Protective Effects of Bromelain against Cadmium-Induced Pulmonary Intoxication in Rats: A Histopathologic and Cytologic Study.
Bromelain is the active substance of pineapple with a variety of therapeutic properties. In this study, the possible protective effects of bromelain were assessed against cadmium acute intratracheal exposure and its bronchopulmonary cytologic and histopathologic consequences. For this purpose, the following treatments were performed on 11 groups of Wistar rats: group 1 was negative control; groups2 and 3 received Cadmium Chloride (CdCl2) 400 µg/rat intratracheally and sampled after 5 and 10 days, respectively; groups4 and 5received bromelain 20 mg/kg orally (PO) from 14 days before until 5 and 10 days after CdCl2 instillation, respectively; groups6 and 7received bromelain 40 mg/kg from 14 days before until 5 and 10 days after CdCl2 instillation, respectively; group 8received bromelain 40 mg/kg for 24 days; groups9 and 10: celecoxib 25 mg/kg PO from 1day before until 5 and 10 days after CdCl2 instillation, respectively; group 11 received celecoxib for 11 days. Cytologic evaluation of bronchoalveolar lavage fluid revealed that intratracheal cadmium administration resulted in a significant rise in total cell count, epithelial cells, neutrophils, and eosinophils, 5- and 10-days post-exposure. Treatment with bromelain either in low or high doses in cadmium-exposed rats resulted in a significant reduction of neutrophil count. Bromelain treatment could not completely prevent or recover interstitial pneumonia and fibrinous bronchopneumonia in cadmium exposed rats. However, administration of low doses resulted in a significant decrease of semi quantitative histopathologic scores, including pneumonia and cellular infiltration indices. In conclusion, bromelain may help to improve the cytological and histopathological complications following cadmium intoxication in the lungs.


[Pathological changes of cat brain tissues after cranial gunshot wound in hot and humid environment].
To investigate pathological changes in cat brain tissues after gunshot wound in the head in hot and humid environments. Sixteen cats were randomly divided into 4 groups, namely the normal environment (group 1), gunshot in normal environment (group 2), hot and humid environment (group 3), and gunshot wound in hot and humid environment (group 4) groups. Pathological changes of the cat brain tissues were observed with both optical and electron microscopes. The early-stage changes in group 2 were high-lighted by vasomotor dysfunction, with the coexistence of both vascular spasm and dilation. In group 3, vascular spasm was depressed while hemorrhagic changes increased. On the brain tissue sections in group 4 for optical microscopic observation and ultra-thin sections for electron microscopic examination, the number of viable neural cells was obviously reduced, and edema, degeneration of the organelle occurred; loosening of the capillary tight junction, rupture and bleeding of the blood vessels, as well as degeneration and loosening of the myelin sheath were observed by transmission and scanning electron microscopes, and such changes were more serious than those in group 2. The hot and humid environment can significantly affect the pathological changes in the brain tissues of cat with cranial gunshot wound.


Biocompatible PEGylated bismuth nanocrystals: "All-in-one" theranostic agent with triple-modal imaging and efficient in vivo photothermal ablation of tumors.
Biocompatible single-component theranostic agents integrating multimodal imaging and therapeutic functions (namely, "all-in one" agents) are highly desired for clinical cancer treatments. Herein, PEGylated pure metallic bismuth nanocrystals (Bi-PEG NCs) have been developed to be a competent theranostic agent for in vivo high-performance multimodal bio-imaging and photothermal ablation of tumors. The resultant Bi-PEG NCs show excellent physiological stability, biocompatibility, prolonged blood circulation half-life and preferential tumor accumulation. Thanking to the strong near-infrared (NIR) absorbance as well as the high photothermal conversion efficiency and conversion stability, highly effective in vivo photothermal ablation on tumors has been realized upon NIR irradiation, without noticeable toxicity. Impressively, the Bi-PEG NCs show ultrahigh X-ray computed topography (CT) enhancement efficiency (∼60.3 HU mL mg-1), overwhelming all CT contrast agents reported so far. Combining the strong CT contrast ability and photoacoustic/photothermal effect, high-contrast CT, photoacoustic (PA) and infrared thermal (IRT) triple-modal imaging have been demonstrated both in vitro and in vivo. This work highlights the potentials of such NCs as a powerful "all-in-one" theranostic nanoplatform for bioimaging and antitumor therapy, and may have provided a rather promising candidate for clinically-applied antitumor treatments based on single-component agents.


Retinitis pigmentosa and allied diseases: numerous diseases, genes, and inheritance patterns.
Retinitis pigmentosa (RP) and allied diseases are heterogeneous clinically and genetically. Here we summarize the retinal cell types involved in these diseases, the large number of genes that cause them, and the variety of inheritance patterns that the affected families display. Special consideration is given to unusual inheritance patterns. The aggregate carrier frequency for recessive RP alleles may be as high as 10%.


Multidetector row CT of superior mesenteric artery syndrome.
The purpose of this case series is to illustrate the diagnostic criteria of superior mesenteric artery syndrome (SMAS) using 16-slice multidetector row computed tomography (MDCT) angiography with multiplanar and 3-dimensional reconstructions. SMAS is a rare condition causing functional obstruction of the third portion of the duodenum. When suspected, diagnostic imaging can be performed with upper gastrointestinal, arteriography, or CT. Four patients with clinical symptoms and correlative CT evidence of SMAS are described. Axial, multiplanar, and 3-dimensional rendered MDCT images were retrospectively reviewed by 1 investigator, who measured the aortomesenteric angle and aortomesenteric distance on a sagittal maximum intensity projection rendering, and compared these values with normal ranges described in the literature. In each patient, MDCT demonstrated gastric and proximal duodenal dilatation with abrupt narrowing of the third portion of the duodenum between the aorta and SMA. Sagittal maximum intensity projection images reliably demonstrated the decreased aortomesenteric angle (mean in subjects 13.5 degrees, normal range 28 to 65 degrees) and distance (mean in subjects 4.4 mm, normal range 10 to 34 mm) in all 4 patients. As opposed to traditional imaging modalities like upper gastrointestinal and mesenteric arteriography, which depict either the bowel or vasculature respectively, CT enables direct visualization of obstructed bowel owing to duodenal compression by the SMA. Multiplanar MDCT with 3-dimensional rendering provides sagittal reconstructions that can be used to confirm the CT criteria of decreased aortomesenteric angle and distance in SMAS.


Reactivity with Tris(hydroxymethyl)aminomethane confounds immunodetection of acrolein-adducted proteins.
The toxic alpha,beta-unsaturated aldehyde acrolein readily attacks proteins, generating adducts at cysteine, histidine, and lysine residues. In this study, rabbit antiserum was raised against acrolein-modified keyhole limpet hemocyanin in the expectation that it would allow immunodetection of adducted proteins in biological samples. Using slot-blot and enzyme-linked immunosorbent assays, the antiserum detected acrolein-modified protein with high sensitivity and specificity. Adduct immunodetection was strongly inhibited by acrolein-modified polylysine but not polyhistidine. Efforts to develop a Western blotting method for detecting adducted proteins in cell lysates were hampered by irreproducible outcomes, evidently due to adduct instability during SDS-PAGE. Indeed, adducts generated via brief exposure of a model protein to acrolein displayed pH- and concentration-dependent instability to tris(hydroxymethyl)aminomethane (Tris), a nucleophilic buffer used in protein electrophoresis. The effect was most striking when Tris solutions were buffered to pH 8.0 and higher. In contrast, adducts formed during extended exposure to acrolein (> or =60 min) were completely stable to Tris. The time dependence of susceptibility raised the possibility that Tris interfered with specific steps in lysine modification, which involves stepwise Michael addition of two molecules of acrolein to the same residue, followed by condensation and dehydration to form a heterocyclic adduct, N(epsilon)-(3-formyl-3,4-dehydropiperidino)lysine. We hypothesize that carbonyl-retaining Michael adducts may react with Tris by forming imines with the primary amine of the buffer. Consistent with this idea, triethanolamine, a tertiary amine buffer unable to form imines, had no effect on acrolein-adducted protein. These effects of Tris may explain difficulties in the detection of acrolein-adducted proteins during conventional Western blotting procedures.


The human V kappa locus. Characterization of extended immunoglobulin gene regions by cosmid cloning.
As part of the ongoing work in our laboratory on the structural organization of the human V kappa locus we screened cosmid libraries with V kappa gene probes and obtained numerous V kappa gene-containing cosmid clones. Several genomic regions of the V kappa locus were reconstructed from overlapping cosmid inserts and were extended by one step of chromosomal walking. The regions that are called Wa, Wb, Oa, Ob and Ob' comprise about 370 kb (10(3) bases) of DNA and contain 24 V kappa genes and pseudogenes. The V kappa genes belong to the three dominant subgroups (V kappa I, V kappa II, V kappa III) and are arranged to form mixed clusters with members of the different subgroups being intermingled with each other. The distances between the genes range from 1 to 15 kb. Three genes of the Wa and Wb regions that were sequenced turned out to be pseudogenes. Terminal parts of the regions Wa and Ob that do not contain V kappa genes of one of the known subgroups may represent extended spacer regions within the V kappa locus. Wa and Wb are duplicated regions located at different positions of the locus. Region Wb was found to comprise inversely repeated sections of at least 14 kb each that contain V kappa genes oriented in opposite polarity. This finding is consistent with inversion-deletion models of V-J joining; it also shows that the V kappa locus contains not only unique and duplicated but also triplicated parts. The data on the W and O regions are discussed together with those on the L regions and on other regions established in our laboratory. Although the picture of the human V kappa locus with, to date, about 70 different non-allelic V kappa genes is still incomplete, some general features with respect to the organization of the genes and the limited duplication of genomic regions have emerged.


Cerebral palsy: a 1987 perspective.
Changing views on reaching a diagnosis, methods of assessment, and management are apparent for neurological disorders in general, and cerebral palsy in particular. A personal approach to the problems associated with the evaluation and care of children and young people with cerebral palsy is outlined, with particular emphasis on the contributions form, and optimal use of, the multidisciplinary assessment team.


A developmental neurobiological model of motivated behavior: anatomy, connectivity and ontogeny of the triadic nodes.
Adolescence is the transition period that prepares individuals for fulfilling their role as adults. Most conspicuous in this transition period is the peak level of risk-taking behaviors that characterize adolescent motivated behavior. Significant neural remodeling contributes to this change. This review focuses on the functional neuroanatomy underlying motivated behavior, and how ontogenic changes can explain the typical behavioral patterns in adolescence. To help model these changes and provide testable hypotheses, a neural systems-based theory is presented. In short, the Triadic Model proposes that motivated behavior is governed by a carefully orchestrated articulation among three systems, approach, avoidance and regulatory. These three systems map to distinct, but overlapping, neural circuits, whose representatives are the striatum, the amygdala and the medial prefrontal cortex. Each of these system-representatives will be described from a functional anatomy perspective that includes a review of their connectivity and what is known of their ontogenic changes.


