Urban mosquito distributions are modulated by socioeconomic status and environmental traits in the USA.
The distribution of mosquitoes and associated vector diseases (e.g., West Nile, dengue, and Zika viruses) is likely to be a function of environmental conditions in the landscape. Urban environments are highly heterogeneous in the amount of vegetation, standing water, and concrete structures covering the land at a given time, each having the capacity to influence mosquito abundance and disease transmission. Previous research suggests that socioeconomic status is correlated with the ecology of the landscape, with lower-income neighborhoods generally having more concrete structures and standing water via residential abandonment, garbage dumps, and inadequate sewage. Whether these socioecological factors affect mosquito distributions across urban environments in the USA remains unclear. Here, we present a meta-analysis of 42 paired observations from 18 articles testing how socioeconomic status relates to the overall mosquito burden in urban landscapes in the USA. We also analyzed how socioecological covariates (e.g., abandoned buildings, vegetation, education, and garbage containers) varied across socioeconomic status in the same mosquito studies. The meta-analysis revealed that lower-income neighborhoods (regions with median household incomes <US$50,000 per household per year) are exposed to 63% greater mosquito densities and mosquito-borne illnesses compared with higher-income neighborhoods (≥US$50,000 per household per year). One common species of urban mosquito (Aedes aegypti) showed the strongest relationship with socioeconomic status, with Ae. aegypti being 126% higher in low-income than high-income neighborhoods. We also found that certain socioecological covariates correlated with median household income. Garbage, trash, and plastic containers were found to be 67% higher in low-income neighborhoods, whereas high-income neighborhoods tended to have higher levels of education. Together, these results indicate that socioecological factors can lead to disproportionate impacts of mosquitoes on humans in urban landscapes. Thus, concerted efforts to manage mosquito populations in low-income urban neighborhoods are required to reduce mosquito burden for the communities most vulnerable to human disease.


Impact of Coenzyme Q10 and Selenium on Seminal Fluid Parameters and Antioxidant Status in Men with Idiopathic Infertility.
Oxidative stress (OS) is a key contributing factor in 30-80% of male infertility cases. To date, several antioxidant treatments have been put forth to manage OS-induced male infertility. This study intended to elucidate the impact of coenzyme Q10 (CoQ10) and selenium on seminal fluid parameters and antioxidant status in infertile men with idiopathic oligoasthenoteratospermia (OAT). In this prospective study, 70 patients with idiopathic OAT were randomly allocated to receive CoQ10 (200 mg/day) or selenium (200 μg/day) for 3 months. Semen quality parameters (following WHO guidelines, 5th edition), total antioxidant capacity (TAC), catalase (CAT), and superoxide dismutase (SOD) activities were compared before and after the treatment. The results of the study showed an increase in sperm concentration with CoQ10 treatment (p < 0.01) as well as increased progressive sperm motility (p < 0.01 and p < 0.05) and total sperm motility (p < 0.01 and p < 0.05) with CoQ10 and selenium treatment respectively. There was also a significant improvement in TAC (p < 0.01 and p < 0.05) and SOD (p < 0.01 and p < 0.05) following treatment with CoQ10 and selenium respectively while CAT improved only with CoQ10 therapy (p < 0.05). Sperm concentration, motility, and morphology also correlated significantly with TAC, SOD, and CAT (r = 0.37-0.76). In conclusion, treatment with CoQ10 (200 mg) or selenium (200 μg) could improve sperm concentration, motility, and antioxidant status in infertile men with idiopathic OAT with CoQ10 providing the higher improvement.


Evaluation of Newcastle disease virus chimeras expressing the Hemagglutinin-Neuraminidase protein of velogenic strains in the context of a mesogenic recombinant virus backbone.
A major factor in the pathogenicity of Newcastle disease virus (NDV) is the amino acid sequence of the fusion protein cleavage site, but the role of other viral genes that contribute to virulence and different clinical forms of the disease remain undefined. To assess the role of other NDV genes in virus pathogenicity, a reverse genetics system was developed using the mesogenic NDV Anhinga strain to provide a backbone for generating gene mutations or gene exchanges in attempts to enhance or attenuate the virulence of that virus. Chimeras created by exchange of the Anhinga Hemagglutinin-Neuraminidase (HN) gene with HN genes of neurotropic and viscerotropic velogenic viruses produced no significant change in virus pathogenicity as assessed by conducting the mean death time and intracerebral pathogenicity index assays and by inoculation of susceptible day-old SPF chickens. Inclusion in the recombinant construct of homotypic F genes, obtained from the parental viruses, also failed to enhance the pathotype of the recombinant viruses to a velogenic pathotype. A HN gene exchange alone within the context of the NDV Anhinga backbone failed to increase virus virulence from mesogenic to velogenic pathotype and suggests a multigenic role for NDV pathogenicity.


Synaptophysin is an autoantigen in paraneoplastic neuropathy.
Paraneoplastic neurological syndromes (PNS) are often associated with antineuronal autoantibodies and many of them could be identified in the recent years. However, there are still new antineuronal binding patterns with yet unidentified autoantigens. We here describe a new autoantibody associated with paraneoplastic sensorimotor and autonomic neuropathy in a patient with small cell lung cancer. In indirect immunofluorescence test, the patient's serum colocalised with the synaptic protein synaptophysin in the cerebellum and myenteric plexus of the gut. Immunoblotting showed a 38 kDa reactivity, which is also the molecular weight of synaptophysin. Therefore a Western Blot with recombinant synaptophysin has been used and revealed reactivity of the serum against synaptophysin. In patients with non-paraneoplastic neuropathies or healthy controls, anti-synaptophysin autoantibodies were not detectable. In 20 SCLC patients without neurological syndromes, two patients had low-titer anti-synaptophysin autoantibodies. The patient's serum and IgG fraction showed cytotoxicity to primary cultured myenteric plexus neurons. We conclude that synaptophysin is an autoantigen in paraneoplastic neurological syndromes.


Endoscopic laser therapy for gastrointestinal neoplasms.
Neoplasms of the esophagus, stomach, duodenum, ampulla, colon, and rectum have been treated with endoscopic laser therapy. For the most part, the therapy has been palliative, although curative treatment has sometimes been achieved. Considerations involved in management of cancers of the GI tract by the laser are discussed and future options envisioned.


Menopause hormone therapy, migraines, and thromboembolism.
Migraine, a common form of headache, is a highly prevalent and disabling condition with a predilection for females. Migraines are neurovascular diseases. The two main types of migraines are migraines with and without aura, and several subtypes exist. There is a strong link between sex steroids and migraines. In women, migraine remissions are associated with stable and critical oestrogen levels. The literature reveals an association between migraine with aura and stroke, with a higher incidence in the young compared with that in the old. The absolute risk of stroke is low; tobacco use and a high dose of oral oestrogens may increase the risk. Early diagnosis, follow-up, and nonhormonal symptomatic and preventive treatments address the neglected area of migraines. Judicious use of hormones throughout the lifespan as needed would improve the quality of life.


CTLA-4 (CD152) enhances the Tc17 differentiation program.
Although CD8(+) T cells that produce IL-17 (Tc17 cells) have been linked to host defense, Tc17 cells show reduced cytotoxic activity, which is the characteristic function of CD8(+) T cells. Here, we show that CTLA-4 enhances the frequency of IL-17 in CD8(+) T cells, indicating that CTLA-4 (CD152) specifically promotes Tc17 differentiation. Simultaneous stimulation of CTLA-4(+/+) and CTLA-4(-/-) T cells in cocultures and agonistic CTLA-4 stimulation unambiguously revealed a cell-intrinsic mechanism for IL-17 control by CTLA-4. The quality of CTLA-4-induced Tc17 cells was tested in vivo, utilizing infection with the facultative intracellular bacterium Listeria monocytogenes (LM). Unlike CTLA-4(+/+) Tc17 cells, CTLA-4(-/-) were nearly as efficient as Tc1 CTLA-4(+/+) cells in LM clearance. Additionally, adoptively transferred CTLA-4(-/-) Tc17 cells expressed granzyme B after rechallenge, and produced Tc1 cytokines such as IFN-γ and TNF-α, which strongly correlate with bacterial clearance. CTLA-4(+/+) Tc17 cells demonstrated a high-quality Tc17 differentiation program ex vivo, which was also evident in isolated IL-17-secreting Tc17 cells, with CTLA-4-mediated enhanced upregulation of Tc17-related molecules such as IL-17A, RORγt, and IRF-4. Our results show that CTLA-4 promotes Tc17 differentiation that results in robust Tc17 responses. Its inactivation might therefore represent a central therapeutic target to enhance clearance of infection.


Splenic trauma--nonoperative management and long-term follow-up by scintiscan.
1972 TO April, 1977, 28 children with splenic rupture were managed nonoperatively. The diagnosis was confirmed by splenic scintigraphy with 99mTechnetium-sulfide colloid. Those patients whose condition was stable and satisfactory or maintained stable with intravenous fluids or blood transfusions were not operated upon. All patients sustained their ruptured spleens as a result of trauma, except for one spontaneous rupture in a patients with infectious mononucleosis. Emergency laparotomy for deterioration of clinical condition or late complications was never necessary. Splenic scans were repeated in 22 patients to assess resolution. Fourteen patients had minimal residual defects but there were no late complications detected.


Monitoring membrane protein rotational diffusion using time-averaged phosphorescence.
Rotational motions of membrane proteins have previously been measured using time-dependent phosphorescence techniques. This paper discusses a method of examining membrane protein mobility at temperatures relevant to biological systems, using a technique similar to steady-state fluorescence. The method is demonstrated using sarcoplasmic reticulum ATPase labelled with erythrosin isothiocyanate, both in its natural condition and crosslinked by incubation with glutaraldehyde. The experimentally-observed dependence of phosphorescence anisotropy on temperature is compared to a calculated anisotropy-temperature curve. Comparison is made between the anisotropy decay curves obtained by time-averaged phosphorescence and steady-state fluorescence.


Nerve growth factor stimulates the phosphorylation of a 250 kDa cytoskeletal protein in cell-free extracts of PC12 cells.
Nerve growth factor (NGF) rapidly stimulates the phosphorylation of a 250 kDa cytoskeletally-associated protein (pp250) by a protein kinase which is also associated with structural elements of the cell. We have solubilized these proteins and demonstrated that NGF-stimulated phosphorylation can be observed in cell free extracts of cytoskeletons from NGF-treated PC12 cells. The pp250 substrate and the 250-kinase were solubilized from PC12 cytoskeletons by treatment with 2 M urea. Phosphorylation of pp250 was maximally stimulated following treatment of the cells for 5 min with NGF. This effect was transient, diminishing with longer exposure of the cells to hormone. The 250-kinase preferred Mn2+ over Mg2+ and was inhibited by both Na+ and K+. The phosphorylation of pp250 was not affected by Ca2+. Upon fractionation of the urea-soluble cytoskeletal proteins by gel filtration, the 250-kinase eluted in two peaks; one peak of enzyme activity coeluting with the pp250 substrate, and a second peak of enzyme activity eluting with an apparent Mr of approximately 60 kDa. Treatment of the PC12 cells with the phorbol ester TPA also stimulated the phosphorylation of pp250, although this effect was not as great as that produced by NGF. This cell free system should be a valuable tool in the investigation of the mechanisms of NGF action.


