Supplemental use of antioxidant vitamins and subsequent risk of cognitive decline and dementia.
There are conflicting reports about the potential role of vitamin antioxidants in preventing and/or slowing the progression of various forms of cognitive impairment including Alzheimer's disease (AD). We examined longitudinal data from the Canadian Study of Health and Aging, a population-based, prospective 5-year investigation of the epidemiology of dementia among Canadians aged 65+ years. Our primary objective was to examine the association between supplemental use of antioxidant vitamins and subsequent risk of significant cognitive decline (decrease in 3MS score of 10 points or more) among subjects with no evidence of dementia at baseline (n=894). We also explored the relationship between vitamin supplement use and incident vascular cognitive impairment (VCI; including a diagnosis of vascular dementia, possible AD with vascular components and VCI but not dementia), dementia (all cases) and AD. After adjusting for potential confounding factors assessed at baseline, subjects reporting a combined use of vitamin E and C supplements and/or multivitamin consumption at baseline were significantly less likely (adjusted OR 0.51; 95% CI 0.29-0.90) to experience significant cognitive decline during a 5-year follow-up period. Subjects reporting any antioxidant vitamin use at baseline also showed a significantly lower risk for incident VCI (adjusted OR 0.34, 95% CI 0.13-0.89). A reduced risk for incident dementia or AD was not observed. Our findings suggest a possible protective effect for antioxidant vitamins in relation to cognitive decline but randomized controlled trials are required for confirmation.


New insights into plant salt acclimation: the roles of vesicle trafficking and reactive oxygen species signalling in mitochondria and the endomembrane system.
In this study, we investigated the cellular and molecular mechanisms that regulate salt acclimation. The main objective was to obtain new insights into the molecular mechanisms that control salt acclimation. Therefore, we carried out a multidisciplinary study using proteomic, transcriptomic, subcellular and physiological techniques. We obtained a Nicotiana tabacum BY-2 cell line acclimated to be grown at 258 mM NaCl as a model for this study. The proteomic and transcriptomic data indicate that the molecular response to stress (chaperones, defence proteins, etc.) is highly induced in these salt-acclimated cells. The subcellular results show that salt induces sodium compartmentalization in the cell vacuoles and seems to be mediated by vesicle trafficking in tobacco salt-acclimated cells. Our results demonstrate that abscisic acid (ABA) and proline metabolism are crucial in the cellular signalling of salt acclimation, probably regulating reactive oxygen species (ROS) production in the mitochondria. ROS may act as a retrograde signal, regulating the cell response. The network of endoplasmic reticulum and Golgi apparatus is highly altered in salt-acclimated cells. The molecular and subcellular analysis suggests that the unfolded protein response is induced in salt-acclimated cells. Finally, we propose that this mechanism may mediate cell death in salt-acclimated cells.


Function and organization in dysgenic cortex. Case report.
Cerebral dysgenesis is a subject of interest because of its relationship to cerebral development and dysfunction and to epilepsy. The authors present a detailed study of a 16-year-old boy who underwent surgery for a severe seizure disorder. This patient had dysgenesis of the right hemisphere, which was composed of a giant central frontoparietal nodular gray matter heterotopia with overlying large islands of cortical dysplasia around a displaced central fissure. Exceptional insight into the function, biochemistry, electrophysiology, and histological structure of this lesion was obtained from neurological studies that revealed complementary information: magnetic resonance (MR) imaging, [18]fluoro-2-deoxy-D-glucose positron emission tomography (PET), functional PET scanning, proton MR spectroscopic (1H-MRS) imaging, intraoperative cortical mapping and electrocorticography, in vitro electrophysiology, and immunocytochemistry. These studies demonstrated compensatory cortical reorganization and showed that large areas of heterotopia and cortical dysplasia in the central area may retain normal motor and sensory function despite strikingly altered cytoarchitectonic organization and neuronal metabolism. Such lesions necessitate appropriate functional imaging studies prior to surgery and cortical mapping to avoid creating neurological deficits. Integrated studies, such as PET, 1H-MRS imaging, cortical mapping, immunocytochemistry, and electrophysiology may provide information on the function of developmental disorders of cerebral organization.


Interleukin-1 alpha producing synovial sarcoma with prolonged fever: a case report.
The patient had a synovial sarcoma of the monophasic fibrous type accompanied by prolonged spike fever. Wide excision of the tumor resulted in the disappearance of her fever. The tumor cells showed interleukin-1 alpha (IL-1 alpha) expression immunohistochemically. IL-1 alpha cDNA was detected in the tumor by RT-PCR, the sequences of which were identical with those of normal human IL-1 alpha molecules. These results indicated that IL-1 alpha, one of the fever-inducing cytokines, was expressed by sarcoma cells in the present case, which were thought to be a causative factor of the fever.


BLOOD GROUPS OF CHIMPANZEES: DEMONSTRATED WITH ISOIMMUNE SERUMS.
Of five chimpanzees injected with blood of other chimpanzees in Freund's adjuvant, three produced antiserums for simian blood factors designated A(c), B(c), and C(c), respectively. Factors Ac and Bc determine four blood groups which were distributed among 60 chimpanzees in conformity with the triple-allele hypothesis. Factor C(c) appears to belong to an independent blood group system. All three simian blood factors are distributed independently of sex. An antithetical relation exists between the simian blood factor A(c) and blood factor N(v), the latter being a blood factor shared by all human N cells. Since the simian blood factors A(c) and B(c) are also related, the three blood factors A(c), B(c), and N(v) must belong to one and the same blood group system, which is named the V-A-B blood group system of chimpanzees. The V-A-B blood group system of chimpanzees appears to be the counterpart of the M-N-S blood group system of man.


Oxidative stress and antioxidant defence responses in two marine copepods in a high CO2 experiment.
We collected samples for oxidative stress and antioxidants in a high CO2 mesocosm experiment for two weeks, focussing on two common crustacean copepods Calanus finmarchicus and Temora longicornis. The samples were collected during a field experiment campaign studying responses of plankton communities to future ocean acidification (OA), off the Norwegian coast south of Bergen. The main results showed that there were species-specific differences between Temora and Calanus, especially in antioxidant defences (glutathione system) and oxidative stress (lipid peroxidation and reduced:oxidised glutathione ratio). Regular monitoring of chlorophyll a and jellyfish abundances taking place during the field campaign revealed that both chl a and predators may have affected the eco-physiological response. Antioxidant and oxidative stress levels are known to respond sensitively to both the food quality and quantity and the predator pressure, apart from environmental (i.e., abiotic) changes. Calanus was more robust towards OA, perhaps due to its high tolerance to a wide range of vertical physical-chemical conditions. Both top-down and bottom-up factors seem to play a role for the outcome of copepod responses to future ocean acidification.


Synapses lacking astrocyte appear in the amygdala during consolidation of Pavlovian threat conditioning.
There is growing evidence that astrocytes, long held to merely provide metabolic support in the adult brain, participate in both synaptic plasticity and learning and memory. Astrocytic processes are sometimes present at the synaptic cleft, suggesting that they might act directly at individual synapses. Associative learning induces synaptic plasticity and morphological changes at synapses in the lateral amygdala (LA). To determine whether astrocytic contacts are involved in these changes, we examined LA synapses after either threat conditioning (also called fear conditioning) or conditioned inhibition in adult rats by using serial section transmission electron microscopy (ssTEM) reconstructions. There was a transient increase in the density of synapses with no astrocytic contact after threat conditioning, especially on enlarged spines containing both polyribosomes and a spine apparatus. In contrast, synapses with astrocytic contacts were smaller after conditioned inhibition. This suggests that during memory consolidation astrocytic processes are absent if synapses are enlarging but present if they are shrinking. We measured the perimeter of each synapse and its degree of astrocyte coverage, and found that only about 20-30% of each synapse was ensheathed. The amount of synapse perimeter surrounded by astrocyte did not scale with synapse size, giving large synapses a disproportionately long astrocyte-free perimeter and resulting in a net increase in astrocyte-free perimeter after threat conditioning. Thus astrocytic processes do not mechanically isolate LA synapses, but may instead interact through local signaling, possibly via cell-surface receptors. Our results suggest that contact with astrocytic processes opposes synapse growth during memory consolidation.


Properties of natural animal gamma-interferons and peculiarities of their action.
According to new biotechnology natural gamma-IFNs of swine and cattle as well as of laboratory animals (rabbits, rats, mice) were obtained. By trials in vitro and in vivo the preparations of swine and cattle gamma-IFNs have been tested. It was shown, that in vitro and in vivo functional activity of phagocytes (monocytes and neutrophils) sharply increased. There were increased phagocytic number, phagocytic index, bactericidal action, including functional reserve, the difference between spontaneous and stimulated by Staphylococcus antigen levels of bactericidity. Additional treatment by gamma-IFNs of animals after immunization by colibacteriosis vaccine increased antibody genesis 3-8 times in comparison with the control, but these titers were more stable during two months after revaccination. Besides antiviral activity, preparations of these gamma-IFNs had antibactericidal and antitoxic action of wide spectrum of specificity. The studied preparations are perspective means at usage in infectious pathology of animals, leukoses, immunodeficiencies.


A complex regulatory network controls aerobic ethanol oxidation in Pseudomonas aeruginosa: indication of four levels of sensor kinases and response regulators.
In addition to the known response regulator ErbR (former AgmR) and the two-component regulatory system EraSR (former ExaDE), three additional regulatory proteins have been identified as being involved in controlling transcription of the aerobic ethanol oxidation system in Pseudomonas aeruginosa. Two putative sensor kinases, ErcS and ErcS', and a response regulator, ErdR, were found, all of which show significant similarity to the two-component flhSR system that controls methanol and formaldehyde metabolism in Paracoccus denitrificans. All three identified response regulators, EraR (formerly ExaE), ErbR (formerly AgmR) and ErdR, are members of the luxR family. The three sensor kinases EraS (formerly ExaD), ErcS and ErcS' do not contain a membrane domain. Apparently, they are localized in the cytoplasm and recognize cytoplasmic signals. Inactivation of gene ercS caused an extended lag phase on ethanol. Inactivation of both genes, ercS and ercS', resulted in no growth at all on ethanol, as did inactivation of erdR. Of the three sensor kinases and three response regulators identified thus far, only the EraSR (formerly ExaDE) system forms a corresponding kinase/regulator pair. Using reporter gene constructs of all identified regulatory genes in different mutants allowed the hierarchy of a hypothetical complex regulatory network to be established. Probably, two additional sensor kinases and two additional response regulators, which are hidden among the numerous regulatory genes annotated in the genome of P. aeruginosa, remain to be identified.