Relationship of Enhanced Liver Fibrosis Score with Pediatric Nonalcoholic Fatty Liver Disease Histology and Response to Vitamin E or Metformin.
To study the diagnostic performance of the enhanced liver fibrosis score (ELF) for detecting different stages of fibrosis and its usefulness in detecting histologic response to vitamin E or metformin in children with nonalcoholic fatty liver disease who participated in the Vitamin E or Metformin for the Treatment Of NAFLD In Children (TONIC) trial. ELF was measured at baseline and weeks 24, 48, and 96 on sera from 166 TONIC participants. Associations between ELF with baseline and end of trial (EOT) fibrosis stages and other histologic features were assessed using χ2 tests and logistic regression models. ELF was significantly associated with severity of fibrosis at baseline and EOT. ELF areas under the curve for discriminating patients with clinically significant and advanced fibrosis were 0.70 (95% CI, 0.60-0.80) and 0.79 (95% CI, 0.69-0.89), respectively. A 1-unit decrease in ELF at EOT was associated with overall histologic improvement (OR, 1.86; 95% CI, 1.11-3.14; P = .02), resolution of steatohepatitis (OR, 1.88; 95% CI, 1.09-3.25; P = .02), improvement in steatosis grade (OR, 1.76; 95% CI, 1.06-2.82; P = .03), and hepatocellular ballooning (OR, 1.79; 95% CI, 1.06-3.00; P = .03), but not with improvement in fibrosis stage (OR, 1.26; 95% CI, 0.78-2.03; P = .34). ELF was associated with fibrosis stage in children who participated in TONIC. Although not associated with improvement in fibrosis, a decrease in ELF at EOT was associated with Nonalcoholic Steatohepatitis resolution and improvement in nonalcoholic fatty liver disease histology. ELF may be a useful noninvasive test to monitor treatment response in children with nonalcoholic fatty liver disease.


Ventral Striatal D2/3 Receptor Availability Is Associated with Impulsive Choice Behavior As Well As Limbic Corticostriatal Connectivity.
Low dopamine D2/3 receptor availability in the nucleus accumbens shell is associated with highly impulsive behavior in rats as measured by premature responses in a cued attentional task. However, it is unclear whether dopamine D2/3 receptor availability in the nucleus accumbens is equally linked to intolerance for delayed rewards, a related form of impulsivity. We investigated the relationship between D2/3 receptor availability in the nucleus accumbens and impulsivity in a delay-discounting task where animals must choose between immediate, small-magnitude rewards and delayed, larger-magnitude rewards. Corticostriatal D2/3 receptor availability was measured in rats stratified for high and low impulsivity using in vivo [18F]fallypride positron emission tomography and ex vivo [3H]raclopride autoradiography. Resting-state functional connectivity in limbic corticostriatal networks was also assessed using fMRI. Delay-discounting task impulsivity was inversely related to D2/3 receptor availability in the nucleus accumbens core but not the dorsal striatum, with higher D2/3 binding in the nucleus accumbens shell of high-impulsive rats compared with low-impulsive rats. D2/3 receptor availability was associated with stronger connectivity between the cingulate cortex and hippocampus of high- vs low-impulsive rats. We conclude that delay-discounting task impulsivity is associated with low D2/3 receptor binding in the nucleus accumbens core. Thus, two related forms of waiting impulsivity-premature responding and delay intolerance in a delay-of-reward task-implicate an involvement of D2/3 receptor availability in the nucleus accumbens shell and core, respectively. This dissociation may be causal or consequential to enhanced functional connectivity of limbic brain circuitry and hold relevance for attention-deficit/hyperactivity disorder, drug addiction, and other psychiatric disorders.


Controlling two-center interference in molecular high harmonic generation.
We experimentally investigate the process of intramolecular quantum interference in high-order harmonic generation in impulsively aligned CO2 molecules. The recombination interference effect is clearly seen through the order dependence of the harmonic yield in an aligned sample. The experimental results can be well modeled assuming that the effective de Broglie wavelength of the returning electron wave is not significantly altered by the Coulomb field of the molecular ion. We demonstrate that such interference effects can be effectively controlled by changing the ellipticity of the driving laser field.


Bacterial enzymes in uremia management.
The theoretical background for a conservative therapeutic treatment of uremia is described, with illustrative results from preliminary clinical trials in 10 patients and 10 normal reference subjects. The proposed treatment focuses upon the patient's gastrointestinal tract--the normal site for metabolism of both exogenous (dietary) and endogenous (recycled) protein--enabling it to behave like the rumen of the cow. The objective is to induce the uremic's organism to utilize its own "waste" substances. The patient swallows enterosoluble capsules containing specifically adapted enzymes (immobilized or free) from apathogenic soil microorganisms. These are pre-adapted to convert urea, creatinine, uric acid, guanidino derivatives, and other nonprotein nitrogen compounds (NPN). The enzymes utilize many other substances, in particular ammonia, potassium, phosphorus, and several other factors potentially dangerous for the uremic. The enzymes apparently cleave vasoconstrictatory peptides in the intestines. In the course of the therapy, renoparenchymal hypertension decreased significantly, and increased again when the regimen was interrupted. The results from the present studies are in full accord with the information published in the relevant fields. The time appears ripe for large-scale trials of the therapeutic regimen outlined, especially as many commercial microbial enzymes already have a long history of safe use in food processing.


Staple food intake in a rural village in Verata, Fiji.
An assessment of food intake and body composition in twenty women in a relatively isolated rural village in Fiji was made. Subcutaneous fat distribution was assessed by the measurement of subscapular and triceps skin folds. Compared with measurements made on Polynesian and European women in New Zealand it was found that the Fiji women had relatively more central subcutaneous fat than Polynesian or European. Diet was assessed by two 7 day periods of diet diaries and analysed by food type. The two main foods eaten were cassava and flour based goods.


Mesenchymal stem cell differentiation in an experimental cartilage defect: restriction of hypertrophy to bone-close neocartilage.
Mesenchymal stem cells (MSCs) are promising for the treatment of articular cartilage defects; however, common protocols for in vitro chondrogenesis induce typical features of hypertrophic chondrocytes reminiscent of endochondral bone formation. Aim of the study was to compare chondrogenic differentiation of MSCs in vitro and in vivo in experimental full-thickness cartilage defects, asking whether MSCs can differentiate into collagen type X-negative chondrocytes in an orthotopic environment. Cartilage defects in knees of minipigs were covered with a collagen type I/III membrane, and half of them received transplantation of expanded autologous MSCs. At 1, 3, and 8 weeks, morphological and molecular aspects of repair were assessed. The orthotopic environment triggered a spatially organized repair tissue with upper fibrous, intermediate chondrogenic, and low layer hypertrophic differentiation of cells and a trend to more safranin-O and collagen type II-positive samples after MSC transplantation at 8 weeks. Compared to in vitro chondrogenesis, significant lower COL10A1/COL2A1 and MMP13/COL2A1 ratios were obtained for in vivo differentiation. This indicates that, as opposed to in vitro chondrogenic induction of MSCs, the in vivo signaling molecules and biomechanical stimuli provide an appropriate environment for progenitor cells to differentiate into collagen type X-negative chondrocytes. Thus, until better in vitro induction protocols become available for chondrogenesis of MSCs, their predifferentiation before transplantation may be unfavorable.


DNA-dependent protein kinase complex: a multifunctional protein in DNA repair and damage checkpoint.
DNA-dependent protein kinase (DNA-PK) is a nuclear serine/threonine protein kinase that is activated upon DNA damage generated by ionizing radiation or UV-irradiation. It is a three-protein complex consisting of a 470-kDa catalytic subunit (DNA-PKcs) and the regulatory DNA binding subunits, Ku heterodimer (Ku70 and Ku80). Mouse and human cells deficient in DNA-PKcs are hypersensitive to ionizing radiation and defective in V(D)J recombination, suggesting a role for the kinase in double-strand break repair and recombination. The Ku heterodimer binds to double-strand DNA breaks produced by either DNA damage or recombination, protects DNA ends from degradation, orients DNA ends for re-ligation, and recruits its catalytic subunit and additional factors necessary for successful end-joining. DNA-PK is also involved in an early stage of damage-induced cell cycle arrest, however, it remains unclear how the enzyme senses DNA damage and transmits signals to downstream gene(s) and proteins.


Dictyosomes participate in the intracellular pathway of storage proteins in developing Vicia faba cotyledons.
The main storage globulins of Vicia faba seeds, vicilin and legumin, were localized in ultrathin sections of developing cotyledons employing the protein A/colloidal gold-technique. Double labelling experiments with monospecific immunoglobulins directed against vicilin or legumin using different size classes of protein A-colloidal gold showed that both globulins are associated with protein lumps in the vacuoles of early developmental stages of the seeds and with the rough endoplasmic reticulum, the site of storage protein biosynthesis. Furthermore, vicilin and legumin have been detected in protein-containing vesicles in the cytoplasm as well as in dictyosomes and the dictyosome-derived vesicles. The association of storage globulins with the dictyosomes was also indicated by cell fractionation and immunoblotting of organelle contents derived from microsome, enriched dictyosome and protein body preparations. Protein blotting analyses employing a Concanavalin A/peroxidase technique showed that certain vicilin polypeptides were already glycosylated in the rough endoplasmic reticulum. Another part of the vicilin fraction as well as legumin polypeptides did not show any affinity to Concanavalin A. These data provide a direct evidence for a transient involvement of dictyosomes in the intracellular pathway of legume storage globulins from the rough endoplasmic reticulum to their accumulation site in the protein bodies.


Transforming growth factor beta1 induces IL-1 receptor antagonist production and gene expression in rat vascular smooth muscle cells.
Atherosclerosis is an inflammatory-fibroproliferative process that may represent a possible milieu in which transforming growth factor-beta (TGF-beta) can be involved. Vascular smooth muscle cells (VSMC) may represent a source or a target of a large number of growth factors and proinflammatory cytokines, including interleukin-1 and its receptor antagonist (IL-1Ra). We tested the effect of TGF-beta1, on IL-1Ra production and gene expression in rat VSMC cultures. We found a significant dose (3-30 ng/ml) and time-dependent (0-48 h) increase in IL-1Ra immunoactivity in the supernatant of conditioned medium and cell lysates. The maximal effect was observed with TGF-beta at 30 ng/ml and after 24 h incubation time, respect to untreated cells (320 +/- 26 vs. 211 +/- 20 pg/ml; P < 0.01). Furthermore, TGF-beta1 induced an increased mRNA expression which began at 2 h and peaked at 18 h incubation time (about a 6-fold increase with respect to unstimulated cells). The effect of TGF-beta1 on IL-1Ra production was completely inhibited by an anti-IL-1beta antibody (10 microg/ml) (from 320 +/- 81 to 181 +/- 46 pg/ml). These experiments suggest that TGF-beta1, potentially produced in the vascular wall during atherogenesis, may play a pathophysiological role in the autocrine control of IL-1 actions, via VSMC IL-1Ra production.