Chiral escape of bark beetles from predators responding to a bark beetle pheromone.
Two species of predatory beetles that locate their prey, Ips pini, by responding to its aggregation pheromone have different chiral preferences to ispdienol than does the herbivore. This suggests that chiral disparity may provide some escape for bark beetles from predation, and that geographic variation in herbivore communication systems may be partially due to predator - imposed selection pressures. These results also suggest ways in which the semiochemical and biological control of North America's most damaging group of forest insects can be improved.


Tongue diagnostic parameters-based diagnostic signature in coronary artery disease patients with clopidogrel resistance after percutaneous coronary intervention.
Credible diagnostic stratification remains a challenge for coronary artery disease patients with clopidogrel resistance after percutaneous coronary intervention. Tongue diagnostic parameters-based diagnostic signatures might predict clopidogrel resistance. Clinical and tongue diagnostic parameters data were obtained from coronary artery disease patients with clopidogrel resistance after percutaneous coronary intervention patients and then analyzed. Tongue diagnostic parameters-based diagnostic signatures were developed through univariate and multivariate logistic regression analysis. The diagnostic prediction was assessed using a receiver operating characteristic curve. A total of 101 patients were consecutively identified. Then, tongue diagnostic parameters were identified as significantly associated with clopidogrel resistance diagnosis and were combined with risk factors to develop a model. The receiver operating characteristic curve analysis showed that tongue diagnostic parameters-based diagnostic signatures performed well in diagnosing clopidogrel resistance with an area under the receiver operating characteristic curve value of 0.819. This study identified a novel tongue diagnostic parameters-based diagnostic signature to reliably distinguish clopidogrel resistance diagnosis in coronary artery disease patients undergoing percutaneous coronary intervention. Further larger, multicenter prospective studies are desired to validate this model.


Environmental ozone exposure and oxidative DNA damage in adult residents of Florence, Italy.
In 71 adults residing in Florence, Italy, enrolled in a prospective study, we investigated the correlation between individual levels of oxidative DNA damage detected by the Comet assay in circulating lymphocytes, and a specific ozone exposure score calculated in 10 different time-windows (0-5 to 0-90 days) before blood drawing, based on daily measurements provided by the local environmental monitoring system. Overall, statistically significant positive correlations between average ozone concentrations and DNA damage emerged in almost all time-windows considered; correlations were more evident among males, non-smokers, and traffic-exposed workers. Multivariate regression analyses taking into account selected individual characteristics, showed an independent effect on DNA damage of average ozone concentrations in the last 60-90 days before blood drawing. Local residents showed a divergent pattern with correlations restricted to shorter time-windows. Our results suggest that ozone concentrations at ground levels modulate oxidative DNA damage in circulating lymphocytes of residents of polluted areas.


Cellular, histochemical and connective organization of the hippocampus and fascia dentata transplanted to different regions of immature and adult rat brains.
The aims of the present study were to examine the survival and the cellular and connective differentiation of intracerebral transplants of fascia dentata and hippocampus. Pieces of immature dentate and hippocampal tissue were taken from late embryonic (E18) and early postnatal (1-9 days old) rats and transplanted into the brains of 1- to 13-day-old and adult rats. After survival times from 4 days to 2 years the cellular and connective organization of the transplants was monitored in parallel series of sections stained with thionin (cell bodies), Timm's sulphide silver method (terminal fields). Nauta and Fink-Heimer methods (normal and degenerating fibers) and a method for AChE activity (cholinergic afferents). The transplants survived well in all combinations of donor and recipient ages used, and they survived and differentiated in all parts of the recipient brains, although relations to pial and ventricular surfaces appeared to be optimal. Cell differentiation continued after transplantation, and a characteristic laminar organization was retained, although least in embryonic donor tissues. The distribution of intrinsic connections was determined by the types of subfields present in the transplants and interaction with ingrown host afferents. All aberrant intrinsic connections observed corresponded to aberrant connections formed in the hippocampus and fascia dentata denervated in situ and included supragranular mossy fibers in the fascia dentata, aberrant infrapyramidal mossy fibers in CA3, spread of CA4-associated afferents beyond the normal commissural-associational zone in the dentate molecular layer together with ingrowth of CA3-associated and CA1-subiculum-associated afferents. Most transplants received a cholinergic input of host origin irrespective of the localization in the host brain, but also non-cholinergic host pathways innervated the transplants, in particular when the transplants were in close contact with host fiber tracts, and when the recipients were immature. At various transplant locations the non-cholinergic host afferents belonged to the commissural hippocampo-dentate system, the commissural hippocampal system and the callosal system. Other cases suggested innervation of dentate transplant by host entorhinal afferents. The formation and distribution of intrinsic transplant connections and connections between transplant and host appeared to be regulated by the same factors that regulate the development and reorganization of fiber connections in the normal and the in situ denervated hippocampus and fascia dentata. As a special variety of this, the distribution of cholinergic afferents adjusted to the distribution of the major intrinsic and extrinsic non-cholinergic pathways.


Mature T-cell lymphomagenesis induced by retroviral insertional activation of Janus kinase 1.
Retroviral vectors (RVs) are powerful tools in clinical gene therapy. However, stable genomic integration of RVs can be oncogenic, as reported in several animal models and in clinical trials. Previously, we observed that T-cell receptor (TCR) polyclonal mature T cells are resistant to transformation after gammaretroviral transfer of (proto-)oncogenes, whereas TCR-oligoclonal T cells were transformable in the same setting. Here, we describe the induction of a mature T-cell lymphoma (MTCL) in TCR-oligoclonal OT-I transgenic T cells, transduced with an enhanced green fluorescent protein (EGFP)-encoding gammaretroviral vector. The tumor cells were of a mature T-cell phenotype and serially transplantable. Integration site analysis revealed a proviral hit in Janus kinase 1 (Jak1), which resulted in Jak1 overexpression and Jak/STAT-pathway activation, particularly via signal transducer and activator of transcription 3 (STAT3). Specific inhibition of Jak1 markedly delayed tumor growth. A systematic meta-analysis of available gene expression data on human mature T-cell lymphomas/leukemias confirmed the relevance of Jak/STAT overexpression in sporadic human T-cell tumorigenesis. To our knowledge, this is the first study to describe RV-associated insertional mutagenesis in mature T cells.


Evaluation of right ventricular systolic and diastolic dysfunctions in patients with type 2 diabetes mellitus with poor glycemic control by layer specific global longitudinal strain and strain rate.
In order to evaluate right ventricular (RV) systolic and diastolic dysfunctions in patients with type 2 diabetes mellitus (T2DM) with poor glycemic control by layer specific global longitudinal strain (GLS) and strain rate (GLSr). 68 T2DM patients and 66 normal controls were enrolled for the present study. RV layer specific GLS (GLSEpi, GLSMid and GLSEndo represent the epimyocardial, middle layer and endomyocardial strains, respectively) and GLSr (GLSr-S, GLSr-E and GLSr-A represent the systole, early-diastole and late-diastole strain rate) were calculated by averaging each of the three regional peak systolic strains and strain rates along the entire RV free-wall (RVFW), entire RV free-wall and septal wall (RVFSW) on RV-focused view. The absolute values of RV layer specific GLS (GLSEpi, GLSMid and GLSEndo) in RVFW in T2DM patients were significantly lower than normal controls (P < 0.01), while GLSr-A was significantly larger than normal controls (P < 0.001). The absolute values of RV layer specific GLS (GLSEpi and GLSMid) in RVFSW in T2DM patients were significantly lower than normal controls (P < 0.05), while GLSr-A was significantly larger than normal controls (P < 0.001). HbA1c were poor negatived correlated with GLSEpi in RVFW and RVFSW in T2DM patients (P < 0.05). ROC analysis showed that RV layer specific GLS and GLSr-A had a high diagnostic efficacy in T2DM patients, and GLSr-A in RVFSW have the best diagnostic value in RV diastolic function in T2DM patients (AUC: 0.773). From the research, we found that layer specific GLS and GLSr could detect the RV myocardial dysfunctions and confirmed that the impaired RV systolic and diastole functions in T2DM patients with poor glycemic control. GLSr-A in RVFSW had the best diagnostic value in evaluating RV diastolic function in T2DM patients.


Probable Zika virus-associated Guillain-Barré syndrome: Challenges with clinico-laboratory diagnosis.
A 55year old woman in New York City presented in May 2016 with progressive weakness, ataxia, paresthesia, and areflexia, shortly after returning from the Dominican Republic. Lumbar puncture revealed cytoalbuminological dissociation. Due to her recent travel, Zika-associated Guillain Barré syndrome (GBS) was suspected and she underwent evaluation for recent flavivirus exposure. Zika virus RNA was not detected in serum, but Zika virus immunoglobulin M (IgM) was detected in both serum and cerebrospinal fluid. Dengue virus IgM in serum was equivocal and dengue virus IgG was detected in the serum. Plaque-reduction neutralization testing showed elevated titers to both Zika virus and dengue virus, providing evidence of recent infection with a flavivirus. The patient was diagnosed with probable Zika virus-associated GBS based on clinical findings, ancillary testing, and laboratory assays according to current guidance from the Centers for Disease Control and Prevention and the Council of State and Territorial Epidemiologists. Zika virus transmission in the Americas is resulting in increasing numbers of patients presenting with Zika virus-associated neurological syndromes. Clinical and laboratory diagnosis in these cases can be challenging and may be aided by consultation with CDC, and state and local public health agencies.


Comparison of the cardiovascular effects of isoflurane and sevoflurane as measured by magnetic resonance imaging in children with congenital heart disease.
To compare the cardiovascular effects of isoflurane and sevoflurane at minimum alveolar concentration (MAC) = 1 in children with congenital heart disease using cardiac magnetic resonance imaging. Randomized, crossover, single-blinded study. Tertiary-care teaching hospital. 10 pediatric patients with congenital heart diseases scheduled to undergo cardiac magnetic resonance studies. Patients were randomized to receive either isoflurane or sevoflurane as the "first inhalation agent." After a period or more than 20 minutes, they were crossed over to receive the "second inhalation agent." Heart rate, mean arterial pressure (MAP), cardiac index, stroke volume index, and ejection fraction (EF) at one MAC for both agents were all recorded. Both isoflurane and sevoflurane caused a significant decrease in MAP from the baseline (P = 0.013). The mean values (+/-SD) of stroke volume (mL), cardiac index (L min(-1) m(-2)), and EF (%) for isoflurane versus sevoflurane were 21.5 (+/-9.2) versus 19.6 (+/-6.2), 4.1 (+/-1.2) versus 3.7 (+/-0.87), and 64.2 (+/-14.5) versus 62.5 (+/-13.8), respectively. Both isoflurane and sevoflurane were found to be comparable in terms of cardiovascular effects.


