Prevalence, pathogenesis and spectrum of neurological symptoms in COVID-19 and post-COVID-19 syndrome: a narrative review.
Neurological symptoms are not uncommon during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and reflect a broad spectrum of neurological disorders of which clinicians should be aware. The underlying pathogenesis of neurological disease in coronavirus disease 2019 (COVID-19) may be due to four mechanisms of nervous system dysfunction and injury: i) direct viral neurological invasion; ii) immune dysregulation; iii) endothelial dysfunction and coagulopathy; and iv) severe systemic COVID-19 disease. Neurological manifestations of acute COVID-19 include headache, peripheral neuropathies, seizures, encephalitis, Guillain-Barré syndrome, and cerebrovascular disease. Commonly reported long term neurological sequelae of COVID-19 are cognitive dysfunction and dysautonomia, which despite being associated with severe acute disease are also seen in people with mild disease. Assessment of cognitive dysfunction after COVID-19 is confounded by a high prevalence of comorbid fatigue, anxiety, and mood disorders. However, other markers of neuroaxonal breakdown suggest no significant neuronal injury apart from during severe acute COVID-19. The long term impact of COVID-19 on neurological diseases remains uncertain and requires ongoing vigilance.


Inflammatory, non-antibody lymphocytic mediators (lymphokines).
This paper is a survey of some of the best characterized non-antibody lymphocytic mediators (lymphokines). Special emphasis is laid on the description of the molecular biology of human inflammatory and antigen-nonspecific lymphokines, and where clinical relevant their methods of assay are summarized. The putative role of lymphokines in vivo is briefly discussed.


Genome editing reagent delivery in plants.
Genome editing holds the potential for rapid crop improvement to meet the challenge of feeding the planet in a changing climate. The delivery of gene editing reagents into the plant cells has been dominated by plasmid vectors delivered using agrobacterium or particle bombardment. This approach involves the production of genetically engineered plants, which need to undergo regulatory approvals. There are various reagent delivery approaches available that have enabled the delivery of DNA-free editing reagents. They invariably involve the use of ribonucleoproteins (RNPs), especially in the case of CRISPR/Cas9-mediated gene editing. The explant of choice for most of the non-DNA approaches utilizes protoplasts as the recipient explant. While the editing efficiency is high in protoplasts, the ability to regenerate individual plants from edited protoplasts remains a challenge. There are various innovative delivery approaches being utilized to perform in planta edits that can be incorporated in the germline cells or inherited via seed. With the modification and adoption of various novel approaches currently being used in animal systems, it seems likely that non-transgenic genome editing will become routine in higher plants.


A Cluster of Symptomatic and Asymptomatic Infections of Severe Fever with Thrombocytopenia Syndrome Caused by Person-to-Person Transmission.
Severe fever with thrombocytopenia syndrome virus (SFTSV) is a novel phlebovirus that was identified to be the etiological pathogen of the emerging infectious disease, severe fever with thrombocytopenia syndrome (SFTS). SFTSV could be transmitted through tick bite. Transmission of SFTSV among humans has also been reported mainly through direct blood contact. In July 2014, a cluster of six suspected SFTS cases occurred in Shandong Province, China. In this cluster, both symptomatic and asymptomatic persons were included. By analyzing the clinical data and results of laboratory tests, and conducting the epidemiological interviews with the cases and their families, risk factors responsible for the transmission were evaluated. The findings suggested that SFTSV transmission among humans may cause asymptomatic infection via personal contact without blood exposure.


Linear plasmids and chromosomes in bacteria.
Linear plasmids and chromosomes were unknown in prokaryotes until recently but have now been found in spirochaetes, Gram-positive bacteria, and Gram-negative bacteria. Two structural types of bacterial linear DNA have been characterized. Linear plasmids of the spirochaete Borrelia have a covalently closed hairpin loop at each end and linear plasmids of the Gram-positive filamentous Streptomyces have a covalently attached protein at each end. Replicons with similar structures are more frequent in eukaryotic cells than in prokaryotes. Linear genomic structures are probably more common in bacteria than previously recognized, however, and some replicons may interconvert between circular and linear isomers. The molecular biology of these widely dispersed elements provides clues to explain the origin of linear DNA in bacteria, including evidence for genetic exchange between prokaryotes and eukaryotes.


Fracture strength of flared root canals reinforced using different post and core materials.
To examine the fracture strength and fracture mode of flared root canals reinforced with different post and core materials. Forty endodontically treated bovine teeth structured to mimic human mandibular premolars with flared root canals were reinforced with resin composite and glass fiber post (FRC), composite resin (RC), ceramic core (LD), and ceramic core with resin composite reinforcement (RLD), and restored with single zirconia crowns (n = 10 in each group). The fracture strength and mode of the root canals restored with zirconia crown were assessed. The fracture strength was compared with a one-way analysis of variance (ANOVA) following Tukey HSD tests. A multiple regression analysis was conducted to test the effect of the post/core materials on the fracture loads. Fisher's exact test was used in the failure mode analysis. The mean fracture strength of RLD was significantly higher than RC, FRC, and LD (p < 0.05), while no significant differences were found among RC, FRC, and LD (p < 0.05). The regression analysis found that the fracture strength using the lithium disilicate was significantly lower for the post and higher for the core than that using the resin composite (p < 0.05), and there were no significant difference in the fracture strengths between the resin composite and glass fiber used for the post (p > 0.05). Most of the specimens exhibited root fractures, and no significant differences were observed among the groups (p < 0.05). The results of this study suggest that reinforcement of flared root canals using a combination of resin composite for the core and lithium disilicate ceramic for the post is superior to resin composite and glass fiber in mechanical properties when restoring a single crown.


Social dominance in children with cerebral palsy during a problem-solving task with peers.
Children with cerebral palsy tend to have poorer social competence outcomes than their peers without a disability in mainstream school settings. To understand their social competence, this study compared children with cerebral palsy with paired children without cerebral palsy with respect to their ability to access resources, defined here as "social dominance", in a problem-solving situation. Children with cerebral palsy were randomly paired to a peer (teammate) and put in a competitive context where each team of two children was instructed to solve an impossible problem. To control for social status, a sociometric measure was administered previously in the classroom (Social Preference score). Behaviors related to social dominance (prosocial and coercive behaviors) were coded using an observation scale validated for this study. The results showed that regardless of social status, children with cerebral palsy were less socially dominant than controls without cerebral palsy. Furthermore, their teams seemed to be less dominant than teams composed of two controls. The lower social competence in children with cerebral palsy could be partly explained by their reduced social dominance behavior in activities requiring speed and fluidity as an expression of executive functions. This might be viewed as a marker for social risks in the integration process at school. Implications for rehabilitation Gross Motor Function Classification System level I or II cerebral palsy is a condition that affects not only motor abilities but also social competence in children. Lower social competence in children with cerebral palsy could be partly explained by reduced social dominance behavior in activities such as problem solving with peers. To improve social competence, rehabilitation interventions should include social participation opportunities in which children with cerebral palsy are encouraged to take an active role in the activity.


Omega-3 polyunsaturated fatty acids for cardiovascular diseases: present, past and future.
Large-scale epidemiological studies on Greenlandic, Canadian and Alaskan Eskimos have examined the health benefits of omega-3 fatty acids consumed as part of the diet, and found statistically significant relative reduction in cardiovascular risk in people consuming omega-3 fatty acids. Areas covered: This article reviews studies on omega-3 fatty acids during the last 50 years, and identifies issues relevant to future studies on cardiovascular (CV) risk. Expert commentary: Although a meta-analysis of large-scale prospective cohort studies and randomized studies reported that fish and fish oil consumption reduced coronary heart disease-related mortality and sudden cardiac death, omega-3 fatty acids have not yet been shown to be effective in secondary prevention trials on patients with multiple cardiovascular disease (CVD) risk factors. The ongoing long-term CV interventional outcome studies investigate high-dose, prescription-strength omega-3 fatty acids. The results are expected to clarify the potential role of omega-3 fatty acids in reducing CV risk. The anti-inflammatory properties of omega-3 fatty acids are also important. Future clinical trials should also focus on the role of these anti-inflammatory mediators in human arteriosclerotic diseases as well as inflammatory diseases.


Allergen dependent production of histamine releasing actor by alveolar macrophages.
Human Basophil Degranulation Test (HBDT) has been employed for the research of Histamine Releasing Factor (HRF) from macrophages in asthma. Macrophages have been obtained from broncho-alveolar lavages, incubated with specific allergens and the products of this stimulation added to HBDT preparations. The production of an active HRF has been observed only in macrophages from atopic patients. The effect of this HRF seems to be IgE dependent, the degranulation of human basophils being in general significant only for basophils of atopic patients.


Simultaneous enantioselective determination of amphetamine and congeners in hair specimens by negative chemical ionization gas chromatography-mass spectrometry.
Enantioselective quantification of amphetamine (AM), methamphetamine (MA), 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA) and 3,4-methylenedioxyethylamphetamine (MDEA) enantiomers in hair using gas chromatography-mass spectrometry (GC-MS) is described. Hair specimens were digested with 1M sodium hydroxide at 100 degrees C for 30 min and extracted by a solid phase procedure using Cleanscreen ZSDAU020. Extracted analytes were derivatised with (S)-heptafluorobutyrylprolyl chloride and the resulting diastereoisomers were quantified by GC-MS operating in the negative chemical ionization mode. Extraction yields were between 73.0 and 97.9%. Limits of detection varied in the range of 2.1-45.9 pg/mg hair, whereas the lowest limits of quantification varied between 4.3 and 91.8 pg/mg hair. Intra- and inter-assay precision and respective accuracy were acceptable. The enantiomeric ratios (R versus S) of AM, MA, MDA, MDMA and MDEA were determined in hair from suspected amphetamine abusers. Only MA and AM enantiomers were detectable in this collective and the quantification data showed in most cases higher concentrations of (R)-MA and (R)-AM than those of the corresponding (S)-enantiomers.


Partial distal deployment for precise placement of the GORE Thoracic Endoprosthesis.
The GORE TAG Thoracic Endoprosthesis (TAG) device (W. L. Gore & Associates, Flagstaff, Ariz) and the GORE Conformable TAG Thoracic Endoprosthesis (CTAG) are commonly implanted and effective stent grafts for use during thoracic endovascular aortic repair. Precise placement of the endograft is paramount during thoracic endovascular aortic repair, but like all thoracic stent grafts, maldeployment with inaccurate landing has been reported. The partial distal deployment technique describes an alteration of the TAG and CTAG deployment mechanism to allow isolated deployment of the distal half of the graft, which provides stability during deployment. The graft can be safely repositioned after partial distal deployment, thus allowing precise positioning in the proximal landing zone. Similarly, this technique can be used for precision in the distal landing zone, making the TAG and CTAG devices the only thoracic endografts currently available in the United States with a distal-first deployment option. A discussion of the usefulness of this technique and potential pitfalls is included.


Highly Sensitive Porous PDMS-Based Capacitive Pressure Sensors Fabricated on Fabric Platform for Wearable Applications.
A novel porous polydimethylsiloxane (PDMS)-based capacitive pressure sensor was fabricated by optimizing the dielectric layer porosity for wide-range pressure sensing applications in the sports field. The pressure sensor consists of a porous PDMS dielectric layer and two fabric-based conductive electrodes. The porous PDMS dielectric layer was fabricated by introducing nitric acid (HNO3) into a mixture of PDMS and sodium hydrogen bicarbonate (NaHCO3) to facilitate the liberation of carbon dioxide (CO2) gas, which induces the creation of porous microstructures within the PDMS dielectric layer. Nine different pressure sensors (PS1, PS2,..., PS9) were fabricated in which the porosity (pore size, thickness) and dielectric constant of the PDMS dielectric layers were varied by changing the curing temperature, the mixing proportions of the HNO3/PDMS concentration, and the PDMS mixing ratio. The response of the fabricated pressure sensors was investigated for the applied pressures ranging from 0 to 1000 kPa. A relative capacitance change of ∼100, ∼323, and ∼485% was obtained by increasing the curing temperature from 110 to 140 to 170 °C, respectively. Similarly, a relative capacitance change of ∼170, ∼282, and ∼323% was obtained by increasing the HNO3/PDMS concentration from 10 to 15 to 20%, respectively. In addition, a relative capacitance change of ∼94, ∼323, and ∼460% was obtained by increasing the PDMS elastomer base/curing agent ratio from 5:1 to 10:1 to 15:1, respectively. PS9 exhibited the highest sensitivity over a wide pressure sensing range (low-pressure ranges (<50 Pa), 0.3 kPa-1; high-pressure ranges (0.2-1 MPa), 3.2 MPa-1). From the results, it was observed that the pressure sensors with dielectric layers prepared at relatively higher curing temperatures, higher HNO3 concentrations, and higher PDMS ratios resulted in increased porosity and provided the highest sensitivity. As an application demonstrator, a wearable fit cap was developed using an array of 16 pressure sensors for measuring and mapping the applied pressures on a player's head while wearing a helmet. The pressure mapping aids in observing and understanding the proper fit of the helmet in sports applications.


Risk factors for suicide and other deaths following hospital treated self-poisoning in Australia.
To analyze the risk factors for suicide, premature death and all-cause death in a representative population of hospital-treated deliberate self-poisoning patients. A prospective cohort study using data-linkage between the Hunter Area Toxicology Service Database and the National Death Index of the Australian Institute of Health and Welfare, from January 1991 to December 2000. There were 4105 subjects, of whom 228 (5.6%) died, 122 (2.9%) by premature death and 58 (1.4%) by suicide. The probability of suicide after 10 years follow-up was 2%. The adjusted hazard ratios (95% CI) for suicide were: 'disorders usually diagnosed in infancy, childhood and adolescence', 5.28 (95% CI = 2.04-13.65): male gender, 4.25 (95% CI = 2.21-8.14); discharge to involuntary psychiatric hospital admission, 3.20 (95% CI = 1.78-5.76); and increasing age, 1.02 (95% CI = 1.01-1.04). Men and women showed different patterns of multivariate risks, although increased risk with increasing age and discharge to an involuntary psychiatric admission was true for both. The standardized all-cause mortality ratio (95% CI) was: for men, 6.42 (95% CI = 5.44-7.57), and for women 4.39 (95% CI = 3.56-5.41). The standardized suicide mortality ratio (95% CI) was: for men, 20.55 (95% CI = 15.24-27.73), and for women 22.95 (95% CI = 13.82-38.11). Men and women have different risk factors for subsequent suicide after self-poisoning. Hospital-treated self-poisoning patients have increased risk of subsequent suicide, premature and all-cause death. Psychiatric assessment, leading to discharge decisions, is worthwhile in identifying patients at long-term risk of suicide, premature and all-cause death.


Antiangiogenic activity of synthetic dihydrobenzofuran lignans.
A series of synthetic dihydrobenzofuran lignans, obtained by biomimetic oxidative dimerization of caffeic or ferulic acid methyl ester followed by derivatization reactions, was tested for its antiangiogenic activity in the CAM (chorioallantoic membrane) assay. The dimerization product of caffeic acid methyl ester (2a) (methyl (E)-3-[2-(3,4-dihydroxyphenyl)-7-hydroxy-3-methoxycarbonyl-2,3-dihydro-1-benzofuran-5-yl]prop-2-enoate) showed a pronounced antiangiogenic activity, especially the 2R,3R-enantiomer.


Unraveling the Effect of Surface Ligands on the Auger Process in an Inorganic Perovskite Quantum-Dot System.
This work systematically scrutinizes the role of surface-ligand modification in affecting the Auger process in a porotype perovskite system of CsPbBr3-octanoic acid (OcA) and CsPbBr3-oleic acid (OA) quantum dots (QDs), by means of steady-state/time-resolved/temperature-dependent photoluminescence spectroscopy and ultrafast transient absorption spectroscopy. The difference in the ligand chain length (i.e., C8 and C18 alkyl chains for OcA and OA, respectively) is found to significantly affect Auger recombination and hot-carrier cooling processes. More importantly, we provide fresh insight into the involved carrier dynamics; i.e., the modification of CsPbBr3 QDs with short-chain (long-chain) ligand leads to the formation of trapped (free) carriers, which causes a pronounced difference in the ability to suppress the detrimental Auger process. In addition, a careful analysis of spectral evolution reveals that the Auger suppression is related to the carrier population of a certain transition state. The valuable mechanistic information gleaned from the exciton/carrier dynamics perspective would assist in surface engineering through a facile ligand-modification strategy toward rational design and optimization of QD-based photoelectrochemical applications.


Aripiprazole-induced seizure in a 3-year-old child: a case report and literature review.
Aripiprazole is an atypical antipsychotic medication that is a partial dopamine D(2) and serotonin 5-hydroxytryptamine (1A) receptor agonist and 5-hydroxytryptamine (2A) receptor antagonist. It has a safer profile compared to other antipsychotic medications with regard to its effect on weight, glucose tolerance, prolactin level, and cardiac conduction. The common neurological adverse effects include headache, agitation, insomnia, sleepiness, and extrapyramidal symptoms. Seizures have not been reported in the pediatric population and only twice in adult patients. Here, we report a case of a healthy 3-year-old child who experienced prolonged lethargy, dystonia, and 2 witnessed seizures after incidental ingestion of 30 mg of aripiprazole. To our knowledge, this is the first reported case of aripiprazole-induced seizures in a child.


Comorbid Depression and Other Predictors of PTSD Severity in Urban Public Transit Employees.
The purpose of the study was to determine whether post traumatic stress disorder (PTSD) with Major Depressive Disorder (MDD) among urban public transit employees who were exposed to a workplace traumatic event is associated with greater PTSD severity over the 6-month follow-up period compared to PTSD without MDD, and also to identify predictors of PTSD severity among these employees. Information about Axis-I diagnosis and PTSD severity were collected from the SCID-I and the Modified PTSD Symptom Scale (MPSS) respectively. PTSD without MDD (N = 29) and PTSD with MDD (N = 37) groups were not significantly different in terms of PTSD severity. The severity of depression (p = 0.01), female (p = 0.01), non-Caucasian (p = 0.01), perceived high workplace related stress (p = 0.02), and history of lifetime trauma (p = 0.01) were significantly associated with greater PTSD severity after controlling other variables. This study highlights the importance of modifiable variables for reducing PTSD severity after a workplace traumatic event in transit employees.


Can we prevent long term cardiac damage in Kawasaki disease? Lessons from Lactobacillus casei cell wall-induced arteritis in mice.
A single intraperitoneal injection of sonicated cell walls from group B Lactobacillus casei (LC) produces an acute inflammatory coronary arteritis in mice that closely resembles the coronary arteritis found in children with Kawasaki Disease (KD). The coronary arteritis is accompanied in its early stages by pancarditis and valvulitis, and in its later stages by coronary artery aneurysms, stenoses, and myocardial infarctions. The importance of this model is two-fold. First, it provides the opportunity to study the natural history of coronary artery disease over a relatively short life span. Second, it provides a model system in which the effects of immunological and pharmacological interventions may be tested without putting human life at risk. Studies to date indicate that inflammatory coronary arteritis such as occurs in this model and in children with KD is associated with the accelerated development of coronary artery insufficiency and premature death from cardiovascular disease. The use of immunomodulators or other agents early in the disease course to reduce the frequency and severity of the coronary arteritis appears to reduce the incidence of premature death in this mouse model and may reduce the consequences of KD as well.


Involvement of interleukin-8 in dialysis-related arthritis.
To elucidate the role of interleukin (IL)-8, a chemotactic factor for neutrophils, in dialysis-related arthritis (DRA) of patients on long-term hemodialysis, the concentration of IL-8 was measured in the synovial fluids of DRA patients with acute arthralgia and joint swelling, and was compared with those in patients with rheumatoid arthritis (RA) and patients with osteoarthritis (OA). We noted a marked elevation of IL-8 in the joint fluids of patients with DRA and RA as compared with OA. Furthermore, to determine the role of IL-8 in synovitis, we examined the in vivo effect of intra-articular injection of human recombinant IL-8 on leukocyte infiltration into the joint space of rabbits. A single injection of IL-8 to the joints of rabbits induced rapid infiltration of neutrophils into the joint space and synovial tissues, which reached a maximum in four hours. The oral administration of indometacin farnesil (a prodrug that is converted to indomethacin after intestinal absorption) before the injection of IL-8 alleviated the infiltration of neutrophils. When human synovial cells were incubated with tumor necrosis factor (TNF)-alpha, the expression of IL-8 mRNA and IL-8 production in the cultured synovial cells were increased. The TNF-alpha-stimulated expression of IL-8 mRNA and IL-8 production in the cultured synovial cells were markedly inhibited by dexamethasone. In conclusion, IL-8 levels were markedly elevated in the joint fluids of patients with DRA. Interleukin-8 released from synovial cells may be an important factor to induce acute inflammation in DRA. Dexamethasone and indomethacin may be effective for DRA by inhibiting the production and chemotactic actions of IL-8, respectively.