In vitro and in vivo efficacy study of cefepime, doripenem, tigecycline, and tetracycline against extended-spectrum beta-lactamases Escherichia coli in chickens.
At present, there are no data about the efficacy of some recent antibiotics on Escherichia coli in broiler chickens in the study area. This study was designed to evaluate the in vitro and in vivo efficacy of cefepime, doripenem, tigecycline, and tetracycline against multidrug-resistant-extended-spectrum beta-lactamases (MDR-ESBLs) producing E. coli in broiler chicks. A total of 34 MDR-ESBLs E. coli isolates were used in this study. In vitro evaluation of the antibacterial efficacy of cefepime, doripenem, tigecycline, and tetracycline were performed using disk diffusion and minimum inhibitory concentration (MIC) assays. In vivo evaluation of the efficacy of the antibiotics was perfumed using 180, 2-week-old chicks challenged with MDR-ESBL-producing E. coli strain O78. Chicks were divided into six groups (30 chicks each) according to the treatment regimen. Treatment was administered to chicks in Groups 3-6 intravenously, twice per day for 1 week using one antibiotic per group at concentration 10 times the determined MIC. Chicks in the positive control (Group 1) were challenged and received 0.2 ml of sterile Tryptone Soy Broth (TSB), while those in the negative control (Group 2) were not challenged and received 0.2 ml of sterile TSB. The severity of clinical signs, gross lesions, and mortality rate was scored and compared between groups. All E. coli isolates were sensitive to doripenem and tigecycline, while 88% were sensitive to cefepime and only 23% were sensitive to tetracycline. In vivo antibiotic efficacy evaluation in challenged chicks revealed a significant reduction in the severity of clinical signs, gross lesions, and mortality (3%) in chicks treated with cefepime compared to non-treated chicks (55%). There was no significant effect on the severity of clinical signs, gross lesions, and mortality in chicks treated with doripenem, tigecycline, and tetracycline compared to non-treated chicks. The mortality rates of chicks treated with doripenem, tigecycline, and tetracycline were 57%, 50%, and 90%, respectively. The results of this study indicate that most MDR-ESBLs producing E. coli isolates were sensitive to doripenem, tigecycline, and cefepime. However, in vivo study indicated that only cefepime was effective and resulted in a significant reduction in clinical signs, gross lesions, and mortality in infected chicks. Therefore, cefepime could be used to treat naturally infected chickens with MDR-ESBLs producing strains of E. coli.


Limiting factors in acoustic separation of carbon particles in air.
Particles suspended in a fluid that is exposed to an acoustic standing wave experience a time-averaged force that drives them to either the pressure nodes or anti-nodes of the wave. Several filter designs have been successfully implemented using this force to filter small particles in liquids with low flow rates and small cross-sectional areas. It has been suggested that the filtration of small solid particles out of a gas, such as carbon in air (smoke), would be a possible application of acoustic standing wave based particle separation. This study shows the limiting factors, in both power requirements and design factors, of an acoustic filter designed for filtering smoke particles across large cross-sectional areas. It is shown that while filtration is possible, the power needed is impractical. It is also shown that operating the filter within certain settling time parameters optimizes the energy usage of the filter.


Opsonization of HIV with complement enhances infection of dendritic cells and viral transfer to CD4 T cells in a CR3 and DC-SIGN-dependent manner.
In the present study, we demonstrated that opsonization of primary HIV-1 with human complement enhances infection of immature monocyte-derived dendritic cells (iDC) and transmission in trans of HIV to autologous CD4(+) T lymphocytes. Infection of iDC by opsonized primary R5- and X4-tropic HIV was increased 3- to 5-fold as compared with infection by the corresponding unopsonized HIV. Enhancement of infection was dependent on CR3 as demonstrated by inhibition induced by blocking Abs. The interaction of HIV with CCR5 and CXCR4 on iDC was affected by opsonization. Indeed, stromal-derived factor-1 was more efficient in inhibiting infection of iDC with opsonized R5-tropic HIV-1(BaL) (45%) than with heat-inactivated complement opsonized virus and similarly RANTES inhibited more efficiently infection of iDC with opsonized X4-tropic HIV-1(NDK) (42%) than with heat-inactivated complement opsonized virus. We also showed that attachment of complement-opsonized virus to DC-specific ICAM-grabbing nonintegrin (DC-SIGN) molecule on iDC and HeLa DC-SIGN(+) CR3(-) cells was 46% and 50% higher compared with heat-inactivated complement opsonized virus, respectively. Hence, Abs to DC-SIGN suppressed up to 80% and 60% the binding of opsonized virus to HeLa cells and iDC, respectively. Furthermore, Abs to DC-SIGN inhibited up to 70% of the infection of iDC and up to 65% of infection in trans of autologous lymphocytes with opsonized virus. These results further demonstrated the role of DC-SIGN in complement opsonized virus uptake and infection. Thus, the virus uses complement to its advantage to facilitate early steps leading to infection following mucosal transmission of HIV.


Estradiol metabolism: an endocrine biomarker for modulation of human mammary carcinogenesis.
The natural estrogen 17beta-estradiol (E2) has a profound influence on proliferation and neoplastic transformation of mammary epithelium. The role of cellular metabolism of E2 in mammary carcinogenesis, however, remains to be elucidated. Explant culture and cell culture models developed from noncancerous human mammary tissue were used to examine modulation of E2 metabolism in response to treatment with prototype rodent mammary carcinogens and the ability of the naturally occurring phytochemical indole-3-carbinol (13C) to influence E2 metabolism and regulate aberrant proliferation. In the two models, treatment with the chemical carcinogens 7,12-dimethylbenz[a]anthracene and benzo[a]pyrene altered the metabolism of E2 as determined from the radiometric (tritium release) and gas chromatography-mass spectrometry (GC-MS) assays. This alteration in E2 metabolism was accompanied by aberrant proliferation and abrogation of apoptosis as determined by the extent of replicative DNA synthesis, S-phase fraction and Sub G0 (apoptotic) peak. Exposure of carcinogen-initiated cultures to 13C resulted in induction of C2-hydroxylation of E2 and of apoptosis and downregulation of hyperproliferation. Determination of altered cellular metabolism of E2 in response to initiators and modulators of carcinogenesis and evaluation of cell cycle related markers for proliferation and apoptosis may provide a mechanism-oriented approach to validate E2 metabolism as an endocrine biomarker for induction and prevention of human mammary carcinogenesis.


Back-to-back correlations of high-p(T) hadrons in relativistic heavy-ion collisions.
We investigate the suppression factor and the azimuthal correlation function for high p(T) hadrons in central Au+Au collisions at sqrt[s(NN)]=200 GeV by using a dynamical model in which hydrodynamics is combined with explicitly traveling jets. We study the effects of parton energy loss in a hot medium, intrinsic k(T) of partons in a nucleus, and p (perpendicular) broadening of jets on the back-to-back correlations of high p(T) hadrons. Parton energy loss is found to be a dominant effect on the reduction of the awayside peaks in the correlation function.


Ewing sarcoma/primitive neuroectodermal tumor of the chest wall: impact of initial versus delayed resection on tumor margins, survival, and use of radiation therapy.
To establish outcome and optimal timing of local control for patients with nonmetastatic Ewing sarcoma/primitive neuroectodermal tumor (ES/PNET) of the chest wall. Patients < or =30 years of age with ES/PNET of the chest wall were entered in 2 consecutive protocols. Therapy included multiagent chemotherapy; local control was achieved by resection, radiotherapy, or both. We compared completeness of resection and disease-free survival in patients undergoing initial surgical resection versus those treated with neoadjuvant chemotherapy followed by resection, radiotherapy, or both. Patients with a positive surgical margin received radiotherapy. Ninety-eight (11.3%) of 869 patients had primary tumors of the chest wall. Median follow-up was 3.47 years and 5-year event-free survival was 56% for the chest wall lesions. Ten of 20 (50%) initial resections resulted in negative margins compared with 41 of 53 (77%) negative margins with delayed resections after chemotherapy (P = 0.043). Event-free survival did not differ by timing of surgery (P = 0.69) or type of local control (P = 0.17). Initial chemotherapy decreased the percentage of patients needing radiation therapy. Seventeen of 24 patients (70.8%) with initial surgery received radiotherapy compared with 34 of 71 patients (47.9%) who started with chemotherapy (P = 0.061). If a delayed operation was performed, excluding those patients who received only radiotherapy for local control, only 25 of 62 patients needed radiotherapy (40.3%; P = 0.016). The likelihood of complete tumor resection with a negative microscopic margin and consequent avoidance of external beam radiation and its potential complications is increased with neoadjuvant chemotherapy and delayed resection of chest wall ES/PNET.


Lymph node metastasis in microinvasive epidermoid cancer of the cervix.
A retrospective series of 69 patients indicates that the definition of a diagnosis of microinvasive cancer of the cervix should indicate a lack of blood vessel or lymphatic permeation as well as invasion of not more than 3 mm below the basement membrane. The incidence of lymph node metastases in this group of patients in whom microinvasive cancer of the cervix had been diagnosed was 7.1%. Two of the 4 patients with positive lymph nodes demonstrated lymphatic or blood vessel permeation on preoperative conization and 2 did not, an incidence of 3.6%. One patient had lymphatic invasion on conization with negative lymph nodes on final surgical specimen. Two patients had recurrent epidermoid carcinoma within less than 10 years and died of recurrent carcinoma. Maximum survival can only be achieved by full treatment of Stage IA lesions. Since surgical mortality was absent in our series, surgical extirpation by extensive (radical) hysterectomy and bilateral lymphadenectomy should give optimum results.


Ablative treatment of photoaging.
Despite the burgeoning options available for skin rejuvenation, the benefits of laser skin resurfacing in trained hands remains unequaled. This article will review the preoperative evaluation, lasers and techniques used, postoperative course, and possible complications.


Fabrication of Polymer Optical Fibre (POF) Gratings.
Gratings inscribed in polymer optical fibre (POF) have attracted remarkable interest for many potential applications due to their distinctive properties. This paper overviews the current state of fabrication of POF gratings since their first demonstration in 1999. In particular we summarize and discuss POF materials, POF photosensitivity, techniques and issues of fabricating POF gratings, as well as various types of POF gratings.