Ten cases of Actinobaculum schaalii infection: clinical relevance, bacterial identification, and antibiotic susceptibility.
Nine of 10 strains of Actinobaculum schaalii caused urinary tract infections in predisposed individuals. Identification included 16S rRNA gene sequence analysis and use of the API Coryne and Rapid ID 32 A test systems. A. schaalii is easily overlooked due to its slow growth in ambient air and its resemblance to the normal bacterial flora on skin and mucosa.


Co-ordination behaviour of a novel bisthiourea tripodal ligand: structural, spectroscopic and electrochemical properties of a series of transition metal complexes.
The synthesis of a thiourea substituted derivative of tris(pyridyl-2-methyl)amine (TPA) is reported. Two of the three pyridine rings are substituted in the 6-position with benzoylthiourea groups. These thiourea groups undergo intramolecular hydrogen bonding to form six-membered rings which leaves one N-H group available to form hydrogen bonds with other molecules. This reports details how the complexation of this new ligand with transition metal ions yields complexes with differing geometries. Seven co-ordinate Mn(II) and Cd(II), six co-ordinate Ni(II) and five co-ordinate Co(II), Cu(II) and Zn(II) complexes have been isolated.


Antibodies to heavy neurofilament subunit detect a subpopulation of damaged ganglion cells in retina.
Neurofilaments ( NFs ) consist of three protein subunits with apparent molecular weights of 68,000 ( 68K ), 145K and 200K , which are found closely associated in most but not all locations in the nervous system. One of these exceptions is the inner retina of the mouse, where antibodies to 145K NFs label large ganglion cells throughout the extent of the cells, while antibodies to 200K NFs label only more distal portions of the optic axons but usually fail to label the ganglion cell somata and proximal axons. Very rarely, however, and more often in old mice, anti- 200K NF antibodies do label a ganglion cell completely. To determine whether these rare, completely labelled cells reflect a pathological alteration, we cut the optic axons, and report here that after a few days some of the axotomized cells could be labelled completely, in a Golgi-like fashion, by anti- 200K NF antibodies. These cells seem to represent the population that forms the projection to the bulk of the lateral geniculate nucleus, as suggested by their size, distribution and projection pattern. Hence, antibodies to the heavy NF subunit in combination with lesions may allow selective retrograde tracing of a subpopulation of ganglion cells, and such antibodies can be used to detect damage in NF-rich neurones at a very early stage, long before they eventually degenerate.


The immediate or delayed replacement of teeth by permucosal intra-osseous implants: the Tübingen implant system. Part 2: Surgical and restorative techniques.
The previous paper emphasised the importance of case selection in determining success in the use of the Tübingen implant system. Adherence to strict clinical techniques has an equally important influence on implant success and failure. This paper describes the surgical and restorative techniques involved in the use of the Tübingen implant and comments on the authors' initial experiences with this system.


Acquired immunodeficiency syndrome and the emergency physician.
Aids is a new public health disaster that is unlikely to be resolved quickly. It is manifested by a profound immune deficiency accompanied by the development of KS, PCP, and/or other opportunistic infections. A retrovirus, HTLV-III, is the probable cause of the immunosuppression, and it is transmitted in a manner similar to hepatitis B virus. Groups at highest risk include homosexual men, intravenous drug abusers, Haitians, and hemophiliacs. Therapy is largely experimental, and mortality is high. The emergency physician must be familiar with the signs, symptoms, and early management of AIDS. He should be able to offer guidance on disease prevention to both health care workers and members of high-risk groups. Allocation of major financial resources and intensive investigation are necessary to abort this cruel epidemic that affects primarily younger persons. Such investigation will undoubtedly produce new advances in virology, oncology, and immunology that will benefit medicine and society as a whole.


Rho-associated coiled-coil containing kinase inhibitor improves outcomes of direct-transfer slow-cooled bovine blastocysts.
Direct-transfer slow-cooling cryopreservation is a widely used method for bovine embryo cryopreservation. However, the transfer of cryopreserved embryos is associated with reduced pregnancy rates. Rho-associated coiled-coil containing kinase inhibitor (ROCKi) has shown promise in improving the viability of post-warmed vitrified bovine embryos. Our objective was to investigate the effects of ROCKi treatment prior to slow-cooling or after cryopreservation on embryo viability. In vitro produced bovine embryos (n = 571) were randomly assigned to one of five groups: No-cryopreservation control group (NC-C), C-C group were cryopreserved by slow-rate cooling without ROCKi at any point, R-C group were incubated with ROCKi for 2 h before cryopreservation, C-R group were not exposed to ROCKi prior to cryopreservation but were cultured with ROCKi after cryopreservation, and R-R group were exposed to ROCKi before and after cryopreservation. Treatment group was significantly associated with blastocoel re-expansion, hatching, and degeneration (P < 0.0001). Blastocoel re-expansion rates were lower (P < 0.05) in the C-C (75.2 ± 4.2%) and R-C (85.2 ± 4.7%) groups compared with the NC-C (99.0 ± 0.7%), C-R (94.7 ± 2.6%) and the R-R (94.5 ± 2.9%) groups. The median time to re-expansion was significantly slowest in the C-C group (650, 560-915 min), followed by the R-C group (538, 421-611 min), then the C-R and R-R groups were similar (291, 261-361 and 321, 271-371 min) and the NC-C group was the fastest (196, 161-230 min) (P < 0.05). Similarly, the post-thaw hatching rate was lower, and the median time to hatching slower in the C-C (58.1 ± 7.0%, 2,033, 1634-2820 min) and R-C (65.7 ± 6.9%, 1,853, 1494-2356 min) groups compared with the NC-C (81.7 ± 6.0%, 1,309, 1084-1514 min), C-R (77.2 ± 6.5%, 1,384, 1013-1754 min) and R-R (82.0 ± 5.3%, 1,209, 943-1424 min) groups. ROCKi supplementation after cryopreservation resulted in fewer degenerated embryos (C-R = 8.9 ± 2.8%, and R-R 7.1 ± 2.8%) compared to the C-C (26.8 ± 4.3%) and R-C (17.9 ± 5.7%) groups. Exposure to ROCKi both before cryopreservation and after-cryopreservation yielded the best outcomes, similar to NC-C control group without cryopreservation, and significantly better than the C-C control group without supplements. Exposure to ROCKi after cryopreservation demonstrated greater benefits compared to exposure before cryopreservation alone. These findings suggest that ROCKi can potentially enhance cryosurvival of bovine embryos.


New JCAHO standards are here: what changes do you need to make now?
Now that the long-awaited revised accreditation standards from the Joint Commission on Accreditation of Healthcare Organizations have been unveiled, what changes should you make in the way you prepare for surveys?


Which pamidronate protocol is the best for treating osteoporosis in beta-thalassemia major?
One of the most common complications in thalassemia major patients is osteopenia and osteoporosis. In this study, we compare the therapeutic effect of two treatment protocols involving infusion of 45 mg of pamidronate injection every 6 weeks (P45) and 90 mg pamidronate infusion every 4 weeks (P90). Bone mineral density was measured using dual energy X-ray absorptiometry (DEXA). Z-score of lumbar vertebra (as L total) and the femoral head (as F total) were compared before and after administration of two protocols. Bone density between the two groups was compared by Student t test and by the paired t test before and after the intervention. Data were analyzed using SPSS (18). Ninety-one patients were treated with pamidronate 45 mg (P45), and 36 patients were treated with pamidronate 90 mg (P90). Ninety-one and 36 patients received P45 and P90 protocol, respectively. Mean age was 29.4 ± 8.1 and 30.9 ± 8.0 years old in P45 and P90 groups, respectively. Sixty-two and 58 % of P45 and P90 group were female. The means of F total were -1.73 ± 1.11 and -1.47 ± 0.92 before and after treatment in patients P45 (P = 0.01) and were -1.83 ± 0.75 and -1.57 ± 0.99 in group P90 (P = 0.005), respectively. Before treatment, the means of L total were -2.95 ± 0.81 and -2.92 ± 0.66 (P = 0.8) and after treatment were -2.53 ± 1.13 and 2.81 ± 0.98 (P = 0.1) in P45 and P90 groups, respectively. In P45, between the mean of L total was statistically significant difference before and after treatment (P < 0.0001); however, there was no significant difference in the P90 group (P = 0.3). The study showed effectiveness of both protocols. As the medication is expensive and should be administrated parenterally, we recommend P45 protocol which is less expensive with fewer injections.


Could familial Mediterranean fever gene mutations be related to PFAPA syndrome?
The cause and pathophysiology of PFAPA syndrome is unknown. The aim of this study was to determine all MEFV gene variants relevant to familial Mediterranean fever in children with PFAPA syndrome. All MEFV gene variants were analyzed in patients with PFAPA syndrome. All patients were evaluated using the Gaslini scoring system. Serum immunoglobulin levels were also determined upon admission. We evaluated 64 patients with PFAPA syndrome. The median age at diagnosis was 37.5 (min-max: 6-96) months, and the percentage of male patients was 55.0%. The Gaslini diagnostic score for periodic fever was high in 81.0% of the patients. An MEFV gene mutation was found in 42 (66.0%) children. Mostly, heterozygous or compound heterozygous variants of the MEFV gene were found. Two patients were homozygous for R202Q. MEFV gene mutations were not detected in 22 (34.0%) patients. No significant differences in clinical or laboratory findings were observed between the two groups (p > 0.05), and there were no significant differences in period and duration of the fever episodes (p > 0.05). The fever of all 47 patients (100.0%) who received prednisolone during the episodes decreased within hours and did not recur. Eighteen of the patients using prednisolone underwent prophylaxis with colchicine, and the fever episodes of 9/18 (50.0%) patients using colchicine decreased within months. Most patients presenting with PFAPA syndrome have heterozygous MEFV gene mutations. Whether carrying a heterozygous MEFV gene is the primary cause of this syndrome requires further investigation.


Diabetes-induced alteration in subcellular distribution of poly(A)-rich RNA from skeletal muscle.
Skeletal muscle ribosome preparations from diabetic rats have lower polysome content than those from normal animals. The ratio of poly(A) containing RNA between polysomes and postribosomal supernatant has been measured both in normal and diabetic rats. The results suggest that in diabetic animals there is a greater proportion of free poly(A) containing RNA, in postribosomal supernatant.