The effects of sub-threshold vibratory noise on visuomotor entrainment during human walking and standing in a virtual reality environment.
Humans will naturally synchronize their posture to the motion of a visual surround, but it is unclear if this visuomotor entrainment can be attenuated with an increased sensitivity to somatosensory information. Sub-threshold vibratory noise applied to the Achilles tendons has proven to enhance ankle proprioception through the phenomenon of stochastic resonance. Our purpose was to compare visuomotor entrainment during walking and standing, and to understand how this entrainment might be attenuated by applying sub-threshold vibratory noise over the Achilles tendons. We induced visuomotor entrainment during standing and treadmill walking for ten subjects (24.5 ± 2.9 years) using a speed-matched virtual hallway with continuous mediolateral perturbations at three different frequencies. Vibrotactile motors over the Achilles tendons provided noise (0-400 Hz) with an amplitude set to 90% of each participant's sensory threshold. Mediolateral sacrum, C7, and head motion was greatly amplified (4-8× on average) at the perturbation frequencies during walking, but was much less pronounced during standing. During walking, individuals with greater mediolateral head motion at the fastest perturbation frequency saw the greatest attenuation of that motion with applied noise. Similarly, during standing, individuals who exhibited greater postural sway (as measured by the center of pressure) also saw the greatest reductions in sway with sub-threshold noise applied in three of our summary metrics. Our results suggest that, at least for healthy young adults, sub-threshold vibratory noise over the Achilles tendons can slightly improve postural control during disruptive mediolateral visual perturbations, but the applied noise does not substantially attenuate visuomotor entrainment during walking or standing.


Assessing the evidence of a link between mental illness and violence.
The relationship of mental illness and violence is an issue of longstanding clinical and policy importance, and recent research on this association has sparked renewed debate. The author formulates six statements on the association that seem warranted by recent investigations and reviews the research evidence. In general, contrary to findings of earlier research, an association does appear to exist between mental illness and the likelihood of being involved in violent incidents. A dual diagnosis of mental illness and substance abuse probably significantly increases the risk for violence, and the association between mental illness and violence is probably significant even when demographic characteristics are taken into account. Given the considerable limitations of current research, priorities for future research include attention to the strength of the association for individual subjects, inclusion of adequate comparison groups of non-mentally-ill persons and a broad range of variables, and intensive studies of repetitively violent individuals over time.


Prevalence, Host Range, and Comparative Genomic Analysis of Temperate Ochrobactrum Phages.
Ochrobactrum and Brucella are closely related bacteria that populate different habitats and differ in their pathogenic properties. Only little is known about mobile genetic elements in these genera which might be important for survival and virulence. Previous studies on Brucella lysogeny indicated that active phages are rare in this genus. To gain insight into the presence and nature of prophages in Ochrobactrum, temperate phages were isolated from various species and characterized in detail. In silico analyses disclosed numerous prophages in published Ochrobactrum genomes. Induction experiments showed that Ochrobactrum prophages can be induced by various stress factors and that some strains released phage particles even under non-induced conditions. Sixty percent of lysates prepared from 125 strains revealed lytic activity. The host range and DNA similarities of 19 phages belonging to the families Myoviridae, Siphoviridae, or Podoviridae were determined suggesting that they are highly diverse. Some phages showed relationship to the temperate Brucella inopinata phage BiPB01. The genomic sequences of the myovirus POA1180 (41,655 bp) and podovirus POI1126 (60,065 bp) were analyzed. Phage POA1180 is very similar to a prophage recently identified in a Brucella strain isolated from an exotic frog. The POA1180 genome contains genes which may confer resistance to chromate and the ability to take up sulfate. Phage POI1126 is related to podoviruses of Sinorhizobium meliloti (PCB5), Erwinia pyrifoliae (Pep14), and Burkholderia cenocepacia (BcepIL02) and almost identical to an unnamed plasmid of the Ochrobactrum intermedium strain LMG 3301. Further experiments revealed that the POI1126 prophage indeed replicates as an extrachromosomal element. The data demonstrate for the first time that active prophages are common in Ochrobactrum and suggest that atypical brucellae also may be a reservoir for temperate phages.


An axenic culture system for the transformation of bloodstream forms to procyclic forms of Trypanosoma brucei brucei in vitro.
An axenic culture system for continuous cultivation of bloodstream forms of Trypanosoma brucei GUT at 3.1 and subsequent transformation of bloodstream forms to procyclic forms is described. Bloodstream forms were continuously grown at 37 degrees C in Iscove's modification of Dulbecco's medium (M-DMEM, with bovine serum albumin, transferrin and soybean lecithin supplemented with 100 microM hypoxanthine, 30 microns thymidine, 40 microM adenosine, 1mM sodium pyruvate, 50 microM L-glutamine, 100 microM 2-mercaptoethanol and 20% (v/v) heat-inactivated fetal bovine serum. In this system, 2-mercaptoethanol (2-ME) was essential and in the absence of 2-ME, 100 microM L-cysteine and 10 microM bathocuproine sulfonate could not be substituted for 2-ME. This culture system was useful for long-term culture of bloodstream forms of this clone. Axenic cultivation of bloodstream forms at 27 degrees C resulted in transformation to procyclic forms within 5 days in the same medium supplemented with 5 mM L-proline, 8 micrograms/ml hemin and 4 micrograms/ml hematin, respectively and, instead of FBS, 20% (v/v) hemoglobin-poor fraction of fetal bovine serum.


Fibrosis in small syngeneic rat liver grafts because of damaged bone marrow stem cells from chronic alcohol consumption.
A patient with liver failure due to chronic and acute alcohol abuse under consideration for an urgent liver transplant shortly after stopping alcohol may have residual abnormalities that threaten transplant success, particularly for a small graft. To address this, we studied a model in which reduced-size (50%) Lewis rat livers are transplanted into green fluorescence protein transgenic Lewis recipients after they are fed alcohol or a control diet for 5 weeks. Here we show that normal small Lewis grafts transplanted to alcohol-fed Lewis hosts developed fibrosis, whereas no fibrosis was observed in control-fed recipients. Host-derived CD133 + 8-hydroxy-2'-deoxyguanosine (8-OHdG) cells were significantly increased in livers recovered from both alcohol-fed and control recipients, but only alcohol-fed recipients demonstrated co-staining (a marker of oxidative DNA damage). α smooth muscle actin (α-SMA) staining, a marker for myofibroblasts, also co-localized with CD133 + cells only in the livers of alcohol-fed recipients. Immunostaining and polymerase chain reaction analysis confirmed that chronic alcohol consumption decreased the proportion of bone marrow stem cells (BMSCs) expressing CD133, c-Kit, and chemokine (C-X-C motif) receptor 4 markers and caused oxidative mitochondria DNA (mtDNA) damage. Culture of CD133 + cells from normal rats with medium containing 3% ethanol for 48 hours resulted in elevated mitochondrial 8-OHdG and mtDNA deletion, and ethanol exposure diminished CD133 expression but dramatically increased α-SMA expression. In conclusion, oxidative mtDNA damage and deletions occur in BMSCs of chronic alcohol-fed recipients, and these damaged cells mobilize to the small liver grafts and become myofibroblasts where they play a key role in the subsequent development of fibrosis. Liver Transplantation 23 1564-1576 2017 AASLD.


Simple Thermal-Efficiency Model for CMOS-Microhotplate Design.
Simple, semi-empirical, first-order, analytic approximations to the current, voltage, and power as a function of microhotplate temperature are derived. To lowest order, the voltage is independent of, and the power and current are inversely proportional to, the length of the microhotplate heater legs. A first-order design strategy based on this result is described.


[Self and significant other assessment of hearing device aided communication skills in the elderly with hearing loss].
This study aims to evaluate the communication problems of elderly before and after using hearing aids. Thirty hearing aid users and 10 normal hearing control subjects with their relatives were enrolled in the study. Hearing aid users were divided into three subgroups based on the duration of use. Self Assessment of Communication (SAC) and Significant Other Assessment of Communication (SOAC) questionnaires were administered to hearing aid users, control subjects, as well as to their relatives for the evaluation of communication difficulties due to hearing loss. Intra-group comparisons were carried out in the patients using hearing aids, while inter-group comparisons were performed to evaluate the effects of different aided periods on communication skills. It was found that the communication difficulties reduced in the patients who used hearing aid for minimum one month. For the patients with hearing loss, hearing aid use of six months or more increased SAC and SOAC scores to a level comparable with control subjects. The present study conclude that the elderly patients of 60 years of age or more with moderate sensorineural hearing loss could catch up their normal hearing peers in their communication skills within six months only if they prescribed and used proper hearing aids.


First metatarsophalangeal arthrodesis: a biomechanical comparison of three fixation constructs.
First metatarsophalangeal joint arthrodesis is utilized in the treatment of severe arthritis and hallux valgus. Successful fusion relies on limiting motion at the fusion site and may be achieved through numerous methods. Use of locking plates has recently generated considerable interest, but whether they provide any biomechanical advantage over other available constructs is unclear. Utilizing cyclic loading intended to mimic early weight bearing, the stiffness of three fixation methods for first metatarsophalangeal arthrodesis was compared using Sawbones. The one-third tubular plate completed 1.8 and 2.4 times more cycles before failure than the X-type locking plate or crossed screws, respectively. No difference was detected in cycles to failure between the X-type locking plate and crossed screws. One-third tubular plate mean stiffness was 49% greater than crossed screws at all cycles and greater than X-type locking plate by an average of 25%, beginning at cycle 50.


Molybdate depletes hepatic 3-phosphoadenosine 5-phosphosulfate and impairs the sulfation of acetaminophen in rats.
Molybdate (15 mmol/kg p.o.) decreased serum sulfate concentrations of rats 70% within 6 hr after administration. Parallel to this depletion, there was a dramatic decrease in hepatic sulfate and 3-phosphoadenosine 5-phosphosulfate (PAPS) concentrations (about 40 and 65%, respectively). However, renal PAPS concentrations did not change significantly. Molybdate reduced serum, hepatic and renal sulfate as well as hepatic PAPS concentration in a dose-dependent manner up to the dose of 10 mmol/kg. However, renal PAPS did not change. The results indicate that molybdate reduced not only sulfate concentrations in serum and tissue, but also PAPS concentrations in liver. The effect of molybdate on the pharmacokinetics of acetaminophen (AA, 150 mg/kg i.v.) was also investigated in order to determine whether molybdate-induced depletion of PAPS might be a useful tool for examining the importance of sulfation in the detoxication and toxication of xenobiotics. AA-sulfate concentration in blood decreased 40 and 80% after administration of molybdate at doses of 2.5 and 15 mmol/kg, respectively. Molybdate also decreased the excretion of AA-sulfate into bile and urine by about 60 and 80%, respectively. However, molybdate did not alter the excretion of AA-glucuronide and AA-glutathione/cysteine. The excretion of the parent AA increased 2-fold after molybdate administration (15 mmol/kg). In conclusion, molybdate effectively lowers inorganic sulfate in serum and tissues, and PAPS in the liver. Reduction of hepatic PAPS markedly decreases the sulfation of AA, suggesting that molybdate treatment could be used to study the importance of sulfation in pharmacology and toxicology.


