The role of nitric oxide on matrix metalloproteinase 2 (MMP2) and MMP9 in placenta and fetus from diabetic rats.
Matrix metalloproteinases (MMPs) play an important role in tissue remodeling that accompanies the rapid growth, differentiation, and structural changes of the placenta and several fetal organs. In the present study, we investigated whether the diabetic maternal environment may alter the regulatory homeostasis exerted by nitric oxide (NO) on MMPs activity in the feto-placental unit from rats at midgestation. We found that NADPH-diaphorase activity, which reflects the distribution and activity of NO synthases (NOS), was increased in both placenta and fetuses from diabetic rats when compared with controls. In addition, while a NO donor enhanced MMP2 and MMP9 activities, a NOS inhibitor reduced these activities in the maternal side of the placenta from control rats. This regulatory effect of NO was only observed on MMP9 in the diabetic group. On the other hand, the NO donor did not modify MMP2 and MMP9 activities, while the NOS inhibitor reduced MMP9 activity in the fetal side of both control and diabetic placentas. In the fetuses, MMP2 was enhanced by the NO donor and reduced by the NO inhibitor in both fetuses from control and diabetic rats. Overall, this study demonstrates that NO is able to modulate the activation of MMPs in the feto-placental unit, and provides supportive evidence that increased NOS activity leads to NO overproduction in the feto-placental unit from diabetic rats, an alteration closely related to the observed MMPs dysregulation that may have profound implications in the formation and function of the placenta and the fetal organs.


"She vaccinated my baby and that's all…" Immunisation decision-making and experiences among refugee mothers resettled in Aotearoa New Zealand.
To prevent disease outbreaks, refugee children must be age-appropriately immunised. This qualitative study gained an in-depth understanding of refugee mothers' vaccine decision-making and experiences accessing immunisation services for their children post-resettlement in Aotearoa New Zealand. An interpretive description methodology involving focus groups with refugee mothers (N = 45) was conducted in Auckland, one of the resettlement locations. Mothers were asked about their perceptions of vaccine-preventable diseases and vaccines, their experiences of attending immunisation events, and their suggestions for improvements to immunisation services. Data were analysed following the phases of reflexive thematic analysis. Four themes were constructed. Do I have a choice? Mothers displayed pro-vaccination sentiments and parental obligation to vaccinate their children to protect their health, which underpinned their compliance with the national vaccine schedule. Transnational vaccine perceptions and behaviours It was evident that comparing their health experiences in their origin countries reinforced their positive perceptions of and trust in vaccines, health providers and their recommendations, the health system and government in New Zealand. Information sharing with their transnational networks had the potential to influence vaccine perceptions and behaviours in home and host countries. Unanswered questions and concerns Mothers discussed how many of their questions and concerns about immunisations and post-vaccine management went unanswered. Relationships and experiences matter Mothers stressed the importance of who vaccinated their child and how it was administered, highlighting that health providers' demeanour and competence influence their immunisation experiences. Health providers are encouraged to focus on creating a positive immunisation experience for refugee background families. Qualified interpreters and provision of culturally and linguistically appropriate information are required. Transnationalism at the individual level appears to influence vaccine perceptions and behaviours among refugee-background mothers. Future research focusing on caregivers with child(ren) who are not fully vaccinated would be beneficial.


Usefulness of Ki-67 for predicting the metastatic potential of rectal carcinoids.
Rectal carcinoid <10 mm can be completely removed by endoscopic procedure. However, a few authors reported that small rectal carcinoids have the potential to metastasize. Therefore, histological parameters predicting their metastatic potential are necessary. The aim of the present study was to evaluate the usefulness of Ki-67 positive/negative area ratio (Ki-67 ratio) using computer-assisted image analysis. A total of 43 patients with rectal carcinoids were retrospectively investigated. Twenty-eight patients underwent endoscopic resection and 15 patients underwent surgery. Nine of the 43 patients presented with metastatic disease. The Ki-67 ratio of all specimens was measured. Finally, the Ki-67 ratio was compared with other macroscopic or microscopic parameters for predicting lymph node or distant metastatic disease. The mean Ki-67 ratio of the metastatic and non-metastatic group was 3.9 and 1.0%, respectively (P < 0.01). The Ki-67 ratio was effective because of its high sensitivity (88.9%) and specificity (82.4%). Ki-67 ratio was superior to other microscopic parameters such as variation in nuclear size and vessel permeation. Ki-67 ratio was as effective as the other macroscopic parameters of tumor size and central depression. Based on these results it is suggested that Ki-67 is a reliable microscopic marker to predict metastatic potential of rectal carcinoids.


Notch signaling: a novel regulating differentiation mechanism of human umbilical cord blood-derived mesenchymal stem cells into insulin-producing cells in vitro.
Human umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) could be induced to differentiate into insulin producing cells (IPCs) in vitro, which have good application potential in the cell replacement treatment of type-1 diabetes. However, the mechanisms regulating this differentiation have remained largely unknown. Notch signaling is critical in cell differentiation. This study investigated whether Notch signaling could regulate the IPCs differentiation of human UCB-MSCs. Using an interfering Notch signaling protocol in vitro, we studied the role of Notch signaling in differentiation of human UCB-MSCs into IPCs. In a control group the induction took place without interfering Notch signaling. Human UCB-MSCs expressed the genes of Notch receptors (Notch 1 and Notch 2) and ligands (Jagged 1 and Deltalike 1). Human UCB-MSCs with over-expressing Notch signaling in differentiation resulted in the down-regulation of insulin gene level, proinsulin protein expression, and insulin-positive cells percentage compared with the control group. These results showed that over-expressing Notch signaling inhibited IPCs differentiation. Conversely, when Notch signaling was attenuated by receptor inhibitor, the induced cells increased on average by 3.06-fold (n = 4, P < 0.001) in insulin gene level, 2.60-fold (n = 3, P < 0.02) in proinsulin protein expression, and 1.62-fold (n = 6, P < 0.001) in the rate of IPCs compared with the control group. Notch signaling inhibition significantly promoted IPCs differentiation with about 40% of human UCB-MSCs that converted to IPCs, but these IPCs were not responsive to glucose challenge very well both in vitro and in vivo. Hence, further research has to be carried out in the future. Notch signaling may be an important mechanism regulating IPCs differentiation of human UCB-MSCs in vitro and Notch signaling inhibition may be an efficient way to increase the number of IPCs, which may resolve the shortage of islet of cell replacement treatment of type-1 diabetes.


New-generation radiofrequency technology.
Radiofrequency (RF) technology has become a standard treatment in aesthetic medicine with many indications due to its versatility, efficacy, and safety. It is used worldwide for cellulite reduction; acne scar revision; and treatment of hypertrophic scars and keloids, rosacea, and inflammatory acne in all skin types. However, the most common indication for RF technology is the nonablative tightening of tissue to improve skin laxity and reduce wrinkles. Radiofrequency devices are classified as unipolar, bipolar, or multipolar depending on the number of electrodes used. Additional modalities include fractional RF; sublative RF; phase-controlled RF; and combination RF therapies that apply light, massage, or pulsed electromagnetic fields (PEMFs). This article reviews studies and case series on these devices. Radiofrequency technology for aesthetic medicine has seen rapid advancements since it was used for skin tightening in 2003. Future developments will continue to keep RF technology at the forefront of the dermatologist's armamentarium for skin tightening and rejuvenation.


Papillary thyroid cancer: controversies in the management of neck metastasis.
To describe our institution's experience with the management of cervical metastasis in papillary thyroid carcinoma (PTC) and suggest a treatment strategy based on the incidence of pathologic nodes and cervical recurrence in patients undergoing varied surgical approaches to address lymphadenopathy over the study dates. Between December 1, 1972 and September 1, 2007, 183 total patients diagnosed with PTC at the University of Pittsburgh Medical Center were treated with lymphadenectomy. Pathologic parameters, including number of pathologic nodes and extent of lymphadenectomy were correlated to disease recurrence. Retrospective chart review. The incidence of pathologic nodes in lymphadenectomy specimens (57.9%) and the recurrence rate (33.7%) were high, in our study population. In comparing techniques with address lymphadenopathy, the highest recurrence rate was observed in patients with pathologic nodes treated with "lymph node plucking" procedures at the time of thyroidectomy and those patients with multiple nodes involved. Few patients with no pathologic nodes, regardless of lymphadenectomy extent recurred. Our data show that limited neck dissection and disease burden are associated with the highest rates of cervical recurrence in regional metastatic PTC. Comprehensive functional neck dissection would seem to offer the patient the best opportunity for control of cervical metastasis. The American Thyroid Association recommends thyroglobulin monitoring and ultrasound evaluation of the neck in all postoperative patients. Therefore patients with the diagnosis of papillary thyroid cancer need preoperative ultrasound of the lateral neck and fine needle aspiration of suspicious nodes to avoid under-treating patients scheduled for total thyroidectomy. Neck dissection of the compartments in which pathologic nodes were detected (central, lateral, or both) should then be undertaken at the time of initial thyroidectomy. Eliminating all disease remains elusive and the prognostic significance of cervical disease persistence and recurrence is still unknown. Patients with cervical metastasis are at substantial risk of regional recurrence, necessitating repeat surgery. Parathyroid implantation should be considered at the time of the initial surgery to reduce the risk of hypoparathyroidism should subsequent procedures be required. More information will be necessary to better understand the prognostic significance of these regional metastases. In the interim, many patients may be over-treated, whereas some remain at risk of death because of disease.


Chemical interactions and compromised immune system.
Only a limited number of reports are available on interactions between chemicals in relation to their effects in modifying immune functions. In many cases the exact site of chemical immunotoxicity is not well understood because immune functions are highly complex and multifaceted. Chemical interactions that have been proposed are difficult to investigate. In several cases the immunotoxicity of one chemical has been modified by a second chemical that alters xenobiotic metabolism. Immunomodulation by drugs having opposite effects on the immune system has been reported. Metals can either enhance or suppress immune responses and studies involving interactions of metals suggest both synergistic and antagonistic effects on immune responses. Various environmental chemicals that modify the immune functions may also interact with chemical carcinogens, especially since several carcinogens are also immunosuppressive.


Mechanisms of mutual functional interactions between HNF-4alpha and HNF-1alpha revealed by mutations that cause maturity onset diabetes of the young.
Hepatic nuclear factor (HNF)-4alpha and HNF-1alpha are key endodermal transcriptional regulators that physically and functionally interact. HNF-4alpha and HNF-1alpha cooperatively activate genes with binding sites for both factors, whereas suppressive interactions occur at regulatory sequences with a binding site for only one factor. The liver fatty acid binding protein gene (Fabp1) has binding sites for both factors, and chromatin precipitation assays were utilized to demonstrate that HNF-4alpha increased HNF-1alpha Fabp1 promoter occupancy during cooperative transcriptional activation. The HNF4 P2 promoter contains a HNF-1 but not HNF-4 binding site, and HNF-4alpha suppressed HNF-1alpha HNF4 P2 activation and decreased promoter HNF-1alpha occupancy. The apolipoprotein C III (APOC3) promoter contains a HNF-4 but not HNF-1 binding site, and HNF-1alpha suppressed HNF-4alpha APOC3 activation and decreased HNF-4alpha promoter occupancy. Maturity onset diabetes of the young (MODY) as well as defects in hepatic lipid metabolism result from mutations in either HNF-4alpha or HNF-1alpha. We found that MODY missense mutant R127W HNF-4alpha retained wild-type individual Fabp1 activation and bound to HNF-1alpha better than wild-type HNF-4alpha, yet did not cooperate with HNF-1alpha or increase HNF-1alpha Fabp1 promoter occupancy. The R127W mutant was also defective in both suppressing HNF-1alpha activation of HNF4 P2 and decreasing HNF-1alpha promoter occupancy. The HNF-1alpha R131Q MODY mutant also retained wild-type Fabp1 activation and bound to HNF-4alpha as well as the wild type but was defective in both suppressing HNF-4alpha APOC3 activation and decreasing HNF-4alpha promoter occupancy. These results suggest HNF-1alpha-HNF-4alpha functional interactions are accomplished by regulating factor promoter occupancy and that defective factor-factor interactions may contribute to the MODY phenotype.


Dynamic dual-functional optical wave plate based on phase-change meta-molecules.
Optical metasurfaces have shown great potential for revolutionizing wave plates by enabling compact footprints and diversified functionalities. However, most metasurface wave plates (meta-WPs) are typically passive, featuring defined responses after fabrication, whereas dynamic meta-WPs have so far often been limited to ON and OFF states. Here, we design a dynamic dual-functional meta-WP based on judiciously designed low-loss Sb2Se3 meta-molecules at the telecom wavelength of 1.55 µm which enables reconfigurable linear-to-circular and linear-to-linear polarization conversion for orthogonal linear polarizations when Sb2Se3 transits between amorphous and crystalline states. In addition, a comprehensive electro-thermal simulation is carried out to verify the phase change process for realistic implementation. The designed dynamic dual-functional wave plate may open new avenues for developing integrated adaptive photonics with dynamic and multiplexed functionalities.


Coarse-grained stochastic models for tropical convection and climate.
Prototype coarse-grained stochastic parametrizations for the interaction with unresolved features of tropical convection are developed here. These coarse-grained stochastic parametrizations involve systematically derived birth/death processes with low computational overhead that allow for direct interaction of the coarse-grained dynamical variables with the smaller-scale unresolved fluctuations. It is established here for an idealized prototype climate scenario that, in suitable regimes, these coarse-grained stochastic parametrizations can significantly impact the climatology as well as strongly increase the wave fluctuations about an idealized climatology.


Gene expression of tumor necrosis factor alpha and interferon gamma in the lungs of Mycoplasma pulmonis-infected mice.
ICR mice were infected intranasally with Mycoplasma pulmonis isolated freshly from the lungs of a rat with pneumonia. We demonstrated with high reproducibility the expressions of messenger RNAs of cytokines, tumor necrosis factor alpha (TNF alpha) and interferon gamma (IFN gamma) in the lung tissue of M. pulmonis-infected mice by the reverse transcriptase-polymerase chain reaction and confirmed specific mRNA of the cytokines by restriction endonuclease digestion. Both the viable population of M. pulmonis in the lung tissue and the titers of the neutralizing antibody in the serum increased between 7 and 21 days, and reached their maximum 35 days after infection. The pneumonia in mice progresses with the development of lung lesions after 7 days of infection. The early lesions are characterized primarily by neutrophils and edema in the alveolar spaces. mRNAs prepared from the lung tissue of M. pulmonis-infected and -uninfected mice were also tested for the presence of messages specific to TNF alpha and IFN gamma by the reverse transcriptase-polymerase chain reaction. The expression of the genes encoding TNF alpha and IFN gamma was constitutively demonstrated from 24 hr through 35 days after the intranasal inoculation of M. pulmonis. Furthermore, cells of two types, adherent and nonadherent cells, in bronchoalveolar lavage fluids obtained from the mice 3 weeks after inoculation of M. pulmonis were also found to express the genes of TNF alpha and IFN gamma respectively. These data suggest that these cytokines would play a role in both stimulation in the development of pathological changes in mycoplasmal infection, affecting the inflammatory responses.


Hippocampal-Medial Prefrontal Event Segmentation and Integration Contribute to Episodic Memory Formation.
How do we encode our continuous life experiences for later retrieval? Theories of event segmentation and integration suggest that the hippocampus binds separately represented events into an ordered narrative. Using a functional Magnetic Resonance Imaging (fMRI) movie watching-recall dataset, we quantified two types of neural similarities (i.e., "activation pattern" similarity and within-region voxel-based "connectivity pattern" similarity) between separate events during movie watching and related them to subsequent retrieval of events as well as retrieval of sequential order. We demonstrated that compared with forgotten events, successfully remembered events were associated with distinct "activation patterns" in the hippocampus and medial prefrontal cortex. In contrast, similar "connectivity pattern" between events were associated with memory formation and were also relevant for retaining events in the correct order. We applied the same approaches to an independent movie watching fMRI dataset as validation and highlighted again the role of hippocampal activation pattern and connectivity pattern in memory formation. We propose that distinct activation patterns represent neural segmentation of events, while similar connectivity patterns encode context information and, therefore, integrate events into a narrative. Our results provide novel evidence for the role of hippocampal-medial prefrontal event segmentation and integration in episodic memory formation of real-life experience.


Inferences on the inheritance of congenital anomalies from temporal and spatial patterns of occurrence.
Most congenital anomalies are believed to result from interactions between genetic and environmental determinants, whose relative importance is not generally established. Temporal and spatial patterns allow inferences on the underlying transmission processes; in particular, it is possible to discriminate between sporadic and nonsporadic genetic factors, and to find evidence for the effects of environmental heterogeneity in time and space. We studied the occurrence of 14 anomalies in 14 registries of Western Europe. Four basic patterns have been identified: (1) Chromosomal abnormalities have uniform incidences and do not show significant geographical variation, in agreement with the expected consequences of randomly scattered nondisjunction events. (2) The homogeneous spatial distributions of three severe malformations (renal agenesis, oesophageal atresia, ano-rectal atresia) are consistent with both the effects of fresh mutation and segregation of detrimental alleles. (3) A decrease of similarity of incidences with distance has been observed for neural tube defects, and this is the expected consequence of isolation by distance on genetically determined traits. (4) For facial clefts, polydactyly, and hypospadias, all postulated processes poorly account for the observed temporal and spatial patterns.


Coexpression of connexin45 and -32 in oligodendrocytes of rat brain.
Connexin proteins are the subunits of gap junction channels, and are encoded by a gene family. Although several connexin mRNAs were detected in brain, only a few connexin-proteins have been localized to specific cell types in this tissue. Here we describe expression of connexin45 protein in oligodendrocytes in rat hippocampus. Double immunofluorescent staining using specific antibodies to connexin45 and connexin32 paired with cell-type specific marker proteins revealed that connexin45 and connexin32 were co-expressed and colocalized in oligodendrocytes. Each of the connexin antibodies gave rise to the same pattern of punctate fluorescence in the plasma membrane of cell bodies and proximal processes of oligodendrocytes. Connexins in the plasma membrane of oligodendrocytes may form gap junctions between oligodendrocytes, or between oligodendrocytes and astrocytes. Expression of connexin45 in oligodendrocytes may prevent dysmyelinating effects of connexin32 mutations in the central nervous system of Charcot-Marie-Tooth (X-type) patients.


Preconditioning and neurotrophins: a model for brain adaptation to seizures, ischemia and other stressful stimuli.
The amino acid glutamate, the major excitatory neurotransmitter in the central nervous system, activates receptors coupled to calcium influx. Excessive activation of glutamate receptors in conditions such as severe epileptic seizures or stroke can kill neurons in a process called excitotoxicity. However, subtoxic levels of activation of the N-methyl-D-aspartate (NMDA) type of glutamate receptor elicit adaptive responses in neurons that enhance their ability to withstand more severe stress. A variety of stimuli induce adaptive responses to protect neurons. For example, sublethal ischemic episodes or a mild epileptic insult can protect neurons in a process referred to as tolerance. The molecular mechanisms that protect neurons by these different stressful stimuli are largely unknown but they share common features such as the transcription factor, nuclear factor kappa B (NF-kappaB), which is activated by ischemic and epileptic preconditioning as well as exposure to subtoxic NMDA concentrations. In this article, we describe stress-induced neuroprotective mechanisms highlighting the role of brain-derived neurotrophic factor (BDNF), a protein that plays a crucial role in neuronal survival and maintenance, neurogenesis and learning and memory.


[The diagnosis and treatment of ureteral fistulae].
Causes and duration of ureteral fistula development were analyzed for 96 patients treated in the last decade. The study was performed of three variants of a clinical picture prior to the fistula onset, renal and ureteral function. The duration of the fistula, urinary and bioelectric ureteral changes were related. Indications are specified for each method of the operative treatment of the fistula. The transabdominal approach in ureterocystoneostomy turned out most beneficial.


Development, Optimization, and Field Evaluation of the Novel Collapsible Passive Trap for Collection of Mosquitoes.
Disease surveillance for mosquito-borne pathogens in remote areas can be challenging. Most traps used to collect mosquitoes either need a source of electricity or are bulky and inflexible, making transportation awkward. To reduce these issues we developed three Collapsible Passive Traps (CPTs) and conducted trials in Cairns, Australia to evaluate the optimal design for a CPT and compared them to traditionally-used traps such as Centers for Disease Control and Prevention (CDC) and Encephalitis Vector Surveillance (EVS) light traps. We found that two of the CPTs collected comparable numbers of mosquitoes and that one of the CPTs outperformed the CDC light trap in collecting Aedes species. Mosquitoes did not have to pass through a fan while entering the CPT, and thus were not damaged and were often alive. Our results suggest that the CPT can be an effective trap for mosquito surveillance, especially in remote areas.