Noise Reduction in Solid-State NMR Spectra Using Principal Component Analysis.
A noise reduction method was developed for solid-state nuclear magnetic resonance spectroscopy using multivariate analysis. Principal component analysis was first applied for cross-polarization/magic angle spinning and 13C spin-lattice relaxation measurements of solid-state nuclear magnetic resonance array spectra. The contact time of cross-polarization/magic angle spinning and the delay time in spin-lattice relaxation measurements were continuously changed to obtain a series of spectra, which were used for noise reduction using principal component analysis. The noise reduction method successfully produced spectra with improved signal-to-noise ratios. This noise reduction method shortens the measurement time and allows for detection of components with minute signals.


Responses of respiratory modulated and tonic units in the retrotrapezoid nucleus to CO2.
We hypothesized that the retrotrapezoid nucleus (RTN) contains both respiratory modulated (RM) and non-respiratory modulated (NRM) neurons which participate in the ventilatory response to increased CO2. We made extracellular recordings of the activity of 46 single units in the RTN of 9 decerebrate, paralyzed, ventilated cats (5 intact; 4 with carotid body and sinus ablation) under eucapnic (PCO2 = 34.2 +/- 3.5 mmHg; mean +/- SD) and hypercapnic (PCO2 = 47.4 +/- 3.4 conditions. To define a RM unit, we used the eta 2 statistic which is the ratio of the variance of the unit firing rate within respiratory cycles to that across respiratory cycles. We classified the units as RM (N = 17) if the eta 2 values in eucapnia or hypercapnia were > or = 0.25 and as NRM (N = 29) if the values were < 0.25. Overall, 19/46 units (41%) increased their firing rate with increased CO2, 5 decreased their firing rate, and 22 had no significant change in firing rate. Of 17 RM units, 8 (47%) increased their mean firing rate with hypercapnia from 7.6 +/- 3.9 to 23.2 +/- 6.8 spikes/sec. These included 5 inspiratory units, 2 inspiratory units that had an onset of firing in late expiration (Pre-I/I), and 1 expiratory unit. Seven of these also changed their discharge pattern (eucapnic eta 2 = 0.02 to 0.12; hypercapnic eta 2 = 0.34 to 0.79) Of 29 NRM units, 11 (38%) showed a significant increase in mean firing rate with CO2 stimulation from 19.8 +/- 7.2 to 31.3 +/- 8.2 spikes/sec. The RTN has RM units which change their discharge pattern and firing rate in response to increased CO2, as do units within the medulla and pons, and it has NRM units which are also responsive to increased CO2. These data indicate that some neurons of the RTN are involved in the central chemoreceptor response but they provide no direct evidence that chemoreception resides within the RTN.


Transcriptional regulation of cpsQ-mfpABC and mfpABC by CalR in Vibrio parahaemolyticus.
The cpsQ-mfpABC locus is transcribed as two operons, i.e., cpsQ-mfpABC and mfpABC, in Vibrio parahaemolyticus, and both of them are all required for biofilm formation. CalR belongs to the LysR-type transcriptional regulator family, and was originally identified as a repressor of the swarming motility and T3SS1 genes expression in V. parahaemolyticus. In the present work, a combination of qRT-PCR, primer extension, LacZ fusion expression, electrophoretic mobility shift assay, and DNase I footprinting assays were employed to elucidate the regulatory mechanisms of cpsQ-mfpABC and mfpABC by CalR. One transcription start site for each operon was detected and their activities were activated by CalR. His-CalR protected two DNA regions upstream of mfpABC against DNase I digestion, but no binding sites were detected in the promoter region of cpsQ-mfpABC, suggesting a direct and an indirect regulatory manner for mfpABC and cpsQ-mfpABC transcription by CalR, respectively. Collectively, the results presented here confirmed a new physiological role for CalR that acts as an activator for cpsQ-mfpABC and mfpABC transcription.


Primary acute myeloid leukaemia blasts resistant to cytokine-induced differentiation to dendritic-like leukaemia cells can be forced to differentiate by the addition of bryostatin-1.
Primary acute myeloid leukaemia (AML) blasts can be induced to differentiate into dendritic-like leukaemia cells (DLLC) by culture with certain cytokine combinations. DLLC offer potential for use as autologous vaccines based on their ability to present putative leukaemia-specific antigens to T cells. It has been reported, however, that in around 30-50% of AML cases the leukaemia cells are not capable of undergoing DLLC differentiation. The purpose of this study was to identify the features that represent successful DLLC differentiation and, for those cases shown to be resistant to cytokine-induced differentiation, to use differentiating agents in an attempt to overcome the differentiation block. Leukaemia cells derived from 42 patients with AML were cultured in vitro with cytokines GM-CSF, IL-4 and TNFalpha/CD40L. In 22 cases the leukaemic cells underwent DLLC differentiation based on characteristic morphological changes and expression of costimulatory and dendritic cell-associated molecules. Four cases were not evaluable because of poor viability over the culture period. The remaining 16 cases failed to show evidence of DLLC differentiation. Many of these differentiation resistant cases were associated with poor risk karyotypic features. Nine of the resistant cases were selected for further study. Differentiating agents trichostatin (TSA), azacytidine (AZA) and bryostatin (BRYO) were used in combination with cytokines for the first 96 h of the culture period. Bryostatin (BRYO) alone was shown to be capable of overcoming differentiation resistance and allowing DLLC differentiation to proceed.


Infections as Risk Factor of Sjögren's Syndrome.
Sjögren's syndrome (SS) is an autoimmune disease targeting exocrine glands, leading to low body fluids production, especially on the salivary and lacrimal glands. Due to the low saliva and tear production, the common symptoms of Sjögren's syndrome are dry eyes and dry mouth, later on leading to uncomfortable sensations on the eye surface, cornea destruction, dental caries, and oral cavity infections. Several infections are known to cause similar side-effects to Sjögren's syndrome symptoms, including low saliva flow; therefore, infection is hypothesized as one of the risk factors of Sjögren's syndrome. Based on our literature research, there are several infectious agents which cause similar disease manifestations to Sjögren's syndrome, including infections of hepatitis C virus, Epstein-Barr virus, cytomegalovirus, and human T-lymphotropic virus-1 (HTLV-1), and these four agents are found to cause persistent infection on the salivary gland after the first infection and later lead to organ destruction, thus causing sicca syndrome in the oral cavity. Other findings show possible Heliobacter pylori infection might lead on the increasing level of anti-Ro/SSA and anti-La/SSB of infected individuals. Some research has shown persistent infection could trigger autoimmune disorders due to continuous T-cells and B-cells activation in an attempt of infected cells eradication, leading to autoimmune reaction and high autoreactive cells concentration around the healthy cells causing the immune cells to eradicate the healthy cells nearby. However, the results in this literature study found persistent infection is not the only risk factor of Sjögren's syndrome but there are various unknown factors that trigger infection to develop into Sjögren's syndrome.


Congestive heart failure due to reversible cardiomyopathy in patients with hyperthyroidism.
The authors describe the clinical characteristics and response to therapy of seven patients with hyperthyroidism, dilated cardiomyopathy, and low-output cardiac failure. All patients (4 women and 3 men, age 47 +/- 4 years, mean +/- standard error of the mean) were admitted with the primary diagnosis of congestive heart failure. The cause of hyperthyroidism was Graves' disease in six patients, and toxic multinodular goiter in one. On admission, the mean serum T4 was 21 +/- 1 microgram/dL and mean serum T3:411 +/- 77 ng/mL, and serum thyroid-stimulating hormone was suppressed ( < 0.03 microU/mL) in all patients. Two-dimensional echocardiogram showed biventricular or four chamber dilatation and impaired left ventricular performance. Therapy of heart failure and hyperthyroidism resulted in rapid clinical improvement. During follow-up (5 months to 9 years), left ventricular ejection fraction improved from a mean of 28% to a mean ejection fraction of 55% (P < 0.01). Resolution of dilated cardiomyopathy with normalization of systolic function was achieved in five patients, and improvement from severe to mild left ventricular dysfunction was observed in two patients. We conclude that some patients with hyperthyroidism may have a reversible form of dilated cardiomyopathy and "low-output failure." Assessment of thyroid hormone status in patients with heart failure might permit the identification of patients with dilated cardiomyopathy and thyrotoxicosis who are likely to have reversible cardia dysfunction.


Functional correlation between olfaction and various sectioning of the lateral olfactory tract.
The lateral olfactory tract (LOT) is a central olfactory pathway, and efferent projections from the olfactory bulb are conveyed to the olfactory-related cortical structures via the LOT. The purpose of the present study is to determine the exact site of the LOT causing functional impairment in animals. After ablation of the right olfactory bulb, rats received rostrocaudal transection injuries on the left LOT at different levels between the olfactory bulb and the middle cerebral artery. Olfactory function of LOT-transected rats was studied by examining their olfactory ability to discriminate between the smell of water and cycloheximide solution, a strong repellent for rodents. Rats were divided into two groups based on their olfactory discriminative abilities. The olfaction positive (+) group achieved 83%± 1% correct responses and the distances of the LOT-transected sites from the middle cerebral artery of this group ranged between 0.8 and 2.4mm (n=8). The olfaction negative (-) group achieved 48%± 1% correct responses and the distances of the LOT-transected sites from the middle cerebral artery ranged between 2.5 and 4.2mm (n=10). From these data, we concluded that the site of the LOT critical for olfactory function is located approximately 2.5mm from the middle cerebral artery.


EX VIVO MODEL OF RABBIT INTESTINAL EPITHELIUM APPLIED TO THE STUDY OF COLONIZATION BY ENTEROAGGREGATIVE ESCHERICHIA COLI.
The diarrheal syndrome is considered a serious public health problem all over the world and is considered a major cause of morbidity and mortality in developing countries. The high incidence of enteroaggregative Escherichia coli in diarrheal syndromes classified as an emerging pathogen of gastrointestinal infections. After decades of study, your pathogenesis remains uncertain and has been investigated mainly using in vitro models of adhesion in cellular lines. The present study investigated the interaction of enteroaggregative Escherichia coli strains isolated from childhood diarrhea with rabbit ileal and colonic mucosa ex vivo, using the in vitro organ culture model. The in vitro adhesion assays using cultured tissue were performed with the strains co-incubated with intestinal fragments of ileum and colon over a period of 6 hours. Each strain was tested with three intestinal fragments for each region. The fragments were analysed by scanning electron microscopy. Through scanning electron microscopy we observed that all strains adhered to rabbit ileal and colonic mucosa, with the typical aggregative adherence pattern of "stacked bricks" on the epithelium. However, the highest degree of adherence was observed on colonic mucosa. Threadlike structures were found in greater numbers in the ileum compared to the colon. These data showed that enteroaggregative Escherichia coli may have a high tropism for the human colon, which was ratified by the higher degree of adherence on the rabbit colonic mucosa. Finally, data indicated that in vitro organ culture of intestinal mucosa from rabbit may be used to elucidate the enteroaggregative Escherichia coli pathogenesis.