High affinity interaction of syntaxin and SNAP-25 on the plasma membrane is abolished by botulinum toxin E.
The release of hormones and neurotransmitters requires the fusion of cargo-containing vesicles with the plasma membrane. This process of exocytosis relies on three SNARE proteins, namely syntaxin and SNAP-25 on the target plasma membrane and synaptobrevin on the vesicular membrane. In this study we examined the molecular assembly pathway that leads to formation of the fusogenic SNARE complex. We now show that the plasma membrane syntaxin and SNAP-25 interact with high affinity and equimolar stoichiometry to form a stable dimer on the pathway to the ternary SNARE complex. In bovine chromaffin cells, syntaxin and SNAP-25 colocalize in defined clusters that average 700 nm in diameter and cover 10% of the plasma membrane. Removal of the C terminus of SNAP-25 by botulinum neurotoxin E, a known neuroparalytic agent, dissociates the target SNARE dimer in vitro and disrupts the SNARE clustering in vivo. Together, our data uncover formation of stable syntaxin/SNAP-25 dimers as a central principle of the SNARE assembly pathway underlying regulated exocytosis.


Periovarian peritoneal adhesions in women with endometriosis. Structural patterns.
To draw attention to the structural features of adhesions associated with pelvic endometriosis since they are less well studied than endometriosis proper. Sixty-two samples of periovarian adhesions were laparoscopically obtained from 24 infertile women 26-38 years of age and were prepared for detailed histologic analyses. Macroscopically, the adhesions were either velamentous or cordlike and grossly were free of endometriosis. Most adhesions were attached to the connective tissue of the ovarian tunica albuginea; in two cases they were attached to the corpus luteum. Upon microscopic analysis, velamentous adhesions consisted of fibrous sheets of collagen connective tissue, with the surface lined with single-layered coelomic epithelium. The cord-like adhesions consisted of "hyalinized" fibrous tissue and were either avascular or vascularized. Irregular cystic or tubular structures that could be regarded as endometriosis were found in four patients. Hyaline cartilage within the tissue of the adhesion was an unexpected finding in one patient. Microscopic analysis permitted grouping of the adhesions in the following way: (1) Connective tissue adhesions (23 patients) with the following subcategories: (A) fibrous, either avascular or encompassing degenerating blood vessels (6 patients); (B) vascularized, containing granulomatous tissue (12 patients); (C) vascularized with stromoglandular endometrioid cysts or tubules (4 patients); (D) rare types, such as that encompassing hyaline cartilage (1 patient). (2) Fibrin adhesions (1 patient). From the clinical point of view, the presence of endometrial tissue within adhesions raises the question of whether there is a need for removal, rather than just lysis, of adhesions to avoid persistent pain.


Identification of an epitope of type 1 streptococcal M protein that is shared with a 43-kDa protein of human myocardium and renal glomeruli.
The localization of opsonic and tissue-cross-reactive epitopes within the amino terminus of type 1 streptococcal M protein was investigated by using murine mAb raised against synthetic peptides of type 1 M protein. Two mAb (IIIA2 and IIIB8) reacted with epitopes located within amino acid residues 1-12 of type 1 M protein. These antibodies opsonized type 1 streptococci and did not cross-react with human kidney and heart tissue. Another mAb (IC7) reacted with mesangial cells of renal glomeruli and human myocardium. The cross-reactive epitope of mAb IC7 was localized to position 13-19, indicating that it is not the same epitope as the previously described vimentin-cross-reactive epitope at position 23-26 of type 1 M protein. In Western blots of mesangial cell and myocardial proteins, mAb IC7 cross-reacted with a 43-kDa protein. Neither vimentin nor actin inhibited the binding of mAb IC7 to the cross-reactive protein, as determined by Western blot or immunofluorescence inhibition tests. These results provide evidence that type 1 M protein contains at least one autoimmune epitope shared with both human glomeruli and myocardium.


Enhanced atheroprotection and lesion remodelling by targeting the foam cell and increasing plasma cholesterol acceptors.
Atherosclerosis development can be ameliorated by promoting reverse cholesterol transport (RCT) from arteries. The process involves cholesterol efflux from foam cells to extracellular acceptors such as apolipoprotein A-I (apoA-I) and high-density lipoprotein (HDL) that mediate transport to the liver. Perilipin-2 (PLIN2) is a lipid droplet (LD)-associated protein that in macrophages facilitates cholesterol storage and prevents efflux. We hypothesized that atheroprotection would be enhanced by concurrently targeting PLIN2 to increase the efflux capacity of foam cells and increasing plasma apoA-I and HDL. PLIN2-knockout and wild-type mice lacking apolipoprotein E (PLIN2(-/-)/apoE(-/-) and PLIN2(+/+)/apoE(-/-)) were treated with a helper-dependent adenoviral vector encoding human apoA-I (HDAd-AI) or with control empty vector. Treatment with HDAd-AI increased hepatic apoA-I production, plasma apoA-I and HDL-cholesterol (HDL-C), and apoA-I deposition in lesions to a similar extent in PLIN2(-/-)/apoE(-/-) and PLIN2(+/+)/apoE(-/-) mice. However, atherosclerosis development at the aortic sinus was considerably lower in HDAd-AI-treated PLIN2(-/-)/apoE(-/-) mice. A more stable lesion phenotype, with increased collagen content, was primarily associated to treatment with HDAd-AI, but was enhanced under PLIN2 deficiency. PLIN2 deficiency and apoA-I cumulatively reduced LDs and cholesterol ester content in cultured macrophages. Neutral lipid in atheroma was significantly reduced in HDAd-AI-treated PLIN2(-/-)/apoE(-/-) mice, and RCT from macrophages to feces was enhanced in PLIN2(-/-) macrophages. These studies demonstrate a mutually beneficial relationship between PLIN2 deficiency and elevated apoA-I/HDL-C in preventing atherosclerosis development. The data support that targeting foam cell components to mobilize cholesterol may be a promising strategy to enhance the atheroprotection of plasma cholesterol acceptors.


Spectrophotofluorometric method for quantitative determination of sulpiride in human plasma and urine.
A new spectorophotofluorometric method for the determination of sulpiride (S) in the human plasma and urine is described. The plasma concentrations (0--24 hours) and renal excretions (0--48 hours) of sulpiride were measured after Dogmatil forte (Schürholtz), or Sulpiril (Leiras) tablets both containing 200 mg of sulpiride, after two Sulpiril capsules (Leiras) containing 50 mg of sulpiride in each capsule, and after 20 ml Dogmatil saft (Schürholtz) and 20 ml Sulpiril mixt. (Leiras) both containing 5 mg/ml of sulpiride. There were no significant differences in the sulpiride concentrations in plasma or cumulative urinary excretion of sulpiride after Dogmatil forte (200 mg S) or Sulpiril tablet (200 mg S). Two Sulpiril capsules (100 mg S) produced significantly lower plasma concentrations of sulpiride at 3 hours than a Sulpiril tablet (200 mg S) and these were also lower at 4 and 6 hours than with either a Dogmatil forte (200 mg S) or a Sulpiril tablet (200 mg S). Two Sulpiril capsules (100 mg S) gave significantly higher plasma sulpiride concentrations from 1 to 6 hours than 20 ml Sulpiril mixt. (100 mg S) and from 2 to 6 hours higher than 20 ml Dogmatil saft (100 mg S). The plasma half-life of sulpiride measured after two Sulpiril capsules, 20 ml Dogmatil saft and 20 ml Sulpiril mixt., was 9.4 hours, 9.5 hours, and 10.2 hours, respectively. The renal excretion of sulpiride after two Sulpiril capsules (100 mg S) was significantly lower than after a Sulpiril tablet (200 mg S) from 8 to 48 hours, and also significantly lower than after a Dogmatil forte tablet (200 mg S) from 24 to 48 hours. Two Sulpiril capsules (100 mg S) gave significantly higher sulpiride urine concentrations from 8 to 24 hours than 20 ml Sulpiril mixt. (100 mg S) and from 24 to 48 hours than 20 ml Dogmatil saft (100 mg S). There was no significantly differences in this respect between either a Dogmatil forte tablet (200 mg S) and a Sulpiril tablet (200 mg S) or between Dogmatil saft (100 mg S) and Sulpiril mixt. (100 mg S). Comparied with a Dogmatil forte tablet, the bioavailability, calculated by the AUC24 for a Sulpiril tablet was 159%, for a Sulpiril capsule 118%, for Dogmatil saft 77%, and for Sulpiril mixt. 89%. The same values calculated from the sulpiride urine concentrations were 118%, 114%, 71%, and 67%, respectively. There were no significant differences in the blood pressure or heart rate of the volunteers during the experiment. 2 volunteers reported a sedative effect after a Dogmatil forte tablet.


Thoracoomphalopagus diagnosed before delivery.
Twins may be dizygotic or monozygotic. Of the monozygotic twins, 25% to 30% are dichorionic and 70% to 75% are monochorionic. Whilst all the dichorionic twins are diamniotic, very occasionally some monochlorionic ones may be monoamniotic; some of these may be conjoined. A case of conjoined twins was diagnosed during pregnancy. The two girls were delivered by elective classical caesarean section. They were joined together from just above the xiphisternum to the umbilicus and were successfully separated. Recent literature is reviewed.


Subclavian Steal Syndrome Caused by Thrombosis Associated with COVID-19: a Case Report.
Thromboembolic complications are a frequent occurrence during COVID-19. This report presents a patient with signs of subclavian steal syndrome (SSS) caused by a thrombus in the initial part of the right subclavian artery. Pathological occlusive changes, such as thrombosis, are four times more common on the left subclavian. Thrombosis of the subclavian artery occurs in about 1% of the population, but atherosclerotic changes are common and usually asymptomatic. The aim of this report is to present a patient with signs of subclavian steal syndrome (SSS) caused by a thrombus in the initial part of the right subclavian artery associated with symptoms of COVID-19. A 56-year-old female patient presented with tremor, numbness and prickling in the right hand, tinnitus, blurred vision, vertigo, syncope, trismus and headaches. The formation of a thrombus caused neurological symptoms in the right hand with a stronger pronounced tremor, headache and syncopal episodes. Routine CT with angiography did not reveal significant subocclusions of the neck arteries or significant ischemic changes in the brain. The patient was treated as Parkinsonismus (disease) with syncopal and collapsing episodes. Due to worsening subjective complaints, CT angiography of the neck and head blood vessels was repeated with iterative 3D reconstruction. The examination, as mentioned above, revealed atherosclerotic changes with thrombosis and stronger subocclusion of the right subclavian artery (RSA) proximal to the origin of the arteria vertebralis. Both vertebral arteries, as well as arteria basilaris, had a normal appearance. During physical exertion of the right arm doppler examination of neck blood vessels revealed the presence of reverse blood flow in the right vertebral artery. Haematological tests and high D-dimer also confirmed the diagnosis. After anticoagulant therapy, the thrombotic mass on the mural calcified RSA plaque disappeared. With the reduced physical strain on the right hand and a lifestyle change, syncopal conditions and headaches stopped. There was a reduction in tremors and tingling in the right hand as well. We reported a case of subclavian steal syndrome caused by thrombosis associated with OVID-19. Thromboembolic complications are common in the course of this disease. The diagnosis was confirmed with advanced diagnostic tools (CTA with 3D reconstruction), laboratory tests (D-dimer) and doppler ultrasound. When routine CT angiography is not completely clear, 3D reconstruction is necessary.


In situ nick translation of the fragile X region.
At the present time, the molecular nature of the fragile site at Xq27.3 is not well understood. To examine the sensitivity of this region to DNAase I, in situ nick translation was performed on metaphase chromosomes from a fragile X (fra(X] positive individual. In this technique DNAase I is used to nick regions of chromosomal DNA that are in "open" conformation. Biotinylated dUTP was incorporated by nick translation at these sites. The incorporation was identified by double antibody labeling and avidin-horseradish peroxidase staining. Spreads, which had been stained with this technique, were photographed and subsequently trypsin-Giemsa G banded (post-GTG banded) for chromosome identification. In 36 of 44 (82%) fra(X) positive male cells, the region distal to fra(X) (q27.3) was prominently stained in contrast to its light staining appearance in GTG preparations. The fragile site itself was outlined more clearly than can be achieved by GTG or homogeneous staining. When autosomal fragile sites were induced by the addition of 1.5 microM aphidicolin 17 hours prior to harvest, 24 of 27 (89%) fragile sites on the ends of autosomes were prominently stained in regions distal to the break. Because the fra(X) and autosomal fragile regions behaved similarly, this suggests that they have a similar conformation. Thus, while autosomal and Xq27.3 fragile sites are strongly induced by different means, the organization of these sites and the regions distal to them appear to be similar.


Preclinical toxicological assessment of a phytotherapeutic product--CPV (based on dry extracts of Crataegus oxyacantha L., Passiflora incarnata L., and Valeriana officinalis L.).
Associations of plants have been widely used, for centuries, in Ayurveda and in Chinese medicine and have been increasingly acknowledged in Western medicine. The objective of this study is to assess the level of toxicity of an association of three plants: Crataegus oxyacantha, Passiflora incarnata, and Valeriana officinalis (CPV extract). This association was administered to rats, mice, and dogs, both acute and chronically for 180 days. The tests used in the acute experiments were: observational pharmacological screening, LD(50), motor coordination and motor activity. Chronic tests carried out were: weight gain/loss and behavioral parameters in rats and in mice; estrus cycle, effects on fertility, and teratogenic studies in rats and of mutagenic features in mice, in addition to the Ames test. The following parameters were assessed in dogs: weight gain/loss, general physical conditions, water/food consumption and anatomopathological examination of the organs subsequent to the 180 days of treatment. All of the results were negative, showing that CPV administered in high doses and over a long period of time presents no toxicity, suggestive of the fact that this is an association devoid of risk for human beings.


Lactogen and LH receptors. Rat P-450 17 alpha, structural analysis and hormonal regulation of mRNA levels in the Leydig cell.
A complete amino acid sequence for rat testis P-450 17 alpha was deduced from nucleotide analysis of a cDNA clone isolated from a rat Leydig cell library. This cDNA expressed in COS-1 cells both 17 alpha-hydroxylase and 17,20 lyase activities. Rat P-450 17 alpha exhibited significant similarity to the nucleotide and deduced amino acid sequences of the bovine and human P-450 17 alpha, particularly with the highly conserved regions and secondary structure. The rat P-450 17 alpha is anchored to the ER by two transmembrane regions: the N-terminal insertion peptide and the stop-transfer sequence. The C-terminal is associated with the ER by four hydrophobic clefts including the steroid-binding site. We have demonstrated a dual effect of hCG, causing early increases of Leydig cell P-450 17 alpha mRNA levels at low doses, while higher desensitizing doses caused marked subsequent reduction of mRNA levels. Our studies demonstrate that gonadotropin stimulation and desensitization of P-450 17 alpha dependent enzymes (17 alpha-hydroxylase/17,20 desmolase) in the adult rat testis and E2 induced desensitization in fetal Leydig cells are related to levels of P-450 17 alpha mRNA.


Idiopathic left ventricular outflow tract ectopy: a single focus with extremely divergent breakouts.
Idiopathic ventricular tachycardia (VT) and/or premature ventricular contractions (PVCs) arise most commonly from the right ventricular outflow tract and less frequently from the left ventricular outflow tract (LVOT), either below or above the semilunar valves. We report a case of 24-year-old man with idiopathic ventricular tachycardia from a single focus in the supravalvular left ventricular outflow tract with two extremely divergent breakouts observed during the ablation procedure. Focal sources of ventricular arrhythmia in the aortic root may have different preferential exits and meticulous activation sequence mapping is the preferable strategy to delineate the site of origin.


Cu/Zn superoxide dismutase (VdSOD1) mediates reactive oxygen species detoxification and modulates virulence in Verticillium dahliae.
The accumulation of reactive oxygen species (ROS) is a widespread defence mechanism in higher plants against pathogen attack and sometimes is the cause of cell death that facilitates attack by necrotrophic pathogens. Plant pathogens use superoxide dismutase (SOD) to scavenge ROS derived from their own metabolism or generated from host defence. The significance and roles of SODs in the vascular plant pathogen Verticillium dahliae are unclear. Our previous study showed a significant upregulation of Cu/Zn-SOD1 (VdSOD1) in cotton tissues following V. dahliae infection, suggesting that it may play a role in pathogen virulence. Here, we constructed VdSOD1 deletion mutants (ΔSOD1) and investigated its function in scavenging ROS and promoting pathogen virulence. ΔSOD1 had normal growth and conidiation but exhibited significantly higher sensitivity to the intracellular ROS generator menadione. Despite lacking a signal peptide, assays in vitro by western blot and in vivo by confocal microscopy revealed that secretion of VdSOD1 is dependent on the Golgi reassembly stacking protein (VdGRASP). Both menadione-treated ΔSOD1 and cotton roots infected with ΔSOD1 accumulated more O2- and less H2 O2 than with the wildtype strain. The absence of a functioning VdSOD1 significantly reduced symptom severity and pathogen colonization in both cotton and Nicotiana benthamiana. VdSOD1 is nonessential for growth or viability of V. dahliae, but is involved in the detoxification of both intracellular ROS and host-generated extracellular ROS, and contributes significantly to virulence in V. dahliae.


Fetal Programming and Sexual Dimorphism of Mitochondrial Protein Expression and Activity of Hearts of Prenatally Hypoxic Guinea Pig Offspring.
Chronic intrauterine hypoxia is a programming stimulus of cardiovascular dysfunction. While the fetal heart adapts to the reduced oxygenation, the offspring heart becomes vulnerable to subsequent metabolic challenges as an adult. Cardiac mitochondria are key organelles responsible for an efficient energy supply but are subject to damage under hypoxic conditions. We propose that intrauterine hypoxia alters mitochondrial function as an underlying programming mechanism of contractile dysfunction in the offspring. Indices of mitochondrial function such as mitochondrial DNA content, Complex (C) I-V expression, and CI/CIV enzyme activity were measured in hearts of male and female offspring at 90 days old exposed to prenatal hypoxia (10.5% O2) for 14 d prior to term (65 d). Both left ventricular tissue and cardiomyocytes exhibited decreased mitochondrial DNA content, expression of CIV, and CI/CIV activity in male hearts. In female cardiomyocytes, hypoxia had no effect on protein expression of CI-CV nor on CI/CIV activity. This study suggests that chronic intrauterine hypoxia alters the intrinsic properties of select respiratory complexes as a programming mechanism of cardiac dysfunction in the offspring. Sex differences in mitochondrial function may underlie the increased vulnerability of age-matched males compared to females in cardiovascular disease and heart failure.


Electron transfer reactions of redox cofactors in spinach photosystem I reaction center protein in lipid films on electrodes.
Thin film voltammetry was used to obtain direct, reversible, electron transfer between electrodes and spinach Photosystem I reaction center (PS I) in lipid films for the first time. This reaction center (RC) protein retains its native conformation in the films, and AFM showed that film structure rearranges during the first several minutes of rehydration of the film. Two well-defined chemically reversible reduction-oxidation peaks were observed for native PS I in the dimyristoylphosphatidylcholine films, and were assigned to phylloquinone, A(1) (E(m) = -0.54 V) and iron-sulfur clusters, F(A)/F(B) (E(m) = -0.19 V) by comparisons with PS I samples selectively depleted of these cofactors. Observed E(m) values may be influenced by protein-lipid interactions and electrode double-layer effects. Voltammetry was consistent with simple kinetically limited electron transfers, and analysis of reduction-oxidation peak separations gave electrochemical rate constants of 7.2 s(-)(1) for A(1) and 65 s(-)(1) for F(A)/F(B). A catalytic process was observed in which electrons were injected from PS I in films to ferredoxin in solution, mimicking in vivo electron shuttle from the terminal F(A)/F(B) cofactors to soluble ferredoxin during photosynthesis.


Time-resolved spectroscopy of hemoglobin and its complexes with subpicosecond optical pulses.
Subpicosecond optical pulses have been used to study the photolysis of hemoglobin conplexes. Photodissociation of carboxyhemoglobin is found to occur in less than 0.5 picosecond. In hemoglobin and oxyhemoglobin a nondissociative excited state recovery in 2.5 picoseconds is observed.


Association between miRNAs expression and cognitive performances of Pediatric Multiple Sclerosis patients: A pilot study.
The Pediatric onset of Multiple Sclerosis (PedMS) occurs in up to 10% of all cases. Cognitive impairment is one of the frequent symptoms, exerting severe impact in patients' quality of life and school performances. The underlying pathogenic mechanisms are not fully understood, and molecular markers predictive of cognitive dysfunctions need to be identified. On these grounds, we searched for molecular signature/s (i.e., miRNAs and target genes) associated with cognitive impairment in a selected population of PedMS patients. Additionally, changes of their regional brain volumes associated with the miRNAs of interest were investigated. Nineteen PedMS subjects received a full cognitive evaluation; total RNA from peripheral blood samples was processed by next-generation sequencing followed by a bioinformatics/biostatistics analysis. The expression of 11 miRNAs significantly correlated with the scores obtained at different cognitive tests; among the others, eight miRNAs correlated with the Trail Making Tests. The computational target prediction identified 337 genes targeted by the miRNAs of interest; a tangled network of molecular connections was hypothesized, where genes like BST1, NTNG2, SPTB, and STAB1, already associated with cognitive dysfunctions, were nodes of the net. Furthermore, the expression of some miRNAs significantly correlated with cerebral volumes, for example, four miRNAs with the cerebellum cortex. As far as we know, this is the first evaluation exploring miRNAs in the cognitive performances of PedMS. Although none of these results survived the multiple tests' corrections, we believe that they may represent a step forward the identification of biomarkers useful for monitoring and targeting the onset/progression of cognitive impairments in MS.


