Insulin resistance status: predicting weight response in overweight children.
To assess the relationship between insulin resistance and body mass index (BMI) z score associated with dietary modification that focuses on limiting sweetened beverage consumption in overweight children. A retrospective cohort study conducted between July 1, 2004, and April 28, 2006. Community-based primary care practices treating children. Forty-five children (aged < or =18 years) at or above the 95th percentile of BMI for age and sex. Intervention Children and parents were instructed by a dietitian regarding caloric reduction and modification of sweetened beverage intake. Insulin resistance at baseline was calculated from fasting insulin and glucose levels (ie, homeostatic model assessment [HOMA]) and change in BMI z score from baseline to 12-week follow-up. Change in BMI z score in response to a decrease in sweetened beverages correlated (Pearson product moment correlation coefficient = 0.42; P < .01) with baseline insulin resistance. Those with a decrease in or an unchanged BMI z score had significantly greater insulin resistance than those whose BMI z score increased (mean [SD] HOMA, 6.2 [4.2] vs 2.6 [2.0], P < .01). Linear regression confirmed that HOMA was a significant predictor of change in BMI z score when controlling for age, race, and sex. Among overweight children in primary care practices, a significant relationship was found between insulin resistance and the change in BMI z score associated with a dietitian-mediated intervention that includes a focus on decreasing sweetened beverage consumption. Estimating insulin resistance may inform dietary recommendations for overweight children.


Williams Syndrome and Music: A Systematic Integrative Review.
Background: Researchers and clinicians have often cited a strong relationship between individuals with Williams syndrome (WS) and music. This review systematically identified, analyzed, and synthesized research findings related to WS and music. Methods: Thirty-one articles were identified that examined this relationship and were divided into seven areas. This process covered a diverse array of methodologies, with aims to: (1) report current findings; (2) assess methodological quality; and (3) discuss the potential implications and considerations for the clinical use of music with this population. Results: Results indicate that individuals with WS demonstrate a high degree of variability in skill and engagement in music, presenting with musical skills that are more in line with their cognitive abilities than chronological age (CA). Musical strengths for this population appear to be based more in musicality and expressivity than formal musical skills, which are expressed through a heightened interest in music, a greater propensity toward musical activities, and a heightened emotional responsiveness to music. Individuals with WS seem to conserve the overall structure of musical phrases better than they can discriminate or reproduce them exactly. The affinity for music often found in this population may be rooted in atypical auditory processing, autonomic irregularities, and differential neurobiology. Conclusions: More studies are needed to explore how this affinity for music can be harnessed in clinical and educational interventions.


Presentation format effects in a levels-of-processing task.
Three experiments were conducted to examine better performance in long-term memory when stimulus items are pictures or spoken words compared to printed words. Hypotheses regarding the allocation of attention to printed words, the semantic link between pictures and processing, and a rich long-term representation for pictures were tested. Using levels-of-processing tasks eliminated format effects when no memory test was expected and processing was deep (El), and when study and test formats did not match (E3). Pictures produced superior performance when a memory test was expected (El & 2) and when study and test formats were the same (E3). Results of all experiments support the attenuation of attention model and that picture superiority is due to a more direct access to semantic processing and a richer visual code. General principles to guide the processing of stimulus information are discussed.


Identification and DNA Marker Development for a Wheat-Leymus mollis 2Ns (2D) Disomic Chromosome Substitution.
Leymus mollis (2n = 4x = 28, NsNsXmXm), a wild relative of common wheat (Triticum aestivum L.), carries numerous loci which could potentially be used in wheat improvement. In this study, line 17DM48 was isolated from the progeny of a wheat and L. mollis hybrid. This line has 42 chromosomes forming 21 bivalents at meiotic metaphase I. Genomic in situ hybridization (GISH) demonstrated the presence of a pair chromosomes from the Ns genome of L. mollis. This pair substituted for wheat chromosome 2D, as shown by fluorescence in situ hybridization (FISH), DNA marker analysis, and hybridization to wheat 55K SNP array. Therefore, 17DM48 is a wheat-L. mollis 2Ns (2D) disomic substitution line. It shows longer spike and a high level of stripe rust resistance. Using specific-locus amplified fragment sequencing (SLAF-seq), 13 DNA markers were developed to identify and trace chromosome 2Ns of L. mollis in wheat background. This line provides a potential bridge germplasm for genetic improvement of wheat stripe rust resistance.


Five-year incidence of open-angle glaucoma: the visual impairment project.
To determine the incidence of open-angle glaucoma (OAG) in Melbourne, Victoria, Australia. Population-based cohort study. Total of 3271 participants aged 40 years and older from Melbourne, Victoria, Australia. Five-year incidence of OAG. Participants were recruited through a cluster random sampling from nine urban clusters. Baseline examination was conducted from 1992 through 1994, and the follow-up data were collected from 1997 through 1999. Each participant both at baseline and follow-up underwent a standardized ophthalmic examination including intraocular pressure measurement, visual field assessment, cup-to-disc ratio measurement, and paired stereo photographs of the optic disc. Glaucoma was assessed by a consensus group of six ophthalmologists that included two glaucoma specialists. Glaucoma was diagnosed as possible, probable, or definite. The overall incidence of definite OAG was 0.5% (95% confidence limits [CL], 0.3, 0.7); probable and definite incidence of OAG was 1.1% (95% CL, 0.8,1.4); and possible, probable, and definite OAG incidence was 2.7% (95% CL, 1.8, 3.7). The incidence of possible, probable, and definite OAG increases significantly as age increases (P < 0.001). The incidence of definite OAG increases from 0% of participants aged 40 to 49 years to 4.1% of participants aged 80 years and older. The incidence of probable and definite OAG increases from 0.2% of participants aged 40 to 49 years to 5.4% of participants aged 80 years and older. The incidence of possible, probable, and definite OAG increases from 0.5% of participants aged 40 to 49 years to 11% of participants aged 80 years and older. A nonsignificant but higher incidence of definite OAG among men was observed in this study when compared with women (odds ratio, 2.2; 95% CL, 0.9, 5.9). Fifty percent of the definite OAG participants were undiagnosed. The incidence of OAG increases significantly with age. The undiagnosed cases suggest the need to develop novel community screening strategies for glaucoma.


Molecular, serologic, and functional evidence for an apparent HLA-DR triplet.
During routine typing procedures the individual GER was demonstrated to possess an unusual class II phenotype exhibiting three DR serotypes (DR1, DR2, DRw6). Closer serologic examination on this person's family showed that the DR1 and DR2 antigens segregated together on one haplotype. Biochemical evidence will be presented that the B cell line derived from the individual GER expresses five distinct types of DR molecules. Antigen presentation studies proved that the DR molecules carrying either DR1, DR2, or DRw6 (DRw13) allodeterminants are not only coordinately expressed but also are functional. No evidence could be found for altered DQ expression. The implications of these findings for the evolutionary aspects of the MHC class II region will be discussed.


Alginate Encapsulation of Pluripotent Stem Cells Using a Co-axial Nozzle.
Pluripotent stem cells (PS cells) are the focus of intense research due to their role in regenerative medicine and drug screening. However, the development of a mass culture system would be required for using PS cells in these applications. Suspension culture is one promising culture method for the mass production of PS cells, although some issues such as controlling aggregation and limiting shear stress from the culture medium are still unsolved. In order to solve these problems, we developed a method of calcium alginate (Alg-Ca) encapsulation using a co-axial nozzle. This method can control the size of the capsules easily by co-flowing N₂ gas. The controllable capsule diameter must be larger than 500 µm because too high a flow rate of N₂ gas causes the breakdown of droplets and thus heterogeneous-sized capsules. Moreover, a low concentration of Alg-Na and CaCl₂ causes non-spherical capsules. Although an Alg-Ca capsule without a coating of Alg-PLL easily dissolves enabling the collection of cells, they can also potentially leak out from capsules lacking an Alg-PLL coating. Indeed, an alginate-PLL coating can prevent cellular leakage but is also hard to break. This technology can be used to research the stem cell niche as well as the mass production of PS cells because encapsulation can modify the micro-environment surrounding cells including the extracellular matrix and the concentration of secreted factors.


Homologous recombination protects mammalian cells from replication-associated DNA double-strand breaks arising in response to methyl methanesulfonate.
DNA-methylating agents of the S(N)2 type target DNA mostly at ring nitrogens, producing predominantly N-methylated purines. These adducts are repaired by base excision repair (BER). Since defects in BER cause accumulation of DNA single-strand breaks (SSBs) and sensitize cells to the agents, it has been suggested that some of the lesions on their own or BER intermediates (e.g. apurinic sites) are cytotoxic, blocking DNA replication and inducing replication-mediated DNA double-strand breaks (DSBs). Here, we addressed the question of whether homologous recombination (HR) or non-homologous end-joining (NHEJ) or both are involved in the repair of DSBs formed following treatment of cells with methyl methanesulfonate (MMS). We show that HR defective cells (BRCA2, Rad51D and XRCC3 mutants) are dramatically more sensitive to MMS-induced DNA damage as measured by colony formation, apoptosis and chromosomal aberrations, while NHEJ defective cells (Ku80 and DNA-PK(CS) mutants) are only mildly sensitive to the killing, apoptosis-inducing and clastogenic effects of MMS. On the other hand, the HR mutants were almost completely refractory to the formation of sister chromatid exchanges (SCEs) following MMS treatment. Since DSBs are expected to be formed specifically in the S-phase, we assessed the formation and kinetics of repair of DSBs by γH2AX quantification in a cell cycle specific manner. In the cytotoxic dose range of MMS a significant amount of γH2AX foci was induced in S, but not G1- and G2-phase cells. A major fraction of γH2AX foci colocalized with 53BP1 and phosphorylated ATM, indicating they are representative of DSBs. DSB formation following MMS treatment was also demonstrated by the neutral comet assay. Repair kinetics revealed that HR mutants exhibit a significant delay in DSB repair, while NHEJ mutants completed S-phase specific DSB repair with a kinetic similar to the wildtype. Moreover, DNA-PKcs inhibition in HR mutants did not affect the repair kinetics after MMS treatment. Overall, the data indicate that agents producing N-alkylpurines in the DNA induce replication-dependent DSBs. Further, they show that HR is the major pathway of protection of cells against DSB formation, killing and genotoxicity following S(N)2-alkylating agents.


Role of the OCTA site in regulation of IgH chain gene transcription during B cell activation.
We have evaluated the importance of the OCTA site in both the promoter and enhancer regions for the induction of enhancement of IgH chain gene transcription after B cell activation. These studies show that although occupancy of the OCTA site in the promoter is critical for basal transcription of the mu gene, it is not necessary for the increase in transcription induced by in vivo activation. On the other hand, the OCTA site in the enhancer is necessary for neither basal transcription nor in vivo activation of transcription; however, occupancy of this site is required for further up-regulation in transcription of the mu gene in pre-activated cells. These results indicate that different mechanisms may be involved in the activation of resting versus in vivo stimulated B lymphocytes. The findings are discussed in relation to the phenotype described for Oct-2-deficient mice.


Wound tension in rhytidectomy. Effects of skin-flap undermining and superficial musculoaponeurotic system suspension.
This study was conducted to determine the effects of skin-flap undermining and superficial musculoaponeurotic system (SMAS) suspension on wound-closing tension. Nine sides from five fresh-frozen cadavers were used, with closing tension measured at the two main anchor points, anteriorly (A) and posteriorly (P), with and without SMAS plication for minimal (MIN), intermediate (INT), and maximal (MAX) skin-flap undermining. Results indicated that closing tension was significantly decreased with SMAS plication, both A and P, for all three levels of skin undermining. The average decrease in closing tension with SMAS plication was: A-MIN 191 g, A-INT 95 g, A-MAX 83 g, P-MIN 235 g, P-INT 68 g, and P-MAX 70 g (P < .001 for all). Considering the effect of skin-flap undermining alone, closing tension decreased with wider skin-flap undermining, both with and without SMAS plication. The tension-reducing effect of SMAS plication was decreased with wider skin-flap undermining. Regression analysis determined a second-order exponential curve relating closing tension to skin excision.


Tumor Size in Breast Carcinoma: Gross Measurement Is Important!
The staging of breast carcinoma is mainly dependent on tumor size and lymph node status. Small increments in tumor size upstage the patient. An accurate determination of the tumor size is therefore critically important. Although the final staging is based on microscopic size, pathologists rely on gross measurements in a considerable number of cases. We investigated the concordance between gross and microscopic measurements of breast carcinoma as well as factors affecting this concordance. This study is a retrospective review of surgical pathology reports of invasive breast carcinomas. Data were collected for 411 cases. Concordance was defined as a size difference within ±2 mm. Gross and microscopic sizes were identical in 33.1% of cases. Gross and microscopic size difference was within ±2 mm in 56% of cases. Despite the size difference, stage classification ended up being the same in 68.6% of cases. Tumor stage was over estimated by gross measurement in 17.0% of cases and underestimated in 14.4% of cases. The concordance was significantly higher for those tumors in which final pathologic tumor (pT) size was greater than 2 cm (≥pT2) as compared with those less than or equal to 2 cm (≤pT1; P < .0001). A higher proportion of mastectomy specimens (61.4%) were concordant as compared with lumpectomy specimens (52.1%). Gross and microscopic tumor sizes were concordant in 56% of cases. Stage classification based on gross and microscopic tumor size was different in nearly one third (31.4%) of cases. Gross tumor size is critically important in accurate staging at least in cases where tumor size cannot be confirmed microscopically.


Simplifying HL7 Version 3 messages.
HL7 Version 3 offers a semantically robust method for healthcare interoperability but has been criticized as overly complex to implement. This paper reviews initiatives to simplify HL7 Version 3 messaging and presents a novel approach based on semantic mapping. Based on user-defined definitions, precise transforms between simple and full messages are automatically generated. Systems can be interfaced with the simple messages and achieve interoperability with full Version 3 messages through the transforms. This reduces the costs of HL7 interfacing and will encourage better uptake of HL7 Version 3 and CDA.


[Progress in physiology and ergonomics and its significance for occupational hygiene].
Over the recent decades, advancements in occupational physiology and occupational psychology have primarily been observed in two domains: the increased knowledge of mechanisms responsible for the development of physical and mental fatigue and the elaboration of new methods facilitating their quantitative assessment. The way these advancements have been utilized and the range of their application result from new hygiene requirements imposed by the changed context and organization of work. The integration of these scientific disciplines is best accomplished in ergonomics, particularly through designing and optimization of working conditions in view of the best possible adjustment of technology and work organization to the psycho-physical needs of workers. Changes in occupational activities are associated with a gradual replacement of jobs that require much dynamic effort by those that involve static and mental efforts. Classic occupational physiology dealing with systemic changes occurring during a dynamic effort is largely superseded by studies (biochemical and electrophysiological) of changes in cellular physiology evoked by static effort and changes that accompany mental overload and stress. Over the last few years, occupational physiology and ergonomics have faced a number of macroproblems of demographic nature, e.g. aging of the population, and a growing number of people with disabilities who have to be employed. It is now the responsibility of ergonomics to create working conditions taking account of the needs of these particular occupational groups. A significant methodological progress has been made due to new opportunities, which allow to simulate and model situations with body overload. New methods are based on computerized programs that incorporate data from all fields necessary to assess and design working conditions (anthropometry, biomechanics, safety engineering etc.).


Effects of radiofrequency exposure on in vitro blood-brain barrier permeability in the presence of magnetic nanoparticles.
The blood-brain barrier (BBB) remains a major obstacle for the delivery of drugs in the treatment of many neurological diseases. In this study, we aimed to investigate the effects of radiofrequency electromagnetic fields (RF-EMFs) on the permeability of an in vitro BBB model under RF exposure alone, or in the presence of nanoparticles (NPs). For this purpose, an in vitro BBB model was established by seeding human umbilical vein endothelial cells (HUVECs) and human glioblastoma cell line (T98G) on the apical and basolateral sides of the transwell membrane, respectively. The integrity of the BBB model was confirmed by measuring transendothelial electrical resistance (TEER), and a fluorescein isothiocyanate (FITC)-dextran permeability assay was performed when the resistance reached 120 Ω cm2. After the RF-field exposure (13.56 MHz, 80 W, 10 min), we found that FITC-dextran transported across the in vitro BBB was increased 10-fold compared to FITC-dextran transported without an RF-field. This notable phenomenon, which can be called the burst permeability RF effect (BP-RF), has been proposed for the first time in the literature. Subsequently, the effect of the RF-field on BBB permeability was also investigated in the presence of superparamagnetic iron oxide nanoparticles (SPIONs) and magnetic poly(lactic-co-glycolic acid)-polyethylene glycol (PLGA-b-PEG) nanoparticles (m-PNPs). It was found that the amount of both transported NPs on the basolateral sides increased after exposure to the RF-field. As a result, the RF-field can be applied simultaneously during treatment with clinical agents or nanocarriers, improving the permeability of the BBB, which may contribute to therapeutic efficacy of many drugs that are used in neurological diseases.


Dynamics of Live Oil Droplets and Natural Gas Bubbles in Deep Water.
Explaining the dynamics of gas-saturated live petroleum in deep water remains a challenge. Recently, Pesch et al. [ Environ. Eng. Sci. 2018, 35 (4), 289-299] reported laboratory experiments on methane-saturated oil droplets under emulated deep-water conditions, providing an opportunity to elucidate the underlying dynamical processes. We explain these observations with the Texas A&M Oil spill/Outfall Calculator (TAMOC), which models the pressure-, temperature-, and composition-dependent interactions between oil-gas phase transfer; aqueous dissolution; and densities and volumes of liquid oil droplets, gas bubbles, and two-phase droplet-bubble pairs. TAMOC reveals that aqueous dissolution removed >95% of the methane from ∼3.5 mm live oil droplets within 14.5 min, prior to gas bubble formation, during the experiments of Pesch et al. Additional simulations indicate that aqueous dissolution, fluid density changes, and gas-oil phase transitions (ebullition, condensation) may all contribute to the fates of live oil and gas in deep water, depending on the release conditions. Illustrative model scenarios suggest that 5 mm diameter gas bubbles released at a <470 m water depth can transport methane, ethane, and propane to the water surface. Ethane and propane can reach the water surface from much deeper releases of 5 mm diameter live oil droplets, during which ebullition occurs at water depths of <70 m.


Aphasic mild cognitive impairment in prodromal dementia with Lewy bodies.
This study aimed to determine the characteristics of aphasic mild cognitive impairment (aphasic MCI), which is characterized by a progressive and relatively prominent language impairment compared with other cognitive impairments, in the prodromal phase of dementia with Lewy bodies (DLB). Of the 26 consecutive patients with aphasic MCI who had been prospectively recruited at our hospital, 8 patients were diagnosed with prodromal DLB and underwent language, neurological, neuropsychological, and neuroimaging (N-isopropyl-p-[123I] iodoamphetamine single-photon emission computed tomography; IMP-SPECT) testing. Three of these patients also underwent cholinesterase inhibitor therapy with donepezil. In our aphasic MCI cohort, the clinical diagnosis of probable prodromal DLB accounted for more than 30% of cases; therefore, the presence of language impairment in prodromal DLB was not very uncommon. Five patients were diagnosed with progressive anomic aphasia and three with logopenic progressive aphasia. Anomic aphasia was characterized by apparent anomia but relatively preserved repetition and comprehension ability and logopenic progressive aphasia by anomia, phonemic paraphasia, and impaired repetition. IMP-SPECT revealed hypoperfusion of the temporal and parietal lobes in the left hemisphere in all but one patient. All patients who underwent cholinesterase inhibitor therapy with donepezil showed improvement in general cognitive function, including language function. The clinical and imaging features of aphasic MCI in prodromal DLB are similar to those observed in Alzheimer's disease. Progressive fluent aphasia, such as progressive anomic aphasia and logopenic progressive aphasia, is one of the clinical presentations in prodromal state of DLB. Our findings provide further insight into the clinical spectrum of prodromal DLB and may contribute to the development of medication for progressive aphasia caused by cholinergic insufficiency.


Some emerging issues on the malaria problem in Kenya.
Malaria in Kenya has been characterised by marked variability in its epidemiology, partly reflecting the obstacles and progress made in the control strategies. The impact of anti-vector activities in the 1970s and before have been observed for variable lengths of time afterwards. Malaria has re-emerged in areas previously with little or no transmission. The recovery of infective Anopheles gambiae vector in higher altitudes affirms the potential for transmission in areas where epidemics have been known to occur. Morbidity and mortality patterns in the otherwise endemic lowlands have become increasingly severe, an observation which would be attributed to the increasing inefficacy of chloroquine. Efforts to promote personal protection suffer substantial setbacks in sustainability inspite of apparent acceptability. There are indications that the mosquito vector susceptibility to permethrin and other insecticides will now require continual monitoring in order to detect development of significant resistance. In this communication, we review some emergent issues in malaria transmission in Kenya and the potential for control as adduced from historical and contemporary perspectives.


Do probiotics help prevent ventilator-associated pneumonia in critically ill patients? A systematic review with meta-analysis.
Probiotic treatments might contribute to the prevention of ventilator-associated pneumonia (VAP). Due to its unclear clinical effects, here we intend to assess the preventive effect and safety of probiotics on intensive care unit (ICU) patients. Eligible randomised controlled trials were selected in databases until 30 September 2019. The characteristics of the studies were extracted, including study design, definition of VAP, probiotics intervention, category of included patients, incidence of VAP, mortality, duration of mechanical ventilation (MV) and ICU stay. Heterogeneity was evaluated by Chi-squared and I2 tests. 15 studies involving 2039 patients were identified for analysis. The pooled analysis suggests significant reduction on VAP (risk ratio, 0.68; 95% Cl, 0.60 to 0.77; p<0.00001) in a fixed-effects model. Subgroup analyses performed on the category of clinical and microbiological criteria both support the above conclusion; however, there were no significant differences in duration of MV or length of ICU stay in a random-effects model. Also, no significant differences in total mortality, overall mortality, 28-day mortality or 90-day mortality were found in the fixed-effects model. The probiotics helped to prevent VAP without impacting the duration of MV, length of ICU stay or mortality.


Microendoscopic Decompression for Lumbar Disc Herniations: An Analysis of Short and Long Term Patient Reported Outcome Measures.
Endoscopic spine surgery is increasingly being used, and techniques, platforms, and applications are rapidly evolving. Despite substantial enthusiasm surrounding these techniques, there is a dearth of longer term patient-reported clinical outcomes. Within the United States in particular, there are yet to be reported large cohort studies with a notable follow-up. We sought to characterize the clinical outcomes of patients undergoing microendoscopic decompression (MED) for lumbar disk herniations. The records of patients with symptomatic lumbar disk herniations who underwent MED from May 2018 to February 2021 within a single practice were reviewed. Paired outcomes scores were evaluated using Patient-Reported Outcomes Measurement Information System parameters. Basic perioperative data including length of stay, estimated blood loss, mean opioid use, complication rate, and rate of revision were tabulated. Paired sample Student t-tests and paired Wilcoxon sign tests were used to compare normally distributed and nonparametric data, respectively. Thirty-five patients with complete paired patient-reported outcome measures data and a minimum 6-month follow-up were included; 65.7% of the patients were male with a mean age of 47.1 years (SE 1.8). The mean follow-up was 590.6 days (SE 47.7). In total, 34 of the 35 patients (97.1%) were discharged on the day of their procedure. The estimated blood loss was <25 mL for each procedure. The mean opioid use after extubation and before discharge was 10.4 morphine milligram equivalents. At the 2-week follow-up, there were notable improvements in pain metrics and global health components. At the final follow-up, nearly all parameters showed notable improvement that exceeded minimally clinical important difference values. For most parameters, preoperative values outside of the "normal" range were within normal limits on postoperative testing. MED resulted in sustained notable improvement in patient-reported outcome measures that exceeded minimally clinical important difference values at the average follow-up approximating 2 years. These findings substantiate the utility of this technique and additional investment in endoscopic spine technology. Not publicly available; available upon request.


Improvement on the Antioxidant Activity of Polysaccharides by Submerged Fermentation of Shiraia bambusicola GDMCC 60438 (Ascomycota).
Shiraia bambusicola strain GDMCC 60438, originally isolated from eastern China, was applied for production of polysaccharides through submerged fermentation with glucose and potato extracts. Compared with a polysaccharide content of 3.94 ± 0.92% in natural Sh. bambusicola stroma, 9.12 ± 0.36 g intracellular polysaccharides (SIP) could be produced in 100 g freeze-dried Sh. bambusicola mycelium after an optimized fermentation. The SIP showed an 88.65 ± 2.26% hydroxyl radical scavenging activity (HRSA) at the concentration of 4 mg/mL. It was higher than the 31.48 ± 3.12% HRSA of Sh. bambusicola stroma polysaccharide (SSP). In the meantime, a 5 mg/mL SIP showed an equivalent 2,2'-Azino-bis (3-ethylbenzthiazoline-6-sulfonic) acid radical (ABTS+) scavenging activity to ascorbic acid at 0.025 mg/mL. Gel chromatography analysis showed that the SIP had distinct polysaccharide fractions compared with the SSP. Submerged fermentation showed a promising prospect on high production of Sh. bambusicola polysaccharides with improved antioxidant activities.


Effect of FTY720 on chronic cyclosporine nephropathy in rats.
Long-term treatment with cyclosporine A (CsA) causes tubulointerstitial inflammation and fibrosis in the kidney. To define the role of lymphocytes in this process, the novel lymphocyte-specific inhibitor FTY720 was administered to rats with experimental model of chronic CsA nephropathy. Sprague-Dawley rats were treated daily for 4 weeks with CsA (7.5 mg/kg), or both CsA and FTY720 (0.125 mg/kg). The effects of FTY720 on CsA-induced renal injury were evaluated using renal function tests and histopathology, and the expression of mediators of CsA-induced renal injury (osteopontin, transforming growth factor-beta1 [TGF-beta1], betaig-h3, and angiotensin II). FTY720 treatment significantly decreased T-lymphocyte accumulation in kidneys compared with CsA treatment alone. FTY720 treatment improved not only CsA-induced renal dysfunction but also renal histopathology, demonstrated by decreased macrophage infiltration and interstitial fibrosis. Increased osteopontin, TGF-beta1, betaig-h3, and angiotensin II expression in CsA-treated rat kidneys were decreased with FTY720 treatment. FTY720 treatment prevents CsA-induced renal injury.


[A case of primary malignant lymphoma of the spleen which was difficult to be diagnosed].
A 55-year-old woman who had a chief complaint of left abdominal and back pain. She was diagnosed with pancreatic cancer associated with splenic metastasis (Stage IVb) by CT and MRI study and was treated with chemotherapy of gemcitabine (GEM). Chemotherapy was discontinued due to adverse event (grade 3). CT study at this point reveals the effectiveness of GEM. The tumor was localized, and an operation was performed. The tumor was diagnosed as primary malignant lymphoma (diffuse large B-cell lymphoma) of the spleen. The splentic tumor is extremely rare, so a surgical treatment was indicated for making a correct diagnosis. This was an interesting case of malignant lymphoma that GEM revealed a cytoreductive result.


Prediction of metabolic and cardiopulmonary responses to maximum cycle ergometry: a randomised study.
All of the most widely-cited studies for the prediction of maximum exercise responses have utilized either volunteers or referred subjects. Therefore, selection bias, with overestimation of the reference values, is a likely consequence. In order to establish a set of predictive equations for the gas exchange, ventilatory and cardiovascular responses to maximum ramp-incremental cycle ergometry, this study prospectively evaluated 120 sedentary individuals (60 males, 60 females, aged 20-80), randomly-selected from >8,000 subjects. Regular physical activity pattern by questionnaire, body composition by anthropometry and dual energy X-ray absorptiometry (n = 75) and knee strength by isokinetic dynamometry were also assessed. Previously reported equations typically overestimated the subjects' peak oxygen uptake (p<0.05). Prediction linear equations for the main variables of clinical interest were established by backward stepwise regression analysis including: sex, age, knee extensor peak torque, bone-free lean leg mass, total and lean body mass, height, and physical activity scores. Reference intervals (95% confidence limits) were calculated: some of these values differed markedly from those formerly recommended. The results therefore might provide a more appropriate frame of reference for interpretation of the responses to symptom-limited ramp incremental cycle ergometry in sedentary subjects; i.e. those usually referred for clinical cardiopulmonary exercise tests.


Knowns and unknowns of tissue-resident memory T cells.
Advances in transcriptomics and other approaches are shedding considerable light on tissue-resident immune cells as distinct from recirculating cells. The advances encompass antigen-presenting cell subsets, Tregs and importantly, tissue-resident memory cells (TRM). What are the transcriptional programmes and functional properties that distinguish the requirements for an effective tissue resident cell in brain relative to lung, skin, adipose tissue or the genital tract? Another important conundrum has been the extent to which TRM cells are specialized either as a 'sense and alarm' population or as a local, primed, effector cell population in themselves. These are questions that challenge immunologists to stop thinking in terms of a generic, model, immune response and focus instead on events in the tissue in question.


Clinical effect of imiquimod 5% cream in the treatment of actinic keratosis.
Actinic keratosis (AK) is the earliest clinical manifestation of squamous cell carcinoma. Metastatic SCC causes the majority of the 1300 to 2300 deaths attributed to nonmelanoma skin cancer in the United States each year. Recent studies have shown that intralesional administration of interferon can be used successfully in the treatment of AK. Imiquimod is an immune response modifier, currently approved for the treatment of genital warts. The topically applied immune response modifier acts by up-regulating interferon and other cytokines involved in the cell-mediated immune response at the site of application. The aim of this was to determine the efficacy and safety of imiquimod 5% cream for the treatment of AK. Twenty-two patients with AK lesions were treated with imiquimod 5% cream, initially at 3 times per week for 8 weeks, or until total clearance of lesions. Patients applied imiquimod to lesions on one side of the body and vehicle cream to the other side. A total of 17 patients who completed treatment were evaluated for number of lesions and adverse reactions before treatment and at weeks 2, 4, 6, and 8 after initiation of treatment. AK lesions were also assessed 4 and 8 weeks after treatment. A significant reduction in the average number of lesions per patient was observed for patients treated with imiquimod. The most frequent reactions to treatment were erythema, itching, and scabbing; however, all adverse events were mild to moderate. Imiquimod 5% cream may be a promising treatment for AK.


Research ethics in the era of personalized medicine: updating science's contract with society.
With the completed sequence of the human genome has come the prospect of substantially improving the quality of life for millions through personalized medicine approaches. Still, any advances in this direction require research involving human subjects. For decades science and ethics have enjoyed an allegiance reflected in a common set of ethical principles and procedures guiding the conduct of research with human subjects. Some of these principles emphasize avoiding harm over maximizing benefit. In this paper we revisit the priority given to these ethical principles - particularly the principles that support a cautious approach to science - and propose a reframing of the 'social contract' between science and society that emphasizes reciprocity and meeting public needs.


[Influence of integrated traditional Chinese and Western medicine therapy on serum resistin levels in patients with severe acute pancreatitis: a randomized controlled trial].
Resistin level is high in patients with severe acute pancreatitis (SAP), and resistin is expected to be a new marker for evaluating the severity of acute pancreatitis. To explore the influence of integrated traditional Chinese and Western medicine therapy on serum resistin levels in SAP patients. Twenty-eight SAP patients meeting inclusion criteria from Department of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University were included, and the patients were randomly divided into treatment group and placebo group. There were 13 patients in the treatment group and 15 patients in the placebo group. Patients in the treatment group were given traditional Chinese herbal medicine in addition to the conventional treatment. Patients in the placebo group were given placebo in addition to the conventional treatment. The serum resistin levels on admission, and days 1, 3, 5, and 7 after the admission were detected. The serum resistin levels on admission in all the patients were higher than normal level, and there was no significant difference between the two groups (P>0.05). On days 1, 3, 5, and 7 after admission, the resistin levels in the treatment group were (3.29 + or - 1.66) microg/L, (3.71 + or - 1.05) microg/L, (3.08 + or - 1.47) microg/L and (3.62 + or - 1.67) microg/L, and in the control group (5.16 + or - 1.93) microg/L, (5.07 + or - 1.53) microg/L, (4.88 + or - 1.47) microg/L and (5.12 + or - 1.48) microg/L, respectively. The resistin levels were lower in the treatment group than in the control group (P<0.05). Serum resistin level in SAP patients can be decreased by integrated traditional Chinese medicine and Western medicine therapy.


Crystal Structure, Topology, DFT and Hirshfeld Surface Analysis of a Novel Charge Transfer Complex (L3) of Anthraquinone and 4-{[(anthracen-9-yl)meth-yl] amino}-benzoic Acid (L2) Exhibiting Photocatalytic Properties: An Experimental and Theoretical Approach.
Here, we report a facile route to the synthesizing of a new donor-acceptor complex, L3, using 4-{[(anthracen-9-yl)meth-yl] amino}-benzoic acid, L2, as donor moiety with anthraquinone as an acceptor moiety. The formation of donor-acceptor complex L3 was facilitated via H-bonding and characterized by single-crystal X-ray diffraction. The X-ray diffraction results confirmed the synthesized donor-acceptor complex L3 crystal belongs to the triclinic system possessing the P-1 space group. The complex L3 was also characterized by other spectral techniques, viz., FTIR and UV absorption spectroscopy, which confirmed the formation of new bonds between donor L2 moiety and acceptor anthraquinone molecule. The crystallinity and thermal stability of the newly synthesized complex L3 was confirmed by powdered XRD and TGA analysis and theoretical studies; Hirshfeld surface analysis was performed to define the type of interactions occurring in the complex L3. Interestingly, theoretical results were successfully corroborated with experimental results of FTIR and UV absorption. The density functional theory (DFT) calculations were employed for HOMO to LUMO; the energy gap (∆E) was calculated to be 3.6463 eV. The complex L3 was employed as a photocatalyst for the degradation of MB dye and was found to be quite efficient. The results showed MB dye degraded about 90% in 200 min and followed the pseudo-first-order kinetic with rate constant k = 0.0111 min-1 and R2 = 0.9596. Additionally, molecular docking reveals that the lowest binding energy was -10.8 Kcal/mol which indicates that the L3 complex may be further studied for its biological applications.


Mechanism of action of anticandidal dipeptides containing inhibitors of glucosamine-6-phosphate synthase.
The mechanism of anticandidal action of novel synthetic dipeptides containing N3-(4-methoxyfumaroyl)-L-2,3-diaminopropanoic acid (FMDP) residues was shown to be consistent with the "warhead delivery" concept. FMDP dipeptides were shown to be transported into Candida albicans cells by the di-tripeptide permease and subsequently hydrolyzed by intracellular peptidases, especially aminopeptidase. The anticandidal activity of the particular FMDP dipeptide was influenced by the rate of its transport and, to a lower extent, by the intracellular cleavage rate. A high transport rate accompanied by a high cleavage rate resulted in the high anticandidal activity of L-norvalyl-FMDP. The strong growth-inhibitory effect of this compound was the consequence of inhibition of the enzyme glucosamine-6-phosphate synthase by the released FMDP. The action of L-norvalyl-FMDP on exponentially growing C. albicans cells resulted in a sharp decrease of incorporation of 14C label from [14C]glucose into chitin, mannoprotein, and glucan. This effect, as well as the growth-inhibitory effect, was fully reversed by exogenous N-acetyl-D-glucosamine. Glucosamine-6-phosphate synthase was proved to be the only essential target for FMDP dipeptides. Scanning electron microscopy of C. albicans cells treated with L-norvalyl-FMDP revealed highly distorted, wrinkled, and collapsed forms. Cells formed long, bulbous chains, and partial lysis occurred.


Sudden Intrabulbar Amyloid Increase Simultaneously Disrupts Olfactory Bulb Oscillations and Odor Detection.
There seems to be a correlation between soluble amyloid beta protein (Aβ) accumulation in the main olfactory bulb (OB) and smell deterioration in both Alzheimer's disease (AD) patients and animal models. Moreover, this loss of smell appears to be related to alterations in neural network activity in several olfactory-related circuits, including the OB, as has been observed in anesthetized animals and brain slices. It is possible that there is a correlation between these two pathological phenomena, but a direct and simultaneous evaluation of the acute and direct effect of Aβ on OB activity while animals are actually smelling has not been performed. Thus, here, we tested the effects of acute intrabulbar injection of Aβ at a low dose (200 pmol) on the OB local field potential before and during the presence of a hidden piece of smelly food. Our results show that Aβ decreases the power of OB network activity while impairing the animal's ability to reach the hidden food. We found a strong relationship between the power of the OB oscillations and the correlation between OBs and the olfactory detection test scores. These findings provide a direct link between Aβ-induced OB network dysfunction and smell loss in rodents, which could be extrapolated to AD patients.


Disclosure patterns within social networks of gay men and lesbians.
Gay men and lesbians must make decisions about disclosure of their sexual orientation. Past research has focused on an individual's overall level of disclosure or on disclosure to a specific subset of individuals. This study used a new measure, the Disclosure Grid, to assess the disclosure patterns of 89 gay men and 55 lesbians across their entire social network. In addition to assessing disclosure to each network member, the Grid also assessed perceived relationship quality prior to disclosure and currently. Finally, the Grid assessed perceptions of each network member's initial and current acceptance of the gay or lesbian person's sexual orientation. Data provide a rich portrait of disclosure patterns among a heterogeneous, urban sample of lesbians and gay men. Analyses also found support for three hypotheses about disclosure, relationship quality, and acceptance. For example, it was found that participants have better relationships with individuals they have directly told about their sexual orientation than with people who found out in an indirect manner.


Enhancing disease awareness for tuberous sclerosis complex in patients with radiologic diagnosis of renal angiomyolipoma: an observational study.
Tuberous Sclerosis Complex (TSC) is a genetic disorder, with renal manifestations like angiomyolipoma (AML) occurring in 70-80% of patients. AML usually cause more complications in TCS patients than in non-TSC patients. However, AML patients are not routinely investigated for TSC. Our aim was to retrospectively assess the correlation between radiologically diagnosed AML and TSC. All patients were stratified into AML related vs. unrelated to TSC. Correlations were calculated to determine the association between age, AML, and TSC. Complete data were available for 521 patients with renal AML, in 7 of which the concurrent diagnosis of TSC was found. Younger age significantly positively correlated with the prevalence of TSC in AML patients (p < 0.01). 37 (7%) of the 521 patients were within the age-range of 18-40 years, in which TSC occurred in 6 cases, 4 (66.7%) of which presented with multiple, bilateral renal AML (p < 0.05), and 2 (33.3%) of which with a single, unilateral AML (p < 0.05). In patients with AML but without TSC, unilateral AML was found in 83.9% and bilateral AML in 16.1% (p < 0.05). Simple binary logistic regression analysis revealed bilateral AML (OR 33.0; 95% CI 3.2-344.0; p = 0.003) (but not unilateral AML (OR 0.09; 95% CI 0.01-0.88; p = 0.04)) to be a risk factor for TSC. The presence of bilateral AML in patients within the age-range of 18-40 years should raise suspicion for TSC as the underlying cause. Therefore, our advice is to refer patients with multiple bilateral renal AML for further investigations regarding TSC.


Detection of Serum Allergen-Specific IgE in Atopic Dogs Tested in Northern Italy: Preliminary Study.
Canine atopic dermatitis (CAD) is a pruritic allergic skin disease associated with IgE-mediated hypersensitivity. IgE is detected using Serum Allergen-Specific IgE test (SAT) in order to identify allergens. The present study aims to identify the environmental allergens in atopic dogs living in Northern Italy using SAT. The screening SAT (sSAT), using a monoclonal antibody cocktail-based ELISA to identify indoor and outdoor allergens, was performed. In all positive samples, an anti-IgE monoclonal antibody ELISA test was performed to extend panel of allergens. Out of 117 selected dogs, 69 were included in the study; 71% were positive and 29% were negative to sSAT. Among the 49 positive sSAT, 53% were positive for both indoor and outdoor, 38.8% only for indoor, and 8.2% only for outdoor allergens. This is the first study on the frequency of allergens involved in CAD in Italy using SