Regulation of human osteoclast development by dendritic cell-specific transmembrane protein (DC-STAMP).
Osteoclasts (OC) are bone-resorbing, multinucleated cells that are generated via fusion of OC precursors (OCP). The frequency of OCP is elevated in patients with erosive inflammatory arthritis and metabolic bone diseases. Although many cytokines and cell surface receptors are known to participate in osteoclastogenesis, the molecular mechanisms underlying the regulation of this cellular transformation are poorly understood. Herein, we focused our studies on the dendritic cell-specific transmembrane protein (DC-STAMP), a seven-pass transmembrane receptor-like protein known to be essential for cell-to-cell fusion during osteoclastogenesis. We identified an immunoreceptor tyrosine-based inhibitory motif (ITIM) in the cytoplasmic tail of DC-STAMP, and developed an anti-DC-STAMP monoclonal antibody 1A2 that detected DC-STAMP expression on human tumor giant cells, blocked OC formation in vitro, and distinguished four patterns of human PBMC with a positive correlation to OC potential. In freshly isolated monocytes, DC-STAMP(high) cells produced a higher number of OC in culture than DC-STAMP(low) cells and the surface expression of DC-STAMP gradually declined during osteoclastogenesis. Importantly, we showed that DC-STAMP is phosphorylated on its tyrosine residues and physically interacts with SHP-1 and CD16, an SH2-domain-containing tyrosine phosphatase and an ITAM-associated protein, respectively. Taken together, these data show that DC-STAMP is a potential OCP biomarker in inflammatory arthritis. Moreover, in addition to its effect on cell fusion, DC-STAMP dynamically regulates cell signaling during osteoclastogenesis.


Patient safety goals for the proposed Federal Health Information Technology Safety Center.
The Office of the National Coordinator for Health Information Technology is expected to oversee creation of a Health Information Technology (HIT) Safety Center. While its functions are still being defined, the center is envisioned as a public-private entity focusing on promotion of HIT related patient safety. We propose that the HIT Safety Center leverages its unique position to work with key administrative and policy stakeholders, healthcare organizations (HCOs), and HIT vendors to achieve four goals: (1) facilitate creation of a nationwide 'post-marketing' surveillance system to monitor HIT related safety events; (2) develop methods and governance structures to support investigation of major HIT related safety events; (3) create the infrastructure and methods needed to carry out random assessments of HIT related safety in complex HCOs; and (4) advocate for HIT safety with government and private entities. The convening ability of a federally supported HIT Safety Center could be critically important to our transformation to a safe and effective HIT enabled healthcare system.


Development of Starch-Based Materials Using Current Modification Techniques and Their Applications: A Review.
Starch is one of the most common biodegradable polymers found in nature, and it is widely utilized in the food and beverage, bioplastic industry, paper industry, textile, and biofuel industries. Starch has received significant attention due to its environmental benignity, easy fabrication, relative abundance, non-toxicity, and biodegradability. However, native starch cannot be directly used due to its poor thermo-mechanical properties and higher water absorptivity. Therefore, native starch needs to be modified before its use. Major starch modification techniques include genetic, enzymatic, physical, and chemical. Among those, chemical modification techniques are widely employed in industries. This review presents comprehensive coverage of chemical starch modification techniques and genetic, enzymatic, and physical methods developed over the past few years. In addition, the current applications of chemically modified starch in the fields of packaging, adhesives, pharmaceuticals, agriculture, superabsorbent and wastewater treatment have also been discussed.


Occupational exposure to phenoxy herbicides and chlorophenols and cancer mortality in The Netherlands.
As part of the "IARC International Register of Persons Exposed to Phenoxy Herbicides and Contaminants," a cohort of workers who manufacture and prepare chlorophenoxy herbicides was recruited in The Netherlands. The cohort comprised 2,310 workers from two plants, operated by different companies, who were followed during the periods 1955-1985 and 1965-1986, respectively. In 1963, there had been an industrial accident in one factory with concomitant release of dioxin into the environment. Loss to follow-up was 3%. Mortality data on 963 exposed and 1,111 nonexposed men were evaluated by external and internal comparison. Compared with national rates, total mortality (94 deaths, standardized mortality ratio [SMR] = 101; 95% confidence interval [CI], 82-124) and cancer mortality (31 deaths, SMR = 107; 95% CI, 73-152) for exposed workers were not significantly increased. A statistically insignificant increase was observed for non-Hodgkin's lymphoma (2 deaths, SMR = 299; 95% CI, 36-1,078). No cases of soft-tissue sarcoma were encountered. There was no increase in either total mortality (25 deaths, SMR = 111; 95% CI, 72-163) or cancer mortality (10 deaths, SMR = 137; 95% CI, 66-252) among the 139 workers probably exposed to dioxins during the 2,4,5-trichlorophenol production accident or the subsequent clean-up operations. Compared with nonexposed workers, exposed workers did not exhibit a higher total mortality (rate ratio [RR] = 1.28; 95% CI, 0.89-1.82). Mortality due to all cancers (RR = 1.7; 95% CI, 0.9-3.4) and respiratory cancer (RR = 1.7; 95% CI, 0.5-6.3) was insignificantly elevated. These findings suggest that the increases in cancer mortality among workers exposed to phenoxy herbicides and chlorophenols may be attributable to chance. Lack of power prevented evaluation with respect to specific cancers.


GC-rich regions in genomes as targets for DNA alkylation.
For many DNA-damaging agents, the extent of damage at any given base site is influenced by the DNA sequence surrounding that site. Most agents that alkylate the guanine N7 position, including mechlorethamine (nitrogen mustard) and benzo[a]pyrene diol epoxide, alkylate oligo-guanine sequences preferentially. Since these data suggest that guanine-cytosine(GC)-rich regions in genes could be preferred sites of damage by these agents, GenBank was searched for genes containing 30 bp sequences of greater than 90% GC (GC runs). While primate, rodent, other mammalian, vertebrate and animal virus genes constituted 57% of the annotated entries, they included 90% of the entries with the GC runs. In addition, the percentage of oncogenes in the group of the entries with GC runs was higher than that in the overall database. One gene of interest containing GC runs was the human c-Ha-ras oncogene. All seven GC runs in the c-Ha-ras gene are in the 5'-flanking region, rather than in the coding sequences. In fact, some of the GC runs are contained in Sp1-binding enhancer sequences. Gel analysis of the alkylation of cloned c-Ha-ras DNA by several carcinogenic alkylating agents strongly suggest that in this gene GC runs can be preferred sites of damage. These observations suggest mechanisms by which DNA damage at sites other than oncogene coding sequences may play a role in carcinogenesis and/or chemotherapy.


Glycopolymer Based LbL Multilayer Thin Films with Embedded Liposomes.
Layer-by-layer (LbL) self-assembly emerged as an efficient technique for fabricating coating systems for, e.g., drug delivery systems with great versatility and control. In this work, protecting group free and aqueous-based syntheses of bioinspired glycopolymer electrolytes aredescribed. Thin films of the glycopolymers are fabricated by LbL self-assembly and function as scaffolds for liposomes, which potentially can encapsulate active substances. The adsorbed mass, pH stability, and integrity of glycopolymer coatings as well as the embedded liposomes are investigated via whispering gallery mode (WGM) technology and quartz crystal microbalance with dissipation (QCM-D) monitoring , which enable label-free characterization. Glycopolymer thin films, with and without liposomes, are stable in the physiological pH range. QCM-D measurements verify the integrity of lipid vesicles. Thus, the fabrication of glycopolymer-based surface coatings with embedded and intact liposomes is presented.


Trunk Rotation and Weight Transfer Patterns between Skilled and Low Skilled Golfers.
The purpose of this study was to examine trunk rotational patterns and weight transfer patterns that may differentiate swing skill level in golfers. Thirteen skilled golfers (mean handicap = 0.8 ± 2.6) and seventeen low skilled golfers (mean handicap = 30.8 ± 5.5) participated in this study. Kinematic and kinetic data were obtained through high-speed 3-D videography and force plates while the participant performed a full shot golf swing with a driver. Data at six temporal events during the swing were selected for the analysis. The results indicated that significant differences existed between the groups in the multiple events, as the skilled golfers showed the following motion patterns when compared to the low skilled golfers; 1) An earlier trunk horizontal rotation with a rapid weight transfer to the trail foot during the backswing; 2) An earlier pelvic horizontal rotation accompanied with an earlier weight transfer to the lead foot during the downswing motion; and 3) Less upper trunk horizontal rotation and more posterior pelvic rotation at the follow through. Collectively, these finding may be useful for instruction of golfers to improve their swing mechanics on a full shot golf swing. Key pointsDifferent trunk rotation and weight transfer patterns were found between skilled and low skilled golfers.Earlier trunk rotation accompanied with earlier weight transfer to the trail foot during the back swing was evident in the skilled golfers.Earlier pelvic horizontal rotation with a rapid weight transfer to the lead foot during the downswing was evident in the skilled golfers.


The temporal relation between pain and fatigue in individuals receiving treatment for chronic musculoskeletal pain.
Numerous investigations have revealed significant relations between pain and fatigue in individuals with persistent pain conditions. However, the direction of influence between pain and fatigue remains unclear. Shortcomings of design and analytic approaches used in previous research limit the nature of conclusions that can be drawn about possible causal or directional relations between pain and fatigue. The present study investigated the temporal relation between changes in pain and changes in fatigue in individuals with musculoskeletal pain enrolled in a 10-week behavioral activation intervention. On the basis of previous findings, it was hypothesized that analyses would support a bi-directional relation between pain and fatigue. The study sample consisted of 104 individuals with chronic musculoskeletal pain participating in a 10-week standardized rehabilitation intervention. Measures of pain intensity and fatigue were completed pre-, mid-, and post-treatment. The three-wave data panel permitted examination of the direction of influence between pain and fatigue through the course of the intervention. A random-intercept cross-lagged panel model (RI-CLPM) was used to examine the temporal relation between pain and fatigue. Consistent with previous research, cross-sectional analyses of pre-treatment data revealed significant correlations between measures of pain and fatigue. Significant reductions in pain and fatigue were observed through the course of treatment (d = 0.33 and d = 0.66, p < .001, respectively). RI-CLPM revealed that pain severity predicted later fatigue (pre to mid-treatment standardized path coefficient (β) = 0.55, p = 0.02; mid to post-treatment β = 0.36, p = 0.001); however, fatigue did not predict later pain severity. Discussion addresses the processes that might underlie the temporal relation between pain and fatigue. Clinical implications of the findings are also discussed.