Evaluation of protein C and other biomarkers as predictors of mortality in a rat cecal ligation and puncture model of sepsis.
To evaluate protein C and other factors associated with the septic response as predictors of mortality in a clinically relevant animal model of sepsis. Laboratory investigation. Eli Lilly and Company discovery research laboratory. Forty female Sprague Dawley rats weighing 245-265 g. Polyethylene catheters were surgically implanted into the femoral vein and sepsis was induced by cecal ligation and puncture (CLP). A solution of 5% dextrose in 0.9 % saline was continuously infused via femoral catheters immediately following surgery. Blood sampling was done before surgery and at 6 and 20 hrs after surgery. Rats were then monitored for survival out to 4 days. Blood collections were used to measure blood glucose, bacteremia, plasma protein C, D-dimer, hormones, chemokines, cytokines, and myoglobin (as a marker of organ damage). Mortality was categorized into three groups: early death (before 30 hrs post-CLP), late death (after 30 hrs post-CLP), and survivors (96 hrs post-CLP). Compared with survivors, early death rats had statistically significant differences in 30 variables indicative of severe inflammation, coagulopathy, and muscle damage including less bacterial clearance, hypoglycemia, lower plasma protein C, higher plasma D dimer, higher plasma cytokine/ chemokines, and higher plasma myoglobin concentrations. Twenty variables had a moderate to strong correlation with time of death. Receiver operator characteristic curves generated from a simple logistic regression model indicated that KC and macrophage inflammatory protein-2, rodent homologues of the human growth related oncogene CXC chemokine family, and protein C were the best predictors of mortality in this model. The data from this study indicate that an early decrease in protein C concentration predicts poor outcome in a rat sepsis model. The data further indicate that increases in the CXC chemokines macrophage inflammatory protein-2 and KC precede poor outcome.


Implementing Evidence-Based Practice Facilitators: A Case Series.
In 2017, the TriService Nursing Research Program completed a strategic planning session, which identified key barriers to implementing evidence-based practice (EBP) within the U.S. Military Health System (MHS) including a focus on readiness training and deployments, frequent staff moves for military members, and relatively junior nurses in clinical roles. To facilitate EBP at individual military treatment facilities (MTFs), an EPB Facilitator role was developed using an evidence-based model and based on validated EBP competencies. This new role was implemented at four MTFs in 2018: Naval Medical Center Portsmouth, 59th Medical Wing at Joint Base San Antonio Lackland, Naval Medical Center San Diego, and David Grant USAF Medical Center at Travis Air Force Base. This case series provides a description of the initial implementation of this role. Common enablers and challenges were identified from the experiences at all four sites. These included the importance of incorporating efforts into existing organizational efforts and infrastructure; the value of nurse leaders inviting EBP facilitators to participate and engage in scheduled meetings and committees; the significance of engaging with existing quality, process improvement, and training initiatives; and the benefit of collaborating with advanced practice nurses within the organization. The common challenges for all EBP facilitators were the frequent staff turnover at all levels and a lack of standardization to review and approve EBP initiatives, which makes it difficult to navigate the complete process of project implementation and collaboration across sites. Another challenge has been the difficulty to measure the impact of this role at the MTF and MHS levels. As EBP efforts continue and the program matures, it is anticipated that the outcomes from the individually completed projects, to include decreases in safety events, fiscal savings, and other improvements in organizational metrics, can be compiled to demonstrate the collective impact of these roles within the MHS.


Using Hamiltonian control to desynchronize Kuramoto oscillators.
Many coordination phenomena are based on a synchronization process, whose global behavior emerges from the interactions among the individual parts. Often in nature, such self-organized mechanism allows the system to behave as a whole and thus grounding its very first existence, or expected functioning, on such process. There are, however, cases where synchronization acts against the stability of the system; for instance in some neurodegenerative diseases or epilepsy or the famous case of Millennium Bridge where the crowd synchronization of the pedestrians seriously endangered the stability of the structure. In this paper we propose an innovative control method to tackle the synchronization process based on the application of the Hamiltonian control theory, by adding a small control term to the system we are able to impede the onset of the synchronization. We present our results on a generalized class of the paradigmatic Kuramoto model.


Cross-validation by downweighting influential cases in structural equation modelling.
In the social and behavioural sciences, structural equation modelling has been widely used to test a substantive theory or causal relationship among latent constructs. Cross-validation (CV) is a valuable tool for selecting the best model among competing structural models. Influential cases or outliers are often present in practical data. Therefore, even the correct model for the majority of the data may not cross-validate well. This paper discusses various drawbacks of CV based on sample covariance matrices, and develops a procedure for using robust covariance matrices in the model calibration and validation stages. Examples illustrate that the CV index based on sample covariance matrices is very sensitive to influential cases, and even a single outlier can cause the CV index to support a wrong model. The CV index based on robust covariance matrices is much less sensitive to influential cases and thus leads to a more valid conclusion about the practical value of a model structure.


The Virginia Racial Integrity Act revisited: the Plecker-Laughlin correspondence: 1928-1930.
Correspondence between Walter Ashby Plecker, Virginia State Registrar of Vital Statistics between 1912 and 1938, and Harry Hamilton Laughlin, Superintendent of the Eugenics Record Office at Cold Spring Harbor between 1910 and 1939, provides evidence of efforts to enforce the Virginia Racial Integrity Act of 1924. After antimiscegenation policy is placed in a historical context, excerpts from the letters are offered to demonstrate the zeal with which one state official pursued this "eugenic" policy.


Polymicrobial synergy and dysbiosis in inflammatory disease.
Uncontrolled inflammation of the periodontal area may arise when complex microbial communities transition from a commensal to a pathogenic entity. Communication among constituent species leads to polymicrobial synergy between metabolically compatible organisms that acquire functional specialization within the developing community. Keystone pathogens, even at low abundance, elevate community virulence, and the resulting dysbiotic community targets specific aspects of host immunity to further disable immune surveillance while promoting an overall inflammatory response. Inflammophilic organisms benefit from proteinaceous substrates derived from inflammatory tissue breakdown. Inflammation and dysbiosis reinforce each other, and the escalating environmental changes further select for a pathobiotic community. We have synthesized the polymicrobial synergy and dysbiotic components of the process into a new model for inflammatory diseases.


The outcome of renal transplantation in children with posterior urethral valves.
The effect of vesical dysfunction on the survival and function of renal transplants was evaluated by a retrospective study in which 18 children with posterior urethral valves and 18 children with vesicoureteral reflux were randomly matched with 36 children used as controls. There was no statistically significant difference in patient survival among the 3 groups. Five years after transplantation 50 per cent of the grafts in children with posterior urethral valves were functioning, while 73 and 75 per cent, respectively, of the grafts were functioning in children with vesicoureteral reflux and in the control group. Renal function during the 5 years was significantly better in children in the control group and in those with vesicoureteral reflux than in children with posterior urethral valves. We believe that the presence of an abnormal bladder may alter graft survival and adversely affect the function of the transplanted kidney.


Sperm pretreatment with heparin and l-glutathione, sex-sorting, and double cryopreservation to improve intracytoplasmic sperm injection in bovine.
In bovine, intracytoplasmic sperm injection (ICSI) remains inefficient partially due to low levels of sperm decondensation. The aim of this study was to determine whether the injection of normal size sperm pretreated with heparin (Hep) and l-glutathione (GSH), the use of sex-sorted sperm, the double round of sperm freezing/thawing (re frozen), or the combination of these approaches can improve sperm decondensation and embryo development after ICSI in cattle. Cleavage and blastocyst rates were evaluated on days 2 and 7 post ICSI. Quality of ICSI blastocysts was analyzed by the relative expression of four genes by qPCR and the DNA fragmentation index by TUNEL assay. For all assays, semen samples were co-incubated with pCX-EGFP 50 ng/μl before ICSI. GFP expression, which can be detected by fluorescence microscopy, was used as a tool to estimate the success of sperm decondensation after ICSI. The use of normal size sperm pretreated with 80 μM Hep-15 mM GSH for 20 h (Hep-GSH) increased cleavage, blastocyst and EGFP + blastocysts rates (60.8, 19.4 and 61.9%) compared to control ICSI (35, 4.9 and 20%) (p < 0.05). Moreover, HMGN1, GLUT5, AQP3 and POU5F1 transcription levels did not differ between ICSI Hep-GSH and IVF embryos. The use of sex-sorted sperm (X, Y) improved cleavage rates and EGFP expression at day 4 (83 and 30.2% for ICSI Y and 83.2 and 31.7% for ICSI X) compared to non-sorted group (50.9 and 15.1%), not showing differences at the blastocyst stage. Finally, sex sorting (X) was combined with Hep-GSH and/or re frozen treatments. The use of Hep-GSH diminished cleavage rates from ICSI X re frozen group (80.4% vs. 94.2%) and blastocyst development from ICSI X group (3.3% vs. 10%), compared with their controls (p < 0.05). While Hep-GSH pretreatment induced lower transgene expression at day 4, no differences were found at the blastocyst stage between ICSI groups (from 58.3 to 80%). TUNEL assay showed higher DNA fragmentation indexes for all ICSI treatments (p < 0.05), except for ICSI X Hep-GSH, which did not differ from IVF X control. In conclusion, the use of normal size sperm pretreated with Hep-GSH, combined or not with sex-sorting by flow cytometry could improve ICSI outcomes in cattle.