Coupled optofluidic ring laser for ultrahigh-sensitive sensing.
Ultrahigh sensitivity is achieved in a new active sensor structure: coupled optofluidic ring laser. The sensor consists of one ring laser and one optofluidic tube. The emission intensity of the multimode whispering gallery resonance from the coupled ring laser is strongly modulated. By using the optofluidic tube as the sensing element, and monitoring the envelope shift of the modulated lasing spectrum, we achieved a sensitivity of 5930 nm/RIU, which is two orders of magnitude higher than a conventional ring resonator sensor.


A single 80 mg intravenous gentamicin dose prior to prostate needle biopsy does not reduce procedural infectious complications.
Rates of infectious complications continue to increase following transrectal ultrasound guided prostate needle biopsy (TRUS PNB). Administration of a parenteral antibiotic at time of procedure represents one potential prophylaxis strategy. The efficacy of this practice remains incompletely defined. Our institutional TRUS PNB database was reviewed to identify consecutive men undergoing a biopsy over a 48-month period. The peri-operative intravenous antibiotic regimen (when used) included gentamicin 80 mg administered intravenously (IV) 30 minutes prior to biopsy. The incidence of infections post-biopsy was compared between patients receiving oral alone versus IV plus oral antibiotic prophylaxis. 182 of 522 men (34.9%) included in this study received peri-procedural IV gentamicin at time of TRUS PNB, with a significant increase in utilization during the study time period (p <0.001). In total, 39 patients (7.5%) developed an infectious complication post-biopsy. No differences in infection rates were observed between patients receiving only oral prophylaxis (27 of 340, 7.9%) versus those receiving oral with IV gentamicin (12 of 182, 6.6%) (p = 0.73). In this 4-year cohort analysis, a single peri-procedural dose of 80 mg of intravenous gentamicin failed to confer a reduction in infectious complications following prostate needle biopsy. Such data underscore the need to better understand the dose, route, and type of antimicrobial therapy to limit procedural infections.


Familial prion disease with a novel 144-bp insertion in the prion protein gene in a Basque family.
Three members of a Basque family carrying a novel six R2 octapeptide repeat 144-bp insertion in the prion protein gene (PRNP) showed a slowly progressive dementia associated with cerebellar signs, myoclonic jerks, and seizures. Although postmortem examination revealed only focal and minimal spongiform degeneration in one subject with a 4-year course, significant astrogliosis and neuronal loss were associated with pronounced spongiform degeneration in the patient with a duration of symptoms of 10 years. Prion protein (PrP)-immunoreactive patches with a unique morphology were present in the molecular layer of the cerebellum in both subjects. Western blot analysis demonstrated the presence of protease-resistant prion protein (PrPres) with the same characteristics (size and ratio of the three differently glycosylated isoforms) of that found in typical sporadic Creutzfeldt-Jakob disease (CJD129M/M, PrPres type 1). The amount of PrPres correlated with presence and severity of spongiform degeneration in the cerebral cortex. The findings suggest that a relatively low rate of PrPres deposition is the cause of the lack of spongiform degeneration in subjects carrying a 144-bp insertion in PRNP. The presence of PrP-immunoreactive patches with unique morphology in the molecular layer of the cerebellum is a hallmark of certain prion encephalopathies with insertional mutations and is useful in the diagnosis of this subtype of human prion disease.


Platelet-derived growth factor-dependent cellular transformation requires either phospholipase Cgamma or phosphatidylinositol 3 kinase.
Although it has been well established that constitutive activation of receptor tyrosine kinases leads to cellular transformation, the signal relay pathways involved have not been systematically investigated. In this study we used a panel of platelet-derived growth factor (PDGF) beta receptor mutants (beta-PDGFR), which selectively activate various signal relay enzymes to define which signaling pathways are required for PDGF-dependent growth of cells in soft agar. The host cell line for these studies was Ph cells, a 3T3-like cell that expresses normal levels of the beta-PDGFR but no PDGF-alpha receptor (alpha-PDGFR). Hence, this cell system can be used to study signaling of mutant alphaPDGFRs or alpha/beta chimeras. We constructed chimeric receptors containing the alphaPDGFR extracellular domain and the betaPDGFR cytoplasmic domain harboring various phosphorylation site mutations. The mutants were expressed in Ph cells, and their ability to drive PDGF-dependent cellular transformation (growth in soft agar) was assayed. Cells infected with an empty expression vector failed to grow in soft agar, whereas introduction of the chimera with a wild-type beta-PDGFR cytoplasmic domain gave rise to a large number of colonies. In contrast, the N2F5 chimera, in which the binding sites for phospholipase Cgamma (PLC-gamma), RasGTPase-activating protein, phosphatidylinositol 3 kinase (PI3K), and SHP-2 were eliminated, failed to trigger proliferation. Restoring the binding sites for RasGTPase-activating protein or SHP-2 did not rescue the PDGF-dependent response. In contrast, receptors capable of associating with either PLC-gamma or PI3K relayed a growth signal that was comparable to wild-type receptors in the soft agar growth assay. These findings indicate that the PDGF receptor activates multiple signaling pathways that lead to cellular transformation, and that either PI3K or PLC-gamma are key initiators of such signal relay cascades.


Coating of titanium alloy with soluble laminin-5 promotes cell attachment and hemidesmosome assembly in gingival epithelial cells: potential application to dental implants.
The formation of a biological seal around the transmucosal portion of dental implants may be crucial for the long-term success of these therapies. Data to date suggest that the gingival epithelium attaches to dental implants through the formation of hemidesmosomes. Biochemical and genetic data indicate that the laminin isoform, laminin-5, a component of basement membranes, plays a crucial role in the assembly and maintenance of hemidesmosomes. We report the use of soluble laminin-5 as a biological coating of titanium-alloy to promote cell attachment of the gingival epithelial cell line, IHGK. Monoclonal antibodies reactive with laminin-5 depleted the coating solution of all cell attachment activity and blocked cell attachment to laminin-5-coated disks. Immunodepletion with antibodies to fibronectin had no effect. Finally, we demonstrate that IHGK cells assembled hemidesmosomes within 24 h of attachment to laminin-5-coated titanium alloy but not to the titanium alloy alone. These results suggest that soluble laminin-5 may have clinical applications as a dental implant coating to promote the formation of a biological seal.


New π-extended catecholato complexes of Pt(ii) and Pd(ii) containing a benzothienobenzothiophene (BTBT) moiety: synthesis, electrochemical behavior and charge transfer properties.
Benzothienobenzothiophene (BTBT) and derivatives have received increasing attention as organic field-effect transistor materials and molecular conductors. This report presents the first synthesis of metal complexes involving a BTBT moiety, which was achieved by complexation of 2,2'-bipyridyl complexes of Pt(ii) and Pd(ii) with dihydroxy-substituted BTBT (1) as a new π-extended catecholato ligand (tBu2Bpy = 4,4'-di-tert-butyl-2,2'-dipyridyl). The resulting complexes M(tBu2Bpy)(O2BTBT) (M = Pt (3Pt) and Pd (3Pd)) were characterized by UV-vis spectroscopy, density functional theory (DFT) calculations, and cyclic voltammetry. The electron donating ability of BTBT was substantially enhanced upon including two oxygen substituents followed by metal coordination. This enabled chemical oxidation of 3Pt and 3Pd with a mild chemical oxidant (ferrocenium hexafluorophosphate) and formation of the one-electron-oxidized state. While 3Pt and 3Pd exhibited an absorption band originating from a catecholate → Bpy ligand-to-ligand charge transfer transition typical of this class of catecholato complexes, the radical cations exhibited a unique π-π* intramolecular charge transfer (ICT) transition absorption in which the π and π* orbitals were the newly incorporated benzothienothiophene-based donor and semiquinonato-based acceptor, respectively. The BTBT+ skeleton was electronically divided into two sites by the present chemical modification. The ICT properties of the complexes were found to be modulated by varying the metal ions. These findings offer a new approach to molecular design for (semi)conducting materials using optical properties.


Vid22p, a novel plasma membrane protein, is required for the fructose-1,6-bisphosphatase degradation pathway.
Fructose-1,6-bisphosphatase (FBPase), an important enzyme in the gluconeogenic pathway in Saccharomyces cerevisiae, is expressed when cells are grown in media containing a poor carbon source. Following glucose replenishment, FBPase is targeted from the cytosol to intermediate Vid (vacuole import and degradation) vesicles and then to the vacuole for degradation. Recently, several vid mutants that are unable to degrade FBPase in response to glucose were identified. Here, we present VID22, a novel gene involved in FBPase degradation. VID22 encodes a glycosylated integral membrane protein that localizes to the plasma membrane. Newly synthesized Vid22p was found in the cytoplasm and then targeted to the plasma membrane independent of the classical secretory pathway. A null mutation of VID22 failed to degrade FBPase following a glucose shift and accumulated FBPase in the cytosol. Furthermore, the majority of FBPase remained in a proteinase K sensitive compartment in the Deltavid22 mutant, implying that VID22 is involved in FBPase transport from the cytosol to Vid vesicles. By contrast, starvation-induced autophagy and peroxisome degradation were not impaired in the Deltavid22 mutant. This strain also exhibited the proper processing of carboxypeptidase Y and aminopeptidase I in the vacuole. Therefore, Vid22p appears to play a specific role in the FBPase trafficking pathway.


Inclusion filters: a class of self-dual connected operators.
In this paper, we define a connected operator that either fills or retains the holes of the connected sets depending on application-specific criteria that are increasing in the set theoretic sense. We refer to this class of connected operators as inclusion filters, which are shown to be increasing, idempotent, and self dual (gray-level inversion invariance). We demonstrate self duality for 8-adjacency on a discrete Cartesian grid. Inclusion filters are defined first for binary-valued images, and then the definition is extended to grayscale imagery. It is also shown that inclusion filters are levelings, a larger class of connected operators. Several important applications of inclusion filters are demonstrated-automatic segmentation of the lung cavities from magnetic resonance imagery, user interactive shape delineation in content-based image retrieval, registration of intravital microscopic video sequences, and detection and tracking of cells from these sequences. The numerical performance measures on 100-cell tracking experiments show that the use of inclusion filter improves the total number of frames successfully tracked by five times and provides a threefold reduction in the overall position error.