The AluI-induced bands in great apes and man: implication for heterochromatin characterization and satellite DNA distribution.
Restriction endonucleases have recently been proved to be active on fixed chromatin, producing differences in staining of metaphase chromosomes. In this paper we show the results obtained by treating the metaphase chromosomes of Pan troglodytes, Pan paniscus, and Gorilla gorilla with the restriction enzyme AluI. These results demonstrate qualitative differences in the telomeric heterochromatin between Pan and Gorilla despite the fact that these areas appear homogeneous in the two genera by the C-banding method. The results found with individual chromosomes in the different species also appear relevant, in the light of the evolutionary relationships between these nonhuman primates and man. Lastly, the results suggest the presence, in great apes, of some highly repetitive DNA sequences different from the human satellites I-IV.


Cellular responses and gene expression profile changes due to bleomycin-induced DNA damage in human fibroblasts in space.
Living organisms in space are constantly exposed to radiation, toxic chemicals or reactive oxygen species generated due to increased levels of environmental and psychological stresses. Understanding the impact of spaceflight factors, microgravity in particular, on cellular responses to DNA damage is essential for assessing the radiation risk for astronauts and the mutation rate in microorganisms. In a study conducted on the International Space Station, confluent human fibroblasts in culture were treated with bleomycin for three hours in the true microgravity environment. The degree of DNA damage was quantified by immunofluorescence staining for γ-H2AX, which is manifested in three types of staining patterns. Although similar percentages of these types of patterns were found between flight and ground cells, there was a slight shift in the distribution of foci counts in the flown cells with countable numbers of γ-H2AX foci. Comparison of the cells in confluent and in exponential growth conditions indicated that the proliferation rate between flight and the ground may be responsible for such a shift. We also performed a microarray analysis of gene expressions in response to bleomycin treatment. A qualitative comparison of the responsive pathways between the flown and ground cells showed similar responses with the p53 network being the top upstream regulator. The microarray data was confirmed with a PCR array analysis containing a set of genes involved in DNA damage signaling; with BBC3, CDKN1A, PCNA and PPM1D being significantly upregulated in both flight and ground cells after bleomycin treatment. Our results suggest that whether microgravity affects DNA damage response in space can be dependent on the cell type and cell growth condition.


glp-1 and inductions establishing embryonic axes in C. elegans.
Two successive inductions specify blastomere identities, that is complex cell lineages and not specific tissues, in a major part of the early C. elegans embryo. The first induction acts along the anterior-posterior axis of the embryo and the second along the left-right axis. During the first induction a specific lineage program is induced in the posterior of the two AB blastomeres present in the four cell embryo. During the second induction, almost all of the left-right differences of the embryo are specified by interactions between a single signalling blastomere, MS, and the AB blastomeres that surround it. In both cases the inductions break the equivalence of pairs of blastomeres. The inductions correlate with the cell-cell contacts to the inducing blastomeres. The stereotype cleavage patterns of the early embryo results in invariant cell-cell contacts that guarantee the specificity of the inductions. Both inductions are affected in embryos mutant for glp-1 suggesting that in both cases glp-1 is involved in the reception of the signal.


Alpha-l-Fucosidase Immunoassay for Early Detection of Hepatocellular Carcinoma.
Detection of alpha-l-fucosidase has been shown to have relevance in diagnosing hepatocellular carcinoma. Few assays have been developed to measure this enzyme, with most relying on colorimetric techniques involving the enzyme's kinetics. While these assays are facile and quick, the sensitivity is not always sufficient for early tumor detection. To improve upon previous assays for alpha-l-fucosidase, a fluorescence based immunoassay was produced implementing an alpha-l-fucosidase specific antibody (FUCA2). The immobilization of the alpha-l-fucosidase-specific antibody onto a quartz slide was investigated with several bioconjugation approaches and an immunoassay for detection of alpha-l-fucosidase was produced. The immunoassay was utilized to produce calibration curves for quantifying alpha-l-fucosidase concentrations in both PBS and human blood serum. A detection limit of 10 nM was found using human blood serum, which is well below the diagnostic cutoff point of 80 nM.


Effect of cold atmospheric plasma versus conventional surface treatments on the bond strength between CAD-CAM zirconia and resin cement.
To evaluate the shear bond strength of two different resin cements to zirconia after treatment with cold atmospheric pressure plasma (CAPP) and other surface modification methods. 189 specimens fabricated from Vita YZ-HT zirconia discs were divided into nine surface treatment groups: (1) Untreated (U), (2) Sandblasting (S), (3) Laser (L), (4) Plasma (P), (5) Primer (PR), (6) Sandblasting + Primer (SPR), (7) Laser + Primer (LPR), (8) Plasma + Primer (PPR), (9) Laser + Plasma + Primer (LPPR). Surface roughness (Ra) and contact angles were measured (n= 10 each), and scanning electron microscopy (SEM) and energy dispersive spectrometry (EDS) analyses were performed (n= 1 each). Specimens were cemented with RelyX Ultimate Clicker adhesive resin cement or Theracem self-adhesive resin cement. The specimens were subjected to shear bond strength (SBS) test. Modes of failure were examined under a stereomicroscope and visualized by SEM. The S, PR, SPR, PPR and LPPR groups showed significantly greater Ra values than the U group. Significantly lower contact angles were observed in the S, P and L groups versus the U group. The SBS values of SPR, PPR and LPPR groups were significantly greater than those of the U group. CAPP can improve zirconia-resin cement bond strength by increasing the wettability of zirconia surfaces pretreated with the 10-methacryloyloxydecyl dihydrogen phosphate (MDP) primer. The use of cold atmospheric pressure plasma in combination with a primer is a promising clinical procedure for improving resin cement bonding to zirconia surface.


Eosinophilic globules in 3 cases of glomeruloid hemangioma of the head and neck: a characteristic offering more evidence for thanatosomes with or without POEMS.
Glomeruloid hemangiomas (GHs) are glomeruli-like capillary tufts lined by endothelial cells that contain periodic acid-Schiff (PAS) positive eosinophilic globules (EGs). These hemangiomas are characteristic cutaneous manifestation of POEMS syndrome (Polyneuropathy, Organomegaly, Endocrinopathy, M-protein, and Skin changes). Hemangiomas histologically identical to GHs but not associated with POEMS have recently been designated as papillary hemangiomas. In this report, we present solitary head and neck GHs in 3 patients, 2 without POEMS, with particular attention to the characteristic EGs. We performed immunostains for hemoglobin A, kappa and lambda light chains, factor VIII-related antigen, CD31 and CD34, PAS stain after diastase digestion (PASD), and electron microscopic examinations on routinely fixed tissues containing EGs. Eosinophilic globules stained uniformly positive for PASD but only peripherally positive for hemoglobin and light chains on surfaces, with interiors negative for antigens. Factor VIII-related antigen and CD31 and CD34 confirmed cells containing EGs to be endothelial. Electron microscopic examination suggested that EGs are enlarged secondary lysosomes (thanatosomes). These features fail to support red blood cells or immunoglobulins as EG constituents. Glomeruloid hemangiomas may be vascular proliferations stimulated by endothelial cells' protein phagocytosis but not by phagocytosis of either hemoglobin-containing red blood cells or immunoglobulins. The vascular lesions in POEMS syndrome appear identical to papillary hemangioma in cases without the other syndromic manifestations.


Preanalytic Variables and Tissue Stewardship for Reliable Next-Generation Sequencing (NGS) Clinical Analysis.
An enduring goal of personalized medicine in cancer is the ability to identify patients who are likely to respond to specific therapies. Our growing understanding of the biology and molecular signatures of individual tumor types has facilitated the identification of predictive biomarkers and has led to an increasing number of diagnostic tests to be performed, often as serial and distinct assays on limited tumor specimens. The biomarker diagnostics field has been revolutionized by next-generation sequencing (NGS), which provides a comprehensive overview of the genomic profile of a tumor. Many preanalytic variables can influence the accuracy and reliability of NGS results. Standardization of preanalytic variables is, however, complicated by the plethora of specimen acquisition and processing methods. Variables across the tissue journey, including specimen acquisition, specimen fixation, and sectioning, as well as postfixation processing, such as nucleic acid extraction, library preparation, and choice of sequencing methods, are critical for the reliability of NGS analysis; thus, standardization would be beneficial. In this article, each step in the tissue journey is outlined, with specific focus on preanalytic variables that can influence NGS results. Practical considerations for standardization of these variables are provided to facilitate accurate, reliable, and reproducible NGS-based molecular characterization of tumors, ultimately informing diagnosis and guiding treatment.


[Immunopharmacological actions of neurotropin (3): Anti-allergic actions of neurotropin (author's transl)].
Neurotropin (NSP) is an extract isolated from vaccinia virus-inoculated and inflamed skin of rabbits. The anti-allergic actions of NSP were studied in the present paper. Death from anaphylactic shock in BALB/c mice mediated by active systemic anaphylaxis (ASA) or heterologous passive systemic anaphylaxis (PSA) was completely prevented in one of five cases by NSP given 5000 micrograms/animal i.v.. However in mice, NSP at a dose of 10 to 1000 micrograms/animal i.v. did not have any preventive effect on death from anaphylactic shock induced by ASA, homologous PSA, or heterologous PSA. NSP slightly inhibited histamine release from rat mast cells mediated by mouse IgE antibody, calcium ionophore A23187, or compound 48/80, but this inhibition was not in a dose-dependent fashion. NSP did not behave synergistically with isoproterenol- or theophylline- induced inhibition of mouse IgE antibody-mediated histamine release from rat mast cells. NSP did not inhibit D2O-enhanced histamine release from sensitized rat mast cells. NSP clearly inhibited antigen-induced histamine release from leukocytes of mite-sensitive patients with or without asthmatic attack. Potent inhibition was observed when leukocytes taken from patients with asthmatic attack were used. These results suggest that the anti-allergic action of NSP is not responsible for elevation of cyclic AMP levels or disruption of microtubules in target cells.