Sexual Rehabilitation After Treatment for Prostate Cancer-Part 1: Recommendations From the Fourth International Consultation for Sexual Medicine (ICSM 2015).
Sexual dysfunction is common in patients after radical prostatectomy (RP) for prostate cancer. To provide the International Consultation for Sexual Medicine (ICSM) 2015 recommendations concerning prevention and management strategies for post-RP erectile function impairment in terms of preoperative patient characteristics and intraoperative factors that could influence erectile function recovery. A literature search was performed using Google and PubMed databases for English-language original and review articles published up to August 2016. Levels of evidence (LEs) and grades of recommendations (GRs) based on a thorough analysis of the literature and committee consensus. Nine recommendations are provided by the ICSM 2015 committee on sexual rehabilitation after RP. Recommendation 1 states that clinicians should discuss the occurrence of postsurgical erectile dysfunction (temporary or permanent) with every candidate for RP (expert opinion, clinical principle). Recommendation 2 states that validated instruments for assessing erectile function recovery such as the International Index of Erectile Function and Expanded Prostate Cancer Index Composite questionnaires are available to monitor EF recovery after RP (LE = 1, GR = A). Recommendation 3 states there is insufficient evidence that a specific surgical technique (open vs laparoscopic vs robot-assisted radical prostatectomy) promotes better results in postoperative EF recovery (LE = 2, GR = C). Recommendation 4 states that recognized predictors of EF recovery include but are not limited to younger age, preoperative EF, and bilateral nerve-sparing surgery (LE = 2, GR = B). Recommendation 5 states that patients should be informed about key elements of the pathophysiology of postoperative erectile dysfunction, such as nerve injury and cavernous venous leak (expert opinion, clinical principle). This article discusses Recommendations 1 to 5 of the ICSM 2015 committee on sexual rehabilitation after RP. Salonia A, Adaikan G, Buvat J, et al. Sexual Rehabilitation After Treatment for Prostate Cancer-Part 1: Recommendations From the Fourth International Consultation for Sexual Medicine (ICSM 2015). J Sex Med 2017;14:285-296.


Analysis of cellular response to protein overexpression.
The overexpression of secreted proteins is of critical importance to the biotechnology and biomedical fields. A common roadblock to high yields of proteins is in the endoplasmic reticulum (ER) where proofreading for properly folded proteins is often rate limiting. Heterologous expression of secreted proteins can saturate the cell's capacity to properly fold protein, initiating the unfolded protein response (UPR), and resulting in a loss of protein expression. An obvious method for overcoming this block would be to increase the capacity of the folding process (overexpressing chaperones) or decreasing the proofreading process (blocking the down-regulation by the UPR). Unfortunately, these processes are tightly interlinked, whereby modification of one mechanism has unknown effects on the other. Although some success has been achieved in improving expression via co-overexpressing ER chaperones, the results have not lead to a global method for increasing all heterologously overexpressed proteins. Further, many diseases have been linked to extended periods of stress and are not treatable by these approaches. This work utilises both experimental analysis of the interactions within the ER and modelling in order to understand how these interactions affect early secretory pathway dynamics. This study shows that overexpression of the ER chaperone binding protein does not regulate Ire1p and the UPR as predicted by a model based on the published understanding of the molecular mechanism. A new model is proposed for Ire1p regulation and the UPR that better fits the experimental data and recent studies on Ire1p.


Long-term culture of human bone marrow. I. characterization of adherent cells in flow cytometry.
Using long-term culture techniques, we were able to characterize the different adherent cell elements of the in vitro bone marrow microenvironment by flow cytometry. After 2 weeks of culture, four adherent cell subsets, L, MM, F, and M, were distinguished according to their intrinsic cellular characteristics of volume and spontaneous fluorescence. Using four immunological markers, we identified each population as a hematopoietic lymphocytic group (L), CD45+, VIM2-, CD14-; a hematopoietic myelomonocytic group (MM), CD45+, VIM2+, CD14-; a hematopoietic macrophage group (M), brightly autofluorescent, CD45+, VIM2-, CD14+; and a group of fibroblastoid cells (F) with a very high volume, CD45-, VIM2-, CD14-, and collagen III+. Isolation of the different hematopoietic and nonhematopoietic components of long-term bone marrow culture is thus possible using flow cytometry analysis according to the cell characteristic of volume and spontaneous fluorescence alone.


Ticagrelor: Long-Term Therapy in Patients with Coronary Artery Disease.
Atherothrombosis and coronary artery disease affect more than 13 million individuals only in the United States, about 8 millions in Europe and are the major causes of death worldwide. In particular chronic stable angina impairs patient quality of life, is associated with an important health spending and increased patient mortality; it is a prominent symptom of coronary artery disease (CAD), the latter being prevalent worldwide in patients. A key role in pathophysiology of cardiovascular acute events is played by activated platelets. Aspirin and adenosine diphosphate antagonist in addition to it is recommended for 1 year for reduction of cardiovascular events in patients with prior myocardial infarction with a weak recommendation to continue thereafter. P2Y12 receptor antagonists, in addition to aspirin, have been shown in the last years, to reduce ischemic events in patients with acute coronary syndrome but their role in secondary prevention is still new and unclear. The aim of our paper is to review the long-term effect of therapy with ticagrelor on the basis of recent evidence based data. We performed an online search on the major search engines. All the randomized controlled trials were summarized in the table. We included in our paper six randomized controlled trials and we mentioned about ten post - hoc analysis, sub studies and registries. All studies included the type the therapy and a mid or long term clinical follow up. The studies reported in our paper and in particular PEGASUS - TIMI 54 study showed the merit to placing attention of prevention secondary ischemic events after acute coronary syndrome in the context of treatment with dual anti - platelet therapy; it proved a clinical benefit in patients treated with ticagrelor (60 mg x 2) for 3 years. Nevertheless, the effectiveness of these results cannot be generalized to patients with higher bleeding risk or low ischemic risk. In fact prolonged therapy with ticagrelor 60 mg in combination with aspirin could be considered valuable in patients with repeated acute ischemic events or with several coronary revascularizations over time (especially in patients with lower bleeding risk).


Vitamin A receptor in cancers and in vitro-transformed epithelial cells of the rat urinary bladder: its implication in the preventive effect of vitamin A on in vitro keratinization.
Cellular retinol-binding protein (CRBP) in cancers and in vitro-transformed epithelial cells of the ACI/N rat urinary bladder was assayed with radiolabeled retinol by sucrose density gradient centrifugation. CRBP was detected in abundance in tumor tissues of all 5 transplantation bladder cancer lines. However, this protein was below the limits of detection in bladder cancer cells of culture lines that had originated from the same primary cancers as the corresponding transplantation lines. CRBP was detected in small quantity in in vitro-transformed epithelial cells of a culture line but it was absent in another line of similar origin. The addition of retinol to the culture medium prevented the in vitro keratinization of CRBP-positive cells but it had no effect on the keratinization of CRBP-negative cells.


CD16xCD33 Bispecific Killer Cell Engager (BiKE) as potential immunotherapeutic in pediatric patients with AML and biphenotypic ALL.
Similar to pediatric acute myeloid leukemia (AML) the subgroup of biphenotypic acute lymphoblastic leukemia (ALL) is a rare complex entity with adverse outcome, characterized by the surface expression of CD33. Despite novel and promising anti-CD19 targeted immunotherapies such as chimeric antigen receptor T cells and bispecific anti-CD19/CD3 antibodies, relapse and resistance remain a major challenge in about 30% to 60% of patients. To investigate the potential role of the fully humanized bispecific antibody CD16 × CD33 (BiKE) in children with CD33+ acute leukemia, we tested whether the reagent was able to boost NK cell effector functions against CD33+ AML and biphenotypic ALL blasts. Stimulation of primary NK cells from healthy volunteers with 16 × 33 BiKE led to increased cytotoxicity, degranulation and cytokine production against CD33+ cell lines. Moreover, BiKE treatment significantly increased degranulation, IFN-γ and TNF-α production against primary ALL and AML targets. Importantly, also NK cells from leukemic patients profited from restoration of effector functions by BiKE treatment, albeit to a lesser extent than NK cells from healthy donors. In particular, those patients with low perforin and granzyme expression showed compromised cytotoxic function even in the presence of BiKE. In patients with intrinsic NK cell deficiency, combination therapy of CD16xCD33 BiKE and allogeneic NK cells might thus be a promising therapeutic approach. Taken together, CD16xCD33 BiKE successfully increased NK cell effector functions against pediatric AML and biphenotypic ALL blasts and constitutes a promising new option for supporting maintenance therapy or "bridging" consolidation chemotherapy before hematopoietic stem cell transplantation.


[Endocurietherapy of basal-cell epitheliomas of the face (author's transl)].
The diagnosis of basal cell epitheliomas of the face is usually made at an early stage (lesions of less than one centimetre in diameter) in France. Because of their good prognosis, without metastatic risk (95% recovery rate), therapy can be chosen as a function of its cost and the esthetic result obtained. The author considers that surgery, endocurietherapy with iridium, and plesioradiotherapy are equally effective but should be chosen according to the extent and location of the lesion. The ear, and to a lesser degree the nose, are the major indications for curietherapy. For the cyclids and flat surfaces (temporal or frontal regions etc...) surgery, and plesioradiotherapy are the treatment of choice.


Synthesis of haptens and development of an immunoassay for the olive fruit fly pheromone.
An enzyme-linked immunosorbent assay (ELISA) for the olive fruit fly pheromone, Bactrocera oleae Gmelin, was developed. The assay uses polyclonal antibodies, raised in rabbits, against (+/-)-beta-[3-(1,7-dioxaspiro[5.5]undecane)]propionic acid, 2 (hapten I), conjugated to the KLH (keyhole limpet hemocyanin) by the carbodiimide method. A second hapten, (+/-)-delta-[3-(1,7-dioxaspiro[5.5]undecane)]butylamine, 3 (hapten II), after conjugation to a biotin moiety, was used for indirect immobilization onto ELISA microwells precoated with the glycoprotein avidin. The developed ELISA method measures the synthetic olive fruit fly pheromone in concentrations ranging between 0.08 and 10 microg/mL and shows great promise for practical applications for pheromone detection in environmental and biological samples. The results obtained strongly indicate that this technique, to our knowledge the first insect pheromone enzyme-linked immunosorbent assay so far reported, is a fast, sensitive, inexpensive, and highly convenient method for the analysis of a volatile and low molecular weight compound such as 1,7-dioxaspiro[5.5]undecane, 1.