Rheumatoid arthritis and the risk of preterm birth.
During pregnancy, many diseases are correlated with different adverse outcomes. In turn, pregnancy affects the body, leading to increased disease susceptibility. This interplay between diseased states and pregnancy outcomes is illustrated in the effect of the chronic autoimmune disorder, rheumatoid arthritis (RA), and the adverse outcome, preterm birth (PTB). RA is a systemic disorder characterized by inflammation of the joints and other body organs. Joint pain and swelling are the most prominent manifestations of RA during pregnancy. However, the exact role of RA on PTB among pregnant women has yet to be established. This review highlighted the immunologic mechanisms involved in PTB in pregnant patients with RA. The immune cell population in pregnant women with RA exhibited higher activity of macrophages, dendritic cells, neutrophils, helper T (Th) 1 cells, and Vδ1 cells, but lower activity of CD4 + CD25high T regulatory (CD24 + CD25high Treg ), Th2, and Vδ2 cells. Increased pro-inflammatory cytokines IL-6, TNF-α, and IFN-γ and decreased anti-inflammatory cytokines IL-12 and IL-10 are also exhibited by pregnant patients with RA. This review also discussed factors that may predict the risk of PTB in RA. These include disease activity and severity of RA, laboratory parameters (cytokines and immune cell population), and sociodemographic factors such as ethnicity, smoking, alcohol intake, and the level of education. Current findings on the underlying immunological mechanisms of RA can help identify possible strategies to prevent PTB.


Exploring Barriers and Facilitators of Adherence to Artemisinin-Based Combination Therapies for the Treatment of Uncomplicated Malaria in Children in Freetown, Sierra Leone.
Medication adherence is an essential step in the malaria treatment cascade. We conducted a qualitative study embedded within a randomized controlled trial comparing the adherence to the recommended dosing of two artemisinin-based combination therapies (ACT) to treat uncomplicated malaria in Freetown, Sierra Leone. This study explored the circumstances and factors that influenced caregiver adherence to the ACT prescribed for their child in the trial. In-depth interviews were conducted with 49 caregivers; all interviews were recorded, transcribed, and translated. Transcripts were coded and aggregated into themes, applying a thematic content approach. We identified four key factors that influenced optimal treatment adherence: (1) health system influences, (2) health services, (3) caregivers' experiences with malaria illness and treatment, and (4) medication characteristics. Specifically, caregivers reported confidence in the health system as facilities were well maintained and care was free. They also felt that health workers provided quality care, leading them to trust the health workers and believe the test results. Ease of medication administration and perceived risk of side effects coupled with caregivers' prior experience treating malaria influenced how medications were administered. To ensure ACTs achieve maximum effectiveness, consideration of these contextual factors and further development of child-friendly antimalarials are needed.


What influences success in family medicine maternity care education programs? Qualitative exploration.
To ascertain how program leaders in family medicine characterize success in family medicine maternity care education and determine which factors influence the success of training programs. Qualitative research using semistructured telephone interviews. Purposive sample of 6 family medicine programs from 5 Canadian provinces. Eighteen departmental leaders and program directors. Semistructured telephone interviews were conducted with program leaders in family medicine maternity care. Departmental leaders identified maternity care programs deemed to be "successful." Interviews were audiorecorded and transcribed verbatim. Team members conducted thematic analysis. Participants considered their education programs to be successful in family medicine maternity care if residents achieved competency in intrapartum care, if graduates planned to include intrapartum care in their practices, and if their education programs were able to recruit and retain family medicine maternity care faculty. Five key factors were deemed to be critical to a program's success in family medicine maternity care: adequate clinical exposure, the presence of strong family medicine role models, a family medicine-friendly hospital environment, support for the education program from multiple sources, and a dedicated and supportive community of family medicine maternity care providers. Training programs wishing to achieve greater success in family medicine maternity care education should employ a multifaceted strategy that considers all 5 of the interdependent factors uncovered in our research. By paying particular attention to the informal processes that connect these factors, program leaders can preserve the possibility that family medicine residents will graduate with the competence and confidence to practise full-scope maternity care.


Feasibility of A-mode ultrasound based intraoperative registration in computer-aided orthopedic surgery: A simulation and experimental study.
A fast and accurate intraoperative registration method is important for Computer-Aided Orthopedic Surgery (CAOS). A-mode ultrasound (US) is able to acquire bone surface data in a non-invasive manner. To utilize A-mode US in CAOS, a suitable registration algorithm is necessary with a small number of registration points and the presence of measurement errors. Therefore, we investigated the effects of (1) the number of registration points and (2) the Ultrasound Point Localization Error (UPLE) on the overall registration accuracy. We proposed a new registration method (ICP-PS), including the Iterative Closest Points (ICP) algorithm and a Perturbation Search algorithm. This method enables to avoid getting stuck in the local minimum of ICP iterations and to find the adjacent global minimum. This registration method was subsequently validated in a numerical simulation and a cadaveric experiment using a 3D-tracked A-mode US system. The results showed that ICP-PS outperformed the standard ICP algorithm. The registration accuracy improved with the addition of ultrasound registration points. In the numerical simulation, for 25 sample points with zero UPLE, the averaged registration error of ICP-PS reached 0.25 mm, while 1.71 mm for ICP, decreasing by 85.38%. In the cadaver experiment, using 25 registration points, ICP-PS achieved an RMSE of 2.81 mm relative to 5.84 mm for the ICP, decreasing by 51.88%. The simulation approach provided a well-defined framework for estimating the necessary number of ultrasound registration points and acceptable level of UPLE for a given required level of accuracy for intraoperative registration in CAOS. ICP-PS method is suitable for A-mode US based intraoperative registration. This study would facilitate the application of A-mode US probe in registering the point cloud to a known shape model, which also has the potential for accurately estimating bone position and orientation for skeletal motion tracking and surgical navigation.


Femcoat, a novel eggshell protein in Drosophila: functional analysis by double stranded RNA interference.
In Drosophila oogenesis, follicle cells derived from somatic tissue surround the oocyte and play key roles in generating properly polarized oocytes. During the later steps of oogenesis, follicle cells are involved in secretion of proteins that make the eggshell, an essential protective layer for the oocyte. Although studies on the signaling processes to make polarized oocytes have been progressed very far, studies on the mechanisms for eggshell formation is not clear yet. To elucidate the underlying mechanism in eggshell formation, we used a differential display screen to isolate genes that are specifically expressed during the later stages of oogenesis, and isolated a novel gene, Femcoat. Femcoat encodes a putative chorion membrane protein that contains many highly charged residues and has a putative signal peptide. Femcoat is expressed specifically in the follicle cells with a punctate staining pattern typical of secreted proteins, and becomes cross-linked heavily at the final steps of oogenesis. To identify the developmental role of Femcoat in eggshell formation, we performed an inducible double stranded RNA mediated interference (dsRNAi) method to specifically reduce Femcoat expression during oogenesis in adult flies. Electron microscopy analysis of egg chambers from these flies showed defects in chorion formation. These pieces of evidence demonstrated that Femcoat is necessary for eggshell formation, especially during chorion synthesis. Our results demonstrate that inducible dsRNAi analysis can be effective in determining the developmental function of novel genes.


The Incidence and Prevalence of Systemic Lupus Erythematosus in New York County (Manhattan), New York: The Manhattan Lupus Surveillance Program.
The Manhattan Lupus Surveillance Program (MLSP) is a population-based registry designed to determine the prevalence of systemic lupus erythematosus (SLE) in 2007 and the incidence from 2007 to 2009 among residents of New York County (Manhattan), New York, and to characterize cases by race/ethnicity, including Asians and Hispanics, for whom data are lacking. We identified possible SLE cases from hospital records, rheumatologist records, and administrative databases. Cases were defined according to the American College of Rheumatology (ACR) classification criteria, the Systemic Lupus International Collaborating Clinics (SLICC) classification criteria, or the treating rheumatologist's diagnosis. Rates among Manhattan residents were age-standardized, and capture-recapture analyses were conducted to assess case underascertainment. By the ACR definition, the age-standardized prevalence and incidence rates of SLE were 62.2 and 4.6 per 100,000 person-years, respectively. Rates were ∼9 times higher in women than in men for prevalence (107.4 versus 12.5) and incidence (7.9 versus 1.0). Compared with non-Hispanic white women (64.3), prevalence was higher among non-Hispanic black (210.9), Hispanic (138.3), and non-Hispanic Asian (91.2) women. Incidence rates were higher among non-Hispanic black women (15.7) compared with non-Hispanic Asian (6.6), Hispanic (6.5), and non-Hispanic white (6.5) women. Capture-recapture adjustment increased the prevalence and incidence rates (75.9 and 6.0, respectively). Alternate SLE definitions without capture-recapture adjustment revealed higher age-standardized prevalence and incidence rates (73.8 and 6.2, respectively, by the SLICC definition and 72.6 and 5.0 by the rheumatologist definition) than the ACR definition, with similar patterns by sex and race/ethnicity. The MLSP confirms findings from other registries on disparities by sex and race/ethnicity, provides new estimates among Asians and Hispanics, and provides estimates using the SLICC criteria.


Chemical Profile of Essential Oils of Selected Lamiaceae Plants and In Vitro Activity for Varroosis Control in Honeybees (Apis mellifera).
The most significant ectoparasitic mite of honeybees, Varroa destructor, has a detrimental effect on bee health and honey output. The principal strategy used by the control programs is the application of synthetic acaricides. All of this has resulted in drug resistance, which is now a major worry for beekeeping. As a result, research on alternate products and techniques for mite management is now required. The aim of this study was to determine whether essential oils (EOs) extracted from botanical species of Lamiacae, typical of the Calabria region of Southern Italy, could reduce the population of the mite V. destructor. Among the best-known genera of the Lamiaceae family are oregano, rosemary and thyme, whose EOs were employed in this study. By steam distillation, the EOs were extracted from Origanum vulgare subsp. viridulum (Martrin-Donos) Nyman, Thymus capitatus Hoffmanns. and Link, Thymus longicaulis C.Presl and Salvia rosmarinus Schleid. plant species harvested directly on the Calabrian territory in their balsamic time. Each EO went to the test in vitro (contact toxicity) against V. destructor. Fifty adult female mites, five for each EO and the positive and negative control, were used in each experimental replicate. The positive controls comprised five individuals treated to Amitraz dilute in acetone, and the negative controls included five individuals exposed to acetone alone. To create the working solution to be tested (50 μL/tube), the EOs were diluted (0.5 mg/mL, 1 mg/mL, 2 mg/mL and 4 mg/mL) in HPLC-grade acetone. After 1 h of exposure, mite mortality was manually assessed. Origanum vulgare subsp. viridulum, Thymus capitatus and Thymus longicaulis were the EOs with the highest levels of efficiency at 2 mg/mL, neutralizing (dead + inactivated), 94%, 92% and 94% of parasites, respectively. Salvia rosmarinus EO gave a lower efficacy, resulting in a percentage of 38%. Interestingly, no adverse effects were highlighted in toxicity tests on honeybees. These results show that these OEs of the Lamiaceae family have antiparasitic action on V. destructor. Therefore, they could be used, individually or combined, to exploit the synergistic effect for a more sustainable control of this parasite mite in honeybee farms.


Simple lattice model of self-assembling metal-organic layers of pyridyl-substituted porphyrins and copper on Au(111) surface.
A simple lattice model of metal-organic adsorption layers self-assembling on a Au(111) surface and based on pyridyl-substituted porphyrins differing in the number of functional groups and their position has been proposed. The model has been parameterized using DFT methods. The ground state analysis of the considered model demonstrates the variety of surface-confined metal-organic networks (SMONs) containing square, linear, and discrete elements appearing in the adsorption layer depending on the partial pressure of the components. The SMONs comprising more symmetrical molecules with a greater number of pyridyl substituents in the porphyrin core exhibit more diverse phase behavior. Structures of the phase diagrams were verified at nonzero temperatures using Grand Canonical Monte Carlo simulations. It was found that the continuous SMONs have higher thermal stability at relatively low partial pressures of the organic component, while the linear and discrete SMONs are more thermally stable at high pressure. Depending on the partial pressure of the organic component, thermal destruction of continuous SMONs occur either through the formation of defects/islands having structures of the linear SMONs, or through the sublimation of individual structural elements. Melting of linear SMONs reveals the appearance of 2D pores or islands of a purely organic phase. The latter fact is confirmed by the experimentally observed coexistence of these phases.


Measles virus protein-specific IgM, IgA, and IgG subclass responses during the acute and convalescent phase of infection.
The availability of new generation serological assays allowed re-evaluation of the antibody response to measles virus. IgM, IgA, total IgG, and IgG subclass responses were studied to the three major immunogenic measles virus proteins: the fusion protein (F), haemagglutinin (H), and nucleoprotein (N). Plasma samples were obtained from clinically diagnosed measles cases (n = 146) in Khartoum (Sudan) within a week after onset of the rash. Convalescent phase samples were collected from 32 of 117 laboratory-confirmed measles cases at different time points after onset of rash. Glycoprotein-specific IgM, IgG, and IgA antibody levels correlated well to the N-specific response. For IgG and IgA, responses to F were higher than to H. IgA antibody levels were undetectable in about one third of the laboratory-confirmed cases during the acute phase, but positive in all patients tested 1-4 weeks after infection. IgM levels declined rapidly and were lost 3-6 months after infection. IgA levels declined slowly during the first year but did not return to background levels during the subsequent 2 years. IgG avidity maturation was detected during a 3-6 month period after infection. The predominant IgG subclasses during the acute phase were IgG(1) and IgG(3). The latter was lost in the convalescent phase, while the IgG(4) isotype showed a slight rise afterwards. Interestingly, acute phase IgG(3) and IgA responses were associated, and were only detected in samples with high IgG. This study provides a comprehensive perspective on the antibody response to wild-type measles virus infection.


Bodily cues of sex and emotion can interact symmetrically: Evidence from simple categorization and the garner paradigm.
Although much research has investigated how multiple sources of social information derived from faces are processed and integrated, few studies have extended this investigation to bodies. The current study addressed this gap by investigating the nature of the interaction between bodily cues of sex and emotion. Using the Garner paradigm, participants recruited from a university student participant pool categorized the sex or the emotional expression (happy and angry in Experiment 1 [n = 194], angry and sad in Experiment 2 [n = 129]) of bodies across two block types. In orthogonal blocks, participants categorized bodies along one dimension while the second dimension was varied (e.g., categorizing the sex of happy and angry bodies), whereas in control blocks the second dimension was held constant (e.g., categorizing the sex of only happy bodies). Responses were analyzed in two ways. Comparing response times across blocks revealed Garner interference (overall faster categorization in the control than in the orthogonal block) of sex on emotion perception and emotion on sex perception in Experiment 1 but not Experiment 2. Comparing condition level responses in orthogonal blocks indicated that sex cues moderated emotion categorization and emotion cues moderated sex categorization in both experiments. A symmetrical interaction between bodily sex and emotion cues can be observed in simple categorization as well as in the Garner paradigm, though the presence of Garner interference depended on the valence of the expressions used. Given similar results observed in face processing, finding interactivity in body perception is likely to generalize beyond the study sample. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


How to Harness Big Data for the Benefit of Patients.
IMI is a large public private partnership which has committed Euro 5 Billion from the European Commission, the European Pharmaceutical sector and other partners, to enable and accelerate bringing medical innovation to patients. IMI is now 10 years old and already has changed the ecosystem and way of working in developing innovative medicines across the public/private divide. Big data represents a significant piece of this investment and projects in this area are attempting to provide solutions to major challenges including: 1. Data integration from many sources across many jurisdictions and institutions and which need to be validated with regard to their quality and robustness 2. Data interfaces, for example, between research and clinical data and how to overcome the challenges around data protection and access 3. Data standards and who establishes these and how they are deployed 4. How do we scale and sustain some of the successful pilots to ensure the value of the investment? 5. How do we take advantage of the digital revolution to enable more relevant and accurate data capture in the real world? Much has been done already through IMI projects and beyond and now we need to consolidate through intelligent implementation across the European landscape. With a mixture of generic and disease specific investments, and although many challenges remain, significant progress has been made and examples of success will be described.


Copy number analysis of whole-genome data using BIC-seq2 and its application to detection of cancer susceptibility variants.
Whole-genome sequencing data allow detection of copy number variation (CNV) at high resolution. However, estimation based on read coverage along the genome suffers from bias due to GC content and other factors. Here, we develop an algorithm called BIC-seq2 that combines normalization of the data at the nucleotide level and Bayesian information criterion-based segmentation to detect both somatic and germline CNVs accurately. Analysis of simulation data showed that this method outperforms existing methods. We apply this algorithm to low coverage whole-genome sequencing data from peripheral blood of nearly a thousand patients across eleven cancer types in The Cancer Genome Atlas (TCGA) to identify cancer-predisposing CNV regions. We confirm known regions and discover new ones including those covering KMT2C, GOLPH3, ERBB2 and PLAG1 Analysis of colorectal cancer genomes in particular reveals novel recurrent CNVs including deletions at two chromatin-remodeling genes RERE and NPM2 This method will be useful to many researchers interested in profiling CNVs from whole-genome sequencing data.


Longitudinal Evaluation of the Relationship Between Low Socioeconomic Status and Incidence of Chronic Obstructive Pulmonary Disease: Korean Genome and Epidemiology Study (KoGES).
Socioeconomic status (SES) is a strong determinant in the development of various diseases. We evaluated the relationship between SES and the incidence of chronic obstructive pulmonary disease (COPD) by using a community-based cohort data. Four-year follow-up data of 6341 adults (aged ≥ 40 years), who underwent serial pulmonary function test were analyzed. Incidence of COPD in the participants was defined as the absence of airflow obstruction compatible with COPD (pre-bronchodilator forced expiratory volume in 1 second/forced vital capacity ratio of <0.7) at baseline but documentation of airflow obstruction in serial testing. SES of patients was divided into quartiles according to household income and educational level. Multivariate logistic regression analyses were performed to estimate the association between SES and COPD incidence. A total of 280 (4.4%) patients developed COPD during the follow-up. The proportion of subjects with lowest education (elementary school) and lowest household income levels (1st quartile) was significantly higher in the COPD group than in the non-COPD group (37.9% vs 29.5%, p<0.011 and 48.4% vs 30.8%, p<0.001, respectively). Logistic regression analysis revealed that education level of elementary school was independently associated with COPD incidence after adjustment for sex, age, body mass index, white blood cell count, residence area, and occupation (odds ratio 1.879, 95% confidence interval 1.124-3.141, p=0.016). In the general population, educational level of elementary school was an independent risk factor for COPD among the components comprising SES. Our results indicate that the implementation of preventive strategies for COPD in those with low educational status could be beneficial.


Purification and characterization of the membrane-bound complex of an ABC transporter, the histidine permease.
The bacterial histidine permease, an ABC transporter, from Salmonella typhimurium is composed of a membrane-bound complex, HisQMP2, comprising two hydrophobic subunits (HisQ and HisM), two copies of an ATP-hydrolyzing subunit, HisP, and a soluble receptor, HisJ. We describe the purification and characterization of HisQMP2 using a 6-histidines extension at the carboxy terminus of HisP [HisQMP2(his6)]. The purification is rapid and effective, giving a seven-fold purification with a yield of 85 and 98% purity. Two procedures are described differing in the detergent used (decanoylsucrose and octylglucoside, respectively) and in the presence of phospholipid. HisQMP2(his6) has ATPase and transport activities upon reconstitution into proteoliposomes (PLS). HisQMP2(his6) has a low level ATPase activity (intrinsic activity), which is stimulated to a different extent by the receptor--liganded and unliganded. Its pH optimum is 7.8-8.0, it requires a cation for activity and it displays cooperativity for ATP. The effect of various ATP analogs was analyzed. Determination of the molecular size of HisQMP2(his6) indicates that it is a monomer. The permeability properties of two kinds of reconstituted PLS preparations are described.


[Ethics and medicine in Michel Foucault: the humanistic dimension of medicine derived from a genealogy of morality].
The article presents the results of a doctoral dissertation defended at the Universidad de Salamanca, based on Foucault's final decade of writings. If Foucault's goal in writing The History of Sexuality was to fashion a genealogy of ethics, my goal in analyzing this book, along with his other writings, is to demonstrate his last contribution to the history of medicine. He moves from a conception of power over others towards a conception of power over oneself, an exclusive terrain of ancient Greek morality. As a thinker who tries to understand today's problems by going to their roots, Foucault develops less a history than a philosophy of history. Considered an anti-humanist, he leaves us with a portrait of a wholly ethical-humanistic medicine.


Comment on "Thermal compaction of the intrinsically disordered protein tau: entropic, structural, and hydrophobic factors" by A. Battisti, G. Ciasca, A. Grottesi and A. Tenenbaum, Phys. Chem. Chem. Phys., 2017, 19, 8435.
In a recent article, A. Battisti et al., Phys. Chem. Chem. Phys., 2017, 19, 8435, results from SAXS measurements, metadynamic trajectories and classic MD trajectories at different temperatures have been used to study the temperature-induced compaction of the intrinsically disordered protein tau. The analysis, though technically sound, does not provide a clear explanation of hydrophobic interaction strengthening on increasing the temperature and its relationship with the population increase of secondary structural elements. Actually, hydrophobic interaction is driven by the gain in translational entropy of water molecules associated with the decrease in solvent-excluded volume due to chain compaction. The magnitude of this solvent-excluded volume effect increases with temperature in water because the density of water is almost temperature-independent due to the strength of H-bonds. Since α-helix formation leads to a significant decrease in the solvent-excluded volume, the connection with hydrophobic interaction and chain compaction emerges directly.


Delivering the Thinking Healthy Programme for perinatal depression through volunteer peers: a cluster randomised controlled trial in Pakistan.
The Thinking Healthy Programme (THP), which is endorsed by WHO, is an evidence-based intervention for perinatal depression. We adapted THP for delivery by volunteer peers (laywomen from the community) to address the human resource needs in bridging the treatment gap, and we aimed to assess its effectiveness and cost-effectiveness in Rawalpindi, Pakistan. In this cluster randomised controlled trial, we randomly assigned 40 village clusters (1:1) to provide either THP peer-delivered (THPP) and enhanced usual care (EUC; intervention group) or EUC only (control group) to the participants within clusters. These villages were randomly selected from eligible villages by an independent researcher. The participants were pregnant women aged 18 years or older who had scored at least 10 on the Patient Health Questionnaire-9 (PHQ-9), who we recruited from households within communities in Rawalpindi, Pakistan. The research teams who were responsible for recruiting trial participants were masked to treatment allocations. Participants attended follow-up visits at 3 and 6 months after childbirth. The primary outcomes were the severity of depressive symptoms (assessed by PHQ-9 score) and the prevalence of remission (defined as a PHQ-9 score of less than 5) in participants with available data 6 months after childbirth, which was assessed by researchers who were masked to treatment allocations. We analysed outcomes by intention to treat, adjusting for covariates that were defined a priori or that showed imbalance at baseline. The trial was registered with ClinicalTrials.gov, number NCT02111915. Between April 15 and July 30, 2014, we randomly selected 40 of 46 eligible village clusters for assessment, as per sample size calculations. Between Oct 15, 2014, and Feb 25, 2016, we identified and screened 971 women from 20 village clusters that had been randomly assigned to the THPP and EUC group and 939 women from 20 village clusters that had been randomly assigned to the EUC only group. In the intervention group, 79 women were ineligible for inclusion, 11 women refused screening, 597 women screened negative on the PHQ-9, and one woman did not consent to participate. In the control group, 75 women were ineligible for inclusion, 14 women refused screening, 562 women screened negative on the PHQ-9, and one woman did not consent to participate. We enrolled 283 (29%) women in the intervention group and 287 (31%) women in the control group. At 6 months after childbirth, 227 (80%) women in the THPP and EUC group and 226 (79%) women in the EUC only group were assessed for the primary outcome. The severity of depression (assessed by PHQ-9 scores; standardised mean difference -0·13, 95% CI -0·31 to 0·06; p=0·07) and prevalence of remission (49% in the intervention group vs 45% in the control group; prevalence ratio 1·12, 95% CI 0·95 to 1·29; p=0·14) did not significantly differ between the groups 6 months after childbirth. There was no evidence of significant differences in serious adverse events between the groups. THPP had no effect on symptom severity or remission from perinatal depression at 6 months after childbirth, but we found that it was beneficial on some other metrics of severity and disability and that it was cost-effective. THPP could be a step towards use of an unused human resource to address the treatment gap in perinatal depression. National Institute of Mental Health (USA).


Successful endonasal dacryocystorhinostomy in a patient with Wegener's granulomatosis.
Wegener's granulomatosis (WG) is one form of idiopathic autoimmune vasculitis. The disease has a predilection for the upper and lower respiratory tracts (lungs, nose, sinus), and kidneys. WG may be systemic, severe, and potentially lethal, but it may also be limited to the otolaryngological area or to the eyes and the orbits. Obstruction of the lacrimal pathway is a possible complication of the disease that affects approximately 7% of patients with WG. It usually occurs as a direct extension of sinonasal disease and typically is a late manifestation. Management of such a condition is generally viewed as difficult. We report the case of a patient with a quiescent WG limited to the otolaryngological area. This patient presented a bilateral obstruction of the nasolacrimal ducts caused by bilateral extensive adhesions in the nasal cavity. Because she had several episodes of left-side acute dacryocystitis which necessitated several courses of broad-spectrum antibiotics, she successfully underwent an endonasal endoscopic dacryocystorhinostomy using a diode laser and powered instrumentation. The authors describe the clinical case, the surgical technique, and review the literature.


Biomechanical comparison of polyaxial-type locking plates and a fixed-angle locking plate for internal fixation of distal femur fractures.
To test the stability to axial loading of 2 new polyaxial locking screw-plate designs and analyze different angles of screw insertion. The noncontact bridging (NCB) polyaxial locking plate (Zimmer) and the POLYAX plate (DePuy) were compared with a fixed-angle less invasive stabilization system (LISS; Synthes). Twenty-five synthetic femurs were divided into 5 groups and assigned fixation with the LISS plate (group I), POLYAX plate (groups IIA and IIB), or NCB plate (groups IIIA and IIIB). The polyaxial constructs were divided into parallel and crossed distal condylar screw configurations. Each construct was tested under axial loading and stressed to failure at a displacement rate of 5 mm/min with a preload of 100 N. Outcome measurements included stiffness, load to failure, peak force, and mode of failure. All LISS and POLYAX constructs failed by plastic deformation of the plate, whereas 9 of 10 NCB constructs failed by an intra-articular lateral condyle fracture. No failures occurred at the screw-plate interface in either polyaxial constructs. Load to failure of the LISS was 33% greater than the parallel POLYAX (P < 0.01) and 24% greater than the crossed POLYAX (P < 0.01). Load to failure of NCB (parallel and crossed) were 24% greater than the parallel POLYAX (P < 0.01 and P < 0.01, respectively) and 15% greater than the crossed POLYAX (P < 0.01 and P = 0.02, respectively). The POLYAX also had significantly lower stiffness and peak force compared with the LISS and NCB. There was no difference between the LISS and NCB with regard to stiffness, load to failure, and peak force. Parallel and crossed polyaxial constructs showed no difference in stiffness or failure loads. There were no failures of either polyaxial screw-plate interface despite large forces and screw angle did not affect the overall strength of these constructs, supporting the biomechanical soundness of both polyaxial device designs under axial loading. However, the POLYAX supported smaller loads compared with the LISS and NCB while under axial loading. In addition, the mode of failure of the NCB plate, creating an intra-articular fracture propagating from the distal posterior screw hole, may be of some concern. Additional testing is needed to determine the clinical importance of the demonstrated differences among these plate designs.


[Immunodiagnosis of schistosomiasis mansoni with a low parasitic load].
Presently, the schistosomiasis mansoni with low worm burden is frequent, thus immunologic assays of interest for the field diagnosis of Schistosoma mansoni light infections were evaluated here. Assays not assessed before (group I) and those requiring better validation (group II) for the screening of light infections were included in this study. In the group I, the immunofluorescence assays for the detection of IgM antibodies to worm antigens (IgM IFAw) and IgG antibodies to egg antigens (IgG IFAe) gave high levels of sensitivity, specificity, efficiency and predictive value of positive. However, the immunoenzymatic assays for the detection of IgM antibodies to worm antigens (IgM ELISAw) and to egg antigens (IgM ELISAe) had lower levels than the former assays. The assays from the group II designed mostly for the detection of IgG antibodies to same parasite antigens showed good diagnostic performance. The data obtained here contributed to evidenciate at least three category of immunoassays, and we concluded that those from the category I are suitable for seroepidemiologic purposes by keeping their diagnostic features unchanged even varying significantly the intensity of S. mansoni infection.


Relationships, partnerships and politics in the lives of the urban poor in AIDS-afflicted Swaziland.
This paper seeks to better understand how poor urban families caring for children are able to access help from beyond the kinship group in a setting where HIV prevalence has risen to over 40%. The fieldwork shows that livelihoods were affected by multiple shocks and families were struggling to provide education, health care, clothing and food for all children in their care. Orphan status or gender did not appear to affect children's access to education. Families turned to neighbours, churches and the work place for assistance. Neighbours varied in their response and were rarely able to give material assistance. Churches were seen solely as sources of emotional and spiritual support. Work-place relationships provided material as well as emotional support. Government and NGO assistance was limited and poorly coordinated at the beginning of the fieldwork and criteria for selection was unclear to many respondents. Some respondents felt marginalised from community structures. Using respondents' experiences when trying to access education and health care, the author illustrates the importance of the quality of relationships and partnerships at all levels (international, national and local) as well as the need for more synergy between top-down and bottom-up approaches. A much stronger coordinating role for government officials and the development of public welfare support are seen as critical to alleviate the poverty in which AIDS thrives.


CircTMCO3 Promotes Gastric Cancer Progression by Regulating miR-577/RAB14 Axis.
Growing evidence indicated that circRNAs played major roles in the progression of human cancer. Nevertheless, the molecular mechanism and effects of circTMCO3 in GC are still unclear. First, qRT-PCR was used to evaluate the levels of circTMCO3 from GC tissues, GC cells, normal tissues and gastric epithelial cells. Then, the GC cells were transfected to analyze the proliferation, migration and invasion of GC cells by MTT, colony formation and transwell assays. Next, the expressions of miR-577 and RAB14 in GC tissues and cells were examined by qRT-PCR following transfection. The target interaction of circTMCO3-miR-577 and miR-577-RAB14 was explored by the dual-luciferase reporter and RNA pull-down assays. In the end, the growth and viability of GC cells were detected by MTT, colony formation and transwell assays, respectively, following the transfection of GC cells. In this research, we found circTMCO3 expressions are significantly up-regulated in GC tissues and cells compared with the normal tissues and gastric epithelial cells. We discovered that the knockdown of circTMCO3 remarkably inhibits the proliferation, migration and invasion of GC cells. Besides, through the prediction of binding sites between circTMCO3, miR-577 and RAB14, we discovered miR-577 is a target of circTMCO3 while RAB14 is a target gene of miR-577. Finally, the results demonstrate the overexpression of miR-577 and the silence of RAB14 could inhibit the effects of circTMCO3 on proliferation, migration and invasion in GC cells. circTMCO3 accelerated the growth and migration of GC cells by regulating miR-577/RAB14 axis.


Clinical importance of plasma cholinesterase for the anaesthetist.
Plasma cholinesterase is a glycoprotein synthesized in the liver and is found in plasma, liver, intestinal mucosa and other tissues. Six percent to 7% of patients in most surgical populations have an abnormal plasma cholinesterase activity and about 65% of all cases of prolonged neuromuscular blockade following succinylcholine are due to genetic factors. This review focuses on the causes and clinical significance of plasma cholinesterase for the hydrolyses of succinylcholine. Diagnosis and treatment of prolonged response to succinylcholine in phenotypically normal patients, heterozygous abnormal patients and patients homozygous for the atypical gene is mentioned. Also presented is the relationship between plasma cholinesterase and the new relaxant mivacurium, and bambuterol, a prodrug to terbutaline. Additionally, the recent developments in the identification of the plasma cholinesterase genotypes are presented.


Modeling the architecture and dynamics of hematopoiesis.
Hematopoiesis is a multistep process that results in the production of a variety of blood cells with different morphologies and diverse functions. All of these cells have their origin in hematopoietic stem cells Hematopoietic Stem Cells (HSCs) that replicate slowly to self-renew and give rise to progeny cells that proceed along the path of differentiation. The process is complex with the cells responding to a wide variety of cytokines and growth factors. We discuss a model of hematopoiesis based on stochastic cell behavior. Multiple compartments are introduced to keep track of each cell division process and increasing differentiation. Despite its simplicity, the model is able to account for the salient features of hematopoiesis and is compatible with considerable and independent experimental data. The model is applicable to hematopoiesis across mammals and can be used to understand the dynamics of various disorders both in humans and in animal models.


The effects of L-theanine, caffeine and their combination on cognition and mood.
L-Theanine is an amino acid found naturally in tea. Despite the common consumption of L-theanine, predominantly in combination with caffeine in the form of tea, only one study to date has examined the cognitive effects of this substance alone, and none have examined its effects when combined with caffeine. The present randomised, placebo-controlled, double-blind, balanced crossover study investigated the acute cognitive and mood effects of L-theanine (250 mg), and caffeine (150 mg), in isolation and in combination. Salivary caffeine levels were co-monitored. L-Theanine increased 'headache' ratings and decreased correct serial seven subtractions. Caffeine led to faster digit vigilance reaction time, improved Rapid Visual Information Processing (RVIP) accuracy and attenuated increases in self-reported 'mental fatigue'. In addition to improving RVIP accuracy and 'mental fatigue' ratings, the combination also led to faster simple reaction time, faster numeric working memory reaction time and improved sentence verification accuracy. 'Headache' and 'tired' ratings were reduced and 'alert' ratings increased. There was also a significant positive caffeine x L-theanine interaction on delayed word recognition reaction time. These results suggest that beverages containing L-theanine and caffeine may have a different pharmacological profile to those containing caffeine alone.


Utilization and Short-Term Outcomes of Computer Navigation in Unicompartmental Knee Arthroplasty.
The use of navigation remains a controversial topic in knee arthroplasty. The purpose of this study is to evaluate current rates of utilization of navigation in unicompartmental knee arthroplasty (UKA) in the United States, as well as the incidence of short-term complications and operative times between navigated and non-navigated UKA. A query of the National Surgical Quality Improvement Project (NSQIP) database was used to identify cases of primary UKA during years 2006-2017. Additional common procedural terminology (CPT) codes were used to identify cases in which navigation was utilized. Operative time, length of stay, and short-term outcomes were compared. Propensity score matching was used to minimize differences in demographics and comorbidities between the navigation and non-navigation cohorts. A total of 10,586 cases of UKA were identified; 343 of these cases (3.2%) utilized navigation. The unadjusted rate of any complication for the entire cohort was 3.6%. Navigated UKA had mean operative times 8 minutes longer than non-navigated UKA (92.1 min vs. 84.3 min; p<0.001). There was no difference in overall complication rates between the matched navigated (3.5%) and non-navigated (3.2%) cohorts (p=0.65). There was no difference in rates of readmission (0.31% vs. 0.58%; p=0.31), reoperation (0.29% vs. 0.29%; p=1.00), and mean length of stay (1.3 ± 1.6 days vs. 1.2 ± 1.9 days; p=0.15). UKA utilizing navigation had a mean operative time 8 minutes longer than non-navigated UKA. We found no difference in rates of short-term complications, readmission, reoperation, or mean length of stay between navigated and non-navigated UKA.Level of Evidence: III.


c-Myb and C/EBPβ regulate OPN and other senescence-associated secretory phenotype factors.
Tumorigenesis results from the convergence of cell autonomous mutations and corresponding stromal changes that promote tumor cell growth. Senescent cells, which secrete a plethora of pro-tumorigenic factors termed the senescence-associated secretory phenotype (SASP), play an important role in tumor formation. Investigation into SASP regulation revealed that many but not all SASP factors are subject to NF-kB and p38MAPK regulation. However, many pro-tumorigenic SASP factors, including osteopontin (OPN), are not responsive to these canonical pathways leaving the regulation of these factors an open question. We report that the transcription factor c-Myb regulates OPN, IL-6, and IL-8 in addition to 57 other SASP factors. The regulation of OPN is direct as c-Myb binds to the OPN promoter in response to senescence. Further, OPN is also regulated by the known SASP regulator C/EBPβ. In response to senescence, the full-length activating C/EBPβ isoform LAP2 increases binding to the OPN, IL-6, and IL-8 promoters. The importance of both c-Myb and C/EBPβ is underscored by our finding that the depletion of either factor reduces the ability of senescent fibroblasts to promote the growth of preneoplastic epithelial cells.


Zinc, pregnancy and parturition.
The role of zinc in the nutrition of pregnant women and its relations to prenatal growth and parturition are reviewed. Zinc deficiency (ZD) affects fetal growth and development both in experimental animals and in man. The teratogenicity of zinc deficiency was widely demonstrated in animals and is also evident in humans. Alcohol intoxication potentiates the effects of ZD in animals. Plasma zinc levels decrease during pregnancy and apparently an adequate and continuous intake of zinc is required for a normal embryonic development. The zinc content of amniotic fluid seems to be related with fetal growth but its value as an indicator of embryonic development is controversial. Zinc deficiency also affects adversely parturition. Mild zinc deficiency may affect a large number of pregnant women, being potentially harmful to the mother and the fetus. This situation requires the screening of high-risk groups, the definition of adequate dietary intakes for each population, and the supplementation with zinc when deficits are detected.


National medical response to mass disasters in the United States. Are we prepared?
Preparing for a resuscitation response to mass disasters, such as major earthquakes or industrial disasters, requires revisions of present local, regional, and national disaster plans. These should include the following: (1) life-supporting first aid and basic rescue capability of the lay public; (2) advanced trauma life support and advanced (heavy) rescue capability brought quickly to the scene from local and surrounding (regional) emergency medical services systems; and (3) trauma hospitals sending medical resuscitation teams to, and receiving casualties from, the disaster scene for resuscitative surgery and definitive care. Local and regional everyday emergency medical services systems would respond first. The armed forces should help, at least for transport and security. We propose that the National Disaster Medical System replace its civil defense model with an emergency medical services model, designed to mobilize rapid support for local emergency medical services systems from regional, state, and national resources. Coordination should be by one federal agency, such as the Federal Emergency Management Agency, which, however, needs to focus more on resuscitation through physician input.


Dental public health post-graduate trainees in the US: Experiences, challenges, and opportunities-A qualitative study.
The goal of this study was to explore challenges and opportunities that dental public health (DPH) residents and recent graduates experienced during and after their residency training programs in the US. In this qualitative study, to recruit participants, study invitations were distributed to 93 DPH postgraduate trainees via social media, email, and an online DPH nationwide course in 2019. Semi-structured in-depth interviews were conducted through Zoom audioconference. The interviews were conducted until thematic saturation was achieved. The audio-recorded interviews were transcribed and crosschecked to ensure accuracy. The interviews were coded using grounded theory. A qualitative analysis software (ATLAS.ti 8.0) was used to facilitate coding and organizing data extraction from transcripts. Eighteen DPH postgraduate trainees from 12 DPH residency programs participated and completed the interview. DPH trainees had experienced educational and financial challenges, difficulty finding DPH-related jobs after graduation, and a complex board examination preparation process. DPH postgraduate trainees and especially foreign-trained dentists experienced serious challenges during and after their postgraduate residency programs. Opportunities exist to enhance the strength of DPH programs to build a competent DPH workforce.


Management of cardiogenic shock in patients with acute coronary syndromes.
Cardiogenic shock remains a major problem affecting a large proportion of patients with acute coronary syndromes, with a persistent high mortality rate. Although mechanical reperfusion with percutaneous coronary intervention has improved outcomes following acute coronary syndromes, there is limited evidence supporting the other current treatments used to manage patients with cardiogenic shock (intra-aortic balloon pumps, percutaneous left ventricular assist devices and extracorporeal membrane oxygenation). This article looks at these options, assessing current evidence and recent advances. It also discusses areas that still require research to ensure there is improvement in these high-risk patients, such as coordinated regionalised approaches to cardiogenic shock management with multidisciplinary care provided in designated tertiary shock centres.


Recognition of Alzheimer's disease: the 7 Minute Screen.
Because Alzheimer's disease (AD) tends to be underdiagnosed, we developed a brief neurocognitive screening battery to identify AD patients. The 7 Minute Screen consists of four individual tests (orientation, memory, clock drawing, verbal fluency). The screen can be rapidly administered and scored and therefore may be appropriate for use in the primary care setting. This study determined the validity and reliability of the 7 Minute Screen in distinguishing patients with AD from healthy controls. The 7 Minute Screen was administered to 60 consecutive referrals to a memory disorders clinic who were subsequently diagnosed with probable AD and to 60 community-dwelling individuals. Analysis of the combined scores on the four individual tests was used to determine the probability of dementia in each subject. We also evaluated test-retest and inter-rater reliability, as well as the time required to administer the battery. When compared with the normal subjects, the patients with AD were significantly more impaired on each of the four tests included in the 7 Minute Screen. When the four tests were combined into a logistic regression model, the battery correctly diagnosed 92% of the patients with AD and 96% of the normal subjects. The battery performed equally well when only patients with mild and very mild AD were included. Mean time for administration and scoring was 7 minutes 42 seconds. The 7 Minute Screen is a reliable and valid instrument for identifying patients with AD. It appears to be a potentially useful tool for identifying patients with AD in a primary care setting.


Mitochondrial DNA Extraction from Burial Soil Samples at Incremental Distances: A Preliminary Study.
Preservation variance of soil DNA is neglected in the literature, and exceptional cases exaggerate amplification capabilities. This study sought to amplify a short mitochondrial fragment (212 bp) specific to Sus scrofa domesticus from the soil surrounding decomposing pig remains from an open-air locale. Samples collected above the body at incremental distances after 145 days of initial placement yielded pig DNA. A secondary sampling was collected in 2017, approximately 768 days after burial. Inhibition tests corroborated that pig DNA was no longer present in the soil resulting in a loss of original DNA between 145 and 768 days. The results provide evidence that genetic material leaches out radially from the source and DNA fragments longer than 200 bp do not persist in soil for a relatively short timeframe in western Montana. The conclusions support the collection of soil in crime scene investigation procedures within the first few months of decomposition.


Detection of deletions and cryptic translocations in Miller-Dieker syndrome by in situ hybridization.
Fluorescence in situ hybridization (FISH) using two cosmid probes (41A and P13) from the Miller-Dieker syndrome (MDS) critical region in 17p13.3 was performed in a blinded comparison of three MDS patients with submicroscopic deletions and in four normal relatives used as controls. The controls showed both chromosome 17 homologues labeled in 85%-95% of cells, while each patient showed only one homologue labeled in 75%-80% of cells. Two MDS patients with cryptic translocations were also studied. In one case, a patient and her mother had the same der(17) (p+), but the reciprocal product of the translocation could not be identified in the mother by G-banding (i.e., it was a "half-cryptic" translocation). FISH revealed a 3q;17p translocation. The other case involved a patient with apparently normal karyotype. Because a large molecular deletion was found, a translocation involving two G-negative telomeres (i.e., a "full-cryptic" translocation) was postulated. FISH studies on her father and normal brother showed an 8q;17p translocation. These studies demonstrate that in situ hybridization is an efficient method for deletion detection in Miller-Dieker syndrome. More important, parental studies by FISH on patients demonstrating molecular deletions and a normal karyotype may identify cryptic translocation events, which cannot be detected by other molecular genetic strategies. Similar in situ strategies for deletion detection can be developed for other microdeletion syndromes, such as Prader-Willi/Angelman syndrome or DiGeorge syndrome.


On Combination of Hadamard-Encoded Multipulses and Multiplane Wave Transmission in Contrast-Enhanced Ultrasound Imaging.
Contrast-enhanced ultrasound (CEUS) imaging has great potential for use in many new ultrasound clinical applications. We recently proposed a novel CEUS imaging sequence, Hadamard-encoded multipulses (HEM), to improve the signal-to-noise ratio (SNR) and the contrast-to-tissue ratio (CTR) as compared to other classic CEUS methods. HEM increases microbubble responses by using longer coded transmit pulses and the fast polarity change between coded pulses. In this study, we propose to combine the HEM pulse with multiplane wave (MW) imaging technique to further improve CEUS imaging SNR and contrast-to-noise ratio. During MW-HEM transmissions, the microbubbles undergo multiple fast pulse polarity changes, leading to significantly improved microbubble nonlinear responses, and thus further enhanced SNR and CTR as compared to HEM alone or other CEUS sequences. This improvement may facilitate more robust CEUS imaging for deep abdominal organs and the heart.


Renewal of opsin in the photoreceptor cells of the mosquito.
Mosquito rhodopsin is a digitonin-soluble membrane protein of molecular weight 39,000 daltons, as determined by sodium dodecyl sulfate gel electrophoresis. The rhodopsin undergoes a spectral transition from R515-520 to M480 after orange illumination. The visual pigment apoprotein, opsin, is the major membrane protein in the eye. Protein synthesis in the photoreceptor cells occurs in the perinuclear cytoplasm and the newly made protein is transported to the rhabdom. Light adaptation increases the rate of turnover of this rhabdomal protein. The turnover of electrophoretically isolated opsin is also stimulated by light adaptation. The changes observed in protein metabolism biochemically, are consistent with previous morphological observations of photoreceptor membrane turnover. The results agree with the hypothesis that the newly synthesized rhabdomal protein is opsin.


Psychotherapeutic Interventions in Irritable Bowel Syndrome.
Irritable bowel syndrome (IBS) is a frequent functional gastrointestinal disorder. The patients complain about various symptoms like change in bowel habits, constipation or diarrhea, abdominal pain, and meteorism leading to a great reduction in quality of life. The pathophysiology is complex and best explained using the biopsychosocial model encompassing biological, psychological as well as (psycho)social factors. In line with the multitude of underlying factors, the treatment is comprised of a multitude of components. Often, patients start with lifestyle changes and dietary advice followed by medical treatment. However, also psychotherapy is an important treatment option for patients with IBS and should not be restricted to those with psychiatric comorbidities. Several evidence-based psychotherapeutic treatment options exist such as psychoeducation, self-help, cognitive behavioral therapy, psychodynamic psychotherapy, hypnotherapy, mindfulness-based therapy, and relaxation therapy which will be discussed in the present review.


[One-stage reconstruction with the pectoralis major myocutaneous flap for the pharyngectomy].
18 patients with the advanced oropharyngeal cancer from October 1983 to July 1992 were retrospectively studied in our hospital. The blood supply of the pectoralis major myocutaneous flap (PMMF). PMMF came mainly from the pectoral branch of the acromiothoracic artery. The flap area ranged from 15 cm x 10 cm to 3 cm x 3 cm. 3 cases had partial necrosis and 4 cases received prophylactic tracheotomy. The cosmetic and functional restoration was satisfactory in most of the patients. The factors which affected the wound healing were also discussed. The 3 year and 5 year survival rates were 61.5% and 40%, respectively. This paper revealed that the PMMF was the first choice for the defect of the pharyngectomy.


Mammalian RNA Decay Pathways Are Highly Specialized and Widely Linked to Translation.
RNA decay is crucial for mRNA turnover and surveillance and misregulated in many diseases. This complex system is challenging to study, particularly in mammals, where it remains unclear whether decay pathways perform specialized versus redundant roles. Cytoplasmic pathways and links to translation are particularly enigmatic. By directly profiling decay factor targets and normal versus aberrant translation in mouse embryonic stem cells (mESCs), we uncovered extensive decay pathway specialization and crosstalk with translation. XRN1 (5'-3') mediates cytoplasmic bulk mRNA turnover whereas SKIV2L (3'-5') is universally recruited by ribosomes, tackling aberrant translation and sometimes modulating mRNA abundance. Further exploring translation surveillance revealed AVEN and FOCAD as SKIV2L interactors. AVEN prevents ribosome stalls at structured regions, which otherwise require SKIV2L for clearance. This pathway is crucial for histone translation, upstream open reading frame (uORF) regulation, and counteracting ribosome arrest on small ORFs. In summary, we uncovered key targets, components, and functions of mammalian RNA decay pathways and extensive coupling to translation.


Matrix metalloproteinase inhibition decreases ischemia-reperfusion injury after lung transplantation.
Increased microvascular permeability and extravasation of inflammatory cells are key events of lung ischemia-reperfusion (IR) injury. The purpose of this study was to investigate the role of matrix metalloproteinases (MMP) in IR-induced alveolar capillary membrane disruption after experimental lung transplantation. We used a rat model of lung orthotopic transplantation (n = 86) with a prolonged cold ischemic phase. MMP2 and MMP9 were elevated 4 h after the onset of ischemia and further increased during reperfusion. Compared to sham values, the alveolar-capillary membrane permeability increased by 105% and 82.6% after 4 h of ischemia and 2 h or 24 h of reperfusion, respectively. A 4- and 5-fold increase of the infiltration of ischemic tissue by neutrophils was also observed after 2 h and 24 h of reperfusion. The PO2/FIO2 ratio dropped significantly from 244 to 76.6 after 2 h of reperfusion and from 296.4 to 127.6 after 24 h of reperfusion. A nonselective inhibitor of MMP, administered to the rats and added to the preservation solution, reduced significantly the alveolar-capillary leakage, the transmigration of neutrophils and improved gas exchanges in animals submitted to 4 h of ischemia combined with 2 h or 24 h of reperfusion. We conclude that inhibition of MMP attenuates IR injury after experimental lung transplantation.


Integrated analysis of HSP20 genes in the developing flesh of peach: identification, expression profiling, and subcellular localization.
Plant HSP20s are not only synthesized in response to heat stress but are also involved in plant biotic and abiotic stress resistance, normal metabolism, development, differentiation, survival, ripening, and death. Thus, HSP20 family genes play very important and diverse roles in plants. To our knowledge, HSP20 family genes in peach have not yet been characterized in detail, and little is known about their possible function in the development of red flesh in peach. In total, 44 PpHSP20 members were identified in the peach genome in this study. Forty-four PpHSP20s were classified into 10 subfamilies, CI, CII, CIII, CV, CVI, CVII, MII, CP, ER, and Po, containing 18, 2, 2, 10, 5, 1, 1, 2, 1, and 2 proteins, respectively. Among the 44 PpHSP20 genes, 6, 4, 4, 3, 7, 11, 5, and 4 PpHSP20 genes were located on chromosomes 1 to 8, respectively. In particular, approximately 15 PpHSP20 genes were located at both termini or one terminus of each chromosome. A total of 15 tandem PpHSP20 genes were found in the peach genome, which belonged to five tandemly duplicated groups. Overall, among the three cultivars, the number of PpHSP20 genes with higher expression levels in red flesh was greater than that in yellow or white flesh. The expression profiling for most of the PpHSP20 genes in the red-fleshed 'BJ' was higher overall at the S3 stage than at the S2, S4-1, and S4-2 stages, with the S3 stage being a very important period of transformation from a white color to the gradual anthocyanin accumulation in the flesh of this cultivar. The subcellular localizations of 16 out of 19 selected PpHSP20 proteins were in accordance with the corresponding subfamily classification and naming. Additionally, to our knowledge, Prupe.3G034800.1 is the first HSP20 found in plants that has the dual targets of both the endoplasmic reticulum and nucleus. This study provides a comprehensive understanding of PpHSP20s, lays a foundation for future analyses of the unknown function of PpHSP20 family genes in red-fleshed peach fruit and advances our understanding of plant HSP20 genes.


Ammonia-induced activation of p53 in cultured astrocytes: role in cell swelling and glutamate uptake.
Cytotoxic brain edema, due principally to astrocyte swelling, is a major neurological complication of the acute form of hepatic encephalopathy (HE) (acute liver failure, ALF), a condition likely caused by elevated levels of brain ammonia. Potential mediators of ammonia-induced astrocyte swelling include oxidative/nitrosative stress (ONS), the mitochondrial permeability transition (mPT), mitogen-activated protein kinases (MAPKs) and nuclear factor-kappaB (NF-kappaB), since blockade of these factors reduces the extent of astrocyte swelling. As p53, a tumor suppressor protein and transcription factor, is a downstream target of ONS and MAPKs, we examined its potential role in the mechanism of ammonia-induced astrocyte swelling. Astrocytes exposed to NH(4)Cl (5mM) showed increased phosphorylation (activation) of p53((Ser392)) at 1h and such phosphorylation was significantly reduced by inhibitors of MAPKs (ERK1/2, JNK and p38-MAPK), antioxidants (vitamin E, catalase, PBN, desferoxamine, MnTBAP), as well as by L-NAME, an inhibitor of nitric oxide synthase, indicating a key role of oxidative/nitrosative stress and MAPKs in the ammonia-induced activation of p53. Since p53 is known to induce the mPT and to activate NF-kappaB (factors leading to ONS and implicated in ammonia-induced astrocyte swelling), we examined whether inhibition of p53 activation blocked mPT induction, NF-kappaB activation, as well as cell swelling. Pifithrin-alpha (PFT), an inhibitor of p53, blocked these processes. Impairment of astrocytic glutamate uptake is another important feature of HE and hyperammonemia. We therefore examined the potential role of p53 in the ammonia-induced inhibition of glutamate uptake and found that PFT also reversed the ammonia-induced inhibition of glutamate uptake. Our results indicate that a potentially important downstream target of ammonia neurotoxicity is p53, whose activation contributes to astrocyte swelling and glutamate uptake inhibition, processes likely a consequence of ONS derived from the mPT and activation of NF-kappaB.


The role of intraluminal sodium in glucose absorption in vivo.
Active glucose absorption is thought to depend on a gradient of sodium ion concentration across the brush border membrane of intestinal epithelial cells. This concept is generally accepted, although its validity has never been adequately evaluated in the human small intestine in vivo. According to this hypothesis, the rate of glucose absorption should decrease markedly if the luminal sodium concentration is markedly reduced, and glucose absorption against a concentration gradient should cease entirely if luminal sodium is lower than intracellular sodium concentration. In the present series of experiments we were not able to show an important role of intraluminal sodium concentration in the active absorption of glucose from the human, rat, and dog ileum in vivo. Specifically, glucose absorption was minimally reduced or not reduced at all when intraluminal sodium concentration was reduced from 140 to as low as 2.5 mEq/liter. The discrepancy between our results and those of previous workers whose data suggest that removal of intraluminal sodium should markedly inhibit active glucose absorption is not entirely clear, but there are a number of differences in experimental design between most previous studies and our own. Although our data show that active glucose absorption proceeds at a near normal rate even when lumen sodium concentration is reduced below 3 mEq/liter, our results do not disprove the sodium gradient theory because of the theoretic possibility that the microclimate adjacent to the brush border has a high concentration of sodium even when luminal sodium concentration is markedly reduced. The validity of the sodium gradient hypothesis would appear to be critically dependent on such a microclimate.


Dyspepsias among the highlanders of Nigeria: an epidemiological survey.
An epidemiological survey of the dyspepsias in a Nigerian Community drawn from five different local government areas, is described. Analysis of the data obtained from 1,151 respondents (684 males and 467 females) showed that 45.0% of this population had complaints of dyspepsia within the immediate six months period preceeding this study. The relevance of the independent variables as age, sex, marital status, family size, place of abode, number of meals per day, type of staple food consumed, self-medication and presence of melaena stool to the prevalence of dyspepsia was statistically analysed using the Chi-square test method. The family size (P < 0.05), occupational scatter (P < 0.001), type of staple food consumed (P < 0.05), presence of melaena stool (P < 0.01) and indulgence in self-medication (P < 0.001) were found to be the most significant variables. Since the vast majority of subjects with complaints of dyspepsia are to be encountered by general practitioners at the Primary Health Care level, it is hoped that the findings will go a long way towards evolving a more meaningful management strategy for this subset of subjects.


A meta-analysis of gene expression data highlights synaptic dysfunction in the hippocampus of brains with Alzheimer's disease.
Since the world population is ageing, dementia is going to be a growing concern. Alzheimer's disease is the most common form of dementia. The pathogenesis of Alzheimer's disease is extensively studied, yet unknown remains. Therefore, we aimed to extract new knowledge from existing data. We analysed about 2700 upregulated genes and 2200 downregulated genes from three studies on the CA1 of the hippocampus of brains with Alzheimer's disease. We found that only the calcium signalling pathway enriched by 48 downregulated genes was consistent between all three studies. We predicted miR-129 to target nine out of 48 genes. Then, we validated miR-129 to regulate six out of nine genes in HEK cells. We noticed that four out of six genes play a role in synaptic plasticity. Finally, we confirmed the upregulation of miR-129 in the hippocampus of brains of rats with scopolamine-induced amnesia as a model of Alzheimer's disease. We suggest that future research should investigate the possible role of miR-129 in synaptic plasticity and Alzheimer's disease. This paper presents a novel framework to gain insight into potential biomarkers and targets for diagnosis and treatment of diseases.


Synthesis and evaluation of sulfonamide-bearing thiazole as carbonic anhydrase isoforms hCA I and hCA II.
Sulfonamide-bearing thiazole compounds were synthesized and their inhibitory effects on the activity of purified human carbonic anhydrase I and II were evaluated. Human carbonic anhydrase isoenzymes (hCA-I and hCA-II) were purified from erythrocyte cells by affinity chromatography. The inhibitory effects of the 12 synthesized sulfonamide (5a-l) on the hydratase and esterase activities of these isoenzymes (hCA-I and hCA-II) were studied in vitro. In relation to these activities, the inhibition equilibrium constants (Ki) were determined. The results showed that all the synthesized compounds inhibited the CA isoenzyme activity. Among them 5b was found to be the most active (IC50 = 0.35 μM; Ki: 0.33 μM) for hCA I and hCA II.


On failing to understand informed consent.
Many doctors view informed consent as merely a medicolegal concept. This article points out that other discourses are possible and that patients would benefit if doctors were to take a wider view.


Altered isoelectric focusing of alpha 2-macroglobulin from plasma of patients with diabetes mellitus.
Plasma from both type I and type II patients with diabetes mellitus displayed elevated alpha 2-macroglobulin trypsin-binding activity relative to normals. Column isoelectric focusing indicated that the average isoelectric point (pI) of the major form of crude alpha 2-macroglobulin was 6.6, 5.9, and 6.2 for normal, type I and type II subjects, respectively. Focused crude diabetic alpha 2-macroglobulin displayed significantly less recovered trypsin-binding activity relative to controls, particularly above a pI value of 6.0. Following preincubation with trypsin, the crude diabetic alpha 2-macroglobulin displayed a single isoelectric form (pI value of 5.3-5.5) and a substantial increase in recovered activity which were both comparable to normal alpha 2-macroglobulin. Purified alpha 2-macroglobulin from both normal and diabetic subjects displayed similar focusing profiles having a distribution of three forms with a pI value of 5.3-5.4 for the principal form. Trypsin-preincubated samples of purified alpha 2-macroglobulin displayed a single form with a pI value of 5.5-6.0. Preincubation of purified normal or diabetic alpha 2-macroglobulin with a plasma preparation devoid of alpha 2-macroglobulin from normal or diabetic plasma resulted in significantly lowered recovery of activity. All of the above studies suggest that the altered focusing properties observed for crude diabetic alpha 2-macroglobulin are due to components of the plasma rather than to alpha 2-macroglobulin itself.


MicroRNA-29 overexpression by adeno-associated virus suppresses fibrosis and restores muscle function in combination with micro-dystrophin.
Duchenne muscular dystrophy (DMD) is caused by dystrophin deficiency resulting in progressive muscle weakness and fibrotic scarring. Muscle fibrosis impairs blood flow, hampering muscle repair and regeneration. Irrespective of the success of gene restoration, functional improvement is limited without reducing fibrosis. The levels of miR-29c, a known regulator of collagen, are reduced in DMD. Our goal is to develop translational, antifibrotic therapy by overexpressing miR-29c. We injected the gastrocnemius muscle with either self-complementary AAV.CMV.miR-29c or single-stranded AAV.MCK.micro-dystrophin alone or in combination in the mdx/utrn+/- mouse, a DMD mouse model. Treatment of 3-month-old mdx/utrn+/- mice with AAV.miR-29c showed a reduction in collagen and increased absolute and specific force compared with untreated animals, but neither parameter reached WT levels. Combinatorial gene delivery in 3-month-old mdx/utrn+/- mice further decreased fibrosis, and showed a reduction of transcript levels for Col1A, Col3A, fibronectin, and Tgfb1. In addition, absolute and specific force was normalized and equivalent to WT. However, protection against eccentric contraction fell short of WT levels at this time point. When this same mouse model was treated with miR-29c/micro-dystrophin combinatorial therapy at 1 month of age, there was complete normalization of specific and absolute force and protection against eccentric contraction-induced injury was comparable to WT. These findings highlight the potential for miR-29c as an important addition to the armamentarium for translational gene therapy, especially when used in combination with micro-dystrophin in DMD.