Chemical probes reveal the timing of early chlorination in vancomycin biosynthesis.
Glycopeptides such as vancomycin are antibiotics of last resort whose biosynthetic pathways still hold undefined details. Chemical probes were used to capture biosynthetic intermediates generated in the nonribosomal peptide formation of vancomycin in vivo. The putative intercepted intermediates were characterised via HR-LC-MS2. These species provided insights into the timing of the first chlorination of the peptide backbone by the halogenase VhaA: this holds significant interest for enzyme engineering towards the making of novel glycopeptides.


Stabilization of microvascular pedicles in intricate locations using fibrin glue.
In reconstructive microsurgery, it is occasionally advantageous to use long recipient or donor vessels for optimal flap inset. These long vessels are prone to kinking or torsion along their longitudinal axis from vessel distension during blood inflow and rising blood pressure. More often than arteries, the veins can also be compressed by overlying tissue sutured under tension or by developing edema. Reanastomosis can no longer be feasible or desirable for several reasons, and the elongated vessels may have to be shifted to a curved course. To avoid detrimental kinking or torsion, fibrin glue can be administered along this new vessel course in order to ensure stabilization. In 20 such cases, we successfully avoided complications when the danger of kinking, torsion, or vein compression was evident after successful anastomosis. On the basis of this experience, we recommend the use of fibrin glue in microsurgical procedures, especially for vessels in intricate geometrical locations.


COVID-19 in Ophthalmology. Current Disease Status and Challenges during Clinical Practice.
Purpose: The novel coronavirus disease 2019 (COVID-19) has raised a global public health concern. The purpose of this review is to summarize the evidence currently available on COVID-19 for its ocular implications and manifestations from both pathogenetic and clinical standpoints. Methods: For this narrative review, more than 100 relevant scientific articles were considered from various databases (PubMed, Google Scholar, and Science Direct) using keywords such as coronavirus outbreak, COVID-19, ophthalmology, ocular symptoms. Results:Daily healthcare both from patient and physician perspective, as well as on some guidelines regarding prevention and management have dramatically changed over the last few months. Although COVID-19 infection mainly affects the respiratory system as well as the gastrointestinal, cardiovascular, and urinary systems, it may cause a wide spectrum of ocular manifestations. Various challenges have to be faced to minimize exposure for both patients and physicians. Conclusion:The risk of COVID-19 infection should be considered and medical care should be prioritized for urgent cases. Appropriate management for patients with chronic cases that may result in adverse outcomes should not be neglected, while patients that can be monitored remotely should be identified.


Highly efficient modification of bacterial artificial chromosomes (BACs) using novel shuttle vectors containing the R6Kgamma origin of replication.
Bacterial artificial chromosome (BAC) mediated transgenesis has proven to be a highly reliable way to obtain accurate transgene expression for in vivo studies of gene expression and function. A rate-limiting step in use of this technology to characterize large numbers of genes has been the process with which BACs can be modified by homologous recombination in Escherichia coli. We report here a highly efficient method for modifying BACs by using a novel set of shuttle vectors that contain the R6Kgamma origin for DNA replication, the E. coli RecA gene for recombination, and the SacB gene for negative selection. These new vectors greatly increased the ease with which one can clone the shuttle vectors, as well as screen for co-integrated and resolved clones. Furthermore, we simplify the shuttle vector cloning to one step by incorporation of a "built-in" resolution cassette for rapid removal of the unwanted vector sequences. This new system has been used to modify a dozen BACs. It is well suited for efficient production of modified BACs for use in a variety of in vivo studies.


let-7d suppresses proliferation and invasion and promotes apoptosis of meningioma by targeting AEG-1.
let-7d has been indicated to act as a tumor suppressor in various cancers. However, the function and molecular mechanism of let-7d in meningioma progression have not been elucidated. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect the expression levels of let-7d and AEG-1 mRNA in meningioma tissues and cell lines. The protein level of AEG-1 was measured by Western blot analysis. MTT assay, Transwell invasion assay and flow cytometry analysis were carried out to determine the proliferation, invasion and apoptosis of IOMM-Lee and CH-157MN cells, respectively. Target gene of let-7d was verified by luciferase reporter analysis. let-7d expression was downregulated, and AEG-1 expression was upregulated in meningioma tumor tissues. let-7d overexpression suppressed proliferation and invasion and induced apoptosis in IOMM-Lee and CH-157MN cells. Moreover, AEG-1 was a direct target of let-7d. Restoration of AEG-1 expression reversed let-7d-mediated suppression of the proliferation and invasion and let-7d-induced apoptosis in IOMM-Lee and CH-157MN cells. let-7d repressed proliferation and invasion and promoted apoptosis of meningioma cells by targeting AEG-1. The present study provided a better understanding of the meningioma pathogenesis and a promising therapeutic target for meningioma patients.


Regulation of TGF-β Superfamily Signaling by SMAD Mono-Ubiquitination.
TGF-β(transforming growth factor-β) superfamily signaling mediators are important regulators of diverse physiological and pathological events. TGF-β signals are transduced by transmembrane type I and type II serine/threonine kinase receptors and their downstream effectors, the SMAD(drosophila mothers against decapentaplegic protein) proteins. Numerous studies have already demonstrated crucial regulatory roles for modification of TGF-β pathway components by poly-ubiquitination. Recently, several studies also uncovered mono-ubiquitination of SMADs as a mechanism for SMAD activation or inactivation. Mono-ubiquitination and subsequent deubiquitination of SMAD proteins accordingly play important roles in the control of TGF-β superfamily signaling. This review highlights the major pathways regulated by SMAD mono-ubiquitination.


Alterations of COX-2, HER-2/neu and E-Cadherin protein expression in the prostatic adenocarcinoma: preliminary findings.
Altered expression of the pro-inflammatory enzyme cyclooxygenase (COX)-2, E-Cadherin cell-cell adhesion protein and Human epidermal growth factor receptor 2 (HER-2/neu, a proto-oncogene) are involved in the pathogenesis of several cancers including the prostatic adenocarcinoma (PRCa). However, to date the results of the previous studies in this neoplasm are controversial, and the relationships among expression of these molecules in benign prostatic hyperplasia (BPH) and PRCa are mostly unknown. We hypothesize that "there are alterations of COX-2, HER-2/neu and E-Cadherin protein expression in PRCa". We carried out this study to test our hypothesis and to assess the relationships among these molecules both in PRCa and BPH. We used immunohistochemistry to evaluate the expression of these proteins in the tissue specimens of both BPH (27 cases) and PRCa (45 cases). Immunohistochemical staining patterns verified over-expression of COX-2 and HER-2/neu proteins in PRCa as compared to BPH. Alternatively, there was an aberrant (reduced) E-Cadherin protein expression in PRCa. There were weak positive correlations between COX-2 versus HER-2/neu expression. A weak negative correlation was noted between COX-2 and E-Cadherin expression. In conclusion, there were alterations of COX-2, HER-2/neu and E-Cadherin proteins in PRCa. The molecular alterations of the relevant genes and the therapeutic ramifications (the development of selective inhibitors to COX-2 and HER-2/neu) of these preliminary findings are open to further investigations.


A unique presentation of 5-fluorouracil (5-FU) induced cerebral encephalopathy.
5-Fluorouracil (5-FU), a commonly used antimetabolite and antineoplastic agent, has been approved for the treatment of various cancers. It is associated with systemic side-effects such as gastrointestinal problems, neutropenia. 5-FU-related encephalopathy is very rarely reported. Imaging with computed tomography (CT) and magnetic resonance imaging (MRI) plays a key role in diagnosing and monitoring the changes. Since the prognosis of cerebral involvement is usually good if recognized and treated in time, the reporting radiologist and treating physician should be familiar with them. We present a rare case of 5-FU-induced encephalopathy that was diagnosed based on her clinical and MRI findings and managed successfully.


Remote microglial activation in the quinolinic acid model of Huntington's disease.
Intrastriatal injection of quinolinic acid (QA) in the rat leads to several structural and biochemical events which resemble neuropathological changes seen in the striatum of Huntington's disease patients. In the present experiment the accompanying microglial response in striatal projection areas following QA injection was studied immunocytochemically using monoclonal macrophage/microglial markers. After injection of 240 nmol of QA a marked microglial reaction was observed in the entire striatum, whereas injection of the same amount of solvent resulted only in a local microglial reaction around the injection site. Activated microglia were also found in the globus pallidus (GP), the entopeduncular nucleus (EP), the substantia nigra (SN), and the ventroanterior/ventrolateral, the ventromedial, and, in some rats, the reticular thalamic nucleus. The remote microglial reaction started in the first-order projection areas at Day 1 (GP) or Day 3 (EP, SN) and was found in the second-order projection areas (thalamic nuclei) by Day 5. Areas projecting to the striatum such as the amygdala and intralaminar thalamic nuclei remained free of activated microglia. It is concluded that a microglial response in striatal projection areas accompanies excitotoxic striatal injury. Anterograde degeneration of striatal projection neurons can explain the microglial activation in first-order projection areas but other mechanisms such as neuronal hyperexcitation following removal of inhibitory striatal input must be responsible for the rapid transsynaptic microglial activation seen in the thalamus.


Induction of cytochrome P4501A1 by ozone-oxidized tryptophan in Hepa lclc7 cells.
The present investigation was undertaken to determine whether administration of O3-oxidized amino acids to mouse hepatoma cells, Hepa lclc7 (Hepa-1), in culture would effect Cyp1a1 gene expression. The results demonstrate that, of all the amino acids tested, only O3-oxidized tryptophan caused a significant induction of CYP1A1-dependent 7-ethoxyresorufin O-deethylase (EROD) activity compared to the controls (p < 0.01). CYP1A1 mRNA and protein were markedly induced in the O3-oxidized tryptophan administered group compared to the controls. Gel mobility shift assays using nuclear extracts of Hepa-1 cells revealed that oxidized products of tryptophan can induce both aryl hydrocarbon receptor (AhR) transformation and binding of the liganded AhR complex to its specific DNA recognition site, thereby initiating transcription of the Cyp1a1 gene with concomitant increase of CYP1A1 protein and EROD activity in Hepa-1 cells.