Changes in B-Cell Counts and Percentages during Primary HIV Infection Associated with Disease Progression in HIV-Infected Men Who Have Sex with Men: A Preliminary Study.
Numerous anomalies in B-cell phenotypes and functions have been described in HIV-infected individuals. However, the actual relationship between B cells and disease progression remains unclear. In this study, we investigated B-cell counts/percentages during a 12-month infection period in HIV-infected individuals that eventually developed into typical progressors (TPs) or rapid progressors (RPs). We found, after 12 months of infection, the baseline B-cell counts/percentages correlated positively with CD4(+) T-cell counts (P = 0.0006 and P = 0.026) and negatively with HIV viral set points (P = 0.014 and P = 0.002). Kaplan-Meier survival analysis showed that high baseline B-cell counts/percentages were associated with a slow CD4-cell decline. B-cell kinetics indicated the baseline B-cell counts/percentages could be factors distinguishing between TPs and RPs. The combination of the baseline B-cell counts and percentages was associated with rapid disease progression (a 80.7% predictive value as measured by the area under the curve). These results indicate that the baseline B-cell counts/percentages might be associated with HIV disease progression.


CD147 expression is associated with poor overall survival in chemotherapy treated triple-negative breast cancer.
In breast cancer models, the functional roles of CD147 in proliferation, invasion and treatment resistance have been widely reported. However, there are only a few studies examining the clinicopathological correlation and prognostic relevance of CD147 in breast cancer, especially in relation to breast cancer molecular subtypes. In this study, we analysed CD147 expression in a large cohort of breast cancers, correlating with clinicopathological features and the expression of a comprehensive panel of biomarkers in triple-negative breast cancer (TNBC) and non-TNBC subsets. Its relationship with patients' survival was also analysed. CD147 was expressed in 11.9%(140/1174) of all cases and in 23.8% (40/168) of TNBC. The expression was associated with tumour histological subtypes (p=0.01) and most commonly seen in carcinoma with medullary features (26.0%). CD147 expression correlated with high tumour grade, presence of necrosis and basal-like breast cancer (BLBC) subtype, high Ki67 and expression of some other basal markers and stem-like markers. CD147 expression was also associated with poor overall survival in chemotherapy treated patients with TNBC. CD147 is a putative marker in identifying TNBC or BLBC, and may be useful as a prognosis indicator for patients with TNBC or BLBC post chemotherapy.


Antigen induced modulation by shed lymphocyte membrane gangliosides.
A unique regulatory mechanism has been proposed for ganglioside which functions to immune responses to temporarily restrain B lymphocytes of all specificities and at various levels of differentiation. Utilizing antigen competition protocols, experiments was designed to exploit and extend the antigen induction properties of this modulation. Spleen cell cultures were prepared from TNP-BGG primed mice. In vitro stimulation of the cultures with ovalbumin (OVA) followed 24 hours later by addition of TNP-BGG resulted in only one weak TNP hemolytic plaque responses when compared to control cultures which did not receive OVA. OVA induced competitive effects were absorbed by anti-Thy-1 or anti-ganglioside. Glycolipids could be extracted from the culture media supernatants of experimental and control groups as a ganglioside fraction containing Thy-1 determinants. These molecules, when formulated into liposomes, produced the same modulatory effect as that of media from the competitive culture group. These results support and extend the proposal that glycolipids released by antigen stimulated T cells provide unrestricted modulation of B cells to prevent overload during T cell maturation. This regulatory mechanism prevents direct antigen binding and prepares B cell receptivity for further stimuli which orchestrate their terminal differentiation into plasma cells.


Safety and efficacy of 2,790-nm laser resurfacing for chest photoaging.
Chest photodamage is a common cosmetic complaint. Laser treatment of the chest may be higher risk than other areas. The objective of this study was to assess the safety and efficacy of 2,790-nm chest resurfacing for photodamage. Twelve patients with Fitzpatrick skin types I-III were enrolled in this university IRB-approved study. Photo documentation was obtained at baseline and each visit. A test spot with the 2,790-nm resurfacing laser was performed on the chest. Patients who did not have adverse effects from the test spot went on to have a full chest resurfacing procedure. Patients were instructed on standardized aftercare, including sunscreen. A 5-point healing and photodamage improvement scale was used to rate improvement by both investigators and the patients and was obtained at 2 weeks, 1 month, 2 months, and 3 months. One pass chest treatment with the 2,790-nm resurfacing laser at fluences greater than or equal to 3.0 mJ with 10% overlap leads to unacceptable rates of hyperpigmentation. Double pass chest treatment at fluences less than or equal to 2.5 mJ with 10% overlap leads to mild improvement in chest photodamage parameters without significant or persistent adverse effects. Laser treatment of aging/photodamaged chest skin remains a challenge due to the delicacy of chest skin. Mild improvement may be obtained with double pass resurfacing with the 2,790-nm wavelength.


An enzyme-linked immunosorbent assay, using an EDTA-extracted antigen for the serology of Haemophilus pleuropneumoniae.
An enzyme-linked immunosorbent assay (ELISA) was proposed as an alternative to the complement-fixation test (CF) for the detection of antibodies of Haemophilus pleuropneumoniae, agent of the pleuropneumonia in pigs. In tests done with different antigen-extraction procedures (including Tween 20, sodium dodecyl sulfate, aqueous phenol, sonification, and heat treatment at 120 C), ethylenediaminetetraacetic acid (EDTA) provided a satisfactorily reactive antigen. Chromatography purification on Sephacryl S200 improved the specificity of this antigen. Using hyperimmune rabbit sera, we investigated the specificity and the sensitivity of the ELISA with the EDTA-purified antigen of the different serotypes of H pleuropneumoniae on selected swine sera in herds with confirmed H pleuropneumoniae infection, from specific-pathogen-free animals showing doubtful CF reactions. The ELISA proved to be highly specific and more sensitive than the CF test. Furthermore, evidence of cross-reactions with H parasuis, a common bacteria isolated in swine populations, was not found.


Distribution of malassezia species on the scalp in korean seborrheic dermatitis patients.
Malassezia species play an important role in the pathogenesis of seborrheic dermatitis. In particular, M. restricta and M. globosa are considered to be the predominant organisms in seborrheic dermatitis of Western countries. However, species distribution of Malassezia in seborrheic dermatitis has not been clearly determined yet in Asia. To identify the distribution of Malassezia species on the scalp of seborrheic dermatitis patients in Korea using 26S rDNA PCR-RFLP analysis. A total of 40 seborrheic dermatitis patients and 100 normal healthy volunteers were included in this study. For the identification of Malassezia species, the scalp scales of the subjects were analyzed by 26S rDNA PCR-RFLP analysis. The most commonly identified Malassezia species were M. restricta in the seborrheic dermatitis patients, and M. globosa in the normal controls. In the seborrheic dermatitis group, M. restricta was identified in 47.5%, M. globosa in 27.5%, M. furfur in 7.5%, and M. sympodialis in 2.5% of patients. In the healthy control group, M. globosa was identified in 32.0%, M. restricta in 25.0%, M. furfur in 8.0%, M. obtusa in 6.0%, M. slooffiae in 6.0%, and M. sympodialis in 4.0% of subjects. M. restricta is considered to be the most important Malassezia species in Korean seborrheic dermatitis patients.


[Structure and functions of the cutaneous nervous system].
Cutaneous nerves are either somatic sensory afferents to ganglion neurons or terminal efferents from the autonomous nervous system. Myelinated somatic nerves form subcutaneous and intradermal plexus from which arise various types of endings: free, dilated and included in corpuscles. Free terminals are ramified in the dermis, epidermis and the epithelial sheet of hairs. Dilated terminals are lanceolate fibres around hairs and those in close contact with Merkel cells. Well identified corpuscles are those of Meissner, Ruffini and Pacini. Physiologically, nerves are involved as mechano-, thermo- and pain receptors. Five mechanoreceptors are recognized according to their rate (slow/fast) of adaptation and their receptive field (type I, small; type II, large): Merkel cells (SA I), Ruffini corpuscles (SA II), Meissner corpuscles (FA I), Pacini corpuscles (FA II) and palisades of lanceolate nerve endings (FA with various field units). Thermo- and nociceptors are mainly thin unmyelinated free nerve endings with various rates of conduction velocity. The autonomic nervous system supplies sympathetic innervation appearing as unmyelinated small nerve endings in close contact with skin appendages, except sebaceous glands. Only sweat glands are innervated by cholinergic terminals.


Studies on immunoassays of peptide factors. V. Synthesis of cholecystokinin-58-[1-11]/iso-1-cytochrome c conjugate.
In previous studies on model compounds we have found that the maleimide function is sufficiently stable under the conditions of peptide synthesis to allow its incorporation at preselected positions of a peptide chain in earlier steps of the synthetic route. Taking advantage of this observation the N-terminal undecapeptide of canine cholecystokinin-58 containing at its N-terminus the maleimide group became accessible in high yields as chromatographically homogenous and analytically well characterized compound. Via the incorporated anchor group the undecapeptide was linked selectively at its N-terminus to the cysteine residue 107 of iso-1-cytochrome c to yield a well characterized conjugate of 1:1 stoichiometry for immunization experiments.


Enteral Nutrition Support Does Not Improve PNI in Radiotherapy Patients with Locally Advanced Esophageal Cancer.
The assessment of prognostic nutritional index (PNI) before and during radiotherapy is an important parameter for the prognosis in patients with cancer. In this study, enteral tube feeding (ETF) was used during radiotherapy in patients with EC. Dynamic changes of various nutritional indicators (including PNI) were monitored. Patients with EC who underwent radiotherapy between June 2016 and July 2017 were enrolled. ETF was performing with the energy of 25 kcal × kg/d. Nutritional status were evaluated. Least significant difference (LSD) was used for multiple comparisons between groups. A total of 148 patients were admitted, including 51 patients fed via ETF. For patients who were not scheduled to nutritional support, significant difference were observed in albumin (ALB) (P < 0.001), prealbimnin (PA) (P = 0.05) and PNI (P < 0.001) compared to levels before radiotherapy. In the patients fed via enteral tube, no significant difference were found in weight, BMI, ALB, retinol binding protein (RBP) and PA before and after radiotherapy, while PNI significantly decreased (P < 0.001). After preforming ETF with the energy of 25 kcal × kg/d in patients with EC during radiotherapy, PNI, the key nutritional index reflecting prognosis, significantly decreased.


Massive calcification of the mitral valve annulus in an adolescent with Marfan syndrome. A case report.
Marfan syndrome (MFS) is an inherited connective tissue disorder, transmitted as an autosomal dominant trait. Its phenotypic and clinical expression is variable and involves several body systems. The ocular, skeletal and cardiovascular systems are characteristically affected. Involvement of the cardiovascular system is the main cause of morbidity and mortality. The authors report the case of a thirteen-year-old girl, with MFS diagnosed at age five, referred to the pediatric cardiology department because of mitral regurgitation. In addition to severe mitral regurgitation due to prolapse of both mitral valve leaflets, diagnostic exams showed massive mitral annulus calcification and ostium secundum atrial septal defect (ASD). The patient underwent successful mitral valve repair and ASD closure surgery. In this report we highlight some features of MFS, stressing the cardiovascular aspects.


