Long saphenous vein stripping and quality of life--a randomised trial.
To assess the quality of life of patients undergoing sapheno-femoral junction (SFJ) ligation and long saphenous vein stripping (LSV), using two different techniques. Prospective, randomised trial. Eighty patients were recruited and randomised to either Perforate Invagination (PIN) stripping (43) or Conventional stripping (37). Patients completed the Short Form 36 (SF-36) and EuroQol (EQ) questionnaires preoperatively, and postoperatively at 6 weeks and 6 months. Bodily pain, role function and physical summary were significantly improved at 6 months in the PIN stripping group. In the Conventional group, bodily pain and physical function were similarly improved, but not role function. EQ global quality of life was significantly and progressively improved at 6 weeks and 6 months in the PIN group (global score p<0.003; self-rated score p <0.001). In the Conventional group there was no overall improvement in global score or self-rated health. Primary varicose vein surgery is associated with significant and progressive improvements in quality of life scores. Whilst overall quality of health does improve in the Conventional group, this appears to be to a lesser extent than in the PIN group.


Effectiveness of web space pressure inserts for postburn dorsal slant.
Postburn web space scar, if not appropriately treated, can result in the progressive loss of the web space or the increase in angle of the dorsal slant of the web space or both, which will not only lead to cosmetic and hygiene problems, but also to functional limitations. The purpose of this study was to determine the effectiveness of web space pressure inserts for postburn dorsal slants. An individualized custom-made web space pressure insert was fitted into each web space. Inserts were worn underneath the pressure glove to create additional pressure on each web space and to inhibit distal migration of the scar to avoid the increase in the angle of the dorsal slant of the web space. Twenty-four survivors with 36 burned hands, who had been treated in the burn clinic of National Cheng Kung University Hospital, were recruited for this study. When skin wounds were closed, the participants received custom-made web space pressure inserts. The dorsal slant of each web space was measured by a conventional goniometer every time the participants visited the burn clinic. The initial and final measurements were used to compare the change in the angle of the dorsal slant of the web space. Paired t-tests were computed to determine the effectiveness of pressure inserts. The final dorsal slant angle of each web space was also compared with the unburned value by independent t-test. After 234.6 +/- 177.0 days of intervention, the mean dorsal slants of 36 dorsal burn hands' four web spaces were all significantly reduced (P < .001). The most important finding was that the angle of the first dorsal slant could be improved to normal. A custom-made web space pressure insert could be used to improve postburn dorsal slant.


Metabolic syndrome reduces the contribution of K+ channels to ischemic coronary vasodilation.
This investigation tested the hypothesis that metabolic syndrome decreases the relative contribution of specific K(+) channels to coronary reactive hyperemia. Ca(2+)-activated (BK(Ca)), voltage-activated (K(V)), and ATP-dependent (K(ATP)) K(+) channels were investigated. Studies were conducted in anesthetized miniature Ossabaw swine fed a normal maintenance diet (11% kcal from fat) or an excess calorie atherogenic diet (43% kcal from fat, 2% cholesterol, 20% kcal from fructose) for 20 wk. The latter diet induces metabolic syndrome, increasing body weight, fasting glucose, total cholesterol, and triglyceride levels. Ischemic vasodilation was determined by the coronary flow response to a 15-s occlusion before and after cumulative administration of antagonists for BK(Ca) (penitrem A; 10 microg/kg iv), K(V) (4-aminopyridine; 0.3 mg/kg iv) and K(ATP) (glibenclamide; 1 mg/kg iv) channels. Coronary reactive hyperemia was diminished by metabolic syndrome as the repayment of flow debt was reduced approximately 30% compared with lean swine. Inhibition of BK(Ca) channels had no effect on reactive hyperemia in either lean or metabolic syndrome swine. Subsequent inhibition of K(V) channels significantly reduced the repayment of flow debt ( approximately 25%) in both lean and metabolic syndrome swine. Additional blockade of K(ATP) channels further diminished ( approximately 45%) the repayment of flow debt in lean but not metabolic syndrome swine. These data indicate that the metabolic syndrome impairs coronary vasodilation in response to cardiac ischemia via reductions in the contribution of K(+) channels to reactive hyperemia.


Measurements of evaporated perfluorocarbon during partial liquid ventilation by a zeolite absorber.
During partial liquid ventilation (PLV) the knowledge of the quantity of exhaled perfluorocarbon (PFC) allows a continuous substitution of the PFC loss to achieve a constant PFC level in the lungs. The aim of our in vitro study was to determine the PFC loss in the mixed expired gas by an absorber and to investigate the effect of the evaporated PFC on ventilatory measurements. To simulate the PFC loss during PLV, a heated flask was rinsed with a constant airflow of 4 L min(-1) and PFC was infused by different speeds (5, 10, 20 mL h(-1)). An absorber filled with PFC selective zeolites was connected with the flask to measure the PFC in the gas. The evaporated PFC volume and the PFC concentration were determined from the weight gain of the absorber measured by an electronic scale. The PFC-dependent volume error of the CO2SMO plus neonatal pneumotachograph was measured by manual movements of a syringe with volumes of 10 and 28 mL with a rate of 30 min(-1). Under steady state conditions there was a strong correlation (r2 = 0.999) between the infusion speed of PFC and the calculated PFC flow rate. The PFC flow rate was slightly underestimated by 4.3% (p < 0.01). However, this bias was independent from PFC infusion rate. The evaporated PFC volume was precisely measured with errors < 1%. The volume error of the CO2SMO-Plus pneumotachograph increased with increasing PFC content for both tidal volumes (p < 0.01). However for PFC flow rates up to 20 mL/h the error of the measured tidal volumes was < 5%. PFC selective zeolites can be used to quantify accurately the evaporated PFC volume during PLV. With increasing PFC concentrations in the exhaled air the measurement errors of ventilatory parameters have to be taken into account.


Metagenomics Analysis of Thrombus Samples Retrieved from Mechanical Thrombectomy.
The purpose of this study was to assess the microbiota in middle cerebral artery thrombi retrieved in mechanical thrombectomy arising out of symptomatic carotid plaque within 6 hours of acute ischemic stroke. Thrombi were subjected to next-generation sequencing for a bacterial signature to determine their role in atherosclerosis. We included 4 human middle cerebral artery thrombus samples (all patients were male). The median age for the patients was 51±13.6 years. Patients enrolled in the study from Pacific Medical University and Hospital underwent mechanical thrombectomy in the stroke window period. All patients underwent brain magnetic resonance angiography (MRA) and circle of Willis and neck vessel MRA along with the standard stroke workup to establish stroke etiology. Only patients with symptomatic carotid stenosis and tandem lesions with ipsilateral middle cerebral artery occlusion were included in the study. Thrombus samples were collected, stored at -80 degrees, and subjected to metagenomics analysis. Of the 4 patients undergoing thrombectomy for diagnosis with ischemic stroke, all thrombi recovered for bacterial DNA in qPCR were positive. More than 27 bacteria were present in the 4 thrombus samples. The majority of bacteria were Lactobacillus, Stenotrophomonas, Pseudomonas, Staphylococcus, and Finegoldia. Genesis of symptomatic atherosclerotic carotid plaque leading to thromboembolism could be either due to direct mechanisms like acidification and local inflammation of plaque milieu with lactobacillus, biofilm dispersion leading to inflammation like with pseudomonas fluorescence, or enterococci or indirect mechanisms like Toll 2 like signaling by gut microbiota.


Association of Age, Sex, Race, and Geographic Region With Variation of the Ratio of Basal Cell to Cutaneous Squamous Cell Carcinomas in the United States.
Defining which populations are affected by basal cell carcinoma (BCC) vs cutaneous squamous cell carcinoma (cSCC) may inform targeted public health strategies. Incidence of BCC and cSCC is not reported to national cancer registries, but claims data for the treatment of BCC and cSCC provide insights into the epidemiology of keratinocyte carcinoma. To define differences in the ratio of BCC to cSCC in adults (age, ≥18 years) in a large database of patients with commercial insurance and Medicare Advantage coverage. This cross-sectional analysis used deidentified data derived from the Optum Clinformatics Data Mart to perform a retrospective evaluation of a large commercially insured cohort based on treatment claims from January 1, 2012, to December 31, 2016. Patients with a diagnosed and treated BCC or cSCC as determined by codes from the International Classification of Diseases, Ninth Revision, International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, and Current Procedural Terminology were included. Data were analyzed from November 30, 2019, to March 20, 2020. Diagnosis and treatment of BCC or cSCC. The ratio of BCC to cSCC based on age, sex, race, and geographic location. Multivariable logistic regression was used to assess how demographics were associated with the odds of a treated keratinocyte carcinoma being a BCC. Among the 985 317 claims for patients included in the analysis (61.59% for men; mean [SD] age, 69.82 [12.58] years), BCCs were 1.69 (95% CI, 1.6899-1.6901) times more likely than cSCCs to be treated in the United States from 2012 to 2016. Basal cell carcinomas were significantly more prevalent than cSCCs in younger patients (18-39 years, 9.63 [95% CI, 9.6088-9.6574] BCCs per cSCC; 40-64 years, 2.92 [95% CI, 2.9171-2.9187] BCCs per cSCC; and ≥65 years, 1.33 [95% CI, 1.3289-1.3291] BCCs per cSCC; P < .001). Basal cell carcinomas were significantly more prevalent than cSCCs in women vs men, except in adults 65 years or older (odds ratios [ORs], 0.98 [95% CI, 0.97-0.99] vs 1.67 [95% CI, 1.47-1.88] for those aged 18-39 and 1.15 [95% CI, 1.12-1.19] for those aged 40-64 years; P < .001). The difference in BCC:cSCC ratios between men and women diminished with increasing age (OR, 1.67 for 18-39 years, 1.15 for 40-64 years, and 0.98 for 65 years or older). Basal cell carcinoma was more prevalent than cSCC in all races, including Black patients (BCC:SCC ratios, 1.60 for Asian patients, 1.45 for Black patients, 2.00 for Hispanic patients, and 1.69 for White patients of all ages). The BCC:cSCC ratio varied based on geography, with the highest ratio in the West North Central census division (2.12) and the lowest ratio in the South Atlantic census division (1.35). In the absence of a national registry, claims data can improve our understanding of the epidemiology of keratinocyte carcinomas. In this cross-sectional study, basal cell carcinomas were more common than cSCCs for all demographics, including in Black patients. In populations younger than 40 years, BCCs were 12.6 times more likely for women and 7.2 times more likely for men. These demographic groups may benefit from public health education focused on the presentation and management of BCCs.


Medical home services for children with behavioral health conditions.
Whether medical services received by children and youth with behavioral health conditions are consistent with a Medical Home has not been systematically studied. The objectives of this study were to examine the variation among four behavioral health conditions in regard to services related to the Medical Home. Cross-sectional analyses of the 2003 National Survey of Children's Health were conducted. Multiple logistic regression analyses tested the impact of behavioral health conditions on medical needs, on Medical Home components, and on likelihood of having a Medical Home overall. Autism, Depression/Anxiety, and Behavior/Conduct problems were associated with reduced likelihood of having a Medical Home, whereas Attention-Deficit Hyperactivity Disorder was associated with increased likelihood. All health conditions predicted increased access to a primary care physician (PCP) and a preventive visit in the past year. However, all were also associated with higher needs for specialty care and all behavioral health conditions except Attention-Deficit Hyperactivity Disorder were associated with difficulties accessing this care. A detailed examination of the receipt of services among children and youth with behavioral health conditions reveals two primary reasons why such care is less likely to be consistent with a Medical Home model: (1) parents are more likely to report needing specialty care; and (2) these needs are less likely to be met. These data suggest that the reason why services received by children and youth with behavioral health conditions are not consistent with the Medical Home has more to do with difficulty accessing specialty care than with problems accessing quality primary care.


Growing multiconfigurational potential energy surfaces with applications to X + H2 (X = C,N,O) reactions.
A previously developed method, based on a Shepard interpolation procedure to automatically construct a quantum mechanical potential energy surface (PES), is extended to the construction of multiple potential energy surfaces using multiconfigurational wave functions. These calculations are accomplished with the interface of the PES-building program, GROW, and the GAMESS suite of electronic structure programs. The efficient computation of multiconfigurational self-consistent field surfaces is illustrated with the C + H2, N + H2, and O + H2 reactions.


A gene trap approach to isolate mammalian genes involved in the cellular response to genotoxic stress.
Treatment of cells with DNA damaging agents leads to induction of a variety of genes involved in different cellular processes. We have applied a lacZ-based gene trap strategy to search for new mammalian genes induced by genotoxic stress. A population of 32 x 10(3) neo r clones stably transfected with a gene trap vector was obtained, stained with fluorescein di-beta-d-galactopyranoside and analyzed by flow activated cell sorting and replica plating. This strategy allowed isolation of 30 neo r 'putative inducible' cell lines expressing lacZ only after a DNA damaging treatment. For three clones the site of integration and the degree of inducibility after UV treatment were determined by Southern blot and beta-galactosidase measurement respectively. One cell line (clone VI) showed a single integration site and a reproducible 3-fold induction of beta-galactosidase activity following UV irradiation. Fused transcripts were isolated from induced cells and a portion of the trapped gene was amplified by rapid amplification of cDNA ends. Sequence analysis and comparison with available gene and protein databanks revealed that the gene was novel.


The online mindset intervention 'The Growth Factory' for adolescents with intellectual disabilities: moderators and mediators.
The online mindset intervention The Growth Factory (TGF) has shown promising effects-increasing growth mindsets and perseverance and decreasing mental health problems among youth with intellectual disabilities (ID). Studying moderators and mediators of intervention effects is essential to elucidate for whom and why TGF works. Using a randomised controlled trial design, we examined youth's baseline mindset, gender, age, level of ID and intervention satisfaction as moderators of TGF effects and examined whether the intervention effects of TGF on improvements in mental health were mediated by perseverance. The sample consisted of 119 participants with mild to borderline ID (Mage = 15.83; SD = 2.23), randomly assigned to the intervention (n = 60) or passive control group (n = 59). Participants reported mindsets, perseverance, internalising, externalising, attention and total mental health problems at pre-test, at post-test and at 3-month follow-up. Additionally, youth in the intervention group graded their satisfaction with a score at the end of each session. Findings indicated that the effectiveness of TGF was not affected by participants' baseline mindsets, age and ID level. TGF was more effective in reducing internalising problems in girls and increasing perseverance in boys. In addition, in the intervention group TGF was more effective in improving internalising, externalising and total mental health problems for youth who reported higher levels of intervention satisfaction at post-test. Finally, TGF indirectly decreased internalising and externalising problems at follow-up through improvements in perseverance reported at post-test. TGF offers a universal, 'add-on' mindset intervention complementing usual care programmes. It improves mindsets, perseverance and mental health in youth with ID. Both practical and theoretical implications are discussed.


Genomic Tools for the Use of Nonhuman Primates in Translational Research.
Nonhuman primates (NHPs) are important preclinical models for understanding the etiology of human diseases and for developing therapies and vaccines to cure or eliminate disease. Most human diseases have genetic components. Therefore, to be of maximal utility, the NHP species used for translational science should be as well characterized in regard to their genome and transcriptome as possible. This article reviews the current status of genomic information for the five NHP species used most often in translational research: rhesus macaque, cynomolgus macaque, vervet (African green) monkey, baboon, and marmoset NHP. These species have published whole genome sequences (with the exception of the baboon) and relatively well-characterized transcriptomes. Some have also been characterized in regard to specific genetic loci that are particularly related to translational concerns, such as the major histocompatability complex and the cytochrome P40 genes. Genomic resources to aid in stratifying captive populations in regard to genetic and phenotypic characteristics have been developed as an aid to enhancing reproducibility and facilitating more efficient use of animals. Taken together, the current genomic resources and numerous studies currently underway to improve them should enhance the value of NHPs as preclinical models of human disease.


Keeping pace with HIPAA's changes: straight talk from the trenches.
Over the past several months, the Department of Health and Human Services (DHHS) has issued new final and proposed rules pursuant to the Health Insurance Portability and Accountability Act of 1996 (HIPAA). The privacy rule was finalized on August 14, 2002. Changes made to the original rule were in general beneficial to providers. Consent forms will no longer be required for treatment, although providers may choose to continue to use them. Physicians will still be required to use and disclose only the "minimum necessary" protected health information (PHI) to accomplish the purpose for which the information is being used or disclosed, but the new final rule excludes some situations in which the minimum necessary requirement will apply. A model business associates contract is provided in the final rule, making it easier for providers to comply with the rule's requirement that they have written business associate contracts with vendors who need access to the provider's PHI to perform tasks on behalf of providers. Researchers now only need to provide one form for consent and authorization, instead of two. There are also proposed changes in the transaction rule. Certain data elements that were required by the final rule are now situational in the proposed rule. Unnecessary data elements have been removed. Certain items, like special program indicator codes, will now be able to be reported via external code sets rather than as data elements in a transaction. The proposed rule also adopts requests from the industry by adding data elements, codes, or loops to enable covered entities to perform certain business functions in the standardized transactions, such as cross-referencing two subscriber IDs (e.g., surviving spouse and dependents). A final rule was published in May 2002 that created a standard employer identifier. The Employer Identifier Number (EIN) that is already in use by the IRS will be the standardized unique employer identifier number. A proposed rule to cease using the National Drug Codes in transactions for nonretail pharmacy transactions was published in May 2002. DHHS developed the proposal in response to widespread industry concern over the tremendous cost of implementing the National Drug Codes (NDC). The NDC will either not be replaced at all, or will be replaced by the HCPCS. This article is not, and should not be construed as, legal advice or an opinion on specific situations.


Discovery of Pyrazolopyridones as a Novel Class of Gyrase B Inhibitors Using Structure Guided Design.
The ATPase subunit of DNA gyrase B is an attractive antibacterial target due to high conservation across bacteria and the essential role it plays in DNA replication. A novel class of pyrazolopyridone inhibitors was discovered by optimizing a fragment screening hit scaffold using structure guided design. These inhibitors show potent Gram-positive antibacterial activity and low resistance incidence against clinically important pathogens.


An index-based method for evaluating seismic retrofitting techniques. Application to a reinforced concrete primary school in Huelva.
A project named PERSISTAH (Projetos de Escolas Resilientes aos SISmos no Território do Algarve e de Huelva, in Portuguese) is being developed. It aims to cooperatively assess and improve the seismic vulnerability of primary schools in the Algarve (Portugal) and Huelva (Spain). A large number of schools have to be analysed. In order to determine which seismic retrofitting technique is optimal, an index-based method is presented in this paper. It considers three parameters: first, the efficiency of the seismic retrofitting technique in relation to the structural improvement obtained; second, the cost of the implementation of the retrofitting technique; and third, the architectural impact. It should be mentioned that a specific measurement for each solution according to its geometry has been performed. Also, coefficients to consider the singularities of each analysis and the importance of the parameters (number of buildings, typology, available funds, etc.) in the study are considered. The most representative primary school of Huelva has been chosen to test the index-based method. The most suitable retrofitting techniques for this type of buildings have been tested. The retrofitting technique which most increased the seismic performance has been the addition of X and V bracings within the building's bays. Furthermore, the analyses have revealed that adding the retrofitting elements in the most vulnerable direction of the building provides a high efficiency. The results have also shown that implementing techniques of lower architectural impact gives acceptable results. The analysis of the mean damage level index has shown that the building would experiment a severe damage. All the retrofitting techniques applied have reduced it, at least, up to moderate damage. Finally, it should be noted that the position of the retrofitting elements is also paramount for providing an optimal retrofitting.


Reovirus σ3 Protein Limits Interferon Expression and Cell Death Induction.
Induction of necroptosis by mammalian reovirus requires both type I interferon (IFN)-signaling and viral replication events that lead to production of progeny genomic double-stranded RNA (dsRNA). The reovirus outer capsid protein μ1 negatively regulates reovirus-induced necroptosis by limiting RNA synthesis. To determine if the outer capsid protein σ3, which interacts with μ1, also functions in regulating necroptosis, we used small interfering RNA (siRNA)-mediated knockdown. Similarly to what was observed in diminishment of μ1 expression, knockdown of newly synthesized σ3 enhances necroptosis. Knockdown of σ3 does not impact reovirus RNA synthesis. Instead, this increase in necroptosis following σ3 knockdown is accompanied by an increase in IFN production. Furthermore, ectopic expression of σ3 is sufficient to block IFN expression following infection. Surprisingly, the capacity of σ3 protein to bind dsRNA does not impact its capacity to diminish production of IFN. Consistent with this, infection with a virus harboring a mutation in the dsRNA binding domain of σ3 does not result in enhanced production of IFN or necroptosis. Together, these data suggest that σ3 limits the production of IFN to control innate immune signaling and necroptosis following infection through a mechanism that is independent of its dsRNA binding capacity.IMPORTANCE We use mammalian reovirus as a model to study how virus infection modulates innate immune signaling and cell death induction. Here, we sought to determine how viral factors regulate these processes. Our work highlights a previously unknown role for the reovirus outer capsid protein σ3 in limiting the induction of a necrotic form of cell death called necroptosis. Induction of cell death by necroptosis requires production of interferon. The σ3 protein limits the induction of necroptosis by preventing excessive production of interferon following infection.


Detection of galanin receptors in the spinal cord in experimental autoimmune encephalomyelitis.
The neuropeptide galanin is a widely distributed neurotransmitter/neuromodulator that regulates a variety of physiological processes and also participates in the regulation of stress responses. The aims of the present study were to investigate the expression of galanin receptors (GalR1, GalR2, GalR3) in the spinal cords in a murine model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE) using qPCR analysis and to determine GalR1 cellular localization (oligodendrocytes, microglia, astrocytes, ependymal cells, and endothelial cells in the capillaries) by immunohistochemistry. Twelve samples from the EAE group and 14 samples from the control group were analyzed. Spinal cords samples were obtained at the peak of the EAE disease. The GalR1 mRNA level was significantly decreased in the EAE mice compared with the controls (P=0.016), whereas the mRNA levels of GalR2 and GalR3 were not significantly different for the EAE and the control mice. No significant correlations were found between the severity of the EAE disease and the mRNA levels of GalR1, GalR2 and GalR3. Immunochemical detection of the GalR1 revealed its expression in the ependymal and endothelial cells. Additionally, a weak GalR1 immunoreactivity was occasionally detected in the oligodendrocytes. This study provides additional evidence of galanin involvement in EAE pathophysiology, but this has to be further investigated.


Autoantibodies against platelet glycoprotein Ib/IX: a frequent finding in autoimmune thrombocytopenic purpura.
Many autoantibodies involved in the pathogenesis of autoimmune thrombocytopenic purpura (AITP) are directed against epitopes on platelet glycoproteins (GP). These autoantibodies are a specific diagnostic characteristic of patients with AITP. In this study, the relative frequency of antibodies against GPs IIb/IIIa and Ib/IX was assessed in sera from 81 AITP patients with a glycoprotein-specific enzyme immunoassay (MAIPA assay) using monoclonal antibodies against these platelet GPs. All sera contained platelet-specific antibodies which had been detected by platelet immunofluorescence. Of the 81 antibodies tested, 58 (72%) reacted with at least one of the platelet GPs studied. Autoantibodies against GPIb/IX were as common as antibodies against the GPIIb/IIIa complex. The same ratio of specificities was observed on autologous platelets of an independent cohort of 29 patients. The epitope of three autoantibodies against GPIb/IX and of mab Gi10, a monoclonal antibody, which inhibits binding of these autoantibodies, was further characterized. Severity of thrombocytopenia was not related to the GP specificity of the autoantibody. The observation that in 23 (28%) of these sera the antigenic determinants could not be assigned to the glycoproteins under investigation suggests that platelet autoantibodies may react with other GPs or other membrane constituents, e.g. glycolipids.


AML genomics for the clinician.
Acute myeloid leukemia (AML) is a heterogeneous disease, characterized by frequent resistance to available chemotherapeutic agents. The basic therapy for patients with AML has changed little over the past 30 years. Improvements in outcome in recent decades in younger adult cohorts have generally been ascribed to better supportive care (ie, transfusion and antimicrobial therapy); older adults with AML continue to fare poorly. The explosion of new knowledge regarding the AML genome has yet to be translated into therapeutic benefit, but analysis of specific molecular features in AML samples has enabled the field to more accurately parse out prognosis and assign appropriate therapies (eg, chemotherapy vs allogeneic stem cell transplantation) for groups of patients. Cytogenetic analysis, whether by metaphase or interphase analysis, has been the main tool used to divide patients into varying prognostic subsets, but it has been modified in recent years to include assessment of mutations in a small number of genes. In the past several years, new technologies have provided strategies to interrogate individual cancer genomes in a broad and in-depth fashion. The present article discusses the potential of these new technologies, particularly gene panel and whole-exome or whole-genome sequencing, to improve diagnosis, prognosis, and therapeutic outcome in AML.


Age-related morphometrical changes of arteries of uterine wall in mares.
To investigate the morphological changes of uterine wall arteries associated with the progression of age in Thoroughbred broodmares, uterine wall arteries from 13 mares, aged 2 to 31 years, were studied by routine histomorphometry. The ratio of intimal thickness to external diameter increased due to hyperplasia of elastic fibers and was significantly correlated with age (r = 0.95, P < 0.001). The ratio of medial thickness to external diameter decreased and was also significantly correlated with age (r = -0.84, P < 0.001). Using electron microscopy, it was determined that the cross-sectional area of the tunica media occupied by smooth muscle cells gradually decreased with increasing age. These results demonstrate that in arteries of the uterine wall in mares, hyperplasia of intimal elastic fiber and thinning of the medial smooth muscular layer is associated with aging, suggesting that aging may influence endometrial pathology.


The Problem of Questionable Dystonia in the Diagnosis of 'Essential Tremor-Plus'.
In a recent consensus statement on tremor, the task force of the International Parkinson and Movement Disorder Society proposed a new term, 'essential tremor-plus (ET-plus)' which includes patients with the characteristics of essential tremor (ET) and additional soft neurological signs of uncertain significance such as questionable dystonic posturing. The clinical interpretation of questionable dystonia has been left to the investigator. The consensus statement also stated that the ET-plus syndrome does not include other clearly defined syndromes like dystonic tremor. However, the boundary between questionable dystonia and definite dystonia is not distinct leading to diagnostic uncertainty in a clinical setting. A similar case may be classified as ET-plus by one observer and dystonic tremor by another. Following the new definition, many studies have reclassified their ET cohort, and they have highlighted the problem of defining questionable dystonia in the diagnosis of ET plus. ET-plus is likely to be a mixture of patients that actually have dystonia and those that don't, and clinically all we can do is to be suspicious that there might be dystonia. For example, it is not clear whether we should consider spooning and index finger pointing as a sign of questionable or definite dystonia. There are major research and possible therapeutic implications of questionable dystonia in the diagnosis of ET-plus. The concept of ET-plus is extremely difficult to implement without definite guidelines. The resolution will need a biomarker such as physiology or imaging.


Intravenous micafungin versus voriconazole for chronic pulmonary aspergillosis: a multicenter trial in Japan.
Chronic pulmonary aspergillosis (CPA) is slowly progressive inflammatory pulmonary syndrome due to Aspergillus spp. The evidence regarding CPA treatment is limited. We conducted a randomized, multicenter, open-label trial comparing intravenous micafungin (MCFG) of 150-300 mg once daily with intravenous voriconazole (VRCZ) of 6 mg/kg twice on Day 1 followed by 4 mg/kg twice daily for the treatment of 107 in patients with CPA to compare the efficacy and safety of both drugs as initial treatment in Japan. Treatment effectiveness was defined by clinical, mycological, radiological and serological responses 2 weeks after the initial administration and at the end of therapy. The total of 50 and 47 patients were assigned to the MCFG and VRCZ groups, respectively. The difference in efficacy rates between MCFG and VRCZ was not significant, either after 2 weeks [68.0% vs. 58.7%; the absolute difference, 9.3% with a 95% confidence interval (CI), -9.97 to 28.58, P = 0.344] or at the end of therapy (60.0% vs. 53.2%; the absolute difference, 6.8% with a 95% CI, -12.92 to 26.54, P = 0.499). In the safety evaluation, fewer adverse events occurred in the MCFG than VRCZ group (26.4% vs. 61.1%, P = 0.0004). MCFG was as effective as VRCZ and significantly safer than as an initial treatment of CPA. (UMIN Clinical Trials Registry number, UMIN000001786.).


Homocyst(e)ine and cardiovascular disease: a systematic review of the evidence with special emphasis on case-control studies and nested case-control studies.
Elevated concentrations of homocyst(e)ine are thought to increase the risk of vascular diseases including coronary heart disease and cerebrovascular disease. We searched MEDLINE (1966-1999), EMBASE (1974-1999), SciSearch (1974- 1999), and Dissertation Abstracts (1999) for articles and theses about homocyst(e)ine concentration and coronary heart disease and cerebrovascular disease. We included 57 publications (3 cohort studies, 12 nested case-control studies, 42 case-control studies) that reported results on 5518 people with coronary heart disease (11,068 control subjects) and 1817 people with cerebrovascular disease (4787 control subjects) in our analysis. For coronary heart disease, the summary odds ratios (OR) for a 5-micromol/l increase in homocyst(e)ine concentration were 1.06 (95% CI : 0.99-1.13) for 2 publications of cohort studies, 1.23 (95% CI : 1.07-1.41) for 10 publications of nested case-control studies, and 1.70 (95% CI : 1.50-1.93) for 26 publications of case-control studies. For cerebrovascular disease, the summary OR for a 5-micromol/l increase in homocyst(e)ine concentration were 1.10 (95% CI : 0.94-1.28) for 2 publications of cohort studies, 1.58 (95% CI : 1.35-1.85) for 5 publications of nested case-control studies, and 2.16 (95% CI : 1.65-2.82) for 17 publications of case-control studies. Prospective studies offer weaker support than case-control studies for an association between homocyst(e)ine concentration and cardiovascular disease. Although other lines of evidence support a role for homocyst(e)ine in the pathogenesis of cardiovascular disease, more information from prospective epidemiological studies or clinical trials is needed to clarify this role.


Constitutive expression of fibroblast growth factor-4 does not alter the growth or the differentiation of embryonal carcinoma cells.
Previous studies have demonstrated that embryonal carcinoma (EC) cells express both fibroblast growth factor-4 (FGF-4) and FGF receptors. It has also been established that differentiation of EC cells represses the expression of the FGF-4 gene. Currently, the role of FGF-4 in the growth and differentiation of EC cells is unclear. In this study, we examined whether the differentiation of EC cells requires the repression of FGF-4 expression. To address this and related questions, F9 EC cells were transfected with an expression vector that uses the human beta-actin promoter to drive the constitutive expression of recombinant FGF-4. Unlike their untransfected counterparts, F9 EC cells transfected with this plasmid continue to produce recombinant FGF-4 after they differentiate. However, constitutive expression of this growth factor does not block morphological differentiation of the cells, nor does it alter the expression of six genes regulated by the differentiation of EC cells. Constitutive expression of recombinant FGF-4 also did not noticeably alter the growth of the transfected F9 EC cells before or after differentiation. Furthermore, unlike immortalized fibroblasts, which are known to grow in soft agar after transfection with FGF-4 expression plasmids, continued expression of recombinant FGF-4 activity did not enhance the ability of the EC-derived differentiated cells to form colonies in soft agar. These findings argue that continuous expression of recombinant FGF-4 activity does not block the differentiation of EC cells and that repression of the FGF-4 gene after EC cells differentiate does not appear, on its own, to be responsible for the loss of tumorigenicity that accompanies the differentiation of EC cells.


Nuclear gene-regulated expression of chloroplast genes for coupling factor one in maize.
In order to gain a better understanding of the interaction between the chloroplast and nuclear genomes in controlling the expression of plastid genes and the biosynthesis of chloroplast proteins, maize (Zea mays) nuclear gene mutant hcf(*)-38, in which alpha and beta subunits of coupling factor one (CF(1)) are almost completely missing was studied. The mutant possesses all the other subunits of CF(1) but several peptides of photosystem II are present in reduced amounts. A competitive hybridization experiment showed the presence of the same plastid mRNA species in mutant and wild-type plants except for slightly lower levels of some transcripts in the mutant. Northern hybridization and dot blot hybridization experiments showed the features of transcripts for alpha and beta subunits of CF(1) in the mutant to be similar to those in the wild-type maize although their levels are somewhat lower in the mutant. In vivo and in organello protein labeling experiments with L-[(35)S]Met have shown that alpha and beta subunits of CF(1) are synthesized, assembled into CF(1), and probably associated with thylakoid membranes in mutant plants. It is concluded that they are subsequently degraded.


The effect of moderate and high-intensity fatigue on groundstroke accuracy in expert and non-expert tennis players.
Exploring the effects of fatigue on skilled performance in tennis presents a significant challenge to the researcher with respect to ecological validity. This study examined the effects of moderate and high-intensity fatigue on groundstroke accuracy in expert and non-expert tennis players. The research also explored whether the effects of fatigue are the same regardless of gender and player's achievement motivation characteristics. 13 expert (7 male, 6 female) and 17 non-expert (13 male, 4 female) tennis players participated in the study. Groundstroke accuracy was assessed using the modified Loughborough Tennis Skills Test. Fatigue was induced using the Loughborough Intermittent Tennis Test with moderate (70%) and high-intensities (90%) set as a percentage of peak heart rate (attained during a tennis-specific maximal hitting sprint test). Ratings of perceived exertion were used as an adjunct to the monitoring of heart rate. Achievement goal indicators for each player were assessed using the 2 x 2 Achievement Goals Questionnaire for Sport in an effort to examine if this personality characteristic provides insight into how players perform under moderate and high-intensity fatigue conditions. A series of mixed ANOVA's revealed significant fatigue effects on groundstroke accuracy regardless of expertise. The expert players however, maintained better groundstroke accuracy across all conditions compared to the novice players. Nevertheless, in both groups, performance following high-intensity fatigue deteriorated compared to performance at rest and performance while moderately fatigued. Groundstroke accuracy under moderate levels of fatigue was equivalent to that at rest. Fatigue effects were also similar regardless of gender. No fatigue by expertise, or fatigue by gender interactions were found. Fatigue effects were also equivalent regardless of player's achievement goal indicators. Future research is required to explore the effects of fatigue on performance in tennis using ecologically valid designs that mimic more closely the demands of match play. Key PointsGroundstroke accuracy under moderate-intensity fatigue is equivalent to performance at rest.Groundstroke accuracy declines significantly in both expert (40.3% decline) and non-expert (49.6%) tennis players following high-intensity fatigue.Expert players are more consistent, hit more accurate shots and fewer out shots across all fatigue intensities.The effects of fatigue on groundstroke accuracy are the same regardless of gender and player's achievement goal indicators.


Nanoparticle microinjection and Raman spectroscopy as tools for nanotoxicology studies.
Microinjection techniques and Raman spectroscopy have been combined to provide a new methodology to investigate the cytotoxic effects due to the interaction of nanomaterials with cells. In the present work, this novel technique has been used to investigate the effects of Ag and Fe(3)O(4) nanoparticles on Hela cells. The nanoparticles are microinjected inside the cells and these latter ones are probed by means of Raman spectroscopy after a short incubation time, in order to highlight the first and impulsive mechanisms developed by the cells to counteract the presence of the nanoparticles. The results put in evidence a different behaviour of the cells treated with nanoparticles in comparison with the control cells; these differences are supposed to be generated by an emerging oxidative stress due to the nanoparticles. The achieved results demonstrate the suitability of the proposed method as a new tool for nanotoxicity studies.


Long-Term Sustainability of Functional Improvement Following Central Corpectomy for Cervical Spondylotic Myelopathy and Ossification of Posterior Longitudinal Ligament.
Retrospective study. To examine predictors of long-term outcome and sustainability of initial functional improvement in patients undergoing corpectomy for cervical spondylotic myelopathy (CSM) or ossification of the posterior longitudinal ligament (OPLL). There are limited data on the predictors of outcome and sustainability of initial functional improvement on long-term follow-up after cervical corpectomy. We studied the functional outcome at more than 1-year follow-up after central corpectomy in 352 patients with CSM or OPLL. Functional status was evaluated with the Nurick grading system. Analysis was directed at identifying factors associated with both improvement in functional status and the achievement of a "cure" (improvement to a follow-up Nurick grade of 0 or 1). A survival analysis was performed to identify factors associated with sustained functional improvement in patients with serial follow-up evaluations. Nurick grade improved from 3.2 ± 0.1 to 1.9 ± 0.1 over a mean follow-up period of 57.1 months (range 12-228 mo). On multivariate analysis, age ≥50 years (P = 0.008) and symptom duration ≥1 year (P < 0.001) were negatively associated with functional improvement by ≥1 Nurick grade. Independent factors negatively associated with "cure" after surgery included age 50 years or older (P = 0.005), preoperative Nurick grade of 4 or higher (P < 0.001) and symptom duration of 1 or more years (P < 0.001). Early improvement in functional status was maintained in 90.5% and 76.3% of patients at 5 and 10 years follow-up, respectively. On survival analysis, patients with shorter preoperative symptom duration (<1 yr) were more likely to demonstrate sustained improvement in functional status after surgery (P = 0.022). Initial gains in functional status after central corpectomy for CSM and OPLL are maintained in more than 75% of patients at 10 years after surgery. Overall, the most favorable long-term outcomes are achieved in younger patients who present early and with good preoperative functional status. 4.


A metabolome-wide characterization of the diabetic phenotype in ZDF rats and its reversal by pioglitazone.
Type 2 diabetes (T2D) is a complex metabolic disease associated with alterations in glucose, lipid and protein metabolism. In order to characterize the biochemical phenotype of the Zucker diabetic fatty (ZDF) rat, the most common animal model for the study of T2D, and the impact of the insulin sensitizer pioglitazone, a global, mass spectrometry-based analysis of the metabolome was conducted. Overall, 420 metabolites in serum, 443 in the liver and 603 in the intestine were identified at study end. In comparison to two control groups, obese diabetic ZDF rats showed characteristic metabolic signatures that included hyperglycemia, elevated β-oxidation, dyslipidemia-featured by an increase in saturated and monounsaturated fatty acids and a decrease of medium chain and of polyunsaturated fatty acids in serum-and decreased amino acid levels, consistent with their utilization in hepatic gluconeogenesis. A 13-week treatment with the PPARγ agonist pioglitazone reversed most of these signatures: Pioglitazone improved glycemic control and the fatty acid profile, elevated amino acid levels in the liver, but decreased branched chain amino acids in serum. The hitherto most comprehensive metabolic profiling study identified a biochemical blueprint for the ZDF diabetic model and captured the impact of genetic, nutritional and pharmacological perturbations. The in-depth characterization on the molecular level deepens the understanding and further validates the ZDF rat as a suitable preclinical model of diabetes in humans.


Rapid Detection of Mycoplasma pneumoniae by Loop-Mediated Isothermal Amplification (LAMP) in Clinical Respiratory Specimens.
Mycoplasma pneumoniae is a common cause of community-acquired pneumonia (CAP) worldwide, especially among children and debilitated populations. The present study aimed to investigate a loop-mediated isothermal amplification (LAMP) technique for rapid detection of M. pneumoniae in clinical specimens collected from patients with pneumonia. Throat swabs were collected from 110 outpatients who suffered from pneumonia. Throat swab samples were obtained from patients referred to the hospital outpatient clinics of Tehran University hospitals, Iran in 2017. The presence of M. pneumoniae in the clinical specimens was evaluated by LAMP, PCR and culture methods. Sensitivity and specificity of the LAMP and PCR assays were also determined. Out of 110 specimens, LAMP assay detected M. pneumoniae in 35 specimens. Detection limit of the LAMP assay was determined to be 33fg /μL or ∼ 40 genome copies/reaction. Moreover, no cross-reaction with genomic DNA from other bacteria was observed. Only 25 specimens were positive by the culture method. The congruence between LAMP assay and culture method was 'substantial' (ϰ=0.77). Specificity and sensitivity of LAMP assay were 88.2%, 100% in compare with culture. However, the congruence between LAMP assay and PCR assay was 'almost perfect' (ϰ=0.86). Specificity and sensitivity of LAMP assay were 92.5%, 100% in compare with PCR. Overall, the LAMP assay is a rapid and cost-efficient laboratory test in comparison to other methods including PCR and culture. Therefore, the LAMP method can be applied in identification of M. pneumoniae isolates in respiratory specimens.


Design, Synthesis and Evaluation of Inhibitors of the SARS-CoV2 nsp3 Macrodomain.
A series of amino acid based 7H -pyrrolo[2,3- d ]pyrimidines were designed and synthesized to discern the structure activity relationships against the SARS-CoV-2 nsp3 macrodomain (Mac1), an ADP-ribosylhydrolase that is critical for coronavirus replication and pathogenesis. Structure activity studies identified compound 15c as a low-micromolar inhibitor of Mac1 in two ADP-ribose binding assays. This compound also demonstrated inhibition in an enzymatic assay of Mac1 and displayed a thermal shift comparable to ADPr in the melting temperature of Mac1 supporting binding to the target protein. A structural model reproducibly predicted a binding mode where the pyrrolo pyrimidine forms a hydrogen bonding network with Asp 22 and the amide backbone NH of Ile 23 in the adenosine binding pocket and the carboxylate forms hydrogen bonds to the amide backbone of Phe 157 and Asp 156 , part of the oxyanion subsite of Mac1. Compound 15c also demonstrated notable selectivity for coronavirus macrodomains when tested against a panel of ADP-ribose binding proteins. Together, this study identified several low MW, low μM Mac1 inhibitors to use as small molecule chemical probes for this potential anti-viral target and offers starting points for further optimization.


Changes in plasma oxytocin, prostaglandin E1, and 13,14-dihydro-15-keto-prostaglandin F2 alpha during labor induced by prostaglandin E2 or F2 alpha and spontaneous labor.
To observe the changes in endogenous oxytocics during spontaneous and induced labor, the plasma concentrations of oxytocin, prostaglandin E1 (PGE1) and 13,14-dihydro-15-keto-prostaglandin F2 alpha (PGFM) were measured during labor in 9 cases of spontaneous labor (group 1), 10 of PGE2-induced labor (group 2), and 7 of PGF2 alpha-induced labor (group 3). Unextracted samples were used for radioimmunoassay of oxytocin. PGE and PGF were extracted and separated for radioimmunoassays of PGE1 and PGFM. Although oxytocin levels in groups 1 and 3 did not change during labor or slightly increased toward delivery, those in group 2 decreased as labor progressed. The mean oxytocin in group 2 was significantly lower at the times of established labor (15.3 +/- 3.2 microU/ml, mean +/- SE) and crowing of the fetal head (10.8 +/- 2.0 microU/ml) than before labor (52.7 +/- 14.8 microU/ml). Plasma PGE1 levels in groups 1 and 3 were low and did not change during labor. Plasma PGFM levels in groups 1 and 2 gradually rose toward delivery. These results suggest that exogenous PGE2 suppresses oxytocin secretion during labor and stimulates endogenous PGF2 alpha production, that endogenous PGE1 may not play an important role in the progress of spontaneous and PGF2 alpha-induced labor, and that endogenous PGF2 alpha may participate in the promotion of all kinds of labor.


Thermodynamic insights into the binding of Triton X-100 to globular proteins: a calorimetric and spectroscopic investigation.
The interaction of the nonionic surfactant Triton X-100 (TX-100) with two proteins (bovine serum albumin (BSA) and alpha-lactalbumin (alpha-LA)) has been investigated by using a combination of differential scanning calorimetry, isothermal titration calorimetry, and fluorescence and circular dichroism spectroscopies. All of the calorimetric transitions in BSA were partially reversible, while being two-state and reversible in the case of alpha-LA. TX-100 molecules do not reduce the thermal stability of the protein in the monomeric form. However, in the micellar form the protein might become thermally destabilized by the micelles depending upon the nature of the protein. Isothermal titration calorimetry has been used to demonstrate that TX-100 binds to BSA at two sets of sites with 4:1 stoichiometry in each case. The van't Hoff enthalpy calculated from the temperature dependence of the binding constant did not match with the calorimetric enthalpy indicating conformational change in the protein upon surfactant binding. The surfactant binds to alpha-LA with one class of binding site, and the thermal unfolding results indicate it to be a stronger destabilizer than BSA. The fluorescence, circular dichroism, and differential scanning calorimetric results corroborate well with each other. The effect of ionic strength on the binding parameters suggests that TX-100 can bind to the protein surface via both hydrophobic and polar interactions depending upon the nature of the protein. The physical chemistry underlying the interactions between TX-100 and proteins has been presented. The mode of interaction of TX-100 with proteins is via direct binding, which has been discussed quantitatively in this work.


Placental Pathology in Down Syndrome-Associated Transient Abnormal Myelopoiesis.
Transient abnormal myelopoiesis is a hematopoietic disorder that occurs in up to 10% of neonates with Down syndrome. It is characterized by leukocytosis and the presence of circulating blast cells harboring truncating GATA1 mutations with variable multiorgan system involvement. Placental involvement of transient abnormal myelopoiesis is infrequently described. Placental examination and identifying features related to transient abnormal myelopoiesis could be one of the early, if not the only, means of diagnosis of this condition in affected stillbirths, premature infants, and a subset of asymptomatic neonates. This article provides an overview of the placental pathology in transient abnormal myelopoiesis with review of the literature, and also discusses the important differential diagnoses.


Artificial Intelligence applications and psychology: an overview.
Psychotherapy endows a sense of control in patients gripped with emotional conflicts which allow them to handle their reflexes and regain composure through conscious and behavioral alterations. These transformational changes can be brought about by improving their listening skills, observational capacities, creating awareness, making them more attentive and intervening. Conventional psychotherapy calls for one-to-one sessions during treatment. Considering the increased access to information technology in our normal living, the thought of human interaction being replaced by IT tools came to existence. Specialized tools and techniques are employed through the course of therapy which not only alters but also accentuates their cognitive and effective understanding. The idea of amalgamating these two broad ambits - the complexities of psychology and dynamism of artificial intelligence has gained momentum in recent times. The previous reluctance of a few psychologists regarding inculcating expert systems into routine practice due to maybe employment-related insecurities or being swapped by a computer led to underutilization of the latent competence of using IT. Primarily, human behavior itself cannot be copied in totality by technology, and AI has a great deal to cover in this regards, but researchers are doing their best to deliver on these premises. Apart from this patient resistance to this encroachment of technology should also be looked at critically for gaining mass acceptance. This review focuses on how machine intelligence through computer-implemented psychotherapeutic tools can enhance self-awareness.


Assessing peak aerobic capacity in Dutch law enforcement officers.
To cross-validate the existing peak rate of oxygen consumption (VO2peak) prediction equations in Dutch law enforcement officers and to determine whether these prediction equations can be used to predict VO2peak for groups and in a single individual. A further objective was to report normative absolute and relative VO2peak values of a sample of law enforcement officers in the Netherlands. The peak rate of oxygen consumption (ml×kg-1×min-1) was measured using a maximal incremental bicycle test in 1530 subjects, including 1068 male and 461 female police officers. Validity of the prediction equations for groups was assessed by comparing predicted VO2peak with measured VO2peak using paired t-tests. For individual differences limits of agreement (LoA) were calculated. Equations were considered valid for individuals when the difference between measured and predicted VO2peak did not exceed ±1 metabolic equivalent (MET) in 95% of individuals. None of the equations met the validity criterion of 95% of individuals having ±1 MET difference or less than the measured value. Limits of agreement (LoAs) were large in all predictions. At the individual level, none of the equations were valid predictors of VO2peak (ml×kg-1×min-1). Normative values for Dutch law enforcement officers were presented. Substantial differences between measured and predicted VO2peak (ml×kg-1×min-1) were found. Most tested equations were invalid predictors of VO2peak at group level and all were invalid at individual levels.


Education and self-care of patients with low back pain.
Two groups of patients with 'low back pain', comparable regarding sex, age and diagnosis, all hospitalized at the Hospital for Rheumatology, Kristiansand, for a period of 4-6 weeks, were treated as follows: Group I (209 (180) patients): Education program combined with practise of exercises and correct use of the back. Group II (190 (153) patients): Usual physiotherapeutic treatment methods (individual or group exercises in the charge of a physiotherapist). Further, both groups received similar swimming pool exercises and electrotherapy. Group I was studied on the basis of a questionnaire completed by patients before beginning the education program and both groups were studied on a similar basis after 12 months. Results are extracted from these questionnaires. In spite of various and extensive previous treatment (Table I), not many patients in group I had received information prior to the education program. Significantly more patients in group I than in group II stated that they had received tuition at our hospital (p less than 0.01) (Table II). Group I seemed to practise self-care more than group II and was statistically in less need of physiotherapy during the year after leaving the hospital (p less than 0.05). This seems to be beneficial for the patients and of economic importance for society at large. We conclude that education is important and has to be organized in the form of special lessons.


Impact of Unilateral Orbital Radiotherapy on the Structure and Function of Bilateral Human Meibomian Gland.
Radiotherapy (RT) has widely been used to treat ocular tumors, yet the impact of orbital radiation to the meibomian gland has rarely been studied. Our study aims at evaluating the bilateral meibomian gland structure and function 12 months after unilateral orbital RT in patients with ocular tumors. An observational case-control study. A total of 10 eyes 12 months after unilateral orbital RT, 10 contralateral eyes, and 10 normal controls were enrolled. Meibomian gland loss (MGL), lipid layer thickness (LLT), tear film breakup time (TBUT), Schirmer I test, and cornea fluorescein staining were measured. Ocular Surface Disease Index (OSDI) of the RT patients was assessed and compared with normal controls. The cumulative median radiotherapy dosage for the patients was 45 (range: 30, 70) Gy. The OSDI score of the patients was significantly greater than the normal controls (22.92 (range: 10.42, 37.50) vs 6.25 (range: 2.08, 10.42), p ≤ 0.001). Significant differences of upper MGL, lower MGL, LLT, and TBUT were found between the diseased eyes and normal controls (37.79% (range: 12.87, 92.41) vs 12.63% (range: 6.13, 42.34), p=0.007; 61.31% (range: 44.67, 87.98) vs 15.53% (range: 7.65, 45.13), p ≤ 0.001; 40 ICU (range: 23, 100) vs 81.5 ICU (range: 54, 100), p=0.007; 3.5 s (range: 2, 8) vs 6.5 s (range: 5, 10), p=0.002). The upper MGL and TBUT of the contralateral eyes were also considerably damaged compared with normal controls. Lower eyelid MGL and cornea staining score of the diseased eye were significantly correlated with radiation dosage (r = 0.913 and 0.680; p=0.001 and 0.044, respectively). Orbital radiotherapy could cause significant damage to the meibomian gland structure and function, not only the diseased eyes but also the contralateral eyes.


[The experimental study on absorption and utilization of calcium from oyster shell powder mixed with fruit juice].
A new kind of calcium powder was prepared from the shell of oyster and the bones of other sea lives, in which fruit juice was mixed. This calcium powder and other four different forms of calcium (i.e., active calcium, gluconate, lactate, and phosphate) were fed to 4 groups of Wistar rats for 30 days. 3 days calcium metabolism test was done. The absorption and retention rates of calcium powder were 69.2% and 95.1% in the experimental group, which were higher than those in other calcium supplement groups (P < 0.05). The weight of femurs and the total calcium content of femurs had significantly increased in calcium powder group (P < 0.05). These findings indicated that calcium from calcium powder, which was prepared from sea lives and mixed fruit juice was more effective.


High-fructose feeding does not induce steatosis or non-alcoholic fatty liver disease in pigs.
Non-alcoholic fatty liver disease (NAFLD) is an increasingly prevalent condition that has been linked to high-fructose corn syrup consumption with induction of hepatic de novo lipogenesis (DNL) as the suggested central mechanism. Feeding diets very high in fructose (> 60%) rapidly induce several features of NAFLD in rodents, but similar diets have not yet been applied in larger animals, such as pigs. With the aim to develop a large animal NAFLD model, we analysed the effects of feeding a high-fructose (HF, 60% w/w) diet for four weeks to castrated male Danish Landrace-York-Duroc pigs. HF feeding upregulated expression of hepatic DNL proteins, but levels were low compared with adipose tissue. No steatosis or hepatocellular ballooning was seen on histopathological examination, and plasma levels of transaminases were similar between groups. Inflammatory infiltrates and the amount of connective tissue was slightly elevated in liver sections from fructose-fed pigs, which was corroborated by up-regulation of macrophage marker expression in liver homogenates. Supported by RNA-profiling, quantitative protein analysis, histopathological examination, and biochemistry, our data suggest that pigs, contrary to rodents and humans, are protected against fructose-induced steatosis by relying on adipose tissue rather than liver for DNL.


Antarctolichenia onofrii gen. nov. sp. nov. from Antarctic Endolithic Communities Untangles the Evolution of Rock-Inhabiting and Lichenized Fungi in Arthoniomycetes.
Microbial endolithic communities are the main and most widespread life forms in the coldest and hyper-arid desert of the McMurdo Dry Valleys and other ice-free areas across Victoria Land, Antarctica. There, the lichen-dominated communities are complex and self-supporting assemblages of phototrophic and heterotrophic microorganisms, including bacteria, chlorophytes, and both free-living and lichen-forming fungi living at the edge of their physiological adaptability. In particular, among the free-living fungi, microcolonial, melanized, and anamorphic species are highly recurrent, while a few species were sometimes found to be associated with algae. One of these fungi is of paramount importance for its peculiar traits, i.e., a yeast-like habitus, co-growing with algae and being difficult to propagate in pure culture. In the present study, this taxon is herein described as the new genus Antarctolichenia and its type species is A. onofrii, which represents a transitional group between the free-living and symbiotic lifestyle in Arthoniomycetes. The phylogenetic placement of Antarctolichenia was studied using three rDNA molecular markers and morphological characters were described. In this study, we also reappraise the evolution and the connections linking the lichen-forming and rock-inhabiting lifestyles in the basal lineages of Arthoniomycetes (i.e., Lichenostigmatales) and Dothideomycetes.


Microglial immunoreceptor tyrosine-based activation and inhibition motif signaling in neuroinflammation.
Elimination of extracellular aggregates and apoptotic neural membranes without inflammation is crucial for brain tissue homeostasis. In the mammalian central nervous system, essential molecules in this process are the Fc receptors and the DAP12-associated receptors which both trigger the microglial immunoreceptor tyrosine-based activation motif- (ITAM-) Syk-signaling cascade. Microglial triggering receptor expressed on myeloid cells-2 (TREM2), signal regulatory protein-beta1, and complement receptor-3 (CD11b/CD18) signal via the adaptor protein DAP12 and activate phagocytic activity of microglia. Microglial ITAM-signaling receptors are counter-regulated by immunoreceptor tyrosine-based inhibition motif- (ITIM-) signaling molecules such as sialic acid-binding immunoglobulin superfamily lectins (Siglecs). Siglecs can suppress the proinflammatory and phagocytic activity of microglia via ITIM signaling. Moreover, microglial neurotoxicity is alleviated via interaction of Siglec-11 with sialic acids on the neuronal glycocalyx. Thus, ITAM- and ITIM-signaling receptors modulate microglial phagocytosis and cytokine expression during neuroinflammatory processes. Their dysfunction could lead to impaired phagocytic clearance and neurodegeneration triggered by chronic inflammation.


Individualized prediction of survival benefit from postoperative radiotherapy for patients with malignant pleural mesothelioma.
The role of postoperative radiotherapy (PORT) in malignant pleural mesothelioma (MPM) remains controversial and the eighth edition TNM staging scheme for MPM has not been fully verified. We aimed to develop an individualized prediction model for identifying optimal candidates for PORT among MPM patients who received surgery plus chemotherapy and externally validate the performance of the new TNM staging scheme. Detailed characteristics of MPM patients during 2004-2015 were retrieved from SEER registries. Propensity score matching (PSM) was conducted to reduce disparities of baseline characteristics (age, sex, histologic type, stage, and type of surgery) between the PORT group and no-PORT group. A novel nomogram was constructed based on independent prognosticators identified by multivariate Cox regression model. The discriminatory performance and degree of calibration were evaluated. We stratified patients into different risk groups according to nomogram total scores and estimated the survival benefit of PORT in different subgroups in order to identify the optimal candidates. We identified 596 MPM patients, among which 190 patients (31.9%) received PORT. PORT conferred significant survival benefit in the unmatched population, while there was no significant survival difference favoring PORT in the matched population. The C-index of the new TNM staging scheme was closed to 0.5, which represented a poor discriminatory ability. A novel nomogram was constructed based on clinicopathological factors, including age, sex, histology, and N stage. We stratified patients into three risk groups. Subgroup analyses indicated that PORT was beneficial for high-risk group (p = 0.003) rather than low-risk group (p = 0.965) and intermediate-risk group (p = 0.661). We established a novel predictive model, which could make individualized prediction of survival benefit of PORT for MPM and could compensate for weakness in TNM staging system.


Characterization of Plasmacytoid Dendritic Cells, Microbial Sequences, and Identification of a Candidate Public T-Cell Clone in Kikuchi-Fujimoto Disease.
Kikuchi-Fujimoto disease (KFD) is a self-limited lymphadenitis of unclear etiology. We aimed to further characterize this disease in pediatric patients, including evaluation of the CD123 immunohistochemical (IHC) staining and investigation of potential immunologic and infectious causes. Seventeen KFD cases and 12 controls were retrospectively identified, and the histologic and clinical features were evaluated. CD123 IHC staining was quantified by digital image analysis. Next generation sequencing was employed for comparative microbial analysis via RNAseq (5 KFD cases) and to evaluate the immune repertoire (9 KFD cases). In cases of lymphadenitis with necrosis, >0.85% CD123+ cells by IHC was found to be six times more likely in cases with a final diagnosis of KFD (sensitivity 75%, specificity 87.5%). RNAseq based comparative microbial analysis did not detect novel or known pathogen sequences in KFD. A shared complementarity determining region 3 (CDR3) sequence and use of the same T-cell receptor beta variable region family was identified in KFD LNs but not controls, and was not identified in available databases. Digital quantification of CD123 IHC can distinguish KFD from other necrotizing lymphadenitides. The presence of a unique shared CDR3 sequence suggests that a shared antigen underlies KFD pathogenesis.


Kikuchi- Fujimoto disease of mesenteric lymph nodes mimicking acute appendicitis.
Kikuchi-Fujimoto disease, or histiocytic necrotising lymphadenopathy of unknown aetiology, is a rare, benign and self-limiting cause of lymphadenopathy often involving the cervical nodes, and rarely presenting with mesenteric lymphadenopathy. We present a 26-year-old Caucasian male, who presented with right iliac fossa pain and low grade pyrexia, mimicking acute appendicitis. He underwent a laparatomy and an extended right hemi-colectomy for a caecal mass. Histology of the specimen showed lymph nodes with extensive areas of necrosis, with abnormal architecture suggesting Kikuchi-Fujimoto lymphadenopathy. This was further confirmed by immunohistochemistry. In this context maintenance of a high index of suspicion of this condition can avoid major surgical interventions. We describe the management of our case of Kikuchi-Fujimoto's disease involving the mesenteric nodes and provide an up to date review of the pertinent literature on this subject.


Unexpected Synergy Reveals New Therapeutic Strategy in SCLC.
DNA damage repair (DDR) inhibition and immune checkpoint blockade (ICB) have each individually shown modest clinical activity in small cell lung cancer (SCLC). Recently, Sen and colleagues (Cancer Discov. 2019;https://doi.org/10.1158/2159-8290.CD-18-1020) demonstrated that DDR inhibition can activate the stimulator of interferon genes (STING) innate immune pathway, providing strong rationale for combining DDR inhibition and ICB to treat SCLC.


Dissecting the Root Phenotypic and Genotypic Variability of the Iowa Mung Bean Diversity Panel.
Mung bean [Vigna radiata (L.) Wilczek] is a drought-tolerant, short-duration crop, and a rich source of protein and other valuable minerals, vitamins, and antioxidants. The main objectives of this research were (1) to study the root traits related with the phenotypic and genetic diversity of 375 mung bean genotypes of the Iowa (IA) diversity panel and (2) to conduct genome-wide association studies of root-related traits using the Automated Root Image Analysis (ARIA) software. We collected over 9,000 digital images at three-time points (days 12, 15, and 18 after germination). A broad sense heritability for days 15 (0.22-0.73) and 18 (0.23-0.87) was higher than that for day 12 (0.24-0.51). We also reported root ideotype classification, i.e., PI425425 (India), PI425045 (Philippines), PI425551 (Korea), PI264686 (Philippines), and PI425085 (Sri Lanka) that emerged as the top five in the topsoil foraging category, while PI425594 (unknown origin), PI425599 (Thailand), PI425610 (Afghanistan), PI425485 (India), and AVMU0201 (Taiwan) were top five in the drought-tolerant and nutrient uptake "steep, cheap, and deep" ideotype. We identified promising genotypes that can help diversify the gene pool of mung bean breeding stocks and will be useful for further field testing. Using association studies, we identified markers showing significant associations with the lateral root angle (LRA) on chromosomes 2, 6, 7, and 11, length distribution (LED) on chromosome 8, and total root length-growth rate (TRL_GR), volume (VOL), and total dry weight (TDW) on chromosomes 3 and 5. We discussed genes that are potential candidates from these regions. We reported beta-galactosidase 3 associated with the LRA, which has previously been implicated in the adventitious root development via transcriptomic studies in mung bean. Results from this work on the phenotypic characterization, root-based ideotype categories, and significant molecular markers associated with important traits will be useful for the marker-assisted selection and mung bean improvement through breeding.


Prevalence and predictors of sexual aggression in dating relationships of adolescents and young adults.
Dyadic influences among the diverse forms of aggression in dating relationships of adolescents and young adults have been reported in various studies. The goal of this research was to extend a dyadic model of physical aggression against partners to sexual aggression against partners. An urban sample of 4,052 adolescents and young adults of both genders, between 16 and 26 years old, was used. The percentage of male aggressors was significantly higher than that of the females (35.7% vs. 14.9%) and the percentage of victimization was higher for the women (25.1% vs.21.7%). Sexual aggression and sexual victimization was almost solely psychological in nature, that is, verbal coercion. As predicted by the dyadic model of physical aggression in dating relationships, sexual victimization was best predicted by sexual aggression of the individuals in this study both for males and females.


Neighborhood deterioration and self-rated health in later life.
This study examined the relationship between the physical living environment and self-rated health in later life. It is hypothesized that older adults who reside in deteriorated neighborhoods will report more physical health problems than elderly people who live in better physical environments. However, it is further predicted that these effects will only emerge in the most dilapidated living conditions. Data from a nationwide survey of older adults provide support for this complex nonlinear relationship. Further analyses reveal that part of the effect can be attributed to friendship strains that arise in deteriorated neighborhood environments.


[Study on the reversal of cancer multidrug resistance by Chinese medicine Fw13-te41 in nude mice].
We have reported that three reversal agents were sifted out from 32 Chinese galenicals through a series of cell culture tests. Among them, Fw13-te41 has the best effect of reversal cancer multidrug resistance (MDR) in vitro. In this study, the reversal action of Fw13-te41 in vivo was studied on the animal model of nude mice with human leukemia k562/ADR. Twenty SPF BALB/c-nu/nu nude mice with xenograft tumor were randomly divided into the control group (n = 6), VCR group [intraperitoneal (i.p.) VCR 250 micrograms/week, n = 5], VCR + Fw13-te41 group (i.p VCR 250 micrograms/week + Fw13-te41 0.2 ml/day, equivalent to crude drug 10 g/kg, n = 5), and Fw13-te41 group (i.p Fw13-te41 0.2 ml/day, equivalent to crude drug 10 g/kg, n = 4). After 18 days, the rate of tumor inhibition (RTI) of VCR group was 19.79%, but the RTI of VCR + Fw13-te41 group was as high as 86.95% (P < 0.05). There results demonstrate that the Chinese medicine Fw13-te41 has an evident reversal action of malignancy MDR in vitro and in vivo.


Weft-knitted silk-poly(lactide-co-glycolide) mesh scaffold combined with collagen matrix and seeded with mesenchymal stem cells for rabbit Achilles tendon repair.
Natural silk fibroin fiber scaffolds have excellent mechanical properties, but degrade slowly. In this study, we used poly(lactide-co-glycolide) (PLGA, 10:90) fibers to adjust the overall degradation rate of the scaffolds and filled them with collagen to reserve space for cell growth. Silk fibroin-PLGA (36:64) mesh scaffolds were prepared using weft-knitting, filled with type I collagen, and incubated with rabbit autologous bone marrow-derived mesenchymal stem cells (MSCs). These scaffold-cells composites were implanted into rabbit Achilles tendon defects. At 16 weeks after implantation, morphological and histological observations showed formation of tendon-like tissues that expressed type I collagen mRNA and a uniformly dense distribution of collagen fibers. The maximum load of the regenerated Achilles tendon was 58.32% of normal Achilles tendon, which was significantly higher than control group without MSCs. These findings suggest that it is feasible to construct tissue engineered tendon using weft-knitted silk fibroin-PLGA fiber mesh/collagen matrix seeded with MSCs for rabbit Achilles tendon defect repair.


[Progress of the laparoscopic colorectal surgery with special consideration regarding cancer treatment].
The development of laparoscopic surgery began with the diagnostic coelioscopy in 1901 and the first appendectomy in 1983. Its worldwide spread started in 1987 with the cholecystectomy. Four years later the right hemicolectomy and sigmoid resection were also described. The initial euphoria however evaporated when the first reports of port-site-metastasis appeared. The controversy whether one should be allowed or not to operate carcinomas laparoscopically, provoked a boom in research with as result that in 2000 it had been confirmed that the incidence of port-site-metastasis was about the same as drain-site-metastasis after open procedures (0.9%). Randomized studies comparing laparoscopic interventions and open surgery showed no difference in the long-term results of colon-carcinoma. For experienced surgeons this is also the case for rectum-carcinoma. Hereby the learning curve is of great importance and has been put at 30 to 70 procedures, taken into account the duration of the operation or other criteria such as conversion to open surgery and complications. With growing experience the amount of material used during an operation goes down, which results in a lower overall cost of the minimal-invasive technique compared with open surgery. In cost calculations one should also take into account the fact that the recovery time and the return to every-day life is generally quicker for patients after laparoscopic surgery while overall they also have a significant better quality of life score (SF-36) in the longer term. Currently, i.e. in 2006 the laparoscopic colorectal surgery has become an established procedure. It is thought that laparoscopic interventions give additional advantages because the immune system is less affected but this must still be confirmed through research.


Adenocarcinoma of the rectum in a 13-year-old girl with Turner syndrome.
We describe a 13-year-old girl with short stature and delayed puberty who presented with hematochezia and recurrent abdominal pain for 1 year, and progressive weight loss for 6 months. Per rectal examination was suggestive of a rectal mass. Histopathologic evaluation of the proctoscopy-guided biopsy specimen showed rectal adenocarcinoma. Computerized tomography of the abdomen showed hepatic metastases, which was confirmed by fine-needle aspiration cytology of the liver. She also had perirectal, aortocaval, para-aotic, mesenteric, and gastrohepatic ligament lymph node enlargement. GTG-banded chromosomal analysis showed a karyotype of 45, X, confirming Turner syndrome. A brief review of the neoplasms described in literature in association with Turner syndrome, and the possible pathogenetic mechanisms are discussed.


Clinical and biologic features of adenomatosis coli in Northern Italy.
Familial adenomatous polyposis (FAP) is a hereditary disease characterized by more than 100 adenomas scattered in the large bowel and by various extracolonic manifestations. We proposed a) to establish the frequency of the disorder in Northern Italy, b) to describe the most relevant clinical findings, and c) in a subgroup of 21 patients (from 8 families), to evaluate the spectrum of mutations of the APC gene. Patients with FAP diagnosed between 1961 and 1991 were referred to our Study Group from surgery and gastroenterology units of the region Emilia-Romagna. The incidence of FAP was in the order of 1 in 16,500, with about a third of patients being 'single' cases. Colorectal malignancies were present in 75.6% of symptomatic patients but absent in most (93.75%) of the asymptomatic family members ('call-up' individuals). Gastric, duodenal, and jejunal adenomas were found in 8.2%, 30.6% and 53.3% of the investigated patients, respectively. Congenital hypertrophy of the retinal pigment epithelium and occult jaw lesions were seen in 64.7% and 39.5% of FAP patients but only in 0.5% and 2.5% of a matched, by age and sex, control population. These two clinical markers had a specificity of 99% and 97%, although their sensitivity was 64% and 39%. Finally, mutations of the APC gene were detected in 6 families (16 affected individuals) of the 8 families (21 affected individuals) tested; no correlation could be found between genotype and phenotype. This study confirms that early diagnosis is essential for an appropriate management of FAP patients, although this aim remains elusive in single cases. High-risk individuals are ideal candidates for APC gene mutation analysis, which should be offered to all first-degree relatives of affected patients.


DCAMKL1, a brain-specific transmembrane protein on 13q12.3 that is similar to doublecortin (DCX).
Mutations in the human doublecortin (DCX), a brain-specific putative signaling protein, cause X-linked lissencephaly and subcortical band heterotopia. A predicted 740-amino-acid protein from human brain has two distinct regions, an N-terminal 345-amino-acid region 78% similar to the DCX protein and a C-terminal 427-amino-acid region that contains two transmembrane domains and is 98% homologous to a rat Ca2+/calmodulin-dependent protein kinase. We have designated this protein DCAMKL1. It maps to chromosome 13q12.3-q13, within a 540-kb YAC clone containing markers D13S805 and D13S1164. Northern analysis detected three major transcript isoforms of the DCAMKL1 gene expressed differentially and predominantly in human fetal and adult brain and during mouse embryogenesis (11-17 dpc). These results and its homology with the DCX and Ca2+/calmodulin dependent kinase proteins suggest a likely role for DCAMKL1 transmembrane protein in developing and adult brain, possibly in a pathway of cortical development.


[Heterophilic antibodies: be carefull!].
The determination of plasma level of cardiac troponin I or T is recommended by the French Health Authority to diagnose myocardial infarction. However false positive results associated with the presence of heterophilic antibodies are described in the literature. This interference can lead to unnecessary invasive procedures, sometimes even dangerous. We report the case of a patient with falsely elevated troponin Ic concentration due to these antibodies. This case is characterized by the intensity of the abnormalities, the diversity of biological parameters affected and the discrepancies between biology and clinic. This case report confirms that modern immunoassays are always affected by heterophilic antibodies. We present here an example of such interference.


Malignant lymphatic and hematopoietic neoplasms mortality in Serbia, 1991-2010: a joinpoint regression analysis.
Limited data on mortality from malignant lymphatic and hematopoietic neoplasms have been published for Serbia. The study covered population of Serbia during the 1991-2010 period. Mortality trends were assessed using the joinpoint regression analysis. Trend for overall death rates from malignant lymphoid and haematopoietic neoplasms significantly decreased: by -2.16% per year from 1991 through 1998, and then significantly increased by +2.20% per year for the 1998-2010 period. The growth during the entire period was on average +0.8% per year (95% CI 0.3 to 1.3). Mortality was higher among males than among females in all age groups. According to the comparability test, mortality trends from malignant lymphoid and haematopoietic neoplasms in men and women were parallel (final selected model failed to reject parallelism, P = 0.232). Among younger Serbian population (0-44 years old) in both sexes: trends significantly declined in males for the entire period, while in females 15-44 years of age mortality rates significantly declined only from 2003 onwards. Mortality trend significantly increased in elderly in both genders (by +1.7% in males and +1.5% in females in the 60-69 age group, and +3.8% in males and +3.6% in females in the 70+ age group). According to the comparability test, mortality trend for Hodgkin's lymphoma differed significantly from mortality trends for all other types of malignant lymphoid and haematopoietic neoplasms (P<0.05). Unfavourable mortality trend in Serbia requires targeted intervention for risk factors control, early diagnosis and modern therapy.


Hybrid Organic/Inorganic Thiol-ene-Based Photopolymerized Networks.
The thiol-ene reaction serves as a more oxygen tolerant alternative to traditional (meth)acrylate chemistry for forming photopolymerized networks with numerous desirable attributes including energy absorption, optical clarity, and reduced shrinkage stress. However, when utilizing commercially available monomers, many thiol-ene networks also exhibit decreases in properties such as glass transition temperature (T(g)) and crosslink density. In this study, hybrid organic/inorganic thiol-ene resins incorporating silsesquioxane (SSQ) species into the photopolymerized networks were investigated as a route to improve these properties. Thiol- and ene-functionalized SSQs (SH-SSQ and allyl-SSQ, respectively) were synthesized via alkoxysilane hydrolysis/condensation chemistry, using a photopolymerizable monomer [either pentaerythriol tetrakis(3-mercaptopropionate) (PETMP) or 1,3,5-triallyl-1,3,5-triazine-2,4,6(1H,3H,5H)-trione (TATATO)] as the reaction solvent. The resulting SSQ-containing solutions (SSQ-PETMP and SSQ-TATATO) were characterized, and their incorporation into photopolymerized networks was evaluated.


Enhanced immune priming with spatial distribution of paracrine cytokine vaccines.
In preclinical models, tumor cells genetically modified to express cytokines or other costimulatory molecules can generate systemic antitumor immunity. In some cases, these tumor vaccines have been shown to eradicate micrometastases. These results have led to the initiation of numerous phase I clinical trials employing either autologous or allogeneic tumor vaccines genetically modified to express cytokines and other genes. In this report, we use our murine model to identify a number of parameters that may be critical for enhancing vaccine efficacy. In addition to antigen dose and cytokine level, the distribution of vaccine inoculation was found to have a significant impact on vaccine potency. These results require consideration in early clinical trials designed to evaluate cellular vaccine therapy.


Discussion: the coalition for improving maternity services:.
The Ten Steps of Mother-Friendly Care developed by the Coalition for Improving Maternity Services (CIMS) provides guidelines for caregivers, hospitals, birth centers, and home birth services that are committed to ensuring their services are "mother-friendly." The evidence basis compiled by the CIMS Expert Work Group for the Ten Steps of Mother-Friendly Care confirms that substantial support exists for the Ten Steps. Furthermore, the group's findings-along with the results from the Listening to Mothers II survey-support the relevance and continued importance of the Ten Steps, as well as the larger CIMS Mother-Friendly Childbirth Initiative, and suggest future direction for researchers, maternity caregivers, and childbearing women. Suggestions for ongoing research and effective advocacy on behalf of mother-friendly care practices are encouraged.


Artificial Intelligence May Cause a Significant Disruption to the Radiology Workforce.
The increasingly realistic prospect of artificial intelligence (AI) playing an important role in radiology has been welcomed with a mixture of enthusiasm and anxiousness. A consensus has arisen that AI will support radiologists in the interpretation of less challenging cases, which will give the radiologists more time to focus on the challenging tasks as well as interactions with patients and other clinicians. The possibility of AI replacing a large number of radiologists is generally dismissed by the radiology community. The common arguments include the following: (1) AI will never be able to match radiologists' performance; (2) radiologists do more than interpret images; (3) even if AI takes over a large portion of the reading tasks, the radiologists' effort will be shifted toward interactions with patients and other physicians; (4) the FDA would never agree to let machines do the work of radiologist; (5) the issues of legal liability would be insurmountable; and (6) patients would never put complete trust in computer algorithms. In this article, I analyze these arguments in detail. I find a certain level of validity to some of them. However, I conclude that none of the arguments provide sufficient support for the claim that AI will not create a significant disruption in the radiology workforce. Such disruption is a real possibility. Although the radiology specialty has shown an astonishing ability to adapt to the changing technology, the future is uncertain, and an honest, in-depth discussion is needed to guide development of the field.


Disposition of an antineoplastic sesquiterpene lactone, [3H]-plenolin, in BDF1 mice.
The pharmacokinetics of a radiolabelled analog of helenalin, [3H]-plenolin ([3H]-11,13-dihydrohelenalin), was determined in BDF1 mice following intravenous, intraperitoneal, and oral administration. A two-compartment pharmacokinetic model predicted that the maximum terminal (beta) half-life of [3H]-plenolin was 57.3 hours. Urinary excretion accounted for 40.3% to 64.4% of the administered radioactivity, while fecal excretion accounted for 9.3% to 39.7%. The fecal excretion data also suggested that [3H]-plenolin was secreted in the bile. Following intraperitoneal administration of [3H]-plenolin, no radioactivity was sequestered in the major organs. However, radioactivity was sustained in the carcass and skin for 24 days. [3H]-Plenolin was rapidly taken up by murine tumor cells and human fibroblasts. The drug did not significantly associate with DNA, RNA, or protein of P388 leukemia or human fibroblast cells.


[Cesarean section in an orthotopic liver transplantation patient].
We describe the case of a woman with a functioning orthotopic liver transplant who was receiving cyclosporine treatment. An emergency cesarean section was performed, with epidural analgesia, for prolonged pregnancy and an unfavorable cervix. No complications were recorded either during or after surgery. She gave birth to a healthy boy and both were discharged on the fifth day after delivery. Organ transplantation is an increasingly common procedure, and Spain, which has a large number of organ donors, is the country where the largest number of transplants in Europe is performed. Immunosuppressive therapy has advanced greatly, allowing patients to survive longer and enjoy good quality of life. Many transplanted women in their childbearing years consider pregnancy, which can lead to medical problems, a worsened clinical picture or complications related to pregnancy, putting the lives of both mother and fetus at risk. Perioperative management by an anesthesiologist is necessary, whether delivery is vaginal or cesarean. Whenever immunosuppressive therapy is involved, the use of general or regional anesthetics carries risk, as do pregnancy and delivery themselves.


Developmental Biochemistry of Cottonseed Embryogenesis and Germination : XIII. REGULATION OF BIOSYNTHESIS OF PRINCIPAL STORAGE PROTEINS.
The synthesis of the principal cottonseed storage proteins during embryogenesis has been followed by analyses of stained protein gels and of fluorographs of protein synthesized in vivo and from purified RNA in vitro in the wheat germ system. The kinetics of in vivo labeling as well as immunochemical cross-reactivity indicate that the 52- and 48-kilodalton mature storage protein sets are derived from 70- and 67-kilodalton precursor protein sets that are abundant proteins in embryonic cotyledons and disappear in late embryogenesis. Identification of the initial translation products of the storage protein mRNA has not been clearly established although products of apparent molecular weights of 69,000 and 60,000 are the likely storage protein precursors.Storage protein synthesis falls off markedly in late embryogenesis simultaneously with the loss of a superabundant class of mRNAs (shown by cDNA:RNA reassociation) that are presumed to be those for the storage proteins. The synthesis of these proteins ceases abruptly when immature embryos are removed from the boll and allowed to germinate precociously or when this precocious germination is prevented by incubation in abscisic acid. Thus, abscisic acid is not implicated in the expression of the storage protein genes.A scheme involving co-translational processing into vesicles, glycosylation, and slow in situ cleavage to produce the mature storage proteins is proposed.


A comparison between intranasal budesonide aerosol and budesonide dry powder in the treatment of hay fever symptoms.
Sixty patients with seasonal allergic rhinitis due to birch pollen were enrolled in an open, randomized parallel group study. Efficacy and side effects were studied after intranasal administration of budesonide given as a freon propellant aerosol or as dry powder with a sniff actuated inhalation device. Medication started a few days before the actual peak pollen season and lasted for three weeks. The dose was 400 micrograms once daily. Efficacy was assessed daily by patient-rated symptoms scores and by nasal peak inspiratory flow measurements at the visits to the clinic. Safety was assessed by monitoring clinical adverse events. No clear changes in nasal symptom scores or nasal peak flow occurred during the pollen season in either treatment group as compared to the pretreatment period, although the pollen season was very difficult in Finland during the study, ad 12000 grains per m3. Substantial or total control of symptoms was achieved in 93% of the patients in the aerosol group and in 79% in the powder group. Side effects were minimal in both groups. We conclude that dry powder administration of budesonide is as effective and well tolerated as the aerosol in the treatment of seasonal allergic rhinitis.


Radical vaginal trachelectomy after supracervical hysterectomy.
Radical vaginal trachelectomy (RVT) is an acceptable approach when applied toward a select group of patients with early stage cervical carcinoma. It is less invasive, can maintain fertility, and can be ideal in patients with significant comorbid factors compared to abdominal approaches. A small subset of patients with a previous supracervical hysterectomy can pose a surgical dilemma. An 81-year-old woman with a history of severe cardiac disease on routine gynecological examination was found to have adenocarcinoma in situ with a focus suspicious for invasion of the cervical stump diagnosed by cone biopsy. She previously had a supracervical hysterectomy for benign disease of the uterus. A RVT was performed as definitive treatment and the patient recovered without complications. In the rare case that presents with a history of supracervical hysterectomy, RVT with some technical modifications can still be considered as a therapeutic option for early stage cervical carcinoma.


Human immunodeficiency virus/acquired immune deficiency syndrome-related drug therapy: anesthetic implications.
This article reviews advances in the diagnosis and treatment of human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS). Newer drugs used to treat HIV/AIDS, such as protease inhibitors and non-nucleoside reverse transcriptase inhibitors, are described, including their potential interactions with anesthetic drugs. Common areas of concern for CRNAs related to these drugs are reviewed, such as end-organ toxicity, liver and kidney effects, and bone marrow suppression.


Dysregulation of leptin signaling in Alzheimer disease: evidence for neuronal leptin resistance.
Leptin signaling has received considerable attention in the Alzheimer disease (AD) field. Within the past decade, the peptide hormone has been demonstrated to attenuate tau hyperphosphorylation in neuronal cells and to be modulated by amyloid-β. Moreover, a role in neuroprotection and neurogenesis within the hippocampus has been shown in animal models. To further characterize the association between leptin signaling and vulnerable regions in AD, we assessed the profile of leptin and the leptin receptor in AD and control patients. We analyzed leptin levels in CSF, and the concentration and localization of leptin and leptin receptor in the hippocampus. Significant elevations in leptin levels in both CSF and hippocampal tissue of AD patients, compared with age-matched control cases, indicate a physiological up-regulation of leptin in AD. However, the level of leptin receptor mRNA decreased in AD brain and the leptin receptor protein was localized to neurofibrillary tangles, suggesting a severe discontinuity in the leptin signaling pathway. Collectively, our results suggest that leptin resistance in the hippocampus may play a role in the characteristic changes associated with the disease. These findings are the first to demonstrate such dysregulated leptin-signaling circuitry and provide novel insights into the possible role of aberrant leptin signaling in AD. In this study, increased leptin was found in CSF and hippocampus in Alzheimer disease indicating its physiological up-regulation, yet leptin receptor mRNA was decreased and leptin receptor protein was localized to neurofibrillary tangles, suggesting a discontinuity in the leptin signaling pathway. The lack of leptin signaling within degenerating neurons may represent a novel neuronal leptin resistance in Alzheimer disease.