Using Hierarchical Linear Models to Examine Approximate Number System Acuity: The Role of Trial-Level and Participant-Level Characteristics.
The ability to intuitively and quickly compare the number of items in collections without counting is thought to rely on the Approximate Number System (ANS). To assess individual differences in the precision of peoples' ANS representations, researchers often use non-symbolic number comparison tasks in which participants quickly choose the numerically larger of two arrays of dots. However, some researchers debate whether this task actually measures the ability to discriminate approximate numbers or instead measures the ability to discriminate other continuous magnitude dimensions that are often confounded with number (e.g., the total surface area of the dots or the convex hull of the dot arrays). In this study, we used hierarchical linear models (HLMs) to predict 132 adults' accuracy on each trial of a non-symbolic number comparison task from a comprehensive set of trial-level characteristics (including numerosity ratio, surface area, convex hull, and temporal and spatial variations in presentation format) and participant-level controls (including cognitive abilities such as visual-short term memory, working memory, and math ability) in order to gain a more nuanced understanding of how individuals complete this task. Our results indicate that certain trial-level characteristics of the dot arrays contribute to our ability to compare numerosities, yet numerosity ratio, the critical marker of the ANS, remains a highly significant predictor of accuracy above and beyond trial-level characteristics and across individuals with varying levels of math ability and domain-general cognitive abilities.


An Unusual Mass of Posterior Mediastinum: A Case of Retrotracheal Parathyroid Adenoma Presenting With Primary Hyperparathyroidism.
Although parathyroid ectopy in the mediastinum has been the subject of several publications, its location in the posterior mediastinum is very rarely reported. We report a case of a 69-year-old patient who presented with clinical symptoms of malignant hypercalcemia due to a retrotracheal mediastinal parathyroid adenoma. The surgical excision leads to a quick normalisation of the phosphocalcic balance with improvement of the clinical symptoms. Ectopic hypersecreting parathyroid adenoma with life-threatening hypercalcemia should prompt radiological assessment and appropriate surgical management to prevent further clinical complications.


Solving School's Survey Request Overload.
Limited information is available on strategies for managing the large number of survey requests that reach an individual nursing school. This article addresses problems identified in managing survey requests and describes the implementation and evaluation of a solution. Identified problems included the appearance of endorsing studies of varying quality and rigor, overlap and competition between external study requests and internal studies, respondent burden, and level of anonymity and confidentiality. The solution included a school-wide policy for tracking and vetting study requests before they were distributed. Evaluation data show the number of requests received (total, by month and source, by target population), their disposition (withdrawn, approved, not approved for distribution), and quality improvement data on meeting a 30-day target turnaround time. Additional considerations are also discussed.


Identification of an evolutionarily conserved domain in human lens epithelium-derived growth factor/transcriptional co-activator p75 (LEDGF/p75) that binds HIV-1 integrase.
Human lens epithelium-derived growth factor/transcriptional co-activator p75 (LEDGF/p75) protein was recently identified as a binding partner for HIV-1 integrase (IN) in human cells. In this work, we used biochemical and bioinformatic approaches to define the domain organization of LEDGF/p75. Using limited proteolysis and deletion mutagenesis we show that the protein contains a pair of evolutionarily conserved domains, assuming about 35% of its sequence. Whereas the N-terminal PWWP domain had been recognized previously, the second domain is novel. It is comprised of approximately 80 amino acid residues and is both necessary and sufficient for binding to HIV-1 IN. Strikingly, the integrase binding domain (IBD) is not unique to LEDGF/p75, as a second human protein, hepatoma-derived growth factor-related protein 2 (HRP2), contains a homologous sequence. LEDGF/p75 and HRP2 IBDs avidly bound HIV-1 IN in an in vitro GST pull-down assay and each full-length protein potently stimulated HIV-1 IN activity in vitro. LEDGF/p75 and HRP2 are predicted to share a similar domain organization and have an evident evolutionary and likely functional relationship.


12/15-Lipoxygenase inhibition counteracts MAPK phosphorylation in mouse and cell culture models of diabetic peripheral neuropathy.
Increased mitogen-activated protein kinase (MAPK) phosphorylation has been detected in peripheral nerve of human subjects and animal models with diabetes as well as high-glucose exposed human Schwann cells, and have been implicated in diabetic peripheral neuropathy. In our recent studies, leukocytetype 12/15-lipoxygenase inhibition or gene deficiency alleviated large and small nerve fiber dysfunction, but not intraepidermal nerve fiber loss in streptozotocin-diabetic mice. To address a mechanism we evaluated the potential for pharmacological 12/15-lipoxygenase inhibition to counteract excessive MAPK phosphorylation in mouse and cell culture models of diabetic neuropathy. C57Bl6/J mice were made diabetic with streptozotocin and maintained with or without the 12/15-lipoxygenase inhibitor cinnamyl-3,4-dihydroxy-α-cyanocinnamate (CDC). Human Schwann cells were cultured in 5.5 mM or 30 mM glucose with or without CDC. 12(S) HETE concentrations (ELISA), as well as 12/15-lipoxygenase expression and p38 MAPK, ERK, and SAPK/JNK phosphorylation (all by Western blot analysis) were increased in the peripheral nerve and spinal cord of diabetic mice as well as in high glucose-exposed human Schwann cells. CDC counteracted diabetes-induced increase in 12(S)HETE concentrations (a measure of 12/15-lipoxygenase activity), but not 12/15-lipoxygenase overexpression, in sciatic nerve and spinal cord. The inhibitor blunted excessive p38 MAPK and ERK, but not SAPK/ JNK, phosphorylation in sciatic nerve and high glucose exposed human Schwann cells, but did not affect MAPK, ERK, and SAPK/JNK phosphorylation in spinal cord. 12/15-lipoxygenase inhibition counteracts diabetes related MAPK phosphorylation in mouse and cell culture models of diabetic neuropathy and implies that 12/15-lipoxygenase inhibitors may be an effective treatment for diabetic peripheral neuropathy.


Heated tobacco product use, its correlates, and reasons for use among Mexican smokers.
Little is known about the use of novel heated tobacco products (HTPs) in low- and middle-income countries. We examined among smokers in Mexico the prevalence and correlates of HTP use, as well as reasons for using HTPs. We analyzed data from five surveys (November 2019-March 2021) of an open cohort of adult smokers (n = 6500), including an oversample of those who also use e-cigarettes. Mixed-effects multinomial logistic models were used to estimate associations between study variables and current HTP use or prior HTP trial relative to never trying HTPs. The weighted prevalence of current HTP use was 1.1%. Independent correlates of current HTP use included smoking frequency, intention to quit, e-cigarette use, having partners/family-members who use e-cigarettes, friends who use HTPs, and exposure to HTP information inside/outside tobacco shops. Having partners/family members who smoke and not knowing about the harm of HTPs relative to cigarettes were associated with lower likelihood of current HTP use. Having tried HTPs was more likely among light daily smokers, those with family who use HTPs and exposure to HTP information outside shops and on newspapers/magazines. Among current users, the top reasons for using HTPs were greater social acceptability (50.6%) and lower perceived harm (34.9%) relative to cigarettes. Uptake of HTPs appears relatively low among Mexican smokers, and correlates of use are similar to those for e-cigarette use. Further research is needed to determine if HTPs use promotes or impedes smoking cessation, given current HTP users are also likely to use various nicotine products.


Cognitive skills & development competencies for conducting research critiques.
As the nursing profession expands its unique scientific body of knowledge, it is essential that all professional nurses become capable of evaluating the scientific and clinical merits of this information generated by nursing research. Three developmental levels of research critique skills are delineated by the nurse reader's competencies: novice, intermediate, and advanced. Each developmental level is described in relation to five cognitive skills which underlie the proposed competencies: knowledge, comprehension, analysis, evaluation, and synthesis.


Effects of training and experience in interpretation of emergency body CT scans.
To determine the effects of level of training and other factors on the rate of discrepant interpretation of emergency body computed tomographic (CT) scans by trainees and staff radiologists. Five hundred ninety-eight consecutive emergency CT studies were prospectively interpreted by radiology residents or board-certified body imaging fellows over a 12-month period. Each interpretation was reviewed within 12 hours by an attending body CT radiologist. Major discrepancies between staff radiologists' and trainees' interpretations were defined and those with the potential to affect immediate patient therapy; minor discrepancies were defined ad those without such potential. The effects on discrepancy rates were examined for abnormal versus normal CT findings and trauma versus nontrauma cases. Major and minor discrepancy rates were 1.2% and 6.5%, respectively, between interpretations made by the trainee and the staff radiologist. Overall, fellows demonstrated statistically significantly lower discrepancy rates than did senior of junior residents (5.9%, 13.7%, and 13.3%, respectively). The discrepancy rate was higher when CT findings were abnormal than when they were normal (13.5% vs 2.6%). There were no differences between discrepancy rates for trauma and nontrauma cases. Experience appeared to decrease discrepancy rates. Trainees were more likely to miss findings than to read normal scans as abnormal.


[A clinical and pathological analysis of 20 cases of lymphal follicular rectitis].
Lymphal follicular rectitis (LFR) recognized in recent years is a kind of benign lesion localizing in rectum. The lack of specific clinical and endoscopic manifestation causes the difficulty in its diagnosis. It was easily confused with ulcerative rectitis, even there were some cases which were misdiagnosed malignant rectal lymphoma. A retrograde analysis was made in our study in the 176 cases of pathologically diagnosed chronic rectitis between January 1993 and July 1994 in our hospital. Among the 176 cases, 20 were certain to be LFR (2 formerly diagnosed, 18 confirmed in the retrograde study). Endoscopic manifestations are as following: (1) granuliform proliferation, eminence and roughness can be seen in rectal mucosa with hyperemia, edema and vague vessels. The lesion is either diffused or localized. (2) single or multiple smooth polypoid apperances can be observed in rectal mucosa, which are 0.2-0.4 cm in diameter, and its pathological characteristics under microscope are: obvious lymphal follicular hyperplasia in the mucosa. A protecting zone and clear reactive germinal center in the hyperplastic follicules, coalescence of follicules occupying more than half of the lamina propria, a large amount of lymphocytes, some are in karyokinesis phase, some infiltrate the mucosa musculis and vessels proliferation in the hyperplastic lymphal tissue, scattered plasma cells, no neutrophil, no eosinophil and no abscess, which is quite different from ulcerative rectitis. Clinical manifestations of the group include: 7 intermittent hematochezia, 4 abdominal pain associated with alternative constipation and diarrhea, 2 mucous stool, 1 tenesmus, 1 pyohemofecia, 2 abdominal distension and 6 asymptomatic. From our study, the diagnosis of LFR mainly depends on its endoscopic polymorphic characteristics and specific histopathologic appearences. And it is important to differentiated LFR from other rectal diseases with lymphal tissue proliferation.