[Hygienic assessment of the impact of environmental factors of the Primorye Territory on the incidence of thyroid diseases].
The paper gives the ecological and hygienic characteristics of the Primorye Territory. It describes bioclimatic zones and ecological tension areas. The results of studies of the prevalence of thyroid diseases (diffuse endemic goiter, multinodular endemic goiter, subclinical hypothyroidism) associated with iodine deficiency in relation to the bioclimatic zone and the ecological situation are shown. The findings permit the planning and implementation of therapeutic-and-prophylactic measures for prevention iodine deficiency among the population of the Primorye Territory.


The application of quality of life.
Despite its popularity, to date little systematic work has been done in the application of the quality of life (QOL) concept to persons with intellectual disability (ID) and its impact on individuals and families. This article addresses that need. The article summarizes the four application strands suggested by the IASSID SIRG on Quality of Life regarding the application of the QOL concept and discusses critical aspects of each. Examples and guidelines regarding each strand are presented, along with the ongoing need to align conceptualization, application, and research efforts and integrate QOL principles into professional education and training programmes. The QOL concept is now challenging some of the more traditional views and approaches to ID. These challenges are resulting in modifications and adaptations in current services and supports, along with the need to evaluate the outcomes from the application of QOL principles to persons with ID.


Accelerated design of promising mixed lead-free double halide organic-inorganic perovskites for photovoltaics using machine learning.
Mixed double halide organic-inorganic perovskites (MDHOIPs) exhibit both good stability and high power conversion efficiency and have been regarded as attractive photovoltaic materials. Nevertheless, due to the complexity of structures, large-scale screening of thousands of possible candidates remains a great challenge. In this work, advanced machine learning (ML) techniques and first-principles calculations were combined to achieve a rapid screening of MDHOIPs for solar cells. Successfully, 204 stable lead-free MDHOIPs with optimal bandgaps were selected out of 11 370 candidates. The accuracy of ML models for perovskite structure formability and bandgap is over 94% and 97%, respectively. Moreover, representative MDHOIP candidates, MA2GeSnI4Br2 and MA2InBiI2Br4, stand out with suitable direct bandgaps, light carrier effective masses, small exciton binding energies, strong visible light absorption, and good stability against decomposition.


Stability of hematologic analytes in New Zealand white rabbits using an impedance-based analyzer.
The validity of hematologic data is crucial for correctly diagnosing certain conditions and providing accurate research results. However, delays in blood testing are inevitable. This study aimed to determine whether prolonged storage at different temperatures affects CBC measurand stability in rabbit whole blood using the impedance-based Scil Vet ABC hematology analyzer. Hematologic tests were performed on whole blood samples collected from 20 New Zealand white rabbits at <1 hour post-blood collection as the baseline and at 6, 24, 48, and 72 hours post-blood collection, with aliquots stored at 21 and 4°C. CBC measurand stability was determined by comparing the obtained values at each time point to the baseline value. Statistically significant variations were compared with current quality specifications to determine if a meaningful bias existed. Hematocrit, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration remained stable for 72 hours in blood stored at 4°C. No meaningful bias was observed for mean corpuscular volume after 48 and 72 hours of storage at 4°C. Only the white blood cell count was stable for 72 hours at 21°C. The platelet count, hemoglobin concentration, and mean platelet volume were not stable at 6 hours post-blood collection at either temperature. The results of this study showed that the hematocrit can be tested for 72 hours in blood stored at 4°C, without a significant change from the baseline value. However, if all hematologic measurands are of interest, the immediate testing of blood samples, namely <1 hour post-blood collection, remains highly recommended.


[Synthesis of 1,4-dihydropyridines with blood pressure and blood-fat lowering effects].
To develop new drugs with the effects of lowering blood-fat and blood pressure, compounds 1-7 and 10 were synthesized by the reactions of 2-methyl-2-[4-(4-chlorobenzoyl)phenoxy]propionyl chloride with a hydroxyl group in 1,4-dihydropyridines. Compounds 8 and 9 were obtained by the reactions of 2-methyl-2-[4-(4-chlorobenzoyl)phenoxy]propionyl chloride with salicylic aldehyde first, and then with beta-aminocrotonates. All 1-10 are new compounds, and their structures were elucidated by means of 1HNMR and MS. The effects of compounds 1-10 on lowering cholesterol, triglyceride and blood pressure were investigated, and some of which were found to have the effects of lowering triglyceride and blood pressure.


Secondary adrenal insufficiency in pregnancy: any differences?
Secondary adrenal insufficiency may pose specific challenges during pregnancy. The interpretation of diagnostic tests is hindered by physiological adaptations of the hypothalamic-pituitary-adrenal axis. Due the relevant increases in cortisol-binding globulin, measurement of salivary cortisol may be preferable, but lacks sufficiently established cut-offs both for early-morning evaluation and during dynamic testing. Hydrocortisone should be used for replacement to avoid overexposure of the fetus, with dose adjustments according to clinical judgement. To account for increased free cortisol levels during the course of pregnancy, hydrocortisone may be increased by 5-7.5 mg in the third trimester. Patients should be seen at least once every trimester. Counseling of patients is of special importance to manage hyperemesis and infections. For labor, sufficient stress doses need to be applied.


Living-donor liver transplantation--European experiences.
To overcome the problem of organ shortage in recent years, liver transplantation from a living donor has been established. From a surgical standpoint, split liver transplantation and living-donor liver transplantation (LRLTx) are very complex surgical procedures requiring meticulous surgical techniques. LRLTx was first developed and performed in Asia and the USA. In the beginning of the 1990s, LRLTx was introduced in Europe. In Europe, 46 of 118 registered transplant centres had already performed LRLTx in December 2001. Up to this time point, more than 800 LRLTx were performed since 1991. Medical discussions in the field of LRLTx include the need for high quality procedures, simplifying donor evaluation, optimizing surgical techniques and immunosuppression, all of which are current problems. The perioperative morbidity of the donor including all minor complications is stated to be 10-25%. Biliary complications of 5-10% are the major portion. The results of LRLTx for paediatric and adult recipients are comparable. The perioperative complication rate is slightly higher in LRLTx than after cadaver transplantation. This can be explained by the complexity of the surgical intervention with technical complications and the limited experience so far. Other reasons that can be ascertained are extended indications with higher incidence of tumour recurrence and infectious complications in these recipients. In recent years, LRLTx has emerged as a clinically safe alternative to cadaver transplantation in many cases and has further extended the donor pool. LRLTx has been shown to be a good option for patients with liver disease in which a long waiting time is not permitted.


Spiritual crisis: a concept analysis.
This paper is a report of an analysis of the concept of spiritual crisis. The term spiritual crisis has been used ambiguously in the literature, resulting in lack of clarity. A holistic approach includes spirituality in nursing care of the whole person. Papers available online between 1998 and 2007 in the CINAHL, Medline and PsycInfo databases were retrieved for analysis. The search engine Google was also used to examine additional references to 'spiritual crisis'. Spiritual crisis, spiritual emergency and life crisis were the terms initially used to search each database. The search was expanded to include spirituality to draw more literature into the review. Using Walker and Avant's method of concept analysis, a definition of spiritual crisis was identified. Spiritual crisis can be described as a unique form of grieving or loss, marked by a profound questioning of or lack of meaning in life, in which an individual or community reaches a turning point, leading to a significant alteration in the way life is viewed. Possible antecedents include sudden acute illness and loss of important relationships. Potential consequences may include physical and emotional responses. People with terminal illness, depression, and those who are grieving losses may be at special risk of spiritual crisis. The literature suggests an interdisciplinary approach, nurses' self-exploration of spirituality, and refraining from defining spirituality by religious affiliation as part of improving practice.


Histological Observation of Regions around Bone Tunnels after Compression of the Bone Tunnel Wall in Ligament Reconstruction.
The objectives of this study were to investigate the time-course of influence of compression of bone tunnel wall in ligament reconstruction on tissue around the bone tunnel and to histologically examine the mechanism of preventing the complication of bone tunnel dilation, using rabbit tibia. A model in which the femoral origin of the extensor digitorum longus tendon was cut and inserted into a bone tunnel made proximal to the tibia was prepared in the bilateral hind legs of 20 Japanese white rabbits. In each animal, a tunnel was made using a drill only in the right leg, while an undersized bone tunnel was made by drilling and then dilated by compression using a dilator to the same tunnel size as that in the right leg. Animals were sacrificed at 0, 2, 4, 8 and 12 weeks after surgery (4 animals at each time point). Observation of bone tunnels by X-ray radiography showed osteosclerosis in the 2- and 4-week dilation groups. Osteosclerosis appeared as white lines around the bone tunnel on X-ray radiography. This suggests that dilation promotes callus formation in the bone tunnel wall and prevents the complication of bone tunnel enlargement after ligament reconstruction.


Islamic legal perspectives on digital currencies and how they apply to Jordanian legislation.
Background: The industrial transformation requires a speedy shift to financial digitization. One of the needs for financial digitalization in the study of Islamic contracts and Islamic business law is the use of digital platforms with digital currencies. Regarding the merits and downsides of its Sharia restrictions and its halal certification, which is currently under discussion, digital currencies and perks have generated controversy in Jordan and other Islamic countries. Methods: This study intends to analyze the legal foundations of digital currency from Jordanian and Islamic legal perspectives. The descriptive-qualitative research approach was utilized, and data collection processes included documentation and a literature review. All legal possibilities that may be drawn from Islamic law in order to investigate the legality of digital currencies are explored further and used to obtain the conclusions of this study. Results: A review of Sharia reasons and consideration for the wellbeing of the people suggests that digital currencies in their current form are incompatible with it and must adhere to the stipulations of Islamic finance. Therefore, digital currencies are unsuitable as a store of value or wealth due to their erratic swings, lack of purchasing power, and instant responsiveness to any technical problem, technical penetration, or official circumstance. Due to market instability, digital currencies can't be utilized to defer payments, settle debts, or repay loans. Conclusions: Digital currencies are speculative; not real money. Most of those who have this money are speculators seeking a quick payoff. Sharia views digital currency trading as gambling due to its high degree of volatility. Jordan's government should regulate digital currency use to meet demand. Digital currencies must be addressed under e-commerce laws.


Early OCT Angiography Changes of Macular Neovascularization in Patients with Exudative AMD Treated with Brolucizumab in a Real-World Setting.
To report on the short-term outcome of intravitreal brolucizumab in patients with neovascular age-related macular degeneration (nAMD). This is a prospective, interventional, monocentric study on 10 eyes of 10 patients with a treatment-naïve neovascular AMD. Patients were treated according to the HAWK and HARRIER trials. After loading with 3 monthly injections, eyes received an injection 12 weeks after the upload (q12w) or were adjusted to an 8 week interval (q8w), if disease activity was present 8 weeks after the upload. Main outcome measures were the change in central retinal thickness (CRT) assessed by spectral domain optical coherence tomography (SD-OCT), the change in macular neovascularization (MNV) size on optical coherence tomography angiography (OCTA), and the change in best corrected visual acuity (BCVA) 8 and 12 weeks after the upload. We further assessed clinical parameters that predict the treatment response at baseline based on the need of q8w or q12w injections after the upload. CRT decreased significantly from 461.7 ± 82.9 μm to 343.6 ± 74.3 μm (p=0.004) 12 weeks after the upload. The MNV size decreased significantly from 0.85 ± 1.1 to 0.75 ± 1.2 mm2 (p=0.022). BCVA improved from 0.67 ± 0.4 to 0.55 ± 0.4logMAR but without statistical significance. MNV size in eyes on q12w was considerably smaller compared to that in eyes on q8w (0.54 ± 0.7 mm2 vs. 1.98 ± 2.4 mm2). The percentage of eyes without any persistent fluid was 70% (7/10 eyes). Brolucizumab appears to be a valuable tool for the management of patients with nAMD. Furthermore, MNV size at baseline might serve as an early predictor of treatment response.


A complete audit cycle to assess adherence to a lung protective ventilation strategy.
There is clear evidence for the use of a protective ventilation protocol in patients with acute respiratory distress syndrome (ARDS). There is evidence to suggest that protective ventilation is beneficial in patients at risk of ARDS. A protective ventilation strategy was implemented on our intensive care unit in critical care patients who required mechanical ventilation for over 48 h, with and at risk for ARDS. A complete audit cycle was performed over 13 months to assess compliance with a safe ventilation protocol in intensive care. The ARDS network mechanical ventilation protocol was used as the standard for our protective ventilation strategy. This recommends ventilation with a tidal volume (V t) of 6 ml/kg of ideal body weight (IBW) and plateau airway pressure of ≤30 cm H2O. The initial audit failed to meet this standard with V t's of 9.5 ml/kg of IBW. Following the implementation of a ventilation strategy and an educational program, we demonstrate a significant improvement in practice with V t's of 6.6 ml/kg of IBW in the re-audit. This highlights the importance of simple interventions and continuous education in maintaining high standards of care.


[Research on Japanese monograph of comprehensive dietetic materia medica, the Pao chu bei yong wo ming ben cao (Japanese Materia Medica Prepared for Kitchen)].
Japanese physicians of Edo Period (1603-1867) wrote many dietetic books, by combining the knowledge system (content and compiling style) and thoughts of diet therapy from China with local condition in Japan. Among them, the Pao chu bei yong wo ming ben cao(Japanese Materia Medica Prepared for Kitchen), written by Mukai Genshou, a physician in the early Edo, is the earliest comprehensive work of dietetic materia medica. In this book, the choice and usage of Japanese dietetic materia medica reveals obvious Japanese local color, including the name, morphology, cultivation, collection, identification, nature and flavor, and indication etc., reflecting the sprouting idea of edible herbal plant at the beginning of Edo period and the characteristic of absorbing Chinese diet thoughts by Japanese physician. This is the important first-hand historical material to understand the development of Japanese dietetic herbalism in early Edo and its dietotherapy culture.


Localization of serotonin, tyrosine hydroxylase, and leu-enkephalin immunoreactive cells in the brainstem of the horn shark, Heterodontus francisci.
In previous studies on reptiles and elasmobranchs, we determined that some reticular groups are either absent or may be displaced compared to their locations in mammals. For example, nucleus raphe dorsalis, the largest serotoninergic cell group in mammals, is not present in rays, skates, or guitarfish. In the present study, we chose heterodontid sharks, a sister group to these batoids, for an out-group comparison of this and other characters. We identified cells in the brainstem of Heterodontus francisci by use of antibodies against tyrosine hydroxylase, serotonin, or leu-enkephalin and compared the distribution of these nuclei to descriptions in mammals and other elasmobranchs. The majority of tyrosine hydroxylase-positive cells were found in the midbrain tegmentum (A8-A10) and the hypothalamus. In addition, putative A1, A2, A5, A7 (noradrenergic) groups were found in the metencephalon and myelencephalon. Serotonin-positive cells were found in raphe nuclei and scattered lateral to the raphe. We identified probable homologues to raphe pallidus, raphe obscurus, raphe magnus, and raphe centralis superior (B8) cell groups, which have been described in mammals. A cluster of cells dorsomedial to the medial longitudinal fasciculus was identified as raphe dorsalis. The distributions of leu-enkephalin and serotonin immunoreactive cells were similar to each other, but the tyrosine-hydroxylase immunoreactive cells rarely intermingle with the former two immunoreactive cell types. Other reticular groups that contained both serotonin- and leu-enkephalin-positive cells included reticularis (r.) ventralis, r. magnocellularis, r. paragigantocellularis lateralis, r. pontis caudalis, and r. pontis oralis medialis and lateralis. Thus, this shark contains many of the major brainstem raphe and catecholaminergic cell groups described for rats, but the relative distribution of the immunopositive cell groups differs in mammals and cartilaginous fish.


Genetic Algorithm Optimized Printed Circuit Board Ion Funnel Tandem Subambient Pressure Ionization with Nanoelectrospray (SPIN) for High Sensitivity Mass Spectrometry.
The SPIN tandem ion funnel (IF) structure allows for highly sensitive mass spectrometry due to reduced ion losses in the interface region and during transmission; however, IF has an inherent mass discrimination problem, which can greatly restrain the ion transmission efficiency (TE) and therefore requires certain optimization methods. Conventional optimization methods ignore the combined effects of multiple IF characteristic parameters (electrical and dimensional parameters) and are unable to achieve efficient ion transmission over a wide mass range, thus requiring significant tuning time. In this paper, a genetic algorithm (GA)-optimized printed circuit board ion funnel (PCBIF) was designed, fabricated, preliminarily evaluated, and integrated into the SPIN interface to address the ion loss that can occur when mass spectrometers transfer ions at subambient pressure. Simulation studies have showed clearly that the effective automated GA can increase the PCBIF optimization, design, and the ion TE (finding the optimal characteristic parameters within 4 h and achieving 96% ion TE for ions with m/z between 50 and 700). Preliminary tests on built SPIN-PCBIF-MS can lead to an LOD of 0.01 nM and also indirectly suggest the effectiveness of the GA-optimized PCBIF. The proposed GA method helps to guide the design of IF and can also be used for other multivariate mass analyzers or ion transmission devices.


Three-dimensional surface patterning by DNA-modifying enzymes.
Self-assembled patterned multilayers may be fabricated using DNA monolayers and the orchestrated reactions of DNA-modifying enzymes. To demonstrate this approach, DNA monolayers were formed on silicon and cleaved quantitatively with a restriction enzyme. Subsequently, fluorescently labeled nucleotides were covalently incorporated to the cleaved DNA. Nucleotide addition was shown to be highly selective according to the sequence at the cleavage site, and no nonspecific adsorption to the surface was observed. The dual action of the DNA-modifying enzymes was quantitative and could be utilized in the fabrication of multilayered structures. Other DNA-modifying enzymes can be exploited in this manner to enrich the repertoire of self-assembly supramolecular structure fabrication.


Bilateral prehilar multiple branching of renal arteries: a case report and literature review.
Proper knowledge of variations of the arteries supplying the kidney is essential not only to the anatomists but also to the surgeons. In the present paper we are reporting a case of bilateral early and multiple branching of the renal arteries. The origin of the 2 renal arteries was normal but soon after their origin they ended by giving rise to multiple branches. Most of these branches entered the kidney through the hilum. However, on both sides, one of the branches (superior polar artery) passed superolaterally to reach the upper pole of the kidney. The superior polar artery also gave rise to the inferior suprarenal artery. Further, related literature review is done and the urological implications of these variations in renal surgeries are discussed.


Ectopic pregnancy.
Ectopic pregnancy (EP) is a serious and increasing health problem in the United States and other countries. In the United States, it accounts for 15 percent of maternal deaths, 75 percent of which are estimated to be preventable, and its incidence has increased more than 100 percent for some demographic groups over the past 10 years. There are a number of potential contributing factors to ectopic pregnancy; however, their relationship to actual incidence is unclear in some instances. Nonspecific symptoms increase the difficulty of diagnosis. This article presents an overview of the significance of the problem, contributing risk factors, clinical presentation, diagnostic modalities, treatment and nursing implications.


Anisotropic thermoelectric properties of Weyl semimetal NbX (X = P and As): a potential thermoelectric material.
Weyl semimetal, a newly developed thermoelectric material, has aroused much interest due to its extraordinary transport properties. In this work, the thermoelectric transport properties of NbX (X = P and As), a prototypical Weyl semimetal, are investigated using the first-principles calculations together with Boltzmann transport theory. The calculated room-temperature lattice thermal conductivities along the a and c directions are 2.0 W mK-1 and 0.6 W mK-1 for NbP and 1.4 W mK-1 and 0.4 W mK-1 for NbAs, respectively. The low thermal conductivities may be useful in the thermoelectric applications. It is found that the acoustic branches have obvious contribution to the total lattice thermal conductivity, and the size dependence of the thermal conductivities can provide guidance for designing thermoelectric nanostructures. Our results show that the anisotropic structures of these compounds bring about the anisotropy of transport coefficients along the a and c directions, and the preferred direction is the c direction in thermoelectric applications. Moreover, NbP and NbAs show high ZT values of 0.82 and 0.50 along the c direction for p-type at an optimal carrier concentration, indicating that they are potential thermoelectric materials.


Bilateral Second Premolars Agenesia Together with a Unilateral Canine Radiculomegaly.
Congenitally missing teeth is a common feature for the third molars. However, missing teeth, macrodontia and radiculomegaly occurring in a single patient is very rare. This article describes a case of agenesis of mandibular second premolars, radiculomegaly with dilacerations of a canine tooth together with elongated roots of other canines. All these features had been discerned through diagnostic radiographs taken during a routine treatment planning.