Intravenous ketorolac versus morphine in children presenting with suspected appendicitis: a pilot single-centre non-inferiority randomised controlled trial.
Despite a lack of evidence demonstrating superiority to non-steroidal anti-inflammatory drugs, like ketorolac, that are associated with lower risk of harms, opioids remain the most prescribed analgesic for acute abdominal pain. In this pilot trial, we will assess the feasibility of a definitive trial comparing ketorolac with morphine in children with suspected appendicitis. We hypothesise that our study will be feasible based on a 40% consent rate. A single-centre, non-inferiority, blinded (participant, clinician, investigators and outcome assessors), double-dummy randomised controlled trial of children aged 6-17 years presenting to a paediatric emergency department with ≤5 days of moderate to severe abdominal pain (≥5 on a Verbal Numerical Rating Scale) and are investigated for appendicitis. We will use variable randomised blocks of 4-6 and allocate participants in 1:1 ratio to receive either intravenous (IV) ketorolac 0.5 mg/kg+IV morphine placebo or IV morphine 0.1 mg/kg+IV ketorolac placebo. Analgesic co-intervention will be limited to acetaminophen (commonly used as first-line therapy). Participants in both groups will be allowed rescue therapy (morphine 0.5 mg/kg) within 60 min of our intervention. Our primary feasibility outcome is the proportion of eligible patients approached who provide informed consent and are enrolled in our trial. Our threshold for feasibility will be to achieve a ≥40% consent rate, and we will enrol 100 participants into our pilot trial. Our study has received full approval by the Hamilton integrated Research Ethics Board. We will disseminate our study findings at national and international paediatric research conferences to garner interest and engage sites for a future multicentre definitive trial. NCT04528563, Pre-results.


Ultrasonographic assessment of the reticular motility in cows after administration of different doses of metoclopramide and neostigmine.
The aim of the present study was to use of ultrasonography for assessment of reticular motility after administration of various doses of metclopramide and neostigmine in cows. A total of ten Holstein cows were used in six trials in each one single dose of each drug was used. Metoclopramide was used at 0.1, 0.2 and 0.3 mg/kg intramuscularly, whereas neostigmine was used at 0.02, 0.03, and 0.04 mg/kg subcutaneously. Reticular motility was assessed using 3.5 MHz transducer just before drugs administration and every 20 minutes after administration with total time of two hours. At twenty minutes postadministration, metoclopramide at a dose rate of 0.3 mg kg significantly (P<0.01) produced shortening of the interval time between the two biphasic reticular contractions by 25% and significantly (P<0.05) increased the amplitude of the first reticular contraction by 42%, but with mild neurological signs. Neostigmine produced non-significant increase in reticular contraction rate and strength. The results of the present study indicate that metoclopramide and neostigmine at selected doses are not clinically useful agents for increasing reticular contraction rate and strength. The findings of this study in healthy animals may not be extrapolatable to findings in cattle with reticuloruminal hypomotility.


CircRNA0001859, a new diagnostic and prognostic biomarkers for COPD and AECOPD.
Dysregulation of circRNAs has been reported to be functionally associated with chronic obstructive pulmonary disease (COPD). The present investigation elucidated the potential role of CircRNA0001859 in regulating chronic obstructive pulmonary disease acute (COPD) and Acute Exacerbation of COPD (AECOPD). Mice model of COPD was established to screen and verify the dysregulated expression of CircRNA0001859. Fluorescence in situ hybridization (FISH) and quantitative real-time PCR (qRT-PCR) were carried out to detect the expression of CircRNA0001859. 38 stable COPD patients, 24 AECOPD patients, 57 COPD with lung cancer patients and 28 healthy person with age and sex matched to total patients were used for the present investigation. circRNA0001859 was downregulated in the lung tissue of mice after the three kinds of treatments (Cigarette smoke (CS)/NK alone or CS + NNK) for inducing COPD. FISH assay verified the downregulation of circRNA0001859 both in the mice lung and human bronchial epithelial cell of COPD model. Furthermore,, the level of circRNA0001859 was also downregulated in the peripheral blood of COPD and lung cancer patients. CircRNA0001859 might act as a diagnostic and prognostic biomarker for the treatment of in COPD and AECOPD with Are under the receiver operating characteristic curve (ROC curve) (AUC) of 0.7433 and 0.8717, respectively. We explored a novel circRNA0001859, which might act as a potential therapeutic biomarker for the treatment of COPD and AECOPD.


Improving the effectiveness of lifestyle interventions for gestational diabetes prevention: a meta-analysis and meta-regression.
Diet and exercise during pregnancy have been used to prevent gestational diabetes mellitus (GDM) with some success. To examine the effectiveness of lifestyle intervention on GDM prevention and to identify key effectiveness moderators to improve the prevention strategy. Pubmed, Scopus, Cochrane, and cross-references were searched. Randomised controlled trials (RCTs) evaluating lifestyle interventions during pregnancy for GDM prevention. Two independent reviewers extracted data. A random-effects model was used to analyse the relative risk (RR) and 95% confidence interval (95% CI). Meta-regressions and subgroup analyses were used to investigate important moderators of effectiveness. Forty-seven RCTs involving 15 745 participants showed that diet and exercise during pregnancy were preventive of GDM (RR 0.77, 95% CI 0.69-0.87). Four key aspects were identified to improve the preventive effect: targeting the high-risk population; an early initiation of the intervention; the correct intensity and frequency of exercise; and gestational weight gain management. Although 24 RCTs targeted women who were overweight or obese, body mass index (BMI) failed to predict the effectiveness of an intervention. Instead, interventions are most effective in high-incidence populations rather than simply in women who are overweight or obese. Furthermore, exercise of moderate intensity for 50-60 minutes twice a week could lead to an approximately 24% reduction in GDM. The best strategy to prevent GDM is to target the high-risk population predicted by risk evaluation models and to control the gestational weight gain of women through intensified diet and exercise modifications early in their pregnancy. Four key effectiveness moderators of lifestyle interventions for GDM prevention.


Status and collaboration: The case of pro bono network inequalities in corporate law.
We examine how status shapes intersectoral collaboration between large US corporate law firms and public interest legal organizations (PILOs). We draw from status theories to derive competing hypotheses about the status processes that generate organizational collaboration within this network. Supporting a status-signaling hypothesis, high-status law firms tend to collaborate with similarly high-status pro bono organizations. This gives rise to a highly unequal playing field where a handful of PILOs have a wealth of connections to high-status law firms, while the majority of PILOs only collaborate with few -relatively under-resourced- non-high-status firms. We test our hypotheses using latent space models for weighted networks. We further validate our results using more traditional QAP multiple regressions. In closing, we discuss the implications of our findings for scholarship on status and organizations, as well as the role that corporate law firms play in exacerbating inequality in terms of access to justice in the US.


Association between prenatal socioeconomic disadvantage, adverse birth outcomes, and inflammatory response at birth.
Prenatal socioeconomic disadvantage is associated with inflammation in mid- to late-life, yet whether a pro-inflammatory phenotype is present at birth and the role of adverse birth outcomes in this pathway remains unclear. We utilized data on prenatal socioeconomic disadvantage at the individual- (i.e., mother's and father's education level, insurance type, marital status, and Women, Infants, and Children benefit receipt) and census-tract level as well as preterm (< 37 weeks gestation) and small-for-gestational-age (SGA) (i.e., < 10th percentile of sex-specific birth weight for gestational age) birth status, and assessed inflammatory markers (i.e., C-reactive protein, serum amyloid p, haptoglobin, and α-2 macroglobulin) in archived neonatal bloodspots from a Michigan population-based cohort of 1000 neonates. Continuous latent variables measuring individual- and combined individual- and neighborhood-level prenatal socioeconomic disadvantage were constructed and latent profile analysis was used to create a categorical inflammatory response variable (high versus low) based on continuous inflammatory marker levels. Structural equation models were used to estimate the total and direct effect of prenatal socioeconomic disadvantage on the inflammatory response at birth as well as indirect effect via preterm or SGA birth (among term neonates only), adjusting for mother's age, race/ethnicity, body mass index, smoking status, comorbidities, and antibiotic use/infection as well as grandmother's education level. There was a statistically significant total effect of both individual- and combined individual- and neighborhood-level prenatal socioeconomic disadvantage on high inflammatory response among all neonates as well as among term neonates only, and a positive but not statistically significant direct effect in both groups. The indirect effects via preterm and SGA birth were both negative, but not statistically significant. Our findings suggest prenatal socioeconomic disadvantage contributes to elevated neonatal inflammatory response, but via pathways outside of these adverse birth outcomes.


Inhibitory effect of GnRH on isolated rat uterine muscle contractility.
The effect of GnRH upon uterine contractions of both non-pregnant and pregnant rats was examined in vitro. In the non-pregnant rat uterus, GnRH inhibited in a concentration-and-time dependent manner the contractions induced by acetylcholine and oxytocin, but not those caused by bradykinin and angiotensin II. GnRH also inhibited the rhythmic contractions induced by oxytocin in uterine strips from late pregnant rats. These findings show that GnRH has a direct inhibitory effect on the rat uterine contractions, suggesting that GnRH-like substances may exert modulatory influences upon rat uterine contractility.


Effect of galactose treatment in the puffing pattern of Chironomus thummi Balbiani rings.
Galactose feeding of Chironomus thummi larvae induces the regression of Balbiani ring c (BRc) and the full expansion of BRb, both localized in the IV salivary gland chromosome. This effect coincides with that described on BR2 and BR1 of Ch. pallidivittatus and Ch. tentans. The puffing changes of BRb and BRc throughout develoment have been studied and also show identical variations as in BR1 and BR2 of Ch. pallidivittatus and Ch. tentans. The similar behaviour of BRb and BR1, and of BRc and BR2 respectively after galactose treatment and throughout development strongly suggests that these BRs play the same physiological role in the three Chironomus species, with BRb = BR1 and BRc= BR2.


A new method for quantitative determination of dimemorfan in human plasma using monolithic silica solid-phase extraction tips.
Dimemorfan was extracted from human plasma samples (100 μL) using MonoTip C(18) tips, which were packed with a C(18)-bonded monolithic silica gel attached to the inside of the tip. The samples, which contained dimemorfan and trimeprazine as an internal standard (IS), were mixed with 300 μL of distilled water and 50 μL of 1M glycine-sodium hydroxide buffer (pH 10). The mixture was extracted onto the C(18) phase of the tip by 20 sequential aspirating/dispensing cycles using a manual micropipettor. The analytes retained on the C(18) phase were then eluted with methanol by five sequential aspirating/dispensing cycles. The eluate was injected directly into a gas chromatograph and detected by a mass spectrometer with selected ion monitoring in positive electron ionization mode. An Equity-5 fused silica capillary column (30 m × 0.32 mm i.d., film thickness 0.25 μm) gave adequate separation of the dimemorfan, IS, and impurities. The recoveries of dimemorfan and the IS spiked into plasma were ≥83%. The regression equation for dimemorfan showed excellent linearity from 0.25 to 32.0 ng/100 μL of plasma, and the limit of detection was 0.125 ng/100 μL of plasma. The maximum intra-day and inter-day relative standard deviations were 13%, while accuracy ranged from 88% to 105%. Dimemorfan was stable for at least 12 h at 4°C, 4 weeks at -80°C, and three freeze-thaw cycles in plasma. This new method is expected to have application as a pretreatment for the rapid, simple, and quantitative determination of dimemorfan in plasma samples.


Bio-enhanced fraction from Clitoria ternatea root extract ameliorates cognitive functions and in vivo hippocampal neuroplasticity in chronic cerebral hypoperfusion rat model.
Research employing a bio-enhanced fraction of Clitoria ternatea (CT) to treat cognitive decline in the animal model has not yet been found. This study aimed to determine the neuroprotective effect of CT root bioactive fraction (CTRF) in chronic cerebral hypoperfusion (CCH) rat model. CTRF and its major compound, clitorienolactones A (CLA), were obtained using column chromatography. A validated HPLC-UV method was employed for the standardization of CTRF. CCH rats were given orally either vehicle or fraction (10, 20 and 40 mg/kg). Behavioural and hippocampal neuroplasticity studies were conducted following 4 weeks post-surgery. The brain hippocampus was extracted for proteins and neurotransmitters analyses. HPLC analysis showed that CTRF contained 25% (w/w) of CLA. All tested doses of CTRF and CLA (10 mg/kg) significantly restored cognitive deficits and reversed the inhibition of neuroplasticity by CCH. However, only CTRF (40 mg/kg) and CLA (10 mg/kg) significantly reversed the elevation of amyloid-beta plaque. Subsequently, treatment with CTRF (40 mg/kg) and CLA (10 mg/kg) alleviated the downregulation of molecular synaptic signalling proteins levels caused by CCH. The neurotransmitters level was restored following treatment of CTRF and CLA. Our finding suggested that CTRF improves memory and neuroplasticity in CCH rats which was mainly contributed by CLA.


Functional and phenotypic heterogeneity of group 3 innate lymphoid cells.
Group 3 innate lymphoid cells (ILC3), defined by expression of the transcription factor retinoid-related orphan receptor γt, play key roles in the regulation of inflammation and immunity in the gastrointestinal tract and associated lymphoid tissues. ILC3 consist largely of two major subsets, NCR+ ILC3 and LTi-like ILC3, but also demonstrate significant plasticity and heterogeneity. Recent advances have begun to dissect the relationship between ILC3 subsets and to define distinct functional states within the intestinal tissue microenvironment. In this review we discuss the ever-expanding roles of ILC3 in the context of intestinal homeostasis, infection and inflammation - with a focus on comparing and contrasting the relative contributions of ILC3 subsets.


[Clinical and genetic findings in a patient with fundus albipunctatus].
The 38-year-old index patient was examined by visual acuity testing, perimetry, dark adaptometry, funduscopy, electroretinogram (ERG), and multifocal ERG. She was screened for mutations in exons 2-5 and exon/intron boundaries of the 11- cis retinol dehydrogenase gene by direct sequencing. Visual acuity was 1.0, but perimetry revealed paracentral scotomas associated with reading problems. The optic discs were normal. After 45 min of darkness there was nearly no increase of light sensitivity. After 30 min of dark adaptation, the scotopic ERG showed reduced amplitudes, but after 60 min a nearly normal level was reached. The 30-Hz flicker response of the cone ERG showed borderline implicit times, but no reduction of amplitudes. However, multifocal ERG clearly disclosed a paracentral amplitude reduction as the reason for the visual field defects. The fundus was typical for fundus albipunctatus. The patient is a compound heterozygote carrying a Ile33Asn and a Arg157Trp mutation. The paracentral visual field defects were due to cone dysfunction. So far the patient exhibits no cone dystrophy.


INFLECT: an R-package for cytometry cluster evaluation using marker modality.
Current methods of high-dimensional unsupervised clustering of mass cytometry data lack means to monitor and evaluate clustering results. Whether unsupervised clustering is correct is typically evaluated by agreement with dimensionality reduction techniques or based on benchmarking with manually classified cells. The ambiguity and lack of reproducibility of sequential gating has been replaced with ambiguity in interpretation of clustering results. On the other hand, spurious overclustering of data leads to loss of statistical power. We have developed INFLECT, an R-package designed to give insight in clustering results and provide an optimal number of clusters. In our approach, a mass cytometry dataset is overclustered intentionally to ensure the smallest phenotypically different subsets are captured using FlowSOM. A range of metacluster number endpoints are generated and evaluated using marker interquartile range and distribution unimodality checks. The fraction of marker distributions that pass these checks is taken as a measure of clustering success. The fraction of unimodal distributions within metaclusters is plotted against the number of generated metaclusters and reaches a plateau of diminishing returns. The inflection point at which this occurs gives an optimal point of capturing cellular heterogeneity versus statistical power. We applied INFLECT to four publically available mass cytometry datasets of different size and number of markers. The unimodality score consistently reached a plateau, with an inflection point dependent on dataset size and number of dimensions. We tested both ConsenusClusterPlus metaclustering and hierarchical clustering. While hierarchical clustering is less computationally expensive and thus faster, it achieved similar results to ConsensusClusterPlus. The four datasets consisted of labeled data and we compared INFLECT metaclustering to published results. INFLECT identified a higher optimal number of metaclusters for all datasets. We illustrated the underlying heterogeneity within labels, showing that these labels encompass distinct types of cells. INFLECT addresses a knowledge gap in high-dimensional cytometry analysis, namely assessing clustering results. This is done through monitoring marker distributions for interquartile range and unimodality across a range of metacluster numbers. The inflection point is the optimal trade-off between cellular heterogeneity and statistical power, applied in this work for FlowSOM clustering on mass cytometry datasets.


Emerging therapies in bone metastasis.
Skeletal lesions contribute substantially to morbidity and mortality in patients with cancer. Emerging treatments for metastatic bone disease have arisen from our understanding of the biology of bone metastases. Tumour cells alter the functions of bone-resorbing (osteoclasts) and bone-forming (osteoblasts) cells, promoting skeletal destruction. Drugs that inhibit osteoclast-mediated bone resorption (denosumab, bisphosphonates) are the standard of care for patients with skeletal metastases. In this review, we describe the progress and future directions of novel bone-targeted therapies that not only focus on osteoclasts, but also on osteoblasts and the bone microenvironment.


[Gas chromatographic mass spectrometric analysis of neurtral and acid oligosaccharides from human milk as their trimethylsilyl derivatives (author's transl)].
Gas chromatography and the 20 eV mass spectra of the human milk oligosaccharides fucosido-galactose, fucosido-lactose, di-fucosido-lactose, 3'-N-acetylneuraminyl-lactose, 6'-N-acetylneuraminyl-lactose and of N-acetyllactosamine as pertrimethylsilyl (TMS) ethers are described. The gas chromatographic separation of the L-fucose containing oligosaccharides was performed on Silicone SE 30. The sialic acid containing sugars were separated on DEXSIL 300. The correlations between oligosaccharide structures and mass spectrometric fragmentation patterns are discussed.


Visual evoked potentials after optic neuritis. Effect of time interval, age and disease dissemination.
Visual evoked potentials (VEPs) were compared among six groups of patients tested at various times after an episode of acute unilateral optic neuritis (ON). The incidence of abnormalities ranged from above 90% in patients tested during the first 6 months to about 70% when more than 2 years had elapsed. Compared with the acute stage (1-8 weeks), latency prolongation was almost 50% less in patients tested after 2-19 years. In the latter group, latencies were significantly correlated with the patients' age at the time of the attack. The findings confirm and extend the evidence of serial studies which shows that the shortening of VEP latency is a general phenomenon which proceeds for up to 2 years and possibly for longer in younger patients. When the patients with clinically isolated ON were compared with those who had a history of additional neurological episodes suggestive of multiple sclerosis (MS), up to 4 weeks after ON latencies were more prolonged in the MS group but between 4 and 8 weeks amplitudes were larger and between 8 weeks and 2 years latencies were significantly shorter. No significant differences were found in patients tested after more than 2 years. It is suggested that the electrophysiological deficit may initially be more severe in patients with disseminated disease, but that recovery may occur faster.


Effects of cannabinoids on testosterone and protein synthesis in rat testis Leydig cells in vitro.
Various water-insoluble cannabinoids as well as SP-111A, the water-soluble derivative of delta 9-tetrahydrocannabinol (delta 9-THC), reduced hCG and dibutyryl-cAMP stimulated testosterone production by rat testicular Leydig cell preparations. With 0.15 microM (0.05 micrograms/ml) 8-beta-OH-delta 9-THC the inhibition was about 50% of stimulated testosterone synthesis. Dose-related inhibitions were apparent with other cannabinoids and their order of potency in inhibiting stimulated steroidogenesis by the interstitial cells in vitro was found to be: 8-beta-OH-delta 9-THC greater than or equal to 11-OH-delta 9-THC greater than CBN = CBD = CBG greater than or equal delta 9-THC = delta 8-THC. The non-stimulated, basal, steroidogenesis was not affected even with 15 microM cannabinoids. The incorporation of L-[U-14C]leucine into the protein of Leydig cells was markedly reduced by 15 microM cannabinoids under both basal and stimulated conditions. The inhibition of steroidogenesis as well as protein synthesis in rat testicular Leydig cell preparations by various cannabinoids cannot be correlated with their psychoactivity. The present data suggest that cannabinoids at very low concentrations may interfere directly in Leydig cells with both protein and testosterone synthesis, and thus with their function.


Body talk and resilience: Aging men's experiences with mastectomy and prostatectomy.
Men's experiences with gendered cancers hinge on at least two axes - their masculinities and their age. This article offers a thematic synthesis of the qualitative research on men living with breast cancer or prostate cancer. This is a qualitative meta-analysis assessing how masculinities and aging may jointly affect men's narratives post-mastectomy or post-prostatectomy. Of particular interest was whether and how aging mediates the experience of these gendered cancers. Reviewed were all qualitative studies published between 2000 and 2020 addressing men's breast cancer and post-mastectomy experiences (N = 15) and men's lives after their prostatectomy (N = 28). The analysis followed the guidelines for thematic synthesis and grounded theory. Free codes of findings were organized into "descriptive" themes, which are then further interpreted to yield "analytical" themes. Seven descriptive themes were identified and these underlie two analytical themes - body talk and resilience. Collectively, men's illness narratives spoke about how cancer challenges their gendered identities and practices, and how they repair identities. The common experience was one of men coming to live with their post-surgical bodies by practicing 'wider,' hybrid forms of masculinities. The principal finding is that men with either type of cancer saw themselves as men and remained seen by others in terms of their gender, not their anatomically changed bodies. Unresolved was the full way aging complemented and mediated the cancer journey.


A dramatic decline in university hospital admissions of acute rheumatic fever in the eastern region of Saudi Arabia.
Acute rheumatic fever (ARF) and its sequel, chronic valvular heart disease are the most important causes for cardiovascular morbidity and mortality worldwide and mainly in developing countries. However, the incidence of ARF has declined in developed countries during the second half of 20th century. The case files of all patients admitted as new cases of ARF over ∼11 years and 8 months, both in pediatric and medical departments of a university hospital located in the eastern region of Saudi Arabia were reviewed. The demographic and clinical data and the frequency of the new cases were compared with the data that have been published by us 10 years ago from the same hospital during a similar period of time (11 years and 8 months). In the current study there was a significant decline in the frequency of admission of cases of ARF as compared to our previous study during a similar period of time, with a frequency rate of 12 cases per 100.000 hospitalizations versus 45 cases per 100.000 hospitalizations, respectively, P < 0.001. Dyspnea and chest pain as clinical features of acute rheumatic carditis (ARC) were less frequent in the current study as compared to the previous study (35% versus 44%, P = 0.02 and 10% versus 28.6%, P = 0.031). The subgroup analysis revealed also a decreased frequency of the clinical features of ARC in pediatric age group in the current study as compared to our previous study. There is a significant decline in the frequency of new hospital admissions due to ARF. This decline was associated with similar decline in the frequency of the manifestations of ARC especially in pediatric age group (1-12 years).


Bridging human and animal research: a comparative approach to studies of personality and health.
This article evaluates a comparative approach to personality and health research. We (1) review evidence showing that personality exists and can be measured in animals, (2) illustrate the benefits of animal studies for human personality research, (3) illustrate the benefits of human studies for animal personality research, and (4) provide guidelines for making cross-species comparisons. We conclude that a comparative approach can provide unique insights into personality psychology, especially into research on personality, immunity, and health.


Diagnosis and nonsurgical management of bile leak complicated by biloma after blunt liver injury: report of two cases.
We report on two patients with biliary tract injury and associated biloma following blunt abdominal trauma. Both patients underwent emergency surgery because of hemodynamic instability and bloody peritoneal aspiration. Computed tomography in the postoperative days showed severe hepatic parenchymal injury and the presence of hypodense collections with intraparenchymal and subcapsular extension, suggestive for biloma, but otherwise failed to demonstrate the exact location of the bile duct injury. One of them underwent temporary percutaneous drainage. Bile duct injury was well demonstrated on endoscopic retrograde cholangiography (ERCP) and treated by endobiliary stent placement. This report advocates the use of ERCP and endobiliary stenting in the management of biliary injury resulting from liver trauma.


Insecticidal, antimicrobial and antioxidant activities of bulb extracts of Allium sativum.
To evaluate the insecticidal, antimicrobial and antioxidant activities of bulb extracts of Allium sativum (A. sativum). Dried bulbs of A. sativum were extracted with different solvents and evaluated for insecticidal, antimicrobial and antioxidant activities. Aqueous and methanol extracts showed highest insecticidal activity (mortality rate of 81% and 64% respectively) against the larvae of Spodoptera litura (S. litura) at a concentration of 1 000 ppm. With regard to antimicrobial activity, aqueous extract exhibited antibacterial activity against gram positive (Bacillus subtilis, Staphylococcus aureu,) and gram negative (Escherichia coli and Klebsiella pneumonia) strains and antifungal activity against Candida albicans. While methanol extract showed antimicrobial activity against all the tested micro organisms except two (Staphylococcus aureus and Candida albicans), the extracts of hexane, chloroform and ethyl acetate did not show any anti microbial activity. Minimum inhibitory concentration of aqueous and methanol extracts against tested bacterial and fungal strains was 100-150 μg/mL. Antioxidant activity of the bulb extracts was evaluated in terms of inhibition of free radicals by 2, 2'-diphenly-1-picrylhydrazyl. Aqueous and methanol extracts exhibited strong antioxidant activity (80%-90% of the standard). Antioxidant and antimicrobial activity of A. sativum against the tested organisms therefore, provides scientific basis for its utilization in traditional and folk medicine. Also, our results demonstrated the insecticidal efficacy of A. sativum against S. litura, a polyphagous insect.


Later high school start time is associated with lower migraine frequency in adolescents.
To determine whether high school start time is associated with headache frequency in adolescents with migraine. Adolescence is marked by a physiologic delayed circadian phase, characterized by later bedtimes and wake times. The American Academy of Pediatrics (AAP) recommends that high schools start no earlier than 8:30 a.m., but most high schools in the United States start earlier. The study hypothesis was that adolescents with migraine whose high schools start at 8:30 a.m. or later (late group) would have lower headache frequency than those whose schools start earlier than 8:30 a.m. (early group). This was a cross-sectional Internet survey study of US high schoolers with migraine recruited online through social media. Comparisons were made between the late group and the early group. The primary outcome measure was self-reported headache days/month. In total, 1012 respondents constituted the analytic set: n = 503 in the late group versus n = 509 in the early group. Mean (SD) self-reported headache days/month was 4.8 (4.6) versus 7.7 (6.1) in the late and early groups, respectively (p < 0.001); mean difference -2.9 (95% CI -2.2 to -3.6). Mean (SD) self-reported hours of sleep on a school night was 7.9 (0.9) versus 6.9 (1.3), p < 0.001. Adjusting for total hours of sleep, sex, taking a migraine preventive, days of acute medication use, hours of homework, grade level, and missing breakfast, mean (SD) self-reported headache days/month remained lower in the late group than in the early group: 5.8 (95% CI 5.3-6.2) versus 7.1 (95% CI 6.7-7.4), (p < 0.001); mean difference -1.3 (95% CI -1.9 to -0.7). Adolescents with migraine who attend high schools that follow AAP recommendations for start times have lower self-reported headache frequency than those whose high schools start before 8:30 a.m. If prospective studies confirm this finding, shifting to a later high school start time may be an effective strategy for migraine prevention in adolescents.


3-Phenylcoumarin derivatives selectively modulate different steps of reactive oxygen species production by immune complex-stimulated human neutrophils.
Immune complex (IC) deposition in tissues triggers the release of harmful oxidant and lytic compounds by neutrophils. We examined how ten 3-phenylcoumarin derivatives affect the reactive oxygen species (ROS) production by IC-stimulated human neutrophils. Most of the 3-phenylcoumarins inhibited the luminol-enhanced chemiluminescence (CL-lum) more strongly than they inhibited the lucigenin-enhanced chemiluminescence (CL-luc), without clear signs of toxicity. The most effective CL-lum inhibitors, 6,7-dihydroxy-3-[3',4'-methylenedioxyphenyl]-coumarin (5) and 6,7-dihydroxy-3-[3',4'-dihydroxyphenyl]-coumarin (19), also inhibited myeloperoxidase activity more potently and had higher hypochlorous acid scavenging ability, but did not affect the NADPH-oxidase activity. The type, number, and position of the substituent influenced the pharmacological effects of 3-phenylcoumarins; however, the structural requirements for CL-lum and CL-luc inhibition were a little different. Compounds 5 and 19 are promising prototypes of therapeutic molecules to modulate ROS production by neutrophils in IC-mediated inflammatory diseases.


[Nitric oxide inhalation test in patients with ARDS: preliminary assessment of the effect on arterial oxygenation].
Inhaled NO can improve arterial oxygenation in ARDS. We evaluated the incidence and the magnitude of this effect during a short test of NO inhalation. This was performed in 24 consecutive mechanically ventilated patients with ARDS in order to assess the interest of NO for the therapy of hypoxemia in each case. Retro-spective study. ICU in a University Hospital. 24 hypoxemic patients with ARDS (lung injury score, LIS, 2.9 +/- 0.52), treated with conventional mechanical ventilation. Tests were performed using a mean inhalatory NO dose of 14 +/- 6 ppm. A pair of PaO2 data was obtained for each patient from two blood gas analysis, performed one just before and one 15 min after the start of NO inhalation. The mean baseline PaO2 was 76 +/- 21 mmHg and significantly increased with NO inhalation to 97 +/- 34 mmHg (p = 0.0001). Considering the individual response to NO, patients were arbitrarily classified as responders when the increase of PaO2 from baseline was > or = 10%. Sixteen patients were identified as responders, showing a mean increase of PaO2 from baseline by 40 +/- 26%, while the remaining 8 patients resulted non responders (mean change 1 +/- 5.7%). In no case a clinically significant decrease of PaO2 was observed during NO inhalation. The response to NO did not correlate with the LIS (r = 0.019) and with baseline PaO2 (r = 0.31). Inhaled NO doses of 14 +/- 6 ppm increased on the average the PaO2 in a group of ARDS patients, the individual response being however variable. A deterioration of arterial oxygenation was never observed. Even if the criteria for predicting the response to NO still remain to be defined, a short test seems to reliably provide a first estimate of the magnitude of the response.


Epigenetic biomarkers in cancer epidemiology.
Biochemical, epigenetic, genetic, and imaging biomarkers are used to identify people at high risk for developing cancer. In cancer epidemiology, epigenetic biomarkers offer advantages over other types of biomarkers because they are expressed against a person's genetic background and environmental exposure, and because epigenetic events occur early in cancer development. This chapter describes epigenetic biomarkers that are being used to study the epidemiology of different types of cancer. Because epigenetic alterations can be reversed by chemicals and activate gene expression, epigenetic biomarkers potentially have numerous clinical applications in cancer intervention and treatment and significant implications in public health. This review discusses cancer biomarkers, the characteristics of an ideal biomarker for cancer, and technologies for biomarker detection.


Structural analysis, vibrational spectra and coordinated normal of 2R-(-)-6-hydroxytremetone.
We have studied and characterized the structural and vibrational properties of 2R-(-)-6-hydroxytremetone, isolated from Xenophyllum poposum (Phil.) by infrared and Raman spectroscopy in the solid phase. The density functional theory (DFT) method together with Pople's basis set show that two stable molecules for the compound have been theoretically determined in the gas phase and that both conformations are present in the solid phase, as was experimentally observed. The harmonic vibrational wavenumbers for the optimized geometry were calculated at B3LYP/6-31G*and B3LYP/6-311++G** levels. For a complete assignment of the vibrational spectra, DFT calculations were combined with Pulay's Scaled Quantum Mechanics Force Field (SQMFF) methodology in order to fit the theoretical wavenumber values to the experimental ones. Then, a complete assignment of all the observed bands in the infrared spectrum for the compound was performed. The natural bond orbital (NBO) study reveals the characteristics of the electronic delocalization of the two structures, while the corresponding topological properties of electronic charge density are analyzed by employing Bader's Atoms in the Molecules theory (AIM).


Patients' experiences regarding self-monitoring of the disease course: an observational pilot study in patients with inflammatory rheumatic diseases at a rheumatology outpatient clinic in The Netherlands.
Self-monitoring the disease course is a relatively new concept in the management of patients with inflammatory rheumatic diseases (IRDs). The aims of this pilot study were to obtain patients' experiences with online self-monitoring, to assess information about the agreement between the disease course assessed with patient-reported outcome measures (PROMs) and an objectively measured Disease Activity Score 28 (DAS28) by the rheumatologist, and to assess adherence to predetermined PROM frequency intervals. Observational study using qualitative and quantitative methods. The rheumatology outpatient clinic of a teaching hospital in The Netherlands (secondary care). 47 patients with an IRD who regularly attended the outpatient clinic. Patients completed PROMs by using an online self-monitoring program. Their experiences regarding self-monitoring were qualitatively assessed through a focus group discussion and telephone interviews using a thematic analysis approach. Adherence to the predefined PROM frequency (completed PROM assessments within the predetermined frequency) and the agreement between the DAS28 course and PROM values (Rheumatoid Arthritis Disease Activity Index-5 and the Rheumatoid Arthritis Impact of Disease (RAID)) were quantitatively assessed using descriptives. Forty-seven patients participated, most of them diagnosed with rheumatoid arthritis (n=38, 80.9%). Three themes were identified: knowledge about and insight into the disease (activity), patient-professional interaction and functionality of the program. Mean adherence to the predetermined PROM frequency was 68.1%. The RAID showed the best agreement with the DAS28 course. Mean participation time was 350 days. Patients were predominantly positive about online self-monitoring. They indicated that they gained more knowledge about their disease, felt less dependent on the healthcare professional and valued the insight into their long-term disease course. Barriers were mostly related to technical factors. Patients were able to and willing to self-monitor their disease, which could contribute to a more efficient allocation of outpatient consultations in the future.


Cardiac Outcome of Children With SARS-CoV-2 Related Multisystem Inflammatory Syndrome.
To study the cardiac outcomes of patients with multisystem inflammatory syndrome in children (MIS-C) after 6-month of diagnosis. This review of hospital records was conducted on MIS-C patients (aged <21 year) who completed a six-month follow up. The baseline demographic, clinical, laboratory, and treatment characteristics during the acute phase, and echocardiographic findings during follow-up were collected. 116 patients (61.2% male, median age 7 years) with MIS-C were included in the study. At the time of admission, cardiac abnormalities were present in 70.7% of MIS-C patients, and the most common cardiac abnormalities were valve failure (50.9%), followed by ventricular dysfunction (39.7%), and pericardial effusion (23.3%). Six month after diagnosis, cardiac abnormalities were found in 10.3% of patients, and patients had lower rates of ventricular dysfunction (P<0.001), valve failure (P<0.001), pericardial effusion (P<0.001), and coronary involvement (P<0.001) as composed to the baseline. Intravenous immunoglobulin (IVIG) and steroid treatment significantly reduced the odds of occurrence of ventricular dysfunction (P=0.002), valve failure (P=0.004), and low ejection fraction (P=0.002) in comparison to IVIG treatment. While most MIS-C patients had abnormal echocardiographic findings at admission, only 10.3% of patients had cardiac abnormalities during follow up.


Growth factor levels in the platelet-rich plasma produced by 2 different methods: curasan-type PRP kit versus PCCS PRP system.
Potential treatments using autologous thrombocyte growth factors are an important reason to improve methods for isolating platelet-rich plasma (PRP). Two methods for extracting PRP directly by the surgeon are currently available; this study was conducted to compare the growth factor levels in the resulting PRP. Whole blood was drawn from 46 healthy donors (17 men, 29 women) aged 20 to 59 years (29.9 +/- 7.8). PRP was then separated from each sample by both the PCCS (3i) and Curasan (PRP Kit, Curasan) methods. The growth factor content differed significantly for TGF-beta1 (PCCS 467.1 ng/mL; Curasan 79.7 ng/mL) (sign test P < .0001) and PDGF-AB (PCCS 251.8 ng/mL; Curasan 314.1 ng/mL) (P < .0001); this was less significant for IGF-I (PCCS 91.0 ng//mL; Curasan 69.5 ng/mL) (P < .02). The higher platelet count in the PCCS PRP (PCCS 2,232,500/microL; Curasan 1,140,500/microL) seemed to correlate with a higher level of TGF-beta1 (Spearman's correlation coefficient, r(s) = 0.7), whereas the higher leukocyte count in the Curasan PRP (PCCS 15,300/microL; Curasan 33,150/pL) had only a minor correlation with higher levels of PDGF-AB (r(s) = 0.46). The PCCS end product has both a higher platelet count and a higher total content of the growth factors investigated. Nevertheless, the biologic effect of the evaluated growth factor levels remains unknown. The amount of PRP necessary to achieve the intended biologic effects still remains unclear. PRP contains growth factors in high concentrations. Precise predictions of growth factor levels based on the thrombocyte counts of whole blood or PRP appeared limited. There are different sources for growth factors (platelets, leukocytes, plasma).


Breast mass classification on sonographic images on the basis of shape analysis.
To evaluate the efficiency of novel shape features for classification of benign and malignant sonographic breast masses. Mass regions were extracted from the region of interest (ROI) sub-image by applying a segmentation algorithm based on the level set method. Six features (difference area with five features of mass pixel number viewed at different angles) were then extracted for further classification. A multilayered perceptron neural network (MLP) classifier was used to classify breast mass. The leave-one-case-out procedure was used on a database of 81 pathologically proved breast sonographic images of patients (47 benign cases and 34 malignant cases) to evaluate our method. The classification results showed overall accuracy was 93.83%, sensitivity 91.18%, specificity 95.74%, positive predictive value 93.94%, and negative predictive value 93.75%. The experimental results showed that this diagnostic system with the features proposed can improve the positive rate of biopsies, provide a second opinion for physicians, and be used as a useful tool for mass classification.


Synthesis of AC1903 analogs as potent transient receptor potential canonical channel 4/5 inhibitors and biological evaluation.
Transient receptor potential canonical (TRPC) channels are a class of non-selective cation channels expressed in a variety of tissues and organ systems where they functionally regulate physiological and pathological processes. TRPC5 has been shown to be a promising target for focal segmental glomerulosclerosis treatment. In this study, we report the synthesis and biological evaluation of a novel series of benzimidazole-based TRPC5 inhibitors. One compound, 8b, is 100-fold more potent than the parent compound, AC1903, in the suppression of TRPC5 channel activity. Interestingly, both AC1903 and 8b also suppressed TRPC4 channel activity with similar potency. Compound 8b also significantly blunts protamine sulfate-induced reorganization of podocyte cytoskeleton, interleukin (IL)-17-induced cell proliferation, and the expression of proinflammatory mediators in human keratinocyte HaCaT cells.


The Efficacy of Neoadjuvant Gemcitabine and Cisplatin Chemotherapy for cT3N0M0 Upper Tract Urothelial Carcinoma: The Impact of Tumor Location.
Upper tract urothelial carcinoma (UTUC) can be divided into renal pelvis tumor (RPT) and ureteral tumor (UT) based on the tumor origin. This study aimed to evaluate the efficacy of neoadjuvant chemotherapy with gemcitabine and cisplatin (NAC-GC) in terms of the pathological outcomes and oncological prognoses in patients with UTUC. We also compared its efficacy between RPT and UT. Patients who underwent radical nephroureterectomy for clinical T (cT)3N0M0 UTUC between 1999 and 2021 were included. Patients who underwent NAC-GC and those who did not were included in the NAC-GC and non-NAC-GC groups, respectively. Based on the tumor origin, we divided patients with UTUC into RPT and UT groups. Oncological prognosis was assessed using progression-free survival (PFS) and overall survival. Of 44 patients, 20 (45.5%) and 24 (54.5%) patients were in the NAC-GC and non-NAC-GC groups, respectively. The NAC-GC group had significantly lower pathological T stage and negative lymphovascular invasion (LVI), and a better PFS (p < .05) compared to those in the non-NAC-GC group. Among patients with RPT, the NAC-GC group had significantly negative LVI and better PFS than the non-NAC-GC group (p < .05). In contrast, in patients with UT, the NAC-GC group had no significant difference in pathological outcomes, and no significant difference in oncological prognosis was observed between the NAC-GC and non-NAC-GC groups. NAC-GC improves both pathological outcomes and oncological prognosis in patients with cT3N0M0 UTUC. With regard to tumor location, RPT has better pathological outcomes and oncological prognoses than UT.


Fungal glycan interactions with epithelial cells in allergic airway disease.
Human exposure to fungi results in a wide range of health outcomes, from invasive disease or allergy to immune tolerance. Inhaled fungi contact airway epithelial cells as an early event, and this host:fungal interaction can shape the eventual immunological outcome. Emerging evidence points to exposure to fungal cell wall carbohydrates in the development of allergic airway disease. Herein, we describe determinants of fungal allergenicity, and review the responses of airway epithelial cells to fungal carbohydrates. A greater understanding of the recognition of and response to fungal carbohydrates by airway epithelial cells may lead to the development of targeted therapies that ameliorate allergic airway disease.


Placement and Delinquency Outcomes Among System-Involved Youth Referred to Multisystemic Therapy: A Propensity Score Matching Analysis.
Multisystemic therapy (MST) was developed to help youth with serious social, emotional, and behavioral problems. Research on the efficacy and effectiveness of MST has shown positive outcomes in different domains of development and functioning among various populations of youth. Nonetheless, even with a large body of literature investigating the treatment effects of MST, few studies have focused on the effectiveness of MST through large-scale dissemination efforts. Utilizing a large sample of youth involved in a statewide dissemination of MST (n = 740; 43% females; 14% Black; 29% Hispanic; 49% White; Mage = 14.9 years), propensity score matching was employed to account for baseline differences between the treatment (n = 577) and comparison (n = 163) groups. Treatment effects were examined based on three outcomes: out-of-home placement, adjudication, and placement in a juvenile training school over a 6-year period. Significant group differences remained after adjusting for baseline differences, with youth who received MST experiencing better outcomes in offending rates than youth who did not have an opportunity to complete MST due to non-clinical or administrative reasons. Survival analyses revealed rates of all three outcomes were approximately 40% lower among the treatment group. Overall, this study adds to the body of literature supporting the long-term effectiveness of MST in reducing offending among high-risk youth. The findings underscore the potential benefits of taking evidence-based programs such as MST to scale to improve the well-being and functioning of high-risk youth. However, strategies to effectively deliver the program in mental health service settings, and to address the specific needs of high-risk youth are necessary.