[On the methodological approach to the elucidation of mechanisms underlying therapeutic effectiveness of Cigun, Indian and Tibetan Yoga therapy].
The methodological approach is proposed allowing to objectively characterize neurophysiological mechanisms underlying therapeutic effectiveness of Cigun, Indian and Tibetan Yoga therapy. Execution of exercises stipulated in these programs is interpreted as a consciousness-inspired specific form of human behaviour (activity). Step-by-step analysis of mentally-organized body's functional systems as a neurophysiological basis of realizable behaviour is presented. Operational interpretation of internal mechanisms underlying the system's functioning permits to evaluate the stereotype brain condition actualized by specific requirements and motivations that initiates sensory deprivation to ensure priority realization of internal genetically determined activity of the human body. Mobilization of this internal activity is described as a process of selective formation of many complicated interactions between various structures of the reticular formation, limbic system, subcortical centres, and neocortex maintaining priority functioning of homeostatic mechanisms of self-regulation and inborn human behaviour. These mechanisms are believed to underlie the autoreconstructive potential of human organism by ensuring systemic correction and restoration of its functional resources.


Risk Factors for Mortality in Critically Ill Children Requiring Renal Replacement Therapy.
There is an increased mortality risk in critically ill children who require renal replacement therapy for acute kidney injury and fluid overload. Nevertheless, renal replacement therapy is essential in managing these patients. The objective of this study was to identify risk factors for mortality in critically ill children requiring renal replacement therapy. Single-center, retrospective cohort analysis. Tertiary care children's hospital. All patients admitted to an ICU at Boston Children's Hospital from January 2009 to December 2017 who required any form of renal replacement therapy. None. Four-hundred sixty-three patients required inpatient renal replacement therapy over the study period. Of these, there were 98 patients who had 99 unique encounters for renal replacement therapy that met eligibility criteria for analysis. The most common diagnoses were respiratory failure, stem cell transplant, and sepsis. The overall mortality was 55.6%. Nonsurvivors had a lower ICU admission weight compared with survivors (30.0 kg vs 44.0 kg; p = 0.037) and a higher degree of fluid accumulation at the time of renal replacement therapy initiation (17.1% vs 8.1%; p = 0.021). In multivariable logistic regression analysis, invasive mechanical ventilation (odds ratio, 7.22; 95% CI, 1.88-27.7), a longer duration of stage 3 acute kidney injury (odds ratio, 1.08; 95% CI, 1.02-1.15), and higher fluid balance in the 72 hours after initiating renal replacement therapy (odds ratio, 1.12; 95% CI, 1.05-1.20) were associated with an increased odds of mortality. Earlier renal replacement therapy initiation with respect to the development of severe acute kidney injury was associated with lower mortality in this cohort of critically ill children. Additionally, invasive mechanical ventilation at the time of renal replacement therapy initiation and a higher degree of fluid accumulation after initiating renal replacement therapy were associated with increased mortality.


[Modified Body technique in the treatment of epithympanic cholesteatoma. Otologic group, Piacenza].
The Bondy technique is a particular radical, yet conservative, treatment where the intact tympanic-ossicular system is preserved during the operation. This technique was initially introduced by Gustave Bondy in 1910 and has been used at the authors' center since December 1983 with a few modifications. In the twelve years from December 1983 to December 1995 69 cases (66 patients) were treated with this technique: 5.6% of all chronic cholesteatomatose otitis surgically treated during that period. The following indications were applied: purely epitymapnic cholesteatoma, average transmission gap equal to or lower than 25 dB and intact bone chain. During the follow-up no signs of recurrent cholestatoma were found. The average post-operative transmission gap was greater than 25 dB in only 5 of the 54 cases with at least one year of follow-up. When used in selected cases, the modified Bondy technique can be considered an excellent option in the treatment of epitympanic cholesteatoma, making it possible to maintain the good pre-operative hearing without requiring a second operation.


Feasibility of a prospective, longitudinal study of resilience among young military recruits with embedded laboratory sub-study: the ARMOR pilot trial.
Multilevel, longitudinal studies are integral to resilience research; however, they are costly and present unique methodological challenges. The objective of this study was to examine the feasibility of study methods (recruitment, retention, data collection) for a large-scale prospective, longitudinal study of resilience among young National Guard recruits. This feasibility trial used a pre-test/post-test design with embedded laboratory sub-study. Participants were young military recruits who had recently enlisted in the Army National Guard and had not yet shipped to Basic Combat Training (BCT). Recruitment and baseline data collection (Time 1), which included a battery of computerized self-report measures and neurocognitive tests, were conducted at local armories. Participants completed an online follow-up (Time 2) survey outside of drill training after returning from BCT. A subset of participants was recruited to complete extensive laboratory procedures pre-and post-BCT, including clinical interview, additional self-report measures, and performance on a series of neurobehavioral tasks during electroencephalogram recordings and, at pre-BCT only, magnetic resonances imaging. Feasibility outcomes assessed our ability to recruit, retain, and collect data from participants. Analysis of outcomes was based on descriptive statistics and evaluation of the feasibility of the larger study was based on pre-determined go/no go progression criteria. All pre-determined progression criteria were met. A total of 102 (97.1%) of eligible military service members consented to participate. Of these, 73 (73.7%) completed the Time 2 survey. Of the 24 participants approached, 14 agreed to participate in the laboratory sub-study, 13 completed follow-up laboratory visits. Overall, completion of online surveys and laboratory tasks was excellent. However, participants had difficulties completing online surveys during BCT and the computerized neurocognitive testing battery at Time 2. Study methods were feasible, and all predetermined criteria for progression to the large-scale longitudinal study were met. Some minor protocol adaptations were identified from this feasibility study. Lessons learned and recommendations for future research are discussed.


Encephalomyelitis due to a Sarcocystis neurona-like protozoan in a rhesus monkey (Macaca mulatta) infected with simian immunodeficiency virus.
A captive-born rhesus monkey (Macaca mulatta) experimentally infected with simian immunodeficiency virus developed neurologic abnormalities approximately seven months postinoculation. A chronic necrotizing encephalomyelitis with intralesional protozoal schizonts was diagnosed histologically. The protozoa was identified as Sarcocystis neurona based on its morphologic characteristics by light and electron microscopic examination, the developmental stages of the schizonts, and positive staining with antisera against Sarcocystis cruzi by immunocytochemical techniques. Although S. neurona may be confused with Toxoplasma gondii by light microscopy, the former lacks rhoptries, is in direct contact with the host cell cytoplasm, and divides by endopolygeny. Sarcocystis neurona has recently been identified as an etiologic agent of encephalomyelitis in horses, raccoons, and mink.


Opportunities, Technology, and the Joy of Discovery.
My grandparents were immigrants. My paternal grandfather was illiterate. Yet my parents were able to complete college and to become teachers. I had a conventional upbringing in a small town in Florida, graduating from high school in 1960. I was fortunate enough to graduate cum laude from Florida State University and to earn other credentials leading to faculty positions at outstanding institutions of higher education: the University of Chicago and Northwestern University. At a time when women were rarely the leaders of research groups, I was able to establish a well-funded research program and to make contributions to our understanding of viral entry into cells. My best research was done after I became confident enough to seek productive interactions with collaborators. I am grateful for the collaborators and collaborations that moved our field forward and for my trainees who have gone on to successes in many different careers.


Subcellular locations of phosphatidylinositol 4-kinase isoforms.
Phosphatidylinositol (PtdIns) 4-kinase catalyzes the synthesis of PtdIns-4-P, the precursor of an array of lipid second messengers generated by additional phosphorylation by PtdIns-4-P 5-kinase and PtdIns 3-kinase. PtdIns 4-kinase activity is conserved from yeast to higher eukaryotes. Multiple isoforms of mammalian PtdIns 4-kinase have been purified, and the activities have been detected in almost all subcellular locations. We previously reported the cloning and characterization of the first mammalian PtdIns 4-kinase named PI4Kalpha (Wong, K., and Cantley, L. C. (1994) J. Biol. Chem. 269, 28878-28884). Alternatively spliced forms of PI4Kalpha have also been identified from several sources including bovine brain (Gehrmann, T., Vereb, G., Schmidt, M., Klix, D., Meyer, H. E., Varsanyi, M., and Heilmeyer, L. M., Jr. (1996) Biochim. Biophys. Acta 1311, 53-63). Recently we isolated a distinct human PtdIns 4-kinase gene, named PI4Kbeta, that encodes an enzyme that is wortmannin sensitive (Meyers, R., and Cantley, L. C. (1997) J. Biol. Chem. 272, 4384-4390). Here we report the locations of these enzymes and provide evidence for other yet unidentified isoforms present in specific organelles. PI4Kalpha is mostly membrane-bound and located at the endoplasmic reticulum; whereas PI4Kbeta is in the cytosol and also present in the Golgi region. Neither of these isoforms accounts for the major type II PtdIns 4-kinase activity detected in the lysosomes and plasma membrane fraction.


Crystal structure of troponin and the molecular mechanism of muscle regulation.
Troponin plays a central role in the regulation of skeletal and cardiac muscle contraction. The protein consists of three polypeptide chains (TnT, TnI and TnC) and is located on polymerized actin together with tropomyosin, forming muscle thin filament. We have determined the molecular structures of the core domains (relative molecular mass of 46,000 and 52,000) of human cardiac troponin in the Ca2+-saturated form by X-ray crystallography. Analysis of the four structures derived from the two crystal forms reveals that the core domain is further divided into sub-domains, connected by linkers, making the entire molecule highly flexible. The structures of the troponin ternary complex suggests that the Ca2+-binding to the regulatory TnC site displaces the carboxyl-terminal portion of TnI from actin/tropomyosin, thereby altering mobility and/or flexibility of the troponin/tropomyosin strand on the actin filament. These Ca2+-dependent changes in the properties of the tropomyosin strand on the actin filament may in turn alter accessibility of myosin heads (motor protein) to the actin filament.


The AMP-Activated Protein Kinase KIN10 Is Involved in the Regulation of Autophagy in Arabidopsis.
Autophagy is a highly conserved system in eukaryotes for the bulk degradation and recycling of intracellular components. Autophagy is involved in many physiological processes including development, senescence, and responses to abiotic and biotic stress. The adenosine 5'-monophosphate (AMP)-activated protein kinase AMPK positively regulates autophagy in mammals; however, the potential function of AMPK in plant autophagy remains largely unknown. Here, we identified KIN10, a plant ortholog of the mammalian AMPK, as a positive regulator of plant autophagy and showed that it acts by affecting the phosphorylation of ATG1 (AUTOPHAGY-RELATED GENE 1) proteins in Arabidopsis. Transgenic Arabidopsis lines overexpressing KIN10 (KIN10-OE) showed delays in leaf senescence, and increased tolerance to nutrient starvation, these phenotypes required a functional autophagy pathway. Consistent with KIN10 having a potential role in autophagy, the nutrient starvation-induced formation of autophagosomes and cleavage of GFP-ATG8e were accelerated in the KIN10-OE lines compared to the wild type. Moreover, the KIN10-OE lines were less sensitive to drought and hypoxia treatments, compared with wild type. Carbon starvation enhanced the level of phosphorylated YFP-ATG1a in the KIN10-OE lines compared to that of wild type. Together, these findings suggest that KIN10 is involved in positive regulation of autophagy, possibly by affecting the phosphorylation of ATG1s in Arabidopsis.


A glucagon-secreting pancreatic alpha islet cell tumor presenting as spinal cord compression.
We describe a patient with a pancreatic islet carcinoma presenting with spinal cord compression owing to vertebral metastases. Subsequent studies demonstrated a typical islet cell carcinoma by light microscopy. By electron microscopy, the neurosecretory granules were morphologically suggestive of glucagon production. Radioimmunoassay studies revealed markedly elevated levels of serum glucagon. Notably, the patient did not exhibit the characteristic glucagonoma syndrome. This case exemplifies clearly that elevated levels of immunoreactive neuropeptide hormones are not necessarily associated with overt hormonal syndromes. Possible mechanisms for explaining this apparent discrepancy include the production of immunoreactive molecules with weak or absent systemic biological activity. Nevertheless, the determination of immunoreactive hormone levels in neuroendocrine neoplasms is an extremely effective adjunct method for their diagnosis and monitoring.


Leucine-enkephalin as a modulator of neurotransmission in cat lower esophageal sphincter.
Interactions between cholinergic, adrenergic and noncholinergic nonadrenergic inervation in lower esophageal sphincter determine the character of smooth muscle responses to field electrical stimulation. The neurogenic responses of muscle strips from the proximal (LES1), middle (LES2) and lower (LES3) parts of lower esophageal sphincter (LES) are: primary relaxation and secondary contraction in LES1, relaxation in LES2 and primary contraction followed by primary relaxation in LES3. Leucin-enkephalin in concentration of 0.1 microM and 1 microM leads to: increasing of amplitude of the primary relaxation and inhibition of secondary contraction in LES1, enhancing of amplitude of relaxation in LES2 and converts the response in LES3 from two into three component one so that the primary relaxation and the primary contraction are followed by secondary poststimulation relaxation. These effects are most probably the results of inhibition of noradrenaline and acetylcholine releasing under the influence of leucine-enkephalin and of alteration of the correlation between the neurotransmitters. It is assumed that Leucine-enkephalin operates in LES as a neuromodulator inhibiting both the adrenergic and cholinergic neurotransmission.


Conditioning hops increase triceps surae muscle force and Achilles tendon strain energy in the stretch-shortening cycle.
Postactivation potentiation can improve athletic performance, but the underlying mechanisms are poorly understood. This study investigated the effect of conditioning hops on triceps surae muscle force and tendon strain and its contribution to potentiated stretch-shortening cycle (SSC) performance. Thirty-two subjects participated in two experiments. In both experiments, subjects performed three drop jumps (DJs) after prior conditioning with 10 maximal hops, three unconditioned DJs served as control. Ground reaction forces, kinematics, and triceps surae electromyographic activity were recorded. Ultrasound imaging was used to determine fascicle lengths (FASC) of the gastrocnemius (GM) and soleus muscles (experiment 1) and the length of the Achilles tendon (experiment 2) during the DJs. DJ height after the conditioning hops was significantly higher compared to control DJs (experiment 1: +12% and experiment 2: +19%). A significantly shorter GM FASC during the DJs performed after the conditioning hops coincided with an increased force acting on the triceps surae muscle. Moreover, the triceps surae muscle-tendon unit (MTU) showed increased energy absorption during the eccentric phase of the DJs and increased energy release during the concentric phase. The second experiment revealed a higher Achilles tendon strain in DJs performed after the conditioning hops compared to control DJs. No significant differences in muscle activities were observed. The shorter FASC in GM and the larger Achilles tendon strain facilitated MTU energy transfer from the eccentric to the concentric phase during the DJ. Thereby, conditioning hops improved SSC efficacy and DJ performance.


Characterization of a multicomponent lithium lithiate from a combined x-ray diffraction, NMR spectroscopy, and computational approach.
An unusual lithium lithiate [Li(diglyme)2][(diglyme)Li2(C4H3S)3], made up from three carbanions, two lithium cations, and a single donor base molecule in the anion and a single lithium cation, coordinated by two donor base molecules, is investigated in a combined study including X-ray diffraction, NMR spectroscopy and computational approaches in solution and the solid state. While the multicomponent lithiate is the only species present in the solid state, solution NMR spectroscopy and computational methods were employed to identify a second species in solution. The dimer [(diglyme)Li(C4H3S)]2 coexists with the lithiate in solution in a 1:1 ratio, the more the higher the polarity of the solvent is. Only the combination of this multitude of methods provides a firm picture of the whole.


The role of gonadotropin-releasing hormone antagonists for the treatment of benign prostatic hyperplasia.
Medical therapy is the preferred first-line approach in the management of lower urinary tract symptoms in men with benign prostatic hyperplasia. The magnitude of the improvement in lower urinary tract symptoms observed in response to combination therapy (alpha-blocker plus 5-alpha reductase inhibitors) does not approach that achieved with prostatectomy. Various drugs have been under consideration, including BXL628, lonidamine, and phosphodiesterase inhibitors, all of which have had unacceptable side effects. The gonadotropin-releasing hormone antagonist cetrorelix is associated with dose-dependent symptom improvement and reduction of prostate volume. Elucidating the mechanism for cetrorelix-mediated improvement in lower urinary tract symptoms will likely contribute to unraveling the pathophysiology of lower urinary tract symptoms in men.


GW-SEM: A Statistical Package to Conduct Genome-Wide Structural Equation Modeling.
Improving the accuracy of phenotyping through the use of advanced psychometric tools will increase the power to find significant associations with genetic variants and expand the range of possible hypotheses that can be tested on a genome-wide scale. Multivariate methods, such as structural equation modeling (SEM), are valuable in the phenotypic analysis of psychiatric and substance use phenotypes, but these methods have not been integrated into standard genome-wide association analyses because fitting a SEM at each single nucleotide polymorphism (SNP) along the genome was hitherto considered to be too computationally demanding. By developing a method that can efficiently fit SEMs, it is possible to expand the set of models that can be tested. This is particularly necessary in psychiatric and behavioral genetics, where the statistical methods are often handicapped by phenotypes with large components of stochastic variance. Due to the enormous amount of data that genome-wide scans produce, the statistical methods used to analyze the data are relatively elementary and do not directly correspond with the rich theoretical development, and lack the potential to test more complex hypotheses about the measurement of, and interaction between, comorbid traits. In this paper, we present a method to test the association of a SNP with multiple phenotypes or a latent construct on a genome-wide basis using a diagonally weighted least squares (DWLS) estimator for four common SEMs: a one-factor model, a one-factor residuals model, a two-factor model, and a latent growth model. We demonstrate that the DWLS parameters and p-values strongly correspond with the more traditional full information maximum likelihood parameters and p-values. We also present the timing of simulations and power analyses and a comparison with and existing multivariate GWAS software package.


The relation between the extent of radiological findings and respiratory functions in pneumoconiosis cases of dental technicians who are working in Ankara.
In dental technicians, parenchymal changes caused by dust affect pulmonary functions. The evaluation of the relation between radiological scores (chest X-Ray/HRCT) indicating the extent of pulmonary involvement and the severity of functional findings in dental technicians. 440 dental technicians were evaluated with chest X-Ray, pulmonary function tests (PFTs) and high resolution computed tomography (HRCT). The degree of pulmonary involvement in radiological images was categorized based upon emphysema, the profusion of opacities, ground-glass opacity, honey combing and extent of pleural abnormalities. Mean age of the study population was 34.7 ± 8.5 and mean duration of work was 16.5 ± 7.9 years. The prevalance of Dental technicians' pneumoconiosis (DTP) was 11.1%. The most common opacity in HRCT was round opacity with a rate of 89.7%. The rate of large opacity was %14.3. There was positive correlation between ILO score and HRCT score. Negative correlation was found between ILO and HRCT scores and all pulmonary function tests (except for FEV1/FVC), while no relation was found with age, overall duration of exposure, smoking and the age ofwork onset. In Multiple regression analysis, the extent of pulmonary involvement (HRCT scores) was found to be an independent predictor of functional impairment. Functional parameter reflecting the extent of pulmonary involvement most accurately was (FEV1%). It is our suggestion that radiological measurement should be used along with functional measurements in the evaluation of functional impairment in mixed dust exposed dental technicians.


Analysis of risk factors for conversion in laparoscopic adrenalectomy: a single-institution series of 256 patients.
Although introduction of the laparoscopic approach for adrenal gland surgery revolutionized the strategy in management of adrenal gland tumors, open surgery is still a method of choice in some clinical scenarios. Moreover, laparoscopy may have limitations resulting in conversion. To assess risk factors predisposing for conversion based on our own material, including 256 laparoscopic adrenalectomies performed in 2009-2016. A retrospective analysis of patients who underwent adrenalectomies between 2009 and 2016 was conducted. Patients were analyzed for sex, body mass index (BMI), size of the adrenal gland lesion, final histopathological diagnosis and operated side of the adrenal gland, its impact on conversion rate. A total of 256 patients underwent laparoscopic adrenalectomy. The reported study comprised of 94 (36.7%) men and 162 (63.3%) women. The most common indication for adrenalectomy were adrenal cortex adenoma (n = 149; 58.2%) and pheochromocytoma (n = 48; 18.75%). The conversion rate was 3.91% (n = 10 patients). Mean BMI of patients without conversion was 27.6 kg/m2, whereas in the group of patients with conversion, BMI was 29.7 kg/m2 (p > 0.05). The conversion rate was precisely the same when comparing the right (5/126; 3.9%) and left (5/126; 3.9%) adrenal gland. There was no correlation between the size of the adrenal lesion and the risk of conversion. The laparoscopic approach remains an efficient and safe procedure for adrenal gland tumors. Based on our study, obese patients and those with pheochromocytoma are associated with a higher risk of conversion but without any statistical significance. There was no difference in the conversion rate when analyzing the size of the adrenal gland tumor. No difference was also revealed in the conversion rate when comparing both sides of laparoscopic adrenalectomy.


Mothers' experience with household roles and social support during the first postpartum year.
This prospective, longitudinal study was conducted to investigate the changes in the division of household labor, and in the emotional and practical support received by new mothers during the first postpartum year. Questionnaires were completed by 436 married, recently employed mothers at 1, 3, 6, 9, and 12 months after they had delivered their first child. Results showed that women assumed primary responsibility for the majority of household tasks studied, and that they perceived declines over time in their husbands' participation in household chores, their husbands' and others' expressions of caring, and in the frequency with which friends and relatives "helped out" during the year. Women who had had cesarean sections (versus those with vaginal deliveries) and who returned to work (versus those who stayed home) believed their husbands participated more in traditionally feminine household chores. Women's satisfaction with their husbands' contribution to household activities was significantly related to their own mental health, delivery type (cesarean section), job status (being at home vs. back at work), and family income; and to their husbands' occupation, expressions of caring, and participation in child care and certain household chores (house cleaning, grocery shopping, cooking, washing clothes and dishes, household repairs, car maintenance, and garbage removal). Overall, these findings showed diminishing levels of emotional and practical support for women at a time when the need for support was likely greater: following the birth of their first child.


Does parental involvement predict new sexually transmitted diseases in female adolescents?
African American female adolescents living in low-income urban areas are at increased risk for sexually transmitted diseases. To determine if high levels of perceived parental supervision and communication were associated with reduced gonorrhea (GC) and chlamydia (CT) incidence in low-income, African American, sexually experienced female adolescents, aged 14 to 19 years, attending urban health clinics. A prospective cohort study was used to determine the predictive value for high levels of parental supervision and communication on GC and CT infection in 158 adolescent females. Multiple logistic regression analysis explored the association between incident infection and perceived parental supervision and perceived parental communication while controlling for relevant demographic and behavioral factors (age, religious involvement, school enrollment, a 2-parent household, having a main sex partner, and having concurrent sex partners). When adjusted for age and baseline GC and CT infection, high levels of perceived parental supervision were associated with reduced GC and CT incidence (adjusted odds ratio, 0.06; 95% confidence interval, 0.01-0.31). High levels of perceived parental communication were not associated with reduced GC and CT incidence (adjusted odds ratio, 0.55; 95% confidence interval, 0.21-1.42). The link between parental supervision and disease acquisition is particularly valuable because it provides evidence that parental supervision can result in lower sexually transmitted disease rates in urban high-prevalence populations. This is important for interventions designed to increase parental involvement as a strategy for promoting protective sexual behaviors in female adolescents because it indicates that increased parental involvement can also influence subsequent disease acquisition.


Generation of a X-linked juvenile retinoschisis patient-derived induced pluripotent stem cell line ZOCi004-A.
X-linked juvenile retinoschisis (XLRS), caused by the mutation of RS1 gene, is one of the most common causes of macular degeneration for male adolescents. The mutations and clinical manifestations of the disease are diverse. Neither the relationship between the genotypes and phenotypes, nor the radical treatment like gene therapy has been found by now. Retrospective studies have shown that carbonic anhydrase inhibitors can help reduce cysts. However, the specifically pharmacological mechanism remains unknown. Here, we culture induced pluripotent stem cells by drawing peripheral blood from a patient with XLRS, which are supposed to facilitate related researches.


Intranasal melatonin nanoniosomes: pharmacokinetic, pharmacodynamics and toxicity studies.
Intranasal melatonin encapsulated in nanosized niosomes was preclinically evaluated. A formula of melatonin niosomes (MN) was selected through physicochemical and cytotoxic data for pharmacokinetic, pharmacodynamics and toxicity studies in male Wistar rats. Intranasal MN was bioequivalent to intravenous injection of melatonin, providing therapeutic level doses. Acute and subchronic toxicity screening showed no abnormal signs, symptoms or hematological effects in any animals. Transient nasal irritations with no inflammation were observed with intranasal MN, leading it to be categorized as relatively harmless. The intranasal MN could deliver melatonin to the brain to induce sleep and provide delayed systemic circulation, relative to intravenous injection and also distribute to peripheral tissue.


Left atrial dysfunction as a determinant of pulmonary hypertension in patients with severe aortic stenosis and preserved left ventricular ejection fraction.
In patients with severe aortic stenosis (AS), the presence of pulmonary hypertension (PH) has been linked to a poor prognosis. We aimed to assess the main determinants of PH in patients with severe AS and preserved left ventricular ejection fraction (LVEF). We prospectively enrolled 108 consecutive patients with isolated severe AS (indexed aortic valve area <0.6 cm2/m2) and LVEF >50%, in sinus rhythm. Left atrial (LA) function was assessed using longitudinal deformation parameters (by speckle tracking echocardiography). PH (defined as systolic pulmonary artery pressure >40 mmHg) was present in 20 patients. Patients with severe AS and PH were older (p = 0.05), had higher BNP values (p = 0.05) and a greater degree of LV diastolic dysfunction: higher E/e' and E/A ratios and lower EDT values (p < 0.03 for all) compared to patients without PH. There were no differences between groups regarding AS severity and LV systolic function parameters. Patients with PH had a more impaired LA function: lower septal and lateral late diastolic peak velocity a' (p < 0.001 and p = 0.04 respectively) and lower LA peak longitudinal strain and strain rate parameters (p ≤ 0.005 for all). In multivariable analysis, LA late diastolic longitudinal strain rate was the only independent correlate of PH in our patients (p = 0.04). Patients with isolated severe AS, preserved LVEF and PH had larger LA volumes, a more impaired LA function, and higher LV filling pressures compared to those without PH. LA booster pump function, reflected by late diastolic longitudinal strain rate, emerged as an independent correlate of PH in these patients.


Structure and kinetics assays of recombinant Schistosoma mansoni dihydrofolate reductase.
The parasite Schistosoma mansoni possesses all pathways for pyrimidine biosynthesis, in which dihydrofolate reductase (DHFR), thymidylate cycle participants, is essential for nucleotide metabolism to obtain energy and structural nucleic acids. Thus, DHFRs have been widely suggested as therapeutic targets for the treatment of infectious diseases. In this study, we expressed recombinant SmDHFR in a heterologous manner to obtain structural, biochemical and kinetic information. X-ray diffraction of recombinant SmDHFR at 1.95Å resolution showed that the structure exhibited the canonical DHFR fold. Isothermal titration calorimetry was used to determine the kinetic constants for NADP+ and dihydrofolate. Moreover, inhibition assays were performed using the commercial folate analogs methotrexate and aminopterin; these analogs are recognized as folate competitors and are used as chemotherapeutic agents in cancer and autoimmune diseases. This study provides information that may prove useful for the future discovery of novel drugs and for understanding these metabolic steps from this pathway of S. mansoni, thus aiding in our understanding of the function of these essential pathways for parasite metabolism.


Real-time PCR for quantification of eleven individual Fusarium species in cereals.
Contamination of cereals with Fusarium species is one of the major sources of mycotoxins in food and feed. Quantification of biomass of Fusarium species is essential to understand the interactions of individual species in disease development. In this study quantitative real-time PCR assays based on the elongation factor 1 alpha (EF1alpha) gene for the 11 Fusarium species F. graminearum, F. culmorum, F. poae, F. langsethiae, F. sporotrichioides, F. equiseti, F. tricinctum, F. avenaceum, F. verticillioides, F. subglutinans and F. proliferatum were developed and tested on 24 wheat and 24 maize field samples. The assays were found to be specific and sensitive. Generally, the results from the quantitative real-time PCR assays corresponded well with mycotoxin data of the field samples.


Bone marrow stem cell therapy for cardiac repair: challenges and perspectives.
Bone marrow (BM) stem cells can differentiate into multiple cell types, including vascular cells and, possibly, cardiac myocytes. Stem and progenitor cells are mobilized into the peripheral circulation early after myocardial infarction. Experimental evidence suggests that BM-derived cells injected into infarcted hearts can improve cardiac function. However, mechanisms underlying functional improvements remain unclear. Initial randomized, placebo-controlled trials in patients with acute myocardial infarction have provided controversial On the one hand, a modest but significant and sustained improvement in left ventricular function was observed in the Reinfusion of Enriched Progenitor Cells and Infarct Remodeling in Acute Myocardial Infarction (REPAIR-AMI) study contributing to the better clinical course. Results of other studies were neutral. Differences in the study design, cell processing or timing of cell delivery might explain, in part, different outcomes among studies. Furthermore, studies in patients with chronic ischemic heart disease remain observational, and therapeutic effects using surrogate end-points needs to be demonstrated. Thus, there is a need for further coordinated research with well designed, hypothesis-driven clinical trials, in parallel with fundamental research aimed at understanding the mechanisms underlying the biological and functional effects of BM cell therapy for cardiac repair.


Is myopia a public health problem in India?
Myopia, a form of refractive error is a leading cause of visual disability throughout the world. In India uncorrected refractive errors are the most common cause of visual impairment and second major cause of avoidable blindness. Due to this the public health and economic impact of myopia is enormous. Although school vision screening programme is very successful in many states, still a significant number of school going children remain unidentified and the unmet need for correcting refractive errors in children appears to be significant.


Heparanase overexpression down-regulates syndecan-1 expression in a gallbladder carcinoma cell line.
Objective To discuss the relevance of heparanase and syndecan-1 and regulation of the heparanase-syndecan1 axis in the invasiveness of gallbladder carcinoma cells. Methods 1. Generation of a gallbladder cancer cell line overexpressing a heparanase (GBD-SD) transgene. 2. Western blot analysis of syndecan-1 levels of GBD-SD and control gallbladder carcinoma (GBC-SD) cells. 3. RT-PCR analysis of syndecan-1 mRNA levels of GBD-SD and GBC-SD. 4. Evaluation of invasion and migration of GBD-SD and GBC-SD cells. Results 1. Heparanase expression in GBD-SD cells was significantly increased. 2. The syndecan-1 mRNA level of GBD-SD cells was significantly lower compared with that of GBC-SD cells. 3. The syndecan-1 DNA copy number in GBD-SD cells was significantly lower compared with that of GBC-SD. 4. The invasiveness and migration of GBD-SD cells were significantly higher compared with GBC-SD cells. Conclusions 1. The expression of heparanase negatively correlated with that of syndecan-1 in a gallbladder carcinoma cell line. 2. The expression of heparanase and syndecan-1 in gallbladder carcinomas negatively correlated, similar to other tumours. 3. The heparanase/syndecan1 axis in gallbladder carcinoma plays an important role in the invasion and metastasis, thus providing a new therapeutic target. 4. Further research is required to identify the detailed mechanisms.