, albeit noisy and underutilized type of evidence. Generally a case report has a single main finding that represents the reason for writing up the report in the first place. In the present study, we present the results of manual annotation carried out by two individuals on 500 randomly sampled case reports. This corpus contains main finding sentences extracted from title, abstract and full-text of the same article that can be regarded as semantically related and are often paraphrases. The final reconciled corpus of 416 articles comprises an open resource for further study. This is the first step in establishing text mining models and tools that can identify main finding sentences in an automated fashion, and in measuring quantitatively how similar any two main findings are. We envision that case reports in PubMed may be automatically indexed by main finding, so that users can carry out information queries for specific main findings (rather than general topics)-and given one case report, a user can retrieve those having the most similar main findings. The metric of main finding similarity may also potentially be relevant to the modeling of paraphrasing, summarization and entailment within the biomedical literature.


Are YouTube™ videos a reliable source of information about genioplasty?
The aim of this study was to evaluate the accuracy and quality of the information content of popular YouTube™ videos about genioplasty. The keywords "genioplasty, sliding genioplasty and genioplasty surgery" were searched on YouTube™. It was filtered by the view count and the first 70 videos that met the inclusion criteria were evaluated. Each video was scored as ranging from 0 to 8 point and the videos were classified as bad, poor, good and excellent content. Kruskal-Wallis test was performed for statistical analysis. Intra-observer and inter-observer agreement were calculated Cohen's Kappa index. The videos uploaded by the individuals were significantly higher total video duration (P<0.001), number of comments (P=0.048) and viewing rate (P=0.036) than the others and the videos generally included their treatment journey. Most of the videos included bad information content. The number of likes (P=0.037), dislikes (P=0.037) and the interaction index (P=0.026) of the bad information content videos were significantly higher than the others. The other parameters did not show a significant difference (P>0.05). The results of this study would suggest that YouTube™ is not currently an appropriate source of information about genioplasty for the patients.


Health benefits, mechanisms of interaction with food components, and delivery of tea polyphenols: a review.
Tea polyphenols (TPs) are the most important active component of tea and have become a research focus among natural products, thanks to their antioxidant, lipid-lowering, liver-protecting, anti-tumor, and other biological activities. Polyphenols can interact with other food components, such as protein, polysaccharides, lipids, and metal ions to further improve the texture, flavor, and sensory quality of food, and are widely used in food fields, such as food preservatives, antibacterial agents and food packaging. However, the instability of TPs under conditions such as light or heat and their low bioavailability in the gastrointestinal environment also hinder their application in food. In this review, we summarized the health benefits of TPs. In order to better use TPs in food, we analyzed the form and mechanism of interaction between TPs and main food components, such as polysaccharides and proteins. Moreover, we reviewed research into optimizing the applications of TPs in food by bio-based delivery systems, such as liposomes, nanoemulsions, and nanoparticles, so as to improve the stability and bioactivity of TPs in food application. As an effective active ingredient, TPs have great potential to be applied in functional food to produce benefits for human health.


MOF as an evolutionarily conserved histone crotonyltransferase and transcriptional activation by histone acetyltransferase-deficient and crotonyltransferase-competent CBP/p300.
Recent studies indicate that histones are subjected to various types of acylation including acetylation, propionylation and crotonylation. CBP and p300 have been shown to catalyze multiple types of acylation but are not conserved in evolution, raising the question as to the existence of other enzymes for histone acylation and the functional relationship between well-characterized acetylation and other types of acylation. In this study, we focus on enzymes catalyzing histone crotonylation and demonstrate that among the known histone acetyltransferases, MOF, in addition to CBP and p300, also possesses histone crotonyltransferase (HCT) activity and this activity is conserved in evolution. We provide evidence that CBP and p300 are the major HCTs in mammalian cells. Furthermore, we have generated novel CBP/p300 mutants with deficient histone acetyltransferase but competent HCT activity. These CBP/p300 mutants can substitute the endogenous CBP/p300 to enhance transcriptional activation in the cell, which correlates with enhanced promoter crotonylation and recruitment of DPF2, a selective reader for crotonylated histones. Taken together, we have identified MOF as an evolutionarily conserved HCT and provide first cellular evidence that CBP/p300 can facilitate transcriptional activation through histone acylation other than acetylation, thus supporting an emerging role for the non-acetylation type of histone acylation in transcription and possibly other chromatin-based processes.


Physical Properties and Stabilization of Microcapsules Containing Thyme Oil by Complex Coacervation.
The aim of this study was to produce and characterize microcapsules of thyme oil and finally appraise the extent of stability improvement. The optimum process conditions obtained from orthogonal tests were as follows: ratio of core material to wall 0.5, temperature 40 °C, pH value 3.0 and time 20 min, where the practical encapsulation efficiency was 85.17±1.35%. The microcapsules belong to the nanometric range as the average particle diameter was 531.17±77.12 nm. The results from structural analysis indicated that no significant chemical bond occurred during the encapsulation process and the microcapsules remained stable when the encapsulation was conducted at a temperature below 53.1 °C. Especially, the retention rate of thyme oil in microcapsules remained 39.21% at 4 °C, 36.99% at 25 °C and 33.80% at 40 °C after 30 d of storage. Moreover, protection from light exposure presented a positive impact on the storage stability of thyme oil microcapsules.


The long-term consequences of Corona Virus Disease 2019 patients receiving Chinese herbal medicine treatments in acute phase: A protocol for systematic review and meta-analysis.
In December 2019, the first case of Corona Virus Disease 2019 (COVID-19) associated with severe acute respiratory syndrome coronavirus-2 viral infection was described in Wuhan. Similar to SARS in 2003, COVID-19 also had a lasting impact. Approximately 76% of patients discharged after hospitalization for COVID-19 had neurological manifestations which could persist for 6 months, and some long-term consequences such as the gradual loss of lung function due to pulmonary interstitial fibrosis could have comprehensive effects on daily quality of life for people who were initially believed to have recovered from COVID-19. Our comprehensive search strategy developed in consultation with a research librarian. We will search these following electronic databases: PubMed, Cochrane Library, Web of Science, ScienceDirect, Scopus, Google Scholar, Embase, ProQuest, China Science and Technology Journal Database (VIP), China National Knowledge Infrastructure, WANFANG DATA, WHO covid-19 website, and Centers for Disease Control and the Prevention COVID-19 websites of the United States and China. The bias of publication will be confirmed via the P value of Egger test. The quality of studies will be evaluated by the Newcastle-Ottawa Scale. There are no ethical considerations associated with this study protocol for this systematic review which mainly focuses on the examination of secondary data. On completion of this analysis, we will prepare a manuscript for publication in a peer-reviewed medical journal. CRD42021258711.


Characteristics of home cage locomotion in cynomolgus monkeys.
The profiles of home cage locomotor activity and its rhythmicity were investigated using a camera system for 4 consecutive days in cynomolgus monkeys. Nine male and nine female cynomolgus monkeys were used in this study, and were found to have the same profile in nocturnal behavior in that they were mostly inactive during the night. The locomotor activity of both sexes showed a normal activity and inactivity rhythm, which had an inverse relationship between normal activity and inactivity, showing a fluctuation profile of being higher in the light cycle and lower in the dark cycle. The four-day locomotion time of the females was higher than that of the males in the dark period. The females also showed a higher locomotion count and D/L ratio in the dark period than the males during the 4 consecutive days. These findings indicate that the females have greater locomotor activity in the dark period than that of the males. The present findings may serve as useful basic data for the behavioral assessment of overall animal movements in toxicological studies using monkeys.


Altered tumor necrosis factor-alpha (TNF-alpha) processing in adipocytes and increased expression of transmembrane TNF-alpha in obesity.
Tumor necrosis factor-alpha (TNF-alpha) is synthesized as a 26-kDa transmembrane protein (mTNF-alpha), which may present on the cell surface or be processed to release the 17-kDa soluble form (sTNF-alpha). Because regulation of this ectodomain shedding might be critical in the generation of systemic versus local cytokine responses, we examined the rate of mTNF-alpha processing in adipocytes and its regulation in obesity. Here, we demonstrate that the 26-kDa mTNF-alpha is present in adipose tissue and that its production is significantly increased in different rodent obesity models as well as in obese humans. There was no apparent deficiency in the level of the major TNF-alpha converting enzyme in adipose tissue to account for the excess amount of mTNF-alpha produced in obesity. However, experiments in cultured fat cells stably expressing TNF-alpha demonstrated a significantly decreased rate of TNF-alpha cleavage in differentiated adipocytes compared with preadipocytes. Thus, a decreased processing rate of mTNF-alpha in mature adipocytes combined with an increase in TNF-alpha production may be a potential mechanism resulting in elevated membrane-associated TNF-alpha in adipose tissue in obesity.


[Compensated creatinine method and glomerular filtration rate estimation in a heterogeneous population of patients].
Creatinine is a metabolite excreted mainly by glomerular filtration, which makes it an important endogenous indicator of kidney function. Creatinine clearance is defined as the ratio of the concentration of creatinine in serum and urine. It assesses glomerular filtration. Creatinine and creatinine clearance have the leading role in the early diagnosis, monitoring and classification of chronic kidney disease. The routine method for determining the concentration of creatinine is the Jaffé photometric method. A newer version is the compensated method. Furthermore, the recommended equation for the estimation of glomerular filtration rate (GFR) is the one based on the MDRD study (eGFR) intended for people over 18 years. The aim of the study was to evaluate how the introduction of the compensated method would affect the clinical use and influence the assessment of GFR in the interpretation of findings and treatment monitoring for people over 20 years. The study group included 130 men and 142 women whose requested laboratory test was creatinine clearance. Data were collected over 20 days at Sestre milosrdnice University Hospital. Serum creatinine concentration and eGFR were determined by the compensated and uncompensated Jaffé method. In conclusion, the compensated creatinine method is not statistically comparable with the uncompensated method, but is clinically fully applicable to the general population above the age of 20, given that the reference intervals are changed. Comparison of eGFR as estimated by the compensated and uncompensated methods to determine creatinine concentration showed the same results as the comparison of clearance. Using the compensated method yielded statistically incomparable results in GFR estimation. However, in clinical practice, patient classification according to stages of chronic kidney disease (CKD) was comparable in the male group according to clearance and eGFR (pi=0.922 and pi=0.230, respectively), while the female group was classified significantly different according to clearance and eGFR (pi<0.016 and pi<0.001, respectively). Switching to the compensated creatinine method while simultaneously applying the eGFR formula was shown to be valid, as patient classification according to CKD stages was comparable (pi=0.921); thus, the methods are reliable for use instead of creatinine clearance in the general population with various diagnoses, which can be noted in all laboratories and which is, although inhomogeneous, routinely used to measure daily creatinine clearance.


[Clinical study of dermatoses as psychosomatic phenomena].
The aim of this presentation is to introduce some aspects of the global problematics of our Phd research in psychopathology. This thesis shows that all the studies on the relations between body and mind agree to say that there are organic symptoms with a psychical etiology. Some of these symptoms can be called, under certain conditions, "psychosomatic phenomena". We are showing that, in case of a disease, a skin disease in the framework of this research, two questions must be raised: does the disease have a function in the psychical structure? which one? In this view, a case study enables us to examine the link between somatic pathology and psychical features of the subject who is affected by it, and that can be done only by examining the event which brought on the disease.


Topoisomerase II binds importin alpha isoforms and exportin/CRM1 but does not shuttle between the nucleus and cytoplasm in proliferating cells.
Resistance to anticancer drugs that target DNA topoisomerase II (topo II) isoforms alpha and/or beta is associated with decreased nuclear and increased cytoplasmic topo IIalpha. Earlier studies have confirmed that functional nuclear localization and export signal sequences (NLS and NES) are present in both isoforms. In this study, we show that topo II alpha and beta bind and are imported into the nucleus by importin alpha1, alpha3, and alpha5 in conjunction with importin beta. Topo IIalpha also binds exportin/CRM1 in vitro. However, wild-type topo IIalpha has only been observed in the cytoplasm of cells that are entering plateau phase growth. This suggests that topo IIalpha may shuttle between the nucleus and the cytoplasm with the equilibrium towards the nucleus in proliferating cells but towards the cytoplasm in plateau phase cells. The CRM1 inhibitor Leptomycin B increases the nuclear localization of GFP-tagged topo IIalpha with a mutant NLS, suggesting that its export is being inhibited. However, homokaryon shuttling experiments indicate that fluorescence-tagged wild-type topo II alpha and beta proteins do not shuttle in proliferating Cos-1 or HeLa cells. We conclude that topo II alpha and beta nuclear export is inhibited in proliferating cells so that these proteins do not shuttle.


Cytokine regulation of pulmonary fibrosis in scleroderma.
Pulmonary fibrosis occurs in up to 70% of scleroderma patients and progresses to cause severe restrictive lung disease in about 15% of patients. The mechanisms that cause pulmonary fibrosis in scleroderma remain incompletely understood. Increased amounts of mRNA or protein for multiple profibrotic cytokines and chemokines have been identified in lung tissue or broncholveolar lavage samples from scleroderma patients, when compared to healthy controls. These cytokines include transforming growth factor (TGF)-beta, connective tissue growth factor (CTGF), platelet-derived growth factor (PDGF), oncostatin M (OSM), monocyte chemotactic factor-1 and pulmonary and activation-regulated chemokine (PARC). Potential cellular sources of these profibrotic cytokines and chemokines in scleroderma lung disease include alternatively activated macrophages, activated CD8+ T cells, eosinophils, mast cells, epithelial cells and fibroblasts themselves. This review summarizes the literature on involvement of cytokines and chemokines in the development of pulmonary fibrosis in scleroderma.


Classifying non-small cell lung cancer types and transcriptomic subtypes using convolutional neural networks.
Non-small cell lung cancer is a leading cause of cancer death worldwide, and histopathological evaluation plays the primary role in its diagnosis. However, the morphological patterns associated with the molecular subtypes have not been systematically studied. To bridge this gap, we developed a quantitative histopathology analytic framework to identify the types and gene expression subtypes of non-small cell lung cancer objectively. We processed whole-slide histopathology images of lung adenocarcinoma (n = 427) and lung squamous cell carcinoma patients (n = 457) in the Cancer Genome Atlas. We built convolutional neural networks to classify histopathology images, evaluated their performance by the areas under the receiver-operating characteristic curves (AUCs), and validated the results in an independent cohort (n = 125). To establish neural networks for quantitative image analyses, we first built convolutional neural network models to identify tumor regions from adjacent dense benign tissues (AUCs > 0.935) and recapitulated expert pathologists' diagnosis (AUCs > 0.877), with the results validated in an independent cohort (AUCs = 0.726-0.864). We further demonstrated that quantitative histopathology morphology features identified the major transcriptomic subtypes of both adenocarcinoma and squamous cell carcinoma (P < .01). Our study is the first to classify the transcriptomic subtypes of non-small cell lung cancer using fully automated machine learning methods. Our approach does not rely on prior pathology knowledge and can discover novel clinically relevant histopathology patterns objectively. The developed procedure is generalizable to other tumor types or diseases.