State of the art and future trends in heart transplantation and ventricular assist devices.
The authors present a short review of the milestones in clinical heart transplantation and the prerequisites they regarded as indispensable to be able to start a clinical programme in their own centre. Next, they describe various types of ventricular assist devices (VAD) and the indications for their use. In conclusion, the authors discuss the prospects of, and future trends in, heart transplantation and VAD that have become, despite their short history, a clinical reality and whose practical importance is to grow further.


Combined pre-S deletion and core promoter mutations related to hepatocellular carcinoma: A nested case-control study in China.
To investigate the roles of biomedical factors, hepatitis B virus (HBV) DNA levels, genotypes, and specific viral mutation patterns on the progression of hepatocellular carcinoma (HCC) in Qidong, China. A total of 2387 males (aged 20-65 years) who were seropositive for the hepatitis B surface antigen (HBsAg), but had not been diagnosed with HCC, were recruited to a community-based HCC screening study from August, 1996. Evaluation of virological parameters at recruitment was determined for 196 HCC patients during 10 years of follow-up and 323 controls. After adjustment for age at recruitment, history of cigarette smoking and alcohol consumption, alanine aminotransferase (ALT) elevation, alpha-fetoprotein (AFP) levels >20 ng/mL, hepatitis B e antigen positive, HBV DNA levels ≥4.00 log(10) copies/mL, pre-S deletion, T1653 mutation, T1762/A1764 double mutations, and T1766 and/or A1768 mutations were associated with subsequent risk of HCC. A significant biological gradient of HCC risk by HBV DNA levels from less than 2.69 log(10) copies/mL to 6.00 log(10) copies/mL or greater was observed. HBV with a complex mutation combination pattern (pre-S deletion, T1762/A1764 double mutations, and T1766 and/or A1768 mutations) rather than a single mutation was associated with the development of HCC. The longitudinal observation demonstrated a gradual combination of pre-S deletion, T1762/A1764 double mutations, and T1766 and/or A1768 mutations during the development of HCC. AFP levels >20 ng/mL, high HBV DNA levels, pre-S deletion, and T1762/A1764 double mutations at recruitment were independent risk factors of HCC. Combination of pre-S deletion and core promoter mutations increased the risk of HCC.


An examination of affect prior to and following episodes of getting drunk in women with bulimia nervosa.
The current study examined the association between affect and self-reported alcohol intoxication in women with bulimia nervosa (BN; N=133). Participants completed a two-week ecological momentary assessment protocol. Momentary global positive affect (PA) and negative affect (NA), as well as the facets of NA (fear, guilt, hostility and sadness), were measured. Forty-five participants endorsed that they "got drunk" during the study period. Daily mean and variability of global PA and NA were compared between days with self-reported alcohol intoxication and days without self-reported alcohol intoxication. Trajectories of affect were modeled prior to and following episodes of self-reported alcohol intoxication. There were no differences in the mean or variability of PA or NA on days characterized by self-reported alcohol intoxication compared to days with no self-reported alcohol intoxication (ps>0.05). PA decreased significantly prior to self-reported alcohol intoxication and remained stable afterwards. There were no changes in global NA before or after self-reported alcohol intoxication, but an examination of the facets of NA showed that sadness increased following episodes of self-reported alcohol intoxication. These findings showed only partial support for a negative reinforcement model of alcohol use in women with BN.


Recruitment of immune cells across atrial endocardium in human atrial fibrillation.
Although clinical studies have suggested a link between inflammation markers and atrial fibrillation (AF), it is still unclear whether local immunologic responses actually exist in human atria during AF. To address this point, human left appendages were obtained from 16 patients who underwent cardiac surgery (5 with sinus rhythm (SR) and 11 with AF) and subjected to immunohistochemical analysis. In all the AF specimens, adhesion and migration of CD45-reactive cells were consistently observed predominantly in the atrial endo- and subendomyocardium and more prominently than in SR. Most of them were immunologically active CD68-positive macrophages, whereas CD3-positive T cells infiltrated to a lesser extent. Scavenger-receptor A staining revealed maturation of macrophages not in the endocardium but in the midmyocardium, a gradient from endo- to midmyocardium. In the endocardium, along with adhesion molecules (intracellular adhesion molecule-1 and vascular cell adhesion molecule-1), a chemotactic protein-1, which facilitates the recruitment, was more abundantly expressed in AF than in SR. Cytokines including transforming growth factor-beta and interleukin-6 were frequently expressed by these macrophages. These observations collectively imply active adhesion and recruitment of macrophages across the endocardium in human fibrillating atria, thereby supporting the concept of local immunologic inflammatory responses around the atrial endocardium of AF.


Intestinal SIRT1 Deficiency-Related Intestinal Inflammation and Dysbiosis Aggravate TNFα-Mediated Renal Dysfunction in Cirrhotic Ascitic Mice.
In advanced cirrhosis, the TNFα-mediated intestinal inflammation and bacteria dysbiosis are involved in the development of inflammation and vasoconstriction-related renal dysfunction. In colitis and acute kidney injury models, activation of SIRT1 attenuates the TNFα-mediated intestinal and renal abnormalities. This study explores the impacts of intestinal SIRT1 deficiency and TNFα-mediated intestinal abnormalities on the development of cirrhosis-related renal dysfunction. Systemic and renal hemodynamics, intestinal dysbiosis [cirrhosis dysbiosis ratio (CDR) as marker of dysbiosis], and direct renal vasoconstrictive response (renal vascular resistance (RVR) and glomerular filtration rate (GFR)) to cumulative doses of TNFα were measured in bile duct ligated (BDL)-cirrhotic ascitic mice. In SIRT1IEC-KO-BDL-ascitic mice, the worsening of intestinal dysbiosis exacerbates intestinal inflammation/barrier dysfunction, the upregulation of the expressions of intestinal/renal TNFα-related pathogenic signals, higher TNFα-induced increase in RVR, and decrease in GFR in perfused kidney. In intestinal SIRT1 knockout groups, the positive correlations were identified between intestinal SIRT1 activity and CDR. Particularly, the negative correlations were identified between CDR and RVR, with the positive correlation between CDR and GFR. In mice with advanced cirrhosis, the expression of intestinal SIRT1 is involved in the linkage between intestinal dysbiosis and vasoconstriction/hypoperfusion-related renal dysfunction through the crosstalk between intestinal/renal TNFα-related pathogenic inflammatory signals.


Maternal social characteristics and mortality from injuries among infants and toddlers in Estonia.
Injuries are a major cause of ill health among children, with a social gradient in child injuries documented in many countries. The effects of maternal sociodemographic characteristics on injury mortality in Estonian infants and toddlers were investigated. A population-based study using linkage of data from the Estonian Medical Birth Registry with Mortality Database. A total of 148 521 children born 1992-2002 were followed for injury mortality (ICD-9 E800-E999) from birth to third birthday. Associations of maternal age, education, marital status, nationality, place of residence and child's birth order and multiplicity with risk of injury death were studied using logistic regression. Maternal age (<20 years compared with > or =30 years: OR 2.12; 95% CI 1.00 to 4.51), education (basic compared with secondary or higher: OR 3.22; 95% CI 2.12 to 4.87), marital status (single, divorced or widowed compared with married: OR 2.74; 95% CI 1.53 to 4.91), nationality (other compared with Estonian: OR 2.00; 95% CI 1.32 to 3.02), birth order (fourth or higher compared with first: OR 6.66; 95% CI 3.42 to 12.99), and multiple birth (twin or triplet compared with singleton: OR 3.12; 95% CI 1.44 to 6.73) affected the risk of injury death among infants (<1 year). Among toddlers (1-2 years), boys were at higher risk than girls (OR 1.75; 95% CI 1.15 to 2.66) and low mother's education (basic compared with secondary or higher OR 2.08; 95% CI 1.28 to 3.37) and high birth order (fourth or higher compared with first: OR 7.88; 95% CI 3.90 to 15.90) increased the risk of injury death. Maternal sociodemographic characteristics are associated with injury mortality among infants and toddlers. Substantial variation in injury mortality rates within Estonia suggests potential for prevention.


Enterocyte-specific epidermal growth factor prevents barrier dysfunction and improves mortality in murine peritonitis.
Systemic administration of epidermal growth factor (EGF) decreases mortality in a murine model of septic peritonitis. Although EGF can have direct healing effects on the intestinal mucosa, it is unknown whether the benefits of systemic EGF in peritonitis are mediated through the intestine. Here, we demonstrate that enterocyte-specific overexpression of EGF is sufficient to prevent intestinal barrier dysfunction and improve survival in peritonitis. Transgenic FVB/N mice that overexpress EGF exclusively in enterocytes (IFABP-EGF) and wild-type (WT) mice were subjected to either sham laparotomy or cecal ligation and puncture (CLP). Intestinal permeability, expression of the tight junction proteins claudins-1, -2, -3, -4, -5, -7, and -8, occludin, and zonula occludens-1; villus length; intestinal epithelial proliferation; and epithelial apoptosis were evaluated. A separate cohort of mice was followed for survival. Peritonitis induced a threefold increase in intestinal permeability in WT mice. This was associated with increased claudin-2 expression and a change in subcellular localization. Permeability decreased to basal levels in IFABP-EGF septic mice, and claudin-2 expression and localization were similar to those of sham animals. Claudin-4 expression was decreased following CLP but was not different between WT septic mice and IFABP-EGF septic mice. Peritonitis-induced decreases in villus length and proliferation and increases in apoptosis seen in WT septic mice did not occur in IFABP-EGF septic mice. IFABP-EGF mice had improved 7-day mortality compared with WT septic mice (6% vs. 64%). Since enterocyte-specific overexpression of EGF is sufficient to prevent peritonitis-induced intestinal barrier dysfunction and confers a survival advantage, the protective effects of systemic EGF in septic peritonitis appear to be mediated in an intestine-specific fashion.


Comparison of the acute hypotensive effects of renin inhibition, converting enzyme inhibition, and angiotensin II antagonism in rats.
The purpose of this study was to compare the acute hypotensive efficacy of different types of inhibitor of the renin-angiotensin system. A renin inhibitor (RI), CGP 44,099 A, a converting enzyme inhibitor (CEI), enalaprilat, a peptidic angiotensin II (Ang II) antagonist, [Sar1, Ile8]Ang II (P-Ang IIA), and a nonpeptidic Ang II antagonist devoid of agonistic properties, 2-butyl-4-chloro-1- ([2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl)-5- (hydroxymethyl)imidazol (NP-Ang IIA), were administered intravenously to sodium-depleted rats (SDRs), renal hypertensive rats (two-kidney, one-clip) (RHRs), and spontaneously hypertensive rats (SHRs). The four compounds were all effective in lowering blood pressure (BP) in SDRs and RHRs. The maximum hypotensive response observed within 30 min of administration was similar for all four compounds (approximately 30 mm Hg in SDRs and 60 mm Hg in RHRs). In SHRs, the P-Ang IIA induced a pressor response whereas the RI, CEI, and NP-Ang IIA lowered BP to a similar extent (approximately 15 mm Hg). Pretreatment with the CEI completely prevented the hypotensive response to RI in SHRs, and vice versa. These observations indicate that the principal mechanism by which converting enzyme inhibitors lower BP after acute administration in these rat models is by inhibition of the formation of Ang II. The pressor response to the P-Ang IIA in SHRs is probably a consequence of its partial agonistic properties. Renin inhibitors and nonpeptidic Ang II antagonists, devoid of agonistic properties, promise to be effective antihypertensive agents similar to the CEIs.


Genetic variation at the growth hormone locus in a wild pig intercross; test of association to phenotypic traits and linkage to the blood group D locus.
A polymorphism in the TATA-box of the porcine growth hormone (GH) gene was analysed in a wild pig/Large White intercross, in which 129 markers had been scored previously. Linkage analyses demonstrated that the GH locus belonged to a linkage group on chromosome 12 together with a previously unassigned marker, the erythrocyte antigen D (EAD) locus. The linear order of this linkage group is EAD-GH-S0096-S0090-S0106-arachidonate 12-lipoxygenase (ALOX12)-inhibin beta A (INHBA). The length of the linkage group was estimated at 93 cM (sex average). The effects of the GH genotype on growth and fat deposition traits were investigated using phenotypic data from the 191 F2 animals. No significant effect of GH was detected, and we therefore conclude that this locus does not play a major role in defining the genetic differences between the wild and Large White pigs for these traits.


Pediatric skull fracture diagnosis: should 3D CT reconstructions be added as routine imaging?
The authors compared the efficacy of combining 2D+3D CT reconstructions with standard 2D CT images in the diagnosis of linear skull fractures in children with head trauma. This was a retrospective evaluation of consecutive head CT studies of children presenting with head trauma. Two experienced pediatric neuroradiologists in consensus created the standard of reference. Three readers independently evaluated the 2D CT images alone and then in combination with the 3D reconstructions for the diagnosis of linear skull fractures. Sensitivity and specificity in the diagnosis of linear skull fractures utilizing 2D and 2D+3D CT in combination were measured for children less than 2 years of age and for all children for analysis by the 3 readers. Included in the study were 250 consecutive CT studies of 250 patients (167 boys and 83 girls). The mean age of the children was 7.82 years (range 4 days to 17.4 years). 2D+3D CT combined had a higher sensitivity and specificity (83.9% and 97.1%, respectively) compared with 2D alone (78.2% and 92.8%, respectively) with statistical significance for specificity (p < 0.05) in children less than 2 years of age. 2D+3D CT combined had a higher sensitivity and specificity (81.3% and 90.5%, respectively) compared with 2D alone (74.5% and 89.1%, respectively) with statistical significance for sensitivity (p < 0.05) in all children. In this study, 2D+3D CT in combination showed increased sensitivity in the diagnosis of linear skull fractures in all children and increased specificity in children less than 2 years of age. In children less than 2 years of age, added confidence in the interpretation of fractures by distinguishing them from sutures may have a significant implication in the setting of nonaccidental trauma. Furthermore, 3D CT is available at no added cost, scan time, or radiation exposure, providing trainees and clinicians with limited experience an additional valuable tool for routine imaging of pediatric head trauma.


Hybrid therapy with pilsicainide and pulmonary vein isolation for atrial fibrillation.
Pulmonary vein (PV) isolation is commonly performed in patients with drug-refractory atrial fibrillation (AF) and in cases of unsuccessful ablation, antiarrhythmic agents that were ineffective before the ablation sometimes become effective afterward. Therefore, the effects and mechanisms of hybrid therapy with pilsicainide and PV isolation for AF were assessed in the present study. Seventy-four patients with paroxysmal AF in whom pilsicainide was ineffective underwent PV isolation. If AF recurred, a second procedure was performed and if AF recurred again, pilsicainide was re-administered. After the first procedure, AF recurred in 42 patients, and a second procedure was performed in 31 patients, of whom 28 had recovery of left atrial (LA)-PV conduction and non-PV foci were identified in 3. After the second session, ablation eliminated AF without drugs in 53 (72%) patients. Pilsicainide suppressed the conduction properties at the LA-PV junction. In 21 patients with recurrence of AF, pilsicainide was re-administered and eliminated AF in 11 patients (success with pilsicainide: 86%). In cases of unsuccessful PV isolation, pilsicainide may prevent AF by modifying the LA-PV conduction properties. Hybrid therapy with pilsicainide and PV isolation may be an effective therapeutic approach for AF.


A procedure to determine equilibrium postural configurations for arbitrary locations of the feet.
This research was directed toward predicting postural equilibrium configurations in normal humans for asymmetric locations of the feet. The objective of the study was to identify trends in the variation of the location of ground center of pressure (COP) with increasing levels of asymmetry in the foot placement. The procedure developed here minimized the muscular effort (active torques) in the lower extremities while maximizing postural stability margins for given foot locations. Minimizing muscular effort led to fully extended knees, and maximal stability margin led to the COP moving toward the rear foot in asymmetric stance. A combined analytical-numerical optimization scheme was used to avoid singularities that can arise due to the fact that at equilibrium postural configurations, the torso lies at or near the workspace boundary of the lower extremities. Experiments were conducted and the results obtained were in keeping with the model predictions. This basic understanding of asymmetric stance is important for studying asymmetric postural mechanics in the presence of external disturbances, and for extending the results from normal subjects to humans at both ends of the life span.


The effects of a lower body exoskeleton load carriage assistive device on limits of stability and postural sway.
The study investigated the effects of using a lower body prototype exoskeleton (EXO) on static limits of stability and postural sway. Measurements were taken with participants, 10 US Army enlisted men, standing on a force platform. The men were tested with and without the EXO (15 kg) while carrying military loads of 20, 40 and 55 kg. Body lean to the left and right was significantly less and postural sway excursions and maximal range of movement were significantly reduced when the EXO was used. Hurst values indicated that body sway was less random over short-term time intervals and more random over long-term intervals with the EXO than without it. Feedback to the user's balance control mechanisms most likely was changed with the EXO. The reduced sway and relatively small changes in sway with increasing load weights suggest that the EXO structure may have functioned to provide a bracing effect on the body.


Ultrasensitive Detection of Alzheimer's Amyloids on a Plasmonic-Gold Platform.
More than 55 million people live with dementia worldwide in 2021, and there are nearly 10 million new cases every year. Alzheimer's disease (AD) is the most common cause of dementia. Despite urgent need, early detection of AD and long-term monitoring of AD progression have been challenging. This is due to the limited availability of brain imaging facilities and the highly invasive procedure with the cerebrospinal fluid assay to assess the level of AD biomarkers, such as beta-amyloid (Aβ). Reliable measurements of AD biomarkers in blood samples are still difficult because of their very low abundance. Here, we develop a rapid, specific, and ultrasensitive immunoassay using plasmonic-gold nanoisland (pGOLD) chips with near-infrared fluorescence-enhanced detection for Aβ1-40 and Aβ1-42. We show step-by-step processes and results during the platform establishment, including antibody specificity and sensitivity tests, antibody pair examination, condition optimization, and procedure refinement. Finally, we demonstrate the platform performance with detection sensitivity at the subpicogram per milliliter level. This platform, therefore, has a great application potential for early detection of AD using blood samples.


A Bayesian Analysis of Abundance, Trend, and Population Viability for Harbor Seals in Iliamna Lake, Alaska.
Harbor seals in Iliamna Lake, Alaska, are a small, isolated population, and one of only two freshwater populations of harbor seals in the world, yet little is known about their abundance or risk for extinction. Bayesian hierarchical models were used to estimate abundance and trend of this population. Observational models were developed from aerial survey and harvest data, and they included effects for time of year and time of day on survey counts. Underlying models of abundance and trend were based on a Leslie matrix model that used prior information on vital rates from the literature. We developed three scenarios for variability in the priors and used them as part of a sensitivity analysis. The models were fitted using Markov chain Monte Carlo methods. The population production rate implied by the vital rate estimates was about 5% per year, very similar to the average annual harvest rate. After a period of growth in the 1980s, the population appears to be relatively stable at around 400 individuals. A population viability analysis assessing the risk of quasi-extinction, defined as any reduction to 50 animals or below in the next 100 years, ranged from 1% to 3%, depending on the prior scenario. Although this is moderately low risk, it does not include genetic or catastrophic environmental events, which may have occurred to the population in the past, so our results should be applied cautiously.


Effects of metabolic flux on stress response pathways in Lactococcus lactis.
Studies of cellular responses to stress conditions such as heat, oxygen or starvation have revealed the existence of numerous specific or interactive response pathways. We previously observed in Lactococcus lactis that inactivation of the recA gene renders the lactococcal strain sensitive not only to DNA-damaging agents but also to oxygen and heat. To further examine the stress response pathways in L. lactis, we isolated thermoresistant insertional mutants (Trm) of the recA strain. Eighteen independent trm mutations were identified and characterized. We found that mutations map in only seven genes, implicated in purine metabolism (deoB, guaA and tktA), phosphate uptake (pstB and pstS), mRNA stability (pnpA) and in one uncharacterized gene (trmA). All the trm mutations, with the exception of trmA, confer multiple stress resistance to the cell. Some of the mutations confer improved heat stress resistance not only in the recA but also in the wild-type context. Our results reveal that cellular metabolic pathways are intimately related to stress response and that the flux of particular metabolites, notably guanine and phosphate, may be implicated in stress response in lactococci.


Mass spectrometry-based protein profiling to determine the cause of lysosomal storage diseases of unknown etiology.
Diagnosis of lysosomal storage diseases (LSDs) can be problematic in atypical cases where clinical phenotype may overlap with other genetically distinct disorders. In addition, LSDs may result from mutations in genes not yet implicated in disease. Thus, there are individuals that are diagnosed with apparent LSD based upon clinical criteria where the gene defect remains elusive. The objective of this study was to determine whether comparative proteomics approaches could provide useful insights into such cases. Most LSDs arise from mutations in genes encoding lysosomal proteins that contain mannose 6-phosphate, a carbohydrate modification that acts as a signal for intracellular targeting to the lysosome. We purified mannose 6-phosphorylated proteins by affinity chromatography and estimated relative abundance of individual proteins in the mixture by spectral counting of peptides detected by tandem mass spectrometry. Our rationale was that proteins that are decreased or absent in patients compared with controls could represent candidates for the primary defect, directing biochemical or genetics studies. On a survey of brain autopsy specimens from 23 patients with either confirmed or possible lysosomal disease, this approach identified or validated the genetic basis for disease in eight cases. These results indicate that this protein expression approach is useful for identifying defects in cases of undiagnosed lysosomal disease, and we demonstrated that it can be used with more accessible patient samples, e.g. cultured cells. Furthermore this approach was instrumental in the identification or validation of mutations in two lysosomal proteins, CLN5 and sulfamidase, in the adult form of neuronal ceroid lipofuscinosis.


Supplementation of prepartum dairy cows with β-carotene.
The prepartum supplementation of dairy cows with β-carotene was evaluated. Cows were blocked by parity and expected calving date and assigned to a treatment: β-carotene (1.2 g/cow per d) or control (no supplementation). The same total mixed ration batch was offered to all cows, and β-carotene was top dressed to individual cows once per day. The data set contained 283 Holsteins that received a treatment for >14 d (29.1±6.9 d). Frequency distributions were analyzed with the GENMOD procedure of SAS using logistic regression for binomial data. Continuous variables were analyzed with the MIXED procedure of SAS. Within parity, nonparametric estimates of the survivor function for reproductive variables were computed using the product-limit method of the Kaplan-Meier method with the LIFETEST procedure of SAS. Plasma β-carotene concentration before supplementation was similar between supplemented and nonsupplemented cows (2.99µg/mL) and peaked at 3.26±0.175µg/mL on d -15±2.4 precalving for supplemented cows (2.62±0.168µg/mL for control). Colostrum density, milk yield, and milk composition were similar between treatments. β-Carotene tended to increase milk protein content from 2.90 to 2.96% and to decrease the proportion of primiparous cows with a milk fat to protein ratio >1.5 from 22.6 to 6.4%. The proportion of primiparous and multiparous cows with difficult calving, metritis, progesterone >1 ng/mL at 21 d and at 42 d in lactation, % conception at first service, and % pregnancy at 90 and 150 d in lactation were similar between treatments. A trend for decreased incidence of somatic cell count >200,000 cells/mL was present in multiparous cows supplemented with β-carotene (38.9% vs. 28.1%). β-Carotene was associated with a reduction in the proportion of multiparous cows with retained placenta 12 h postpartum from 29.9 to 21.7%; time of placenta release was 392 min (340 to 440) for β-carotene and 490 min (395 to 540) for control (median and 95% confidence interval). For primiparous cows, placenta release was not affected by β-carotene (incidence was 15.4%). The intervals from calving to first estrus, to first service, and to conception were not affected by β-carotene supplementation in either parity. However, independent of treatment, cows with improved reproductive efficiency had increased postpartum β-carotene concentration in plasma. The prepartum supplementation of β-carotene increased plasma concentration around calving. No response in milk yield or reproductive performance was detected. Beta-carotene supplementation was associated with a lower incidence of retained placenta in multiparous cows.


Evidence that the sweetness of odors depends on experience in rats.
Humans describe their perception of certain odorants in terms of taste qualities (e.g., sweet). It has also been found that in humans, novel odorants can rapidly and irreversibly acquire a taste, even after just a single pairing with a taste. It remains unclear whether flavor objects in general, and odor-taste generalizations in particular, are experience-dependent. Interactions might result from a failure by humans to sufficiently analyze the olfactory and gustatory components of compound flavorants. Here, we tested odor-taste generalizations in rats with or without paired exposure to an odorant and a tastant. We evaluated the generalization of conditioned odor aversion to tastants by rats. Our findings suggest that rats behave toward putatively tasteless retronasal odorants as if they were sweet only after prior paired experience of the odorant with a sweet tastant. These data support the hypothesis that taste-like qualities of odors are learned and are not innate. Furthermore, the present results suggest that acquisition of a taste quality by an odor need not depend on higher cognitive abilities. This study helps to establish the rat as a model for the study of behavioral neuroscience of flavor.


Compressive spectral imaging with diffractive lenses.
Compressive spectral imaging enables the reconstruction of an entire 3D spectral cube from a few multiplexed images. Here we develop a novel compressive spectral imaging technique using diffractive lenses. Our technique uses a coded aperture to spatially modulate the optical field from the scene and a diffractive lens such as a photon sieve for both dispersion and focusing. Measurement diversity is achieved by changing the focusing behavior of the diffractive lens. The 3D spectral cube is then reconstructed from highly compressed measurements taken with a monochrome detector. A fast sparse recovery method is developed to solve this large-scale inverse problem. The performance is illustrated for various scenarios with different compression ratios through simulations. The results demonstrate that promising reconstruction performance can be achieved at high compression levels. This opens up new possibilities for high-resolution spectral imaging with simpler and low cost designs.


[Laboratory tests for detection of antiphospholipid antibodies].
Antiphospholipid antibodies(APA) have been reported to be a heterogeneous family of immunoglobulins. Some APA can be detected via phospholipid dependent coagulation assays when they present as an aspecific coagulation inhibitor, lupus anticoagulant(LA), other antibodies can be measured via immunological assays mostly via their capability to bind to immobilized cardiolipin (anticardiolipin antibody; aCL). Despite their name, APA associated with antiphospholipid syndrome(APS) do not bind phospholipids, but are directed at plasma proteins bound with anionic phospholipids. The antigenic targets of these antibodies include beta 2 glycoprotein I(beta 2 GP I), prothrombin, high- and low-molecular-weight kininogens, annexin V, protein C and protein S. In this article, the current knowledge on the methods of detection and their functional properties are reviewed, and the interaction of these antibodies and acquired activated protein C resistance are discussed.


Expression of 20 alpha-hydroxysteroid dehydrogenase activity in human lymphoid and non lymphoid cells.
Expression of 20-alpha-hydroxysteroid dehydrogenase (20 alpha-SDH), a putative T cell marker in the murine system, has been examined in human haematopoietic cells. Higher levels of enzymatic activity were expressed by human peripheral blood mononuclear cells (PBMC) in comparison with thymocytes. When PBMC were fractionated into T and non T cell subsets, the greatest values of 20 alpha-SDH activity were associated with the non T cell population. Cells from bone marrow exhibited lower levels of 20 alpha-SDH than PBMC and thymocytes. Both myeloid and lymphoid leukaemic cells expressed significant 20 alpha-SDH activity. In addition our data in U-937 and CM-S human cell lines indicate that cells belonging to the myelomonocytic precursor compartment constitutively expressed 20 alpha-SDH activity. Furthermore, this activity was less expressed when these cells were induced to monocyte-macrophage differentiation. In conclusion, our data in the human system indicate that 20 alpha-SDH should not be viewed as a lymphoid lineage-restricted marker enzyme.


Congenital dysplasia of the hip: the lax (subluxatable) newborn hip.
During a 4-year period, 15,149 newborns were examined for hip abnormalities. Ninety-two infants (0.61%) were found to have subluxatable (lax, but not dislocatable) hips. The profile of this group was similar to patients with dislocated hips, with an increased frequency of females, breech presentations, left-sided involvement, and associated postural deformities. A significant number showed acetabular dysplasia or persistent hip laxity despite treatment with an abduction brace. We concluded that the newborn subluxatable hip arises from the same antecedents as frank dislocation, is not always benign, and is best managed if detected and treated at birth.


Nutritional Status of Selenium and Its Association with Diet and Indoor Air Pollution among Pregnant Women in a Rural Area of Northern China.
The nutritional status of selenium (Se) in pregnant women in rural areas of northern China and its association with diet and indoor air pollution are rarely reported. We recruited 273 pregnant women in early or middle term in Shanxi and Hebei province and detected their fasting blood selenium. Demographic characteristics, food habits, and indoor air pollution exposure were collected with a questionnaire. Multivariate logistic regression models were used to estimate the adjusted odds ratios (AORs) and their 95% confidence intervals for the factors and relatively low blood levels of Se (below the lower quartile). The median (interquartile range [IQR]) blood concentration of Se was 117.35 (103.90, 129.23) μg/L. The rate of Se deficiency was 4.8%, and the rate of overnutrition was 23.8%. The AORs for the risk for relatively low blood levels of Se were 2.26 (1.15, 4.44) for consuming less beef and pork/mutton; 0.39 (0.19, 0.80) for a lower frequency of vinegar consumption; and 1.41 (0.76, 2.60) and 1.18 (0.59, 2.36) for passive smoking and indoor coal pollution, respectively. In conclusion, the nutritional status of Se in pregnant women in a rural area of northern China was acceptable; diet was the main determinant; no conclusive association was found between indoor air pollution and Se nutritional status.


Photophysics of fluorinated benzene. I. Quantum chemistry.
The electronic structure of energetically low-lying excited singlet states of fluorobenzene molecules is investigated here. Increasing fluorine substitution alters the nature of the excited electronic states and the so-called perfluoro effect is observed for penta- and hexafluorobenzene. Detailed quantum chemistry calculations are carried out at the equation-of-motion coupled-cluster singles and doubles level of theory to establish the potential energy surfaces of the low-lying electronic states of mono-, di- (ortho- and meta-), and pentafluorobenzene molecules. A sequence of low-energy conical intersections among the electronic potential energy surfaces is established. It is found that increasing fluorine substitution lowers the energy of the pisigma* electronic state and leads to conical intersections between the S(1) and S(2) electronic states of pentafluorobenzene. Existence of numerous conical intersections among the excited electronic states of these molecules forms the mechanistic details underlying their nonradiative internal conversion. In particular, the slow and biexponential fluorescence emission in pentafluorobenzene is attributed to the existence of low-lying S(1)-S(2) conical intersections. The electronic structure data are analyzed in detail and the coupling mechanism among various electronic excited states of mono-, di-, and pentafluorobenzene molecules is established.


Drosophila damaged DNA-binding protein 1 is an essential factor for development.
The damaged DNA-binding protein (DDB) complex, thought to recognize (6-4) photoproducts and other lesions in DNA, has been implicated to have a role in global genomic nucleotide excision repair (NER) and E2F-1-mediated transcription. The complex consists of a heterodimer of p127 (DDB1) and p48 (DDB2), the latter also being known as XPE. We reported previously that in Drosophila expression of the DDB1 (D-DDB1) gene is controlled by the DRE/DREF system, and external injury to DNA is not essential for D-DDB1 function. In the present study of the function of D-DDB1 in a multicellular system, we prepared transgenic flies, which were knocked down for the D-DDB1 gene due to RNA interference (RNAi), and performed immunocytochemistry to ascertain the distribution of D-DDB1 in the eye imaginal disc. It was found to be abundant in the anterior of the morphogenetic furrow (MF). Whole-body overexpression of dsRNA of D-DDB1 in Drosophila using a GAL4-UAS targeted expression system induced melanotic tumors and caused complete lethality. When limited to the eye imaginal disc, a severe rough eye phenotype resulted. Correspondingly, all of the D-DDB1 gene knocked-out flies also died. D-DDB1 therefore appears to be an essential development-associated factor in a multicellular organism.


Mindfulness-Based Interventions for Anxiety and Depression.
This article reviews the ways in which mindfulness practices have contributed to cognitive and behavioral treatments for depression and anxiety. Research on mindfulness-based interventions (MBIs) has increased rapidly in the past decade. The most common include mindfulness-based stress reduction and mindfulness-based cognitive therapy. MBIs are effective in reducing anxiety and depression symptom severity in a range of individuals. MBIs consistently outperform non-evidence-based treatments and active control conditions, such as health education, relaxation training, and supportive psychotherapy. MBIs also perform comparably with cognitive behavior therapy (CBT). The treatment principles of MBIs for anxiety and depression are compatible with standard CBT.


Relational aggression, gender, and peer acceptance: invariance across culture, stability over time, and concordance among informants.
It has been proposed that overt physical and verbal aggression are more prevalent among boys and that covert aggression in the context of interpersonal relationships is more typical of girls. The purpose of this study was to replicate and extend American research on this topic to Italy. Italian elementary school pupils (n = 314) and their teachers provided nominations for aggression and prosocial behavior on 2 occasions within a single school year. Both peer and teacher nominations were highly stable, though there was very poor concordance between them. Peer nominations for both overt and relational aggression were linked to peer rejection. Contrary to expectations, boys scored higher than girls in both overt and relational aggression. Nevertheless, on the basis of the gender composition of extreme groups, the authors conclude that the distinction between overt and relational aggression is as useful in facilitating research on aggressiveness among girls in Italy as it is in the United States.


Treatment of methicillin-resistant Staphylococcus aureus infection following tibial plateau leveling osteotomy in a dog.
In recent years, surgical site infections caused by drug-resistant pathogens have emerged as a cause of concern in small animal practice. In this report, methicillin-resistant Staphylococcus aureus (MRSA) infections associated with tibial plateau leveling osteotomy (TPLO) is reported. However, there have been no reports on the treatment of MRSA infection following TPLO in dogs. This case report describes the use of a combination of vancomycin and rifampicin to treat MRSA infection following TPLO in a dog. A 7-year-old spayed female American cocker spaniel was referred for right hind limb lameness that did not improve with conservative treatment. The dog was diagnosed with cranial cruciate ligament rupture, for which TPLO was performed. Once the surgical wound was closed, the dog licked the skin on the surgical site, causing the injury to dehisce. MRSA was detected from the purulent discharge, and chloramphenicol was then administered based on the drug sensitivity test results. Because of the continued drainage, the implants were removed after the bone union of the osteotomy site was observed. Since this did not provide any relief to the existing condition, the antibiotic was changed to vancomycin at 132 days after TPLO surgery, and the infected location was cleaned many times through a drain tube placed into the tibia. However, the infection could not be controlled. Thus, a rifampicin and vancomycin combination was started. As a result, the purulent discharge disappeared and the fistula entirely closed on the 154th day after TPLO surgery. A combination of rifampicin and vancomycin may be effective for treating MRSA infection at the surgical site following TPLO surgery that does not heal despite implant removal and administration of vancomycin.


Endogenous nitric oxide synthesis: biological functions and pathophysiology.
Modern molecular biology has revealed vast numbers of large and complex proteins and genes that regulate body function. By contrast, discoveries over the past ten years indicate that crucial features of neuronal communication, blood vessel modulation and immune response are mediated by a remarkably simple chemical, nitric oxide (NO). Endogenous NO is generated from arginine by a family of three distinct calmodulin- dependent NO synthase (NOS) enzymes. NOS from endothelial cells (eNOS) and neurons (nNOS) are both constitutively expressed enzymes, whose activities are stimulated by increases in intracellular calcium. Immune functions for NO are mediated by a calcium-independent inducible NOS (iNOS). Expression of iNOS protein requires transcriptional activation, which is mediated by specific combinations of cytokines. All three NOS use NADPH as an electron donor and employ five enzyme cofactors to catalyze a five-electron oxidation of arginine to NO with stoichiometric formation of citrulline. The highest levels of NO throughout the body are found in neurons, where NO functions as a unique messenger molecule. In the autonomic nervous system NO functions NO functions as a major non-adrenergic non-cholinergic (NANC) neurotransmitter. This NANC pathway plays a particularly important role in producing relaxation of smooth muscle in the cerebral circulation and the gastrointestinal, urogenital and respiratory tracts. Dysregulation of NOS activity in autonomic nerves plays a major role in diverse pathophysiological conditions including migraine headache, hypertrophic pyloric stenosis and male impotence. In the brain, NO functions as a neuromodulator and appears to mediate aspects of learning and memory. Although endogenous NO was originally appreciated as a mediator of smooth muscle relaxation, NO also plays a major role in skeletal muscle. Physiologically muscle-derived NO regulates skeletal muscle contractility and exercise-induced glucose uptake. nNOS occurs at the plasma membrane of skeletal muscle which facilitates diffusion of NO to the vasculature to regulate muscle perfusion. nNOS protein occurs in the dystrophin complex in skeletal muscle and NO may therefore participate in the pathophysiology of muscular dystrophy. NO signalling in excitable tissues requires rapid and controlled delivery of NO to specific cellular targets. This tight control of NO signalling is largely regulated at the level of NO biosynthesis. Acute control of nNOS activity is mediated by allosteric enzyme regulation, by posttranslational modification and by subcellular targeting of the enzyme. nNOS protein levels are also dynamically regulated by changes in gene transcription, and this affords long-lasting changes in tissue NO levels. While NO normally functions as a physiological neuronal mediator, excess production of NO mediates brain injury. Overactivation of glutamate receptors associated with cerebral ischemia and other excitotoxic processes results in massive release of NO. As a free radical, NO is inherently reactive and mediates cellular toxicity by damaging critical metabolic enzymes and by reacting with superoxide to form an even more potent oxidant, peroxynitrite. Through these mechanisms, NO appears to play a major role in the pathophysiology of stroke, Parkinson's disease, Huntington's disease and amyotrophic lateral sclerosis.


The neural correlates of domain-general visual ability.
People vary in their general ability to compare, identify, and remember objects. Research using latent variable modeling identifies a domain-general visual recognition ability (called o) that reflects correlations among different visual tasks and categories. We measure associations between a psychometrically-sensitive measure of o and a neurometrically-sensitive measure of visual sensitivity to shape. We report evidence for distributed neural correlates of o using functional and anatomical regions-of-interest (ROIs) as well as whole brain analyses. Neural selectivity to shape is associated with o in several regions of the ventral pathway, as well as additional foci in parietal and premotor cortex. Multivariate analyses suggest the distributed effects in ventral cortex reflect a common mechanism. The network of brain areas where neural selectivity predicts o is similar to that evoked by the most informative features for object recognition in prior work, showing convergence of 2 different approaches on identifying areas that support the best object recognition performance. Because o predicts performance across many visual tasks for both novel and familiar objects, we propose that o could predict the magnitude of neural changes in task-relevant areas following experience with specific task and object category.


Blockade of Myd88 signaling by a novel MyD88 inhibitor prevents colitis-associated colorectal cancer development by impairing myeloid-derived suppressor cells.
In cancer, myeloid-derived suppressor cells (MDSCs) are known to escape the host immune system by developing a highly suppressive environment. However, little is known about the molecular mechanism behind MDSC-mediated tumor cell evasion of the immune system. Toll-like receptor (TLR) signaling elicited in the tumor microenvironment has the potential to induce MDSC differentiations in different organs. Therefore, MDSC elimination by blocking the action of myeloid differentiation factor 88 (MyD88), which is a key adaptor-signaling molecule that affects TLR activity, seems to be an ideal tumor immunotherapy. Previous studies have proven that blocking MyD88 signaling with a novel MyD88 inhibitor (TJ-M2010-5, synthesized by Zhou's group) completely prevented colitis-associated colorectal cancer (CAC) development in mice. In the present study, we investigated the impact of the novel MyD88 inhibitor on the number, phenotype, and function of MDSC in the mice model of CAC. We showed that CAC growth inhibition was involved in diminished MDSC generation, expansion, and suppressive function and that MDSC-mediated immune escape was dependent on MyD88 signaling pathway activation. MyD88 inhibitor treatment decreased the accumulation of CD11b+Gr1+ MDSCs in mice with CAC, thereby reducing cytokine (GM-CSF, G-CSF, IL-1β, IL-6 and TGF-β) secretion associated with MDSC accumulation, and reducing the expression of molecules (iNOS, Arg-1 and IDO) associated with the suppressive capacity of MDSCs. In addition, MyD88 inhibitor treatment reduced the differentiation of MDSCs from myeloid cells and the suppressive capacity of MDSCs on the proliferation of activated CD4+ T cells in vitro. MDSCs are primary cellular targets of a novel MyD88 inhibitor during CAC development. Our findings prove that MyD88 signaling is involved in the regulation of the immunosuppressive functions of MDSCs. The novel MyD88 inhibitor TJ-M2010-5 is a new and effective agent that modulates MyD88 signaling to overcome MDSC suppressive functions, enabling the development of successful antitumor immunotherapy.


[Variations in activity and sexual dimorphism of central nervous neurons in the rat in the course of postnatal development].
Processes of growth and differentiation of the neurons are based on adequate metabolic activities of the karyoplasm and cytoplasm and measurable at the volume of the cell nucleus. Furthermore, they are affected by metabolic activities related to special neuronal functions. Studies of neurons related to the Nuclei arcuatus, amygdaloideus medialis, amygdaloideus corticalis and amygdaloideus basolateralis (Pars lateralis of the Nucleus amygdaloideus basalis) as well as to the external granular layer (Lamina granularis externa, Lamina II) of the parietal cortex of female and male Wistar rats resulted in distinct karyovolumetrically verifiable variations of the neuronal activities during the postnatal development (between the 5th and 60th day after birth). The variations of the neuronal activities are characterized by their nuclear specifity and indicate a significant sexual dimorphism, which also is of nuclear specifity. The nuclear specifity of the neuronal activity and the variations of the activities are understood as a total of differentiated developmental rhythms and performances of the studied neurons during the postnatal development. The sexual dimorphism, reflected in the nuclear cell volume resp. in the neuronal activity, is finally related to the sexual specificity of the differentiation of the central nervous system.


Pulmonary metastases from cervical cancer in Sri Lanka.
Cervical cancer is the second commonest malignancy in Sri Lankan women. The records of 2075 patients treated for cervical cancer from 1989 to 1993 were reviewed. Thirty-eight patients (1.8%) developed pulmonary lesions consistent with metastases. The median age at the time of presentation with metastases was 49.8 (range 24-73) years. Ten patients (26.3%) had pulmonary metastases at presentation. Twenty-eight (73.7%) developed metastases during follow-up. By the end of 2 years 27 (96.4%) of these patients had developed pulmonary metastases. The median time from diagnosis of cervical cancer to the detection of pulmonary metastases was 9 months. The commonest histological cell type was the large cell non-keratinising squamous carcinoma. Nine (23.7%) of these patients were asymptomatic. Two patients had lung metastases on initial staging chest X-ray while the other seven were detected during routine 3-monthly surveillance chest X-rays as follow up of primary treatment. This emphasises the importance of incorporating routine surveillance chest X-ray as part of the regular follow up. All patients with pulmonary metastases had abnormal shadows in chest X-rays. Nodular lesions were the commonest radiological findings. Local disease was controlled in 17 (55.3%) of the patients who developed metastases during follow-up, while 11 (28.9%) had active disease. There were 24 patients with spread to other sites at the time of diagnosis of pulmonary metastases. The discovery of effective chemotherapy agents is anticipated.


Photoplethysmography and nociception.
Photoplethysmography (PPG), i.e. pulse oximetric wave, is a non-invasive technique that is used in anaesthesia monitoring primarily to monitor blood oxygenation. The PPG waveform resembles that of the arterial blood pressure but instead of pressure it is related to the volume changes in the measurement site and hence contains information related to the peripheral blood circulation, including skin vasomotion, which is controlled by the sympathetic nervous system. Because of this link, skin vasomotor response and PPG amplitude response have been associated with nociception under general anaesthesia. Recently, there has been interest in monitoring nociception during general anaesthesia. In many of the published studies, PPG waveform information has been included. The focus of this topical review is to provide an overview on the information embedded in the PPG waveform especially in the context of the autonomic nervous system and analgesia monitoring.


[Treatment of avascular necrosis of the femoral head by lesions clearance, compact bone grafting, and porous tantalum rod implantation].
To study the effectiveness of avascular necrosis of the femoral head treated by lesions clearance, Between March 2008 and May 2010, 14 patients (16 compact bone grafting, and porous tantalum rod implantation. hips) with avascular necrosis of the femoral head were treated by lesions clearance, compact bone grafting, and implantation of porous tantalum rod. Of 15 cases, 13 were male (15 hips) and 1 was female (1 hip) with a median age of 42.2 years (range, 18-73 years), including traumatic in 1 case (1 hip), alcoholic in 4 cases (4 hips), and steroid-induced in 9 cases (11 hips); 3 hips were at Association Research Circulation Osseous (ARCO) stage I and 13 hips were at ARCO stage II. The Harris score was 51.89 +/- 12.42, and the X-ray score was 31.88 +/- 4.03. All the cases were diagnosed by X-ray films and MRI. The median disease duration was 2.5 years (range, 6 months to 7 years). All the patients accepted the operation of lesions clearance by slotting at the neck of femur, then, compact bone grafting, and implantation of porous tantalum rod were performed. The affected limb could not bear weight loading at 1-3 months after operation and partly bear weight loading after 3 months of operation. Primary healing of incision was achieved in all patients and no complication occurred. The patients were followed up 24 months on average (range, 13-36 months). Two patients underwent total hip arthroplasty at 4 months and 2 years respectively because of even worsened pain and collapsed femoral heads; 12 patients achieved obvious pain relief with a survival rate 87.5% (14/16). The postoperative Harris score was 84.89 +/- 17.96, showing significant difference when compared with preoperative score (t = -8.038, P = 0.001). The X-ray examination showed definite ossification, increased density, regular arrangement of the trabeculae and no collapsed femoral head. The X-ray score was 32.19 +/- 6.57, showing no significant difference when compared with preoperative score (t = -2.237, P = 0.819). Lesions clearance, compact bone grafting, and implantation of porous tantalum rod for avascular necrosis of the femoral head have a good short-term clinical result.


Correlation of Real Time PCR Cycle Threshold Cut-Off with Bordetella pertussis Clinical Severity.
Bordetella pertussis testing performed using real-time polymerase chain reaction (RT-PCR) is interpreted based on a cycle threshold (Ct) value. At Public Health Ontario Laboratories (PHOL), a Ct value <36 is reported as positive, and Ct values ≥36 and <40 are reported as indeterminate. PHOL reported indeterminate results to physicians and public health units until May 2012, after which these results were only reported to physicians. We investigated the association between Ct value and disease symptom and severity to examine the significance of indeterminate results clinically, epidemiologically and for public health reporting. B. pertussis positive and indeterminate RT-PCR results were linked to pertussis cases reported in the provincial Integrated Public Health Information System (iPHIS), using deterministic linkage. Patients with positive RT-PCR results had a lower median age of 10.8 years compared to 12.0 years for patients with indeterminate results (p = 0.24). Hospitalized patients had significantly lower Ct values than non-hospitalized patients (median Ct values of 20.7 vs. 31.6, p<0.001). The proportion of patients reporting the most indicative symptoms of pertussis did not differ between patients with positive vs. indeterminate RT-PCR results. Taking the most indicative symptoms of pertussis as the gold-standard, the positive predictive value of the RT-PCR test was 68.1%. RT-PCR test results should be interpreted in the context of the clinical symptoms, age, vaccination status, prevalence, and other factors. Further information on interpretation of indeterminate RT-PCR results may be needed, and the utility of reporting to public health practitioners should be re-evaluated.


Responses to donepezil in Alzheimer's disease and Parkinson's disease.
Alzheimer's disease is the most common cause of dementia, but Parkinson's disease also shows dementia in the later stages. Donepezil is a cholinesterase inhibitor used for the treatment of Alzheimer's disease. Variable responses to this drug suggest that Alzheimer's disease is clinically heterogeneous. In the clinical trial of tacrine, a first developed cholinesterase inhibitor, three cases markedly improved and, several years later, they were pathologically confirmed as dementia with Lewy bodies (DLB). In recent years, another cholinesterase inhibitor, rivastigmine, has also been reported to be effective for patients with DLB by a placebo-controlled, double-blind, multicenter study. Parkinson's disease with dementia, which is known to fulfill the pathological criteria of DLB, also shows a favorable response to donepezil. In some cases, not only does cognitive function improve, but also parkinsonism. Both DLB and Parkinson's disease with dementia show characteristic CBF patterns: While the parietal and temporal lobes are involved in Alzheimer's disease, the occipital lobe is additionally affected in these diseases. Alzheimer's disease and Parkinson's disease have been considered discrete disease entities. However, viewed from the aspects of response to donepezil treatment and CBF patterns, both diseases overlapped. A brain SPECT may be a useful tool to detect such treatable conditions.


Incidence, laboratory diagnosis and predictors of tracheobronchial tuberculosis in patients with pulmonary tuberculosis in Chongqing, China.
Tracheobronchial tuberculosis (TBTB) is reported in 10-40% of patients with pulmonary tuberculosis (PTB). Due to its non-specific presentation, the diagnosis and management are frequently delayed. The aim of the present study was to investigate the incidence, predictors and laboratory diagnosis of concomitant TBTB and PTB in Chongqing, China. Bronchoscopy was performed in all patients with newly diagnosed or relapsed PTB in order to detect TBTB between January 2018 and April 2019 in a sub-tertiary hospital in Chongqing, China. The clinical characteristics and laboratory data were analyzed to identify predictors and determine the diagnostic yield of TBTB. A total of 341 (31.4%) of the 1,085 patients with PTB who underwent the bronchoscopic examination presented with concomitant TBTB. The parameters of female sex [odds ratio (OR)=2.57], clinical symptoms (OR=6.26) and atelectasis (OR=4.3) were independent predictors of TBTB. Cough (OR=32.48) and atelectasis (OR=3.14) were independent predictors of TBTB-associated tracheobronchial stenosis. The diagnostic yields of sputum smear, bronchial brush smear, sputum culture, GeneXpert Mycobacterium tuberculosis/rifampicin resistance (GX) using sputum, GX using brushings and in bronchial brush culture used for the diagnosis of TBTB were 44.2, 44.2, 63.5, 57.7, 71.2 and 75%, respectively. GX brushings had higher diagnostic yields compared with sputum or brush smears; however, there was no significant difference between sputum/brushings cultures and GX with sputum. The incidence of TBTB in PTB was 31.4% in Chongqing, China. The parameters of female sex, atelectasis and cough were the major predictors of concomitant TBTB and associated tracheobronchial stenosis. Although GX is an accurate and rapid test to detect TBTB, additional laboratory techniques should also be adopted to improve diagnostic yields in the detection of TBTB in patients with PTB.


Levodopa and monoamine oxidase inhibitor combination therapy. A controlled clinical trial.
During a long-term double-blind study, which began February 1985, we have treated 16 patients with Morbus Parkinson or Parkinson's syndrome with deprenyl or identically appearing placebo tablets. The aim of the study is to ascertain whether a reduction of other antiparkinsonian medication, especially Madopar, can be achieved with deprenyl, in order to minimize the known late undesirable collateral effects ("on-off"-phenomena, dyskinesias). The criteria used in evaluation of the course of disease are the clinical-neurological findings as well as a series of motor performance tests. The results to date indicate that the dose of Madopar could be reduced in 7 of the 16 patients. Two of these patients were receiving Madopar alone, while 5 had been given anti-cholinergics in addition. In one female patient the dose of Madopar had to be reduced due to the development of dyskinesias. It is noteworthy that the psychological condition of the patients remained constant. There was no increase in side-effects, e.g. headaches, dizziness, nausea, etc. with administration of the study substance. In 3 patients with longstanding Parkinson's disease treated with Madopar or Nacom, who were not included in the study, the doses of the above drugs could be maintained or reduced by addition of deprenyl.