Sentinel node biopsy in colorectal cancer: Must we believe it?
Lymph node metastasis predicts survival and recurrence in colon cancer (CC), so decisions regarding adjuvant therapy are largely based on nodal status. Chemotherapy is not a routine treatment for node-negative CC because its toxicity and expense exceed its limited benefit in patients without evidence of nodal involvement. The sentinel lymph node (SLN) procedure is a selective sampling technique that can be used to ultrastage regional nodes. The real problem of SLN biopsy in CC is the procedure sensitivity rate. In future, studies concerning SLNs will have to consider issues such as the role of laparoscopy in colorectal resection (which cause technical difficulties in identification of SLNs) and the risk of overstaging of illness as well as the need to exclude T4 CC and, probably, rectal cancer from the studies. Is this the future of correct staging of colorectal cancer? Lymphadenectomy is at the present an integral part of colorectal surgery and surgeons must perform it correctly to improve their results. Nevertheless, for the future another "staging system" is necessary in colorectal cancer which takes into account biologic aspects of the tumor to identify patients with aggresive illness in order to treat them with more effective and less toxic therapies.


[Determination of ochratoxin A and ochratoxin alpha in wine by ultra-performance liquid chromatography tandem mass spectrometry].
To establish a method for determination of ochratoxin A and ochratoxin alpha in wine by ultra-performance liquid chromatography tandem mass spectrometry(UPLC-MS/MS) based on isotopic internal standard method. The wine sample was adjusted to pH 9. 0 by 5% ammonia and concentrated by a MAX solid phase extraction cartridge. The UPLC separation was performed on a ACQUITY BEH C_(18) column(100 mm×2. 1 mm, 1. 7 μm)with a isocratic elution program of acetonitrile and 5 mmol/L ammonium acetate as the mobile phase. Electrospray ionization was applied and operated in the positive ion mode. The concentration of wine was quantified by isotope internal standard. The calibration curves were linear in the concentration range of 1. 0-50. 0 μg/L, the coefficients of correlation were 0. 9996 and 0. 9993, respectively. The limits of detection(LODs) of both were 0. 10 μg/kg, and the limits of quantitative were 0. 35 μg/kg. The average recoveries at the spiked levels of 0. 35, 2. 00 and 10. 00 mg/kg were 88. 6%-108. 0%, and the relative standard deviations(RSDs) were 2. 1%-9. 2%, respectively. This method is simple, sensitive, accurate and reliable, which is suitable for the determination of ochratoxin A and ochratoxin alpha in wine.


Comparison between conventional and piezoelectric surgical tools for maxillary sinus floor elevation. A randomized controlled clinical trial.
The aim of this study was to assess the performance of conventional rotative instruments and a piezoelectric device for maxillary sinus floor elevation surgery, and to assess whether application of a resorbable membrane reduces resorption of an augmented site in a randomized clinical trial. Thirty-six consecutive patients (59.2 ± 10.7 years, range 38-76 years) needing bilateral sinus floor elevation surgery agreed to participate in this study. In a parallel split mouth design randomized clinical trial, in which the allocation of the surgical technique to be used on the determined sites was randomly assigned, one site was always treated with conventional rotative instruments (control group) and the other site with piezosurgery (test group). In addition, in a random order, the grafted sites were covered with a collagen membrane or no membrane. After a healing period of 3-4 months implants were placed. Comparison of clinical features of the test and control sites revealed no differences with regard to wound healing and complications (perforations of the sinus membrane) during or postsurgery (p = .458, p = 1.0, respectively). A clinically insignificant, but statistically shorter operation time was observed when using conventional rotative instruments (11.1 ± 2.4 minutes) than using piezosurgery (15.1 ± 2.9 minutes; p < .001). In both groups, application of a resorbable membrane did not result in less horizontal bone resorption (membrane: 1.43 mm, no membrane: 1.06 mm; p = .062); All 193 implants could be placed with primary stability. One year after functional loading, survival rate was 100%. It can be concluded that, for maxillary sinus floor elevation surgery, a piezoelectric device shows no advantages over rotative instruments as well as that placement of a barrier membrane did not reduce resorption of the augmented site.


Validation of verbal autopsy procedures for adult deaths in China.
Vital registration of causes of death in China is incomplete with poor coverage of medical certification. Information on the leading causes of mortality will continue to rely on verbal autopsy (VA) methods. A new international VA form is being considered for data collection in China, but it first needs to be validated to determine its operating characteristics. Detailed medical records and clinical evidence for 3290 deaths (mostly adults) among residents of six cities representative of the urban Chinese population were reviewed by a panel of physicians and coded by experts to establish a reference underlying cause of death. Independently, families of the deceased were interviewed using a structured symptomatic questionnaire and a separate death certificate was prepared for each matching case (2102). Validity of the VA procedure was assessed using standard measurement criteria of sensitivity, specificity, and positive predictive value. VA methods perform reasonably well in identifying deaths from several leading causes of adult deaths including stroke, several major cancer sites (lung, liver, stomach, oesophagus, and colorectal), and transport accidents. Sensitivity was less satisfactory in detecting deaths from several causes of major public health concern in China including ischaemic heart disease, chronic obstructive pulmonary disease, diabetes, and tuberculosis, and was particularly poor in diagnosing deaths from viral hepatitis, hypertension, and kidney diseases. VA is an imprecise tool for detecting leading causes of death among adults. However, much of the misclassification generally occurs within broad cause groups (e.g. CVD, respiratory diseases, and liver diseases). Moreover, compensating patterns of misclassification would appear to suggest that, in urban China at least, the method yields population-level cause-specific estimates that are reasonably reliable. These results suggest the possible utility of these methods in rural China, to back up the low coverage of medical certification of cause of death owing to poor access to health facilities there.


The future of CD20 monoclonal antibody therapy in B-cell malignancies.
Limitations of therapeutic options for chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma (NHL) have necessitated the development of novel treatments/strategies. Rituximab (chimeric anti-CD20 monoclonal antibody [mAb]) considerably improved therapeutic outcomes for patients with B-cell malignancies, particularly when combined with chemotherapy; outcomes, however, are limited by rituximab resistance or reduced response upon re-treatment. Novel anti-CD20 mAbs are in development that may enhance mAb therapy. Ofatumumab (human anti-CD20 mAb) induces highly potent cell lysis, including in cells with low CD20 expression, and is the most clinically advanced new anti-CD20 mAb. Positive phase III interim data for ofatumumab in fludarabine-refractory CLL that is also refractory to alemtuzumab or less suitable for alemtuzumab due to bulky (>5 cm) lymphadenopathy has led to FDA approval of this agent in this population. Preclinical and early clinical assessment of other novel anti-CD20 mAbs include: ocrelizumab, veltuzumab, GA101, AME-133v, and PRO131921; data suggest potential for improved efficacy over rituximab that will require substantiation in large-scale clinical trials. New treatment strategies and novel anti-CD20 mAbs have the potential to enhance long-term outcomes for CLL and NHL.


Experimentally Induced Single and Repeated Personal Name Confusions: The Impact of Phonological and Semantic Similarity.
Three experiments investigated a common but intriguing phenomenon, that is, repeated personal name confusion, a phenomenon at the border between language and memory. The purpose of those experiments was to evaluate the impact of the semantic and phonological similarities on name confusion and to compare repeated naming confusions (i.e., repeatedly confounding two names) with single confusions (i.e., confounding two names only once) in a same experimental paradigm. In all experiments, participants (64 middle-aged participants for each experiment) were asked to memorize the association between 16 names and 16 faces (face-name learning task). In Experiments 1 and 2, the two studied variables were the phonological similarity between the confused names and the semantic similarity between the two bearers of the confused names (using a visually derived semantic code in Experiment 1 and an identity-specific semantic code in Experiment 2). In Experiment 3, the impact of those two semantic similarities between the bearers of the confused names was taken into account, whereas the phonological similarity was not taken into account. First, results showed a main effect of the phonological and semantic similarity on name confusion (more confusions when the names were phonologically related or when the bearers of the names were semantically related). Second, we found that (1) the combination of the phonological and the semantic similarity and (2) the combination of the two semantic similarities led to an increase of name confusions. Third, in the three experiments, we found that the semantic and phonological similarities had a similar impact on repeated and single confusions. Finally, results showed that participants always made more single than repeated confusions, except in the case when the bearers of the confused names shared two semantic features.


Mean platelet volume/platelet count ratio as a predictor of 90-day outcome in large artery atherosclerosis stroke patients.
Previous studies reported a lower platelet count (PC) level and a higher mean platelet volume (MPV) level in severe ischemic stroke. We define MPV/PC as the platelet ratio (PR). This study investigates the relationship between PR and 90-day outcome of large artery atherosclerosis (LAA) stroke. A retrospective analysis was conducted on 338 LAA patients in two hospitals by looking up the electronic medical record (EMR). The 90-day functional outcome was divided into good and poor according to the modified Rankin Scale (mRS) score. Multivariate logistic regression analysis of the First Affiliated Hospital of Wenzhou Medical University (Hospital 1) revealed that PR (OR1.083, 95%CI [1.044, 1.123], P < 0.001) and National Institutes of Health Stroke Scale (NIHSS) score were independent predictors of the poor outcome. Analysis from the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University (Hospital 2) showed that PR (OR1.071, 95%CI [1.039, 1.104], P < 0.001), NIHSS score and age were independent adverse prognostic predictors. Furthermore, higher quartiles of PR presented an incremental OR value compared to the first quartile PR in multivariate regression. In Hospital 1, the cut-off value of PR to predict 90-day outcome was 39.23 (sensitivity: 74.24%, specificity: 55.17%, area under the curve (AUC): 0.694, P < 0.001). In Hospital 2, the optimal cut-off value of PR was 46.08 (sensitivity: 61.40%, specificity: 73.74%, AUC: 0.695, P < 0.001). Platelet ratio on admission is an independent predictor for 90-day outcome in LAA stroke patients and it has a good predictive effect.


Sulfated alkenes from the echinus Temnopleurus hardwickii.
Three new sulfated alkenes (1-3), trimethylammonium (5R)-5,9-dimethyl-(3E)-3,8-decadienyl-1-sulfate, dimethylammonium (5R)-5,9-dimethyl-(3E)-3,8-decadienyl-1-sulfate, and 2'-methyl-4'-oxobutan-2-ylammonium (5R)-5,9-dimethyl-(3E)-3,8-decadienyl-1-sulfate, were isolated from an echinoderm, Temnopleurus hardwickii. Their structures were elucidated by spectral analysis and chemical degradation methods.


Primary adenomyoepithelioma of tonsil.
We present a case of adenomyoepithlioma (AME) arising from the tonsil. AME is an uncommon tumor that typically arises in breast, but rarely found in salivary glands, lung, and skin. Its biological features have not been thoroughly characterized. Here we describe a primary AME originating from the tonsil. The pathologic changes were characterized by hypercellularity, the dominance of both epithelial and myoepithelial cells. Malignancy was evidenced by the presence of a high mitotic rate and invasive growth. The epithelial cells express high levels of cytokeratin and epithelial membrane antigen (EMA). The myoepithelial cells show positive staining for calponin, p63, vimentin, and S-100. A thorough review of the literature indicates that this is likely the first reported case of AME from the tonsil. Following descriptions of the diagnosis, treatment, and prognosis of this specific case, pathologic and clinical characteristics of AME from other tissues are also compiled and discussed.


[The Hellp syndrome: a frequent (?) obstetric emergency].
Preeclampsia is a multisystem disorder of pregnancy whose clinical presentation is related to the importance and the extent of maternal microvasculature damage. 16 patients with preeclampsia, thrombocytopenia (< 100,000/mm3), elevated liver enzymes and hemolysis are described. Weinstein in 1982 assigned the acronym of Hellp syndrome for this clinical presentation of preeclampsia. This syndrome was seldom recognized during the first years of the study but was diagnosed later on, in 1 pregnancy out of 600 parturitions and in 5% of preeclampsia in 1991. Two out of the patients developed eclamptic seizures. The mode of delivery was as follows: 9 out of 16 had an emergency Caesarean section; the 7 other patients had vaginal delivery after induction of labor. Delivery occurred before 32 weeks of gestation for 6 out of 17 newborns. Outcome was good for 14 of the 17 newborns (one twin pregnancy). Two fetuses died: one in utero and one during interruption of the pregnancy at 24 weeks of gestation. A small for gestational age preterm of 32 weeks died on his second day of life. Early diagnosis of Hellp Syndrome, especially when abdominal pains are present, allows a prompt management of these patients, including delivery, which appeared in our experience, the only way to avoid fetomaternal complications. The thrombotic microangiopathics and acute fatty liver of pregnancy are potential imitations of Hellp syndrome and they must be considered for differential diagnosis. The frequency of Hellp Syndrome varies from one study to another. It can be increased up to 6 fold if referred to the number of pregnancies and up to 3 fold if referred to the number of preeclampsias. These differences can be real but may be due to bias related to differences in practice between centers and also differences in definitions of Hellp Syndrome and preeclampsia.


[LAPAROSCOPIC APPENDECTOMY: EXPERIENCE IN THIRTY CASES]
Between September 1994 and February 1997, 30 patients with clinical diagnosis of acute appendicitis were subject of laparoscopic appendectomy (LA) at the "Stella Maris" Clinic in Lima - Peru. Only one conversion to an open procedure was practiced to a 69 years old woman with an appendiculate plastron. Out of the other 29 LA cases, 17 were women (58.6%) and 12 were men (41.4%) with an average age of 23 years, average surgery time of 94 minutes, average time of restablishment of food in-take 15 hr. and average post-operation time of hospitalization 27,1 hr. The anatomo-pathologic diagnosis revealed 11 cases of acute appendicitis, 1 case of suppurative acute appendicitis, 6 cases of acute appendicitis + peritonitis, 1 case of chronic periappendicitis, 6 cases of vascular congestion and/or follicular hyperplasia. There were also reported 3 cases of vascular congestion and/or follicular hyperplasia associated to gynecological pathologies that were solved laparoscopycally. A minor wound infection was registered as a post-operative complication. Thus, it is concluded that the LA is a save method of low morbidity, applicable to children, very advantageous in women in fertile age, in obese or fat patients, in the cases of diagnostic doubt and in patients with complicated appendicitis.


The inherited ataxias: genetic heterogeneity, mutation databases, and future directions in research and clinical diagnostics.
The inherited cerebellar ataxias are a diverse group of clinically and genetically heterogeneous neurodegenerative disorders. Inheritance patterns of these disorders can be complex with autosomal dominant, autosomal recessive, X-linked, and mitochondrial inheritance demonstrated by one or more ataxic syndromes. The broad range of mutation types found in inherited ataxia contributes to the complex genetic etiology of these disorders. The majority of inherited ataxias are caused by repeat expansions; however, conventional mutations are important causes of the rarer dominant and recessive ataxias. Advances in sequencing technology have allowed for much broader testing of these rare ataxia genes. This is relevant to the aims of the Human Variome Project, which aims to collate and store gene variation data through mutation databases. Variant data is currently located in a range of public and commercial resources. Few locus-specific databases have been created to catalogue variation in the dominant ataxia genes although there are several databases for some recessive genes. Developing these resources will facilitate a better understanding of the complex genotype-phenotype relationships in these disorders and assist interpretation of gene variants as testing for rarer ataxia genes becomes commonplace.


Neurological symptoms and complications in predominantly hospitalized COVID-19 patients: Results of the European multinational Lean European Open Survey on SARS-Infected Patients (LEOSS).
During acute coronavirus disease 2019 (COVID-19) infection, neurological signs, symptoms and complications occur. We aimed to assess their clinical relevance by evaluating real-world data from a multinational registry. We analyzed COVID-19 patients from 127 centers, diagnosed between January 2020 and February 2021, and registered in the European multinational LEOSS (Lean European Open Survey on SARS-Infected Patients) registry. The effects of prior neurological diseases and the effect of neurological symptoms on outcome were studied using multivariate logistic regression. A total of 6537 COVID-19 patients (97.7% PCR-confirmed) were analyzed, of whom 92.1% were hospitalized and 14.7% died. Commonly, excessive tiredness (28.0%), headache (18.5%), nausea/emesis (16.6%), muscular weakness (17.0%), impaired sense of smell (9.0%) and taste (12.8%), and delirium (6.7%) were reported. In patients with a complicated or critical disease course (53%) the most frequent neurological complications were ischemic stroke (1.0%) and intracerebral bleeding (ICB; 2.2%). ICB peaked in the critical disease phase (5%) and was associated with the administration of anticoagulation and extracorporeal membrane oxygenation (ECMO). Excessive tiredness (odds ratio [OR] 1.42, 95% confidence interval [CI] 1.20-1.68) and prior neurodegenerative diseases (OR 1.32, 95% CI 1.07-1.63) were associated with an increased risk of an unfavorable outcome. Prior cerebrovascular and neuroimmunological diseases were not associated with an unfavorable short-term outcome of COVID-19. Our data on mostly hospitalized COVID-19 patients show that excessive tiredness or prior neurodegenerative disease at first presentation increase the risk of an unfavorable short-term outcome. ICB in critical COVID-19 was associated with therapeutic interventions, such as anticoagulation and ECMO, and thus may be an indirect complication of a life-threatening systemic viral infection.


Alternatives to intensive treatment in patients with AML.
A significant proportion of patients with acute myeloid leukemia (AML) are unable to tolerate standard induction chemotherapy regimens. This is particularly true for patients who are of advanced age, have a poor performance status, and/or have significant medical comorbidities. Recent advances in understanding the genetic and molecular properties of AML have led to a spate of new treatment options for patients considered ineligible for standard chemotherapy. Here, we discuss these new treatment options, provide an overview of the completed and ongoing trials of the new agents, and highlight promising future directions in the treatment of AML in patients ineligible for intensive induction chemotherapy.


[Ethical aspects of clinical trials and patient informed-consent sheet: HIV/AIDS].
The TRT-5 (Treatment and Therapeutic Research) group, created in 1992, is a coalition of eight advocacy and service-providing HIV/AIDS nongovernmental organisations (NGOs) [originally five NGOs] working together on treatment and research issues in the field of HIV/AIDS in France. After 11 years of work in the defending and advocating for the rights and the welfare of HIV+ individuals in the area of drug development and clinical research, we felt authorised to make comments and propose changes to the currently ongoing reform of the French Law (Loi Huriet) defining the legal framework of clinical research in France. Several of our proposals aiming to include into the new law solutions to many of the ethical problems we regularly face in clinical research have been incorporated into amendments submitted to Parliament during the first reading in the lower Chamber last October. Some of these amendments have been approved by the majority of deputies.


The study of sclareol in inhibiting proliferation of osteosarcoma cells by apoptotic induction and loss of mitochondrial membrane potential.
Sclareol (sclarcol) is an organic compound extracted from sage clary plants. Recent study has showed its anti-tumor effects against breast cancer, gastric carcinoma, osteosarcoma and colorectal cancer. However, its exact mechanisms in inhibiting tumor growth remain unknown. This study thus observed the effect of sclareol on the proliferation of osteosarcoma cells, in an attempt to investigate the role of sclarcol on osteosarcoma growth. MG63 osteosarcoma cell was treated with different concentrations of sclarcol. CCK8 assay was used to test its effect on cell proliferation. LC50 value was then determined to obtain optimal treatment dose. MG63 cells were then divided into control and drug treated group, for measuring apoptosis and mitochondrial membrane potential by flow cytometry, and the expression of cytochrome c, Bax and Bcl-2 by western blot. CCK8 analysis showed that sclareol inhibited MG63 cell proliferation, with an LC50 value at 11.0 μM. Flow cytometry results showed the apoptotic cell ratio was 13.8%, 24.1% and 37.3% after treated with 2.0 μM, 4.0 μM and 8.0 μM sclareol respectively. Compared to control group, sclareol significantly depressed mitochondrial membrane potential of MG63 cells, increased the expression of cytochrome c and Bax, but decreased Bcl-2 expression. In conclusion, Sclareol can inhibit the proliferation of MG63 cells, and induce cell apoptosis and decrease mitochondrial membrane potential suggesting the inhibition of osteosarcoma cells by sclareol might be via both apoptosis induction and decreasing mitochondrial membrane potential.


Organogel-based system for transdermal delivery of propranolol.
The reverse micelle-based microemulsion was proposed as a vector for the transdermal delivery of propranolol. Soya-lecithin forms reverse micelle in iso-octane with increased solubilizing potential. The lecithin/iso-octane system was studied for the nature of solubilized water, the effect of added water on viscosity, and drug-micelle interaction. The amount and nature of solubilized water was investigated by spectroscopic methods using potassium nitrate as the polarity probe. With increasing water content the viscosity of the system was found to increase. And at a molar ratio (R) = 3, the system showed gel-like consistency (8.1 x 10(3) poise). The polarity probe study suggested the difference in environment of solubilized water as compared with the bulk water. The permeability rate of propranolol contained in the water/lecithin/iso-octane system was calculated to be 1212.0 micrograms h cm-2 while in the case of petrolatum jelly it was recorded to be 122.8 micrograms h-1 cm-2.


Electroosmosis of polymer solutions in fused silica capillaries.
The classical von Smoluchowski equation predicts that the electroosmotic mobility generated by the wall zeta potential could be suppressed if the viscosity of the solution adjacent to the wall were extremely high. When performing runs in capillaries filled with polymer solutions (2% methyl cellulose solutions with viscosities of 25 cP), however, one consistently finds that the quenching of electroosmotic mobility is substantially less than predicted by the von Smoluchowski relationship. The electroosmotic flow is progressively suppressed with subsequent electrophoretic runs, suggesting a "dynamic coating" of the polymers onto the capillary wall. This progressive reduction of electroosmotic mobility tends to a plateau value which is still substantially higher than the value derived on the basis of the von Smoluchowski relationship. The following explanation is proposed: due to the very high shear rate in the electric double layer, the polymer molecules change their orientation and/or conformation, which lowers the fluid viscosity in this region. A scaling equation for electroosmotic mobility taking into account the non-Newtonian properties of polymer solutions is derived. It predicts electric field dependence of the electroosmotic mobility as the shear rate in the double layer is proportional to the electric field. Experimental measurements confirm the dependence of the electroosmotic mobility on the electric field.


Evaluating sickness absence duration by musculoskeletal and mental health issues: a retrospective cohort study of Scottish healthcare workers.
Sickness absence (SA) among healthcare workers is associated with occupational and non-occupational risk factors and impacts employee health, healthcare delivery and patient health. At the same time, healthcare is one of the employment sectors with the highest rates of work-related ill health in the UK. Musculoskeletal (MSK) and mental health (MH) issues are leading causes of SA, but there is a lack of research on how certain MSK/MH conditions impact on SA duration. The study aim is to determine differences in SA duration by MH and MSK disorders in healthcare employees. Survival analyses were used to estimate SA duration due to MSK and MH problems over 6 years, and Cox's proportional hazards models to determine the HRs of returning to work, using a bespoke Scottish health board database with over 53 000 SA events. SA duration and time to return-to-work (RTW) were estimated for employees by age, gender, job and health conditions. MSK and MH conditions accounted for 27% and 6% of all SA events and 23.7% and 19.5% of all days lost, respectively. Average SA duration was 43.5 days for MSK and 53.9 days for MH conditions. For MSK conditions, employees with low back or neck pain had the fastest RTW (median P50: 7 days), whereas employees absent due to depression took the longest (P50: 54 days). The most influential sociodemographic variables affecting RTW were age, gender and job category. Using a unique and rich database, we found significant differences in SA duration by presenting condition in healthcare workers. MH conditions, and depression specifically, accounted for the most working days' absence. Significant variations in duration were also observed for MSK conditions. Our findings can inform public health practitioners and healthcare managers of the most significant factors impacting MSK-related and MH-related SA to develop and implement tailored and targeted workplace interventions.


Dissipation of phenanthrene and pyrene at the aerobic-anaerobic soil interface: differentiation induced by the rhizosphere of PAH-tolerant and PAH-sensitive rice (Oryza sativa L.) cultivars.
A pot experiment was conducted to reveal the removal of two polycyclic aromatic hydrocarbons (PAHs) (phenanthrene, PHE, and pyrene, PYR) during rice cultivation in a paddy field. The rhizosphere effect on facilitating dissipation of PAHs varied simultaneously as a function of soil properties, PAH types, cultivation time, and genotypes within rice cultivars, with differences performed for PYR but not PHE. Changes in soil PLFA profiles evidenced that the growth of rice roots modified the dominant species within rhizosphere microbial communities and induced a selective enrichment of Gram-negative aerobic bacteria capable of degrading, thereby resulting in the differentiated dissipation of PYR. While the insignificant differences in PHE dissipation might be attributed to its higher solubility and availability under flooded condition that concealed the differences in improvement of bioavailability for microorganisms between rhizosphere and non-rhizosphere, and between both soils and both rice cultivars. Our findings illustrate that the removal of PAHs in paddy soils was more complex relative to those in dryland soils. This was possibly due to the specialty of rice roots for oxygen secretion that provides development of redox heterogeneous microbial habitats at root-soil interface under flooded condition.


Interpretable data-driven modeling of hyperelastic membranes.
We proposed an approach for interpretable data-driven modeling of an isotropic incompressible hyperelastic membrane deformation. The approach is based on the response functions in terms of the Laplace stretch and the finite element method, where response functions are partial derivatives of a hyperelastic potential with respect to the chosen strain measure. The Laplace stretch as the strain measure allows us to recover directly the response functions from experimental data and construct automatically data-driven constitutive relations. All needed formulas were obtained explicitly. We tested our approach for membrane inflation with data-driven constitutive relations based on the perforated membrane extension tests.


Long-term follow-up of children with surgically treated vesicorenal reflux: postoperative incidence of urinary tract infections, renal scars and arterial hypertension.
With a mean follow-up of 10.8 years, 160 female and 29 male patients were investigated after successful correction of vesicoureterorenal reflux. All patients suffered from urinary tract infection (UTI) preoperatively, while postoperatively 42% of the patients developed further UTIs but with a significantly diminished rate of febrile infections. In comparison to a group of patients without postoperative UTI (n = 16), the uroepithelial cells of those patients with a high infection rate after reflux correction showed a significantly lower bacterial growth suppression (n = 37). Renal scars were found in 22% of the investigated renal units with operated ureters (n = 211). Of the preoperatively unscarred kidneys, 3.4% developed new scars during the observation period, mainly within the first 2 years after operation. In 7 (11.5%) of the 61 patients with renal scars, moderate arterial hypertension was found.


Antireticulin antibodies in psoriasis.
Antireticulin antibodies were studied in the sera of 32 patients affected by various clinical forms of psoriasis. The indirect immunofluorescence method was used on histological sections of human kidney and mouse liver and kidney. This method was also used with sera from children with coeliac disease and from healthy controls. In 10 these antibodies were positive, while in 22 they were negative, the intensity of the titres varying with the extent of the disease. These results support the notion that immunological phenomena may be involved in the physiopathological mechanisms of psoriasis.


Nanoplatforms for Delivery of siRNA to the Eye.
Drug delivery to the eye is challenging for formulation scientists due to physiological barriers that separate the eye from the rest of the body. A variety of ocular disorders demand the development of optimal drug delivery systems for the administration of drugs and therapeutic agents that can overcome barriers that restrict drug bioavailability. SiRNA inhibits the expression of target genes and has immense potential as a biological tool for the therapeutic inhibition of disease causing genes; however, delivery of siRNA to ocular tissue is a challenge. Recent literature suggests that nanoplatforms show great promise in enhancing ophthalmic drug delivery. A drug delivery system involving nanoparticles and siRNA could surpass problems faced in ocular delivery with improved biodistribution and lower toxicity. This review covers recent research in the area of nanocarrier siRNA drug delivery for various ocular disorders.


Direct measurements of heating by electromagnetically trapped gold nanoparticles on supported lipid bilayers.
Absorption of electromagnetic irradiation results in significant heating of metallic nanoparticles, an effect which can be advantageously used in biomedical contexts. Also, metallic nanoparticles are presently finding widespread use as handles, contacts, or markers in nanometer scale systems, and for these purposes it is essential that the temperature increase associated with electromagnetic irradiation is not harmful to the environment. Regardless of whether the heating of metallic nanoparticles is desired or not, it is crucial for nanobio assays to know the exact temperature increase associated with electromagnetic irradiation of metallic nanoparticles. We performed direct measurements of the temperature surrounding single gold nanoparticles optically trapped on a lipid bilayer, a biologically relevant matrix. The lipid bilayer had incorporated fluorescent molecules which have a preference for either fluid or gel phases. The heating associated with electromagnetic radiation was measured by visualizing the melted footprint around the irradiated particle. The effect was measured for individual gold nanoparticles of a variety of sizes and for a variety of laser powers. The temperatures were highly dependent on particle size and laser power, with surface temperature increments ranging from a few to hundreds of degrees Celsius. Our results show that by a careful choice of gold nanoparticle size and strength of irradiating electromagnetic field, one can control the exact particle temperature. The method is easily applicable to any type of nanoparticle for which the photothermal effect is sought to be quantified.


Pullorum Disease: Evolution of the Eradication Strategy.
The history of pullorum disease is closely intertwined with the history of avian health research and that of the poultry industry. The seriousness of the disease galvanized the attention and brought together, for the first time, the pioneers of poultry health research to work cooperatively on different aspects of the disease. Control of the disease made it possible for intensive poultry production to develop as the basis for the modern poultry industry. During the early 1900s, bacillary white diarrhea (BWD) was a devastating disease of young chickens threatening the developing poultry industry. Dr. Leo F. Rettger isolated and described the bacterial pathogen, Salmonella enterica serotype Pullorum, for the first time in 1900. BWD was renamed pullorum disease in 1929. In subsequent years, Rettger and coworkers were able to reproduce the disease and fulfill Koch's postulates. Rettger et al. also showed that Salmonella Pullorum was vertically transmitted, which was the first time that a pathogen was shown to be vertically transmitted. The development of serologic tests was of crucial importance because it led to the development of effective eradication methods to identify carrier birds and to exclude these birds from the breeder flocks. The negative impact of pullorum disease on the poultry industry ultimately was one of the major reasons that the National Poultry Improvement Plan (NPIP) was developed by scientists, the poultry industry, and the United States Department of Agriculture (USDA). Needless to say, the work of the pioneering researchers formed the basis for the control of the disease. The NPIP started in 1935, with 34 states participating in testing 4 million birds representing 58.2% of the birds hatched. The program rapidly expanded to 47 states by 1948 and tested more than 30 million birds. In 1967, all commercial chicken hatcheries participating in the NPIP were 100% free of pullorum and typhoid disease caused by Salmonella enterica serotype Gallinarum. This historical overview of pullorum disease describes in some detail the progress made, especially during the early years, toward controlling this disease using methodologies that were often very basic but nonetheless effective. One has to admire the ingenuity and persistence of the early researchers leading to their achievements considering the research tools that were available at the time.


Filter paper as a source of error in the determination of nitrite in meat.
Samples of filter paper were found which contain sufficient nitrite to cause significant error in determining the nitrite content of cured meat products by the official AOAC method. Six of 28 boxes of filter paper examined were contaminated with nitrite. All 6 contaminated boxes were the same brand and grade. These samples of filter paper could contribute from 4.6 to 18.4 ppm nitrite to the amount of nitrite analyzed for in meat.


Localization and H2O2-specific induction of PRDX3 in the eye lens.
Peroxiredoxin III (PRDX3) is a mitochondrial peroxidase that defends cells against oxidative damage and therefore could play a role in cataract formation. To establish a possible role for PRDX3 in lens function, PRDX3 was localized to specific human lens sub-regions and the levels of PRDX3 in human lens cells and rat lenses exposed to exogenously-added oxidative stress determined. PRDX3 levels were monitored by RT-PCR, western analysis, and immunofluorescence. PRDX3 levels in human lens epithelial cells and whole rat lenses exposed to H2O2, TBHP, and heat-treatment were also examined relative to untreated controls by RT-PCR and western analysis. Significant levels of PRDX3 mRNA and protein were detected in human lens epithelia and fiber cells. PRDX3 was localized to the mitochondria in human lens epithelial cells. PRDX3 was highly induced in human lens epithelial cells by as little as 2 microM H2O2 and by 50 microM H2O2 in cultured rat lenses. Induction of PRDX3 was specific for H2O2 in cultured lens cells since sub-lethal levels of TBHP or heat-shock did not result in detectable increases in the level of PRDX3. These data demonstrate that PRDX3 is present throughout the lens and localized to the mitochondria in lens epithelial cells. PRDX3 was specifically induced by low levels of H2O2 in human lens epithelial cells and rat lenses suggesting that induction of PRDX3 is an acute response of the lens to increased H2O2 levels. These data provide evidence for an important role for PRDX3 in lens H2O2-detoxification, mitochondrial maintenance, and possibly cataract formation.


Disruption of muscle renin-angiotensin system in AT1a-/- mice enhances muscle function despite reducing muscle mass but compromises repair after injury.
The role of the renin-angiotensin system (RAS) in vasoregulation is well established, but a localized RAS exists in multiple tissues and exerts diverse functions including autonomic control and thermogenesis. The role of the RAS in the maintenance and function of skeletal muscle is not well understood, especially the role of angiotensin peptides, which appear to contribute to muscle atrophy. We tested the hypothesis that mice lacking the angiotensin type 1A receptor (AT(1A)(-/-)) would exhibit enhanced whole body and skeletal muscle function and improved regeneration after severe injury. Despite 18- to 20-wk-old AT(1A)(-/-) mice exhibiting reduced muscle mass compared with controls (P < 0.05), the tibialis anterior (TA) muscles produced a 25% higher maximum specific (normalized) force (P < 0.05). Average fiber cross-sectional area (CSA) and fiber oxidative capacity was not different between groups, but TA muscles from AT(1A)(-/-) mice had a reduced number of muscle fibers as well as a higher proportion of type IIx/b fibers and a lower proportion of type IIa fibers (P < 0.05). Measures of whole body function (grip strength, rotarod performance, locomotor activity) were all improved in AT(1A)(-/-) mice (P < 0.05). Surprisingly, the recovery of muscle mass and fiber CSA following myotoxic injury was impaired in AT(1A)(-/-) mice, in part by impaired myoblast fusion, prolonged collagen infiltration and inflammation, and delayed expression of myogenic regulatory factors. The findings support the therapeutic potential of RAS inhibition for enhancing whole body and skeletal muscle function, but they also reveal the importance of RAS signaling in the maintenance of muscle mass and for normal fiber repair after injury.


Anticancer effects of sodium butyrate on hepatocellular carcinoma cells in vitro.
In the present study, we investigated the anticancer effects of sodium butyrate (NaBu) on hepatocellular carcinoma (HCC) cells in vitro. As a histone deacetylase (HDAC) inhibitor, NaBu upregulated Ac-H3 and inhibited HDAC4 protein expression in a time- and dose-dependent manner. MTT assays showed that treatment with NaBu at high concentrations significantly inhibited the growth of various HCC cells. Exposure to NaBu for 24 h induced cell cycle arrest in the SMMC-7721 and HepG2 cells. NaBu also induced the apoptosis of SMMC‑7721 cells. The expression levels of cell cycle- and apoptosis-related proteins were further investigated by western blot analysis using specific antibodies. The results provided a possible mechanism responsible for the inhibitory effects of NaBu on the growth of HCC cells. To further analyze the role of NaBu in cell migration, wound healing and Transwell assays were performed, indicating that NaBu significantly inhibits cell migration/invasion in HCC cells. Transforming growth factor-β1 (TGF-β1)-induced epithelial to mesenchymal transition (EMT) has been associated with tumor cell migration and invasion. The EMT markers, E-cadherin, vimentin and N-cadherin, were regulated by TGF-β1, while NaBu inhibited this process in which HDAC4 and matrix metalloproteinase (MMP)7 may be involved. Based on our findings, we propose that NaBu may be useful as an anticancer drug for HCC therapy.


The Impact of a Transition of Care Program on Acute Myocardial Infarction Readmission Rates.
Hospital discharge is a high-risk time period, and acute myocardial infarction (AMI) patients often have early readmissions. The authors hypothesized that a multifaceted AMI care coordination program would reduce early hospital readmission rates. The outcomes of patients receiving care coordination (n = 304) were compared to patients receiving standard care (n = 192). Multivariable analyses of the outcomes were conducted by conditional logistic regression of propensity score matched sets. The primary outcome-hospital readmission within 30 days of discharge-occurred in 18% of standard care patients and 11.8% of care coordination patients. Patients receiving care coordination demonstrated a 48% reduction in odds of readmission within 30 days (odds ratio = 0.52; P = .04; 95% CI = 0.28-0.97). These results are the first to demonstrate that inclusion in an AMI-specific care coordination program is associated with a significantly lower risk of 30-day hospital readmission.


Tail ordering due to headgroup hydrogen bonding interactions in surfactant monolayers at the water-oil interface.
Interactions between surfactants, and the resultant ordering of surfactant assemblies, can be tuned by the appropriate choice of head- and tailgroups. Detailed studies of the ordering of monolayers of long-chain n-alkanoic and n-alkanol monolayers at the water-vapor interface have demonstrated that rigid-rod all-trans ordering of the tailgroups is maintained upon replacing the alcohol with a carboxylic acid headgroup. In contrast, at the water-hexane liquid-liquid interface, we demonstrate that substitution of the -CH(2)OH with the -COOH headgroup produces a major conformational change of the tailgroup from disordered to ordered. This is demonstrated by the electron density profiles of triacontanol (CH(3)(CH(2))(29)OH) and triacontanoic acid (CH(3)(CH(2))(28)COOH) monolayers at the water-hexane interface, as determined by X-ray reflectivity measurements. Molecular dynamics simulations illustrate the presence of hydrogen bonding between the triacontanoic acid headgroups that is likely responsible for the tail ordering. A simple free energy illustrates the interplay between the attractive hydrogen bonding and the ordering of the tailgroup.


Comparisons of verapamil administration twice and three times daily in hypertension.
The antihypertensive effect of verapamil administered either two or three times daily was compared in a double blind, cross over study in 15 patients with mild to moderate essential hypertension. During the dose titration period with t.i.d. administration, normotension was obtained with daily doses of 240 mg in 7 patients, 360 mg in 7 patients and with 480 mg in one patient. Systolic and diastolic blood pressures (BP) in the supine (13/14 mmHg) and standing (14/14 mmHg) positions were significantly (p less than 0.001) reduced during the dose titration period. There was no statistically significant difference in the BP values between the twice and three times a day regimens. Five to 7-fold individual variations in the serum verapamil concentrations between individuals were observed. No significant correlations were found between serum drug concentrations and the change in mean arterial BP. There was no significant difference in the incidence of side effects between the two treatment regimens. Our results suggest that verapamil administered twice daily is effective in mild to moderate hypertension.


Legionella resources on the world wide web.
Internet resources that focus on Legionella and legionnaires disease are presented. Web sites were selected on the basis of their content and adherence to suggested standards of medical Internet publishing. Free, accessible, English-language Web sites were categorized according to users' needs as follows: (1) those with comprehensive information on Legionella infection (including pathophysiologic characteristics, symptoms, and treatment of legionnaires disease), (2) those with information on outbreaks and epidemiology (including information for travelers), (3) those with information for researchers, (4) those about prevention, and (5) those with information for laypersons.


A meta-analysis approach for assessing the diversity and specificity of belowground root and microbial volatiles.
Volatile organic compounds are secondary metabolites emitted by all organisms, especially by plants and microbes. Their role as aboveground signals has been established for decades. Recent evidence suggests that they might have a non-negligible role belowground and might be involved in root-root and root-microbial/pest interactions. Our aim here was to make a comprehensive review of belowground volatile diversity using a meta-analysis approach. At first we synthesized current literature knowledge on plant root volatiles and classified them in terms of chemical diversity. In a second step, relying on the mVOC database of microbial volatiles, we classified volatiles based on their emitters (bacteria vs. fungi) and their specific ecological niche (i.e., rhizosphere, soil). Our results highlight similarities and differences among root and microbial volatiles and also suggest that some might be niche specific. We further explored the possibility that volatiles might be involved in intra- and inter-specific root-root communication and discuss the ecological implications of such scenario. Overall this work synthesizes current knowledge on the belowground volatilome and the potential signaling role of its constituents. It also highlights that the total diversity of belowground volatiles might be orders of magnitude larger that the few hundreds of compounds described to date.


Nerve growth factor modulates in vitro the expression and release of TGF-beta1 by amniotic membrane.
To determinate the basal production of NGF and TGF-beta1 by amniotic membrane (AM) and to verify the presence of NGF receptors (trkA(NGFR) and p75(NTR)) in AM. Thereafter, to evaluate in an in vitro model if increasing concentrations of NGF are able to stimulate AM to produce and release TGF-beta1. Immunohistochemistry, ELISA, in situ hybridization and PCR analysis for NGF, TGF-beta1, trkA(NGFR) and p75(NTR) were performed to study their presence in AM. Amniotic membranes were stimulated in vitro with increasing concentrations of NGF. After 24 h, the amount of TGF- beta1 in the AM tissue and in the culture medium was investigate. AM expressed TGF-beta1, NGF, trkA(NGFR) and p75(NTR) mRNAs and proteins and released basal amounts of NGF and TGF-beta1 in the medium. Stimulation of AM by addition of NGF induced a significant (P<0.05) increase of TGF-beta1 mRNA/protein in AM tissue as well as a release of TGF-beta1 protein into the culture medium, in a dose-dependent fashion. This study demonstrates that amniotic membrane releases basal amounts of NGF and TGF-beta1 and expresses NGF receptors . Moreover, the addition of NGF to the culture medium stimulates the amniotic membrane to significantly increase the production and release of TGF-beta1.


Emergency abdominal surgery in patients with left ventricular assist device: short- and long-term results.
Emergency abdominal surgery (EAS) in patients with long-term mechanical circulatory support and strong anticoagulation is very difficult. To present our experiences regarding the short- and long-term results of patients with a left ventricular assist device (LVAD) who underwent emergency abdominal surgery under general anesthesia at a large tertiary healthcare center. The electronic medical records of 7 patients with LVAD who underwent EAS between January 1, 2010 and December 31, 2016 were retrospectively investigated in order to evaluate perioperative management and outcomes. The patients were divided into two groups based on the need for EAS procedures. Seven (9.2%) of 76 patients with LVAD underwent EAS an average of 79.1 ±79.4 days after implantation. No statistically significant differences were found between the groups with and without EAS with regard to demographic characteristics, type of device, and rate of perioperative mortality (p > 0.05). The indications for surgery, retroperitoneal hematoma in 2 patients and in 5 other patients; ileus, iatrogenic splenic injury associated with thoracentesis, splenic abscess, acute abdominal pain and rectal cancer surgery was a pelvic abscess in a patient who is connected to the stump. In all cases laparotomy was performed with median incision. The perioperative mortality rate was 28.6% (n = 2). Two patients underwent orthotopic heart transplant during long-term follow-up. The EAS is not rare during LVAD treatment but is a rather complex procedure. General surgeons will be increasingly likely to encounter such patients as their numbers rise and their life expectancies are prolonged.


Comparison of the Characteristics, Management, and Outcomes of STEMI Patients Presenting With vs. Those of Patients Presenting Without COVID-19 Infection: A Systematic Review and Meta-Analysis.
This study aimed to investigate the differences in the characteristics, management, and clinical outcomes of patients with and that of those without coronavirus disease 2019 (COVID-19) infection who had ST-segment elevation myocardial infarction (STEMI). Databases including Web of Science, PubMed, Cochrane Library, and Embase were searched up to July 2021. Observational studies that reported on the characteristics, management, or clinical outcomes and those published as full-text articles were included. The Newcastle-Ottawa Scale (NOS) was used to assess the quality of all included studies. A total of 27,742 patients from 13 studies were included in this meta-analysis. Significant delay in symptom onset to first medical contact (SO-to-FMC) time (mean difference = 23.42 min; 95% CI: 5.85-40.99 min; p = 0.009) and door-to-balloon (D2B) time (mean difference = 12.27 min; 95% CI: 5.77-18.78 min; p = 0.0002) was observed in COVID-19 patients. Compared to COVID-19 negative patients, those who are positive patients had significantly higher levels of C-reactive protein, D-dimer, and thrombus grade (p < 0.05) and showed more frequent use of thrombus aspiration and glycoprotein IIbIIIa (Gp2b3a) inhibitor (p < 0.05). COVID-19 positive patients also had higher rates of in-hospital mortality (OR = 5.98, 95% CI: 4.78-7.48, p < 0.0001), cardiogenic shock (OR = 2.75, 95% CI: 2.02-3.76, p < 0.0001), and stent thrombosis (OR = 5.65, 95% CI: 2.41-13.23, p < 0.0001). They were also more likely to be admitted to the intensive care unit (ICU) (OR = 4.26, 95% CI: 2.51-7.22, p < 0.0001) and had a longer length of stay (mean difference = 4.63 days; 95% CI: 2.56-6.69 days; p < 0.0001). This study revealed that COVID-19 infection had an impact on the time of initial medical intervention for patients with STEMI after symptom onset and showed that COVID-19 patients with STEMI were more likely to have thrombosis and had poorer outcomes.


Setting performance goals and evaluating total analytical error for diagnostic assays.
Total analytical error has been a useful metric both to assess laboratory assay quality and to set goals. It is often estimated by combining imprecision (SD) and average bias in the equation: total analytical error = bias + 1.65 x imprecision. This indirect estimation model (referred to as the simple combination model) leads to different estimates of total analytical error than that of a direct estimation method (referred to as the distribution-of-differences method) or of simulation. A review of the literature was undertaken to reconcile the different estimation approaches. The simple combination model can underestimate total analytical error by neglecting random interference bias and by not properly treating other error sources such as linear drift and outliers. A simulation method to estimate total analytical error is outlined, based on the estimation and combination of total analytical error source distributions. Goals for each total analytical error source can be established by allocation of the total analytical error goal. Typically, the allocation is cost-based and uses the probability of combinations of error sources. The distribution-of-differences method, simple combination model, and simulation method to evaluate total analytical error are compared. Outlier results can profoundly influence quality, but their rates are seldom reported. Total analytical error should be estimated either directly by the distribution-of-differences method or by simulation. A systems engineering approach that uses allocation of the total analytical error goal into error source goals provides a cost-effective approach to meeting total analytical error. Because outliers can cause serious laboratory error, the inclusion of outlier rate estimates from large studies (e.g., those conducted by manufacturers) would be helpful in assessing assay quality.


Activity of a deltamethrin shampoo against Ctenocephalides felis and Rhipicephalus sanguineus in dogs.
A controlled clinical trial was undertaken to assess the efficacy of an application of a 0.07% deltamethrin shampoo against fleas and ticks in dogs. Twenty beagles, housed in separate cages, were randomly allocated into two groups of 10. The dogs were infested with 50 Ctenocephalides felis and 50 Rhipicephalus sanguineus each, and parasites were counted 24 h (fleas) and 72 h (ticks) later (Day 0). Dogs, when state, were then treated with 25 ml of a shampoo containing 0.07% deltamethrin (Group 1). Dogs in Group 2 were the controls. Fleas and ticks were counted 24 h (Day 1) and 48 h (Day 2) after the shampoo was applied, and the parasites were then removed. All the dogs were reinfested with fleas and ticks on Days 2, 7, 9, 14, 16 and 20. Parasites were counted 24 and 48 h after each reinfestation. Effectiveness against fleas was calculated 24 h after infestation, and against ticks 48 h after infestation. This study showed that the application of 25 ml of shampoo containing 0.07% deltamethrin to beagle dogs weighing between 10.2 and 12 kg was very well tolerated. It controlled the parasites present on the animals at the time of application: with an efficacy of 100% against fleas 24 h after treatment and an efficacy of 95% against ticks 48 h after treatment. The treatment protected against flea reinfestations with an efficacy of 100% during the first week, >98% in the second week and >95% in the third week. It also gave >99% protection against tick reinfestations in the first week and >96% in the second week.


[The ts phenotype of reisolates from children inoculated with live cold-adapted influenza vaccine type A].
Using mutants of fowl plague virus (FRV) which have single temperature-sensitive (ts) mutations in some genes, an analysis was carried out on reisolates from children of 3-6 years, vaccinated with a monovaccine from recombinant strains of influenza type A virus. The recombinants were obtained by crossing of current epidemic strains of subtypes A (HINI) and a (H3N2) with the cold-adapted (XA) ts-donor of attenuation A/Leningrad/134/47/57 (H2N2) from which they, as a rule, inherited 5 ts-mutations in genes 1 (PB2), 2 (PB1), 5 (NP), 7 (M), and 8 (NS). All the reisolates were shown to retain the ts-phenotype. However, in the recombination test some reisolates (most frequently those isolated at late periods of vaccination infection) no ts-mutations could be found in 1-3 genes coding for proteins of the polymerase complex, less frequently for NP and NS proteins but not for M proteins.


[Overview of the US policies for health information technology and lessons learned for Israel].
The heaLthcare system in the United States (U.S.) faces a number of significant changes aimed at improving the quality and availability of medical services and reducing costs. Implementation of health information technologies, especiaLly ELectronic Health Records (EHR), is central to achieving these goals. Several recent Legislative efforts in the U.S. aim at defining standards and promoting wide scale "Meaningful Use" of the novel technologies. In Israel, the majority of heaLthcare providers adopted EHR throughout the Last decade. Unlike the U.S., the process of EHR adoption occurred spontaneously, without governmental control or the definition of standards. In this article, we review the U.S. health information technology policies and standards and suggest potential lessons Learned for Israel. First, we present the three-staged Meaningful Use regulations that require eligible healthcare practitioners to use EHR in their practice. We also describe the standards for EHR certification and national efforts to create interoperable health information technology networks. Finally, we provide a brief overview of the IsraeLi regulation in the field of EHR. Although the adoption of health information technology is wider in Israel, the Lack of technology standards and governmental control has Led to Large technology gaps between providers. The example of the U.S. Legislation urges the adoption of several critical steps to further enhance the quality and efficiency of the Israeli healthcare system, in particular: strengthening health information technology regulation; developing Licensure criteria for health information technology; bridging the digital gap between healthcare organizations; defining quality measures; and improving the accessibility of health information for patients.


[Severe acute respiratory syndrome--SARS].
Severe Acute Respiratory Syndrome (SARS) is an acute respiratory illness caused by SARS coronavirus. This virus was possibly transmitted from an animal reservoir to humans, and from February 2003, the epidemic was spread internationally by further person-to-person transmission. The SARS epidemic was managed by well-known principles of infection control, including prompt diagnosis, isolation of patients, and quarantine of contacts. The successful control of the outbreak is a remarkable international achievement, though much about SARS remains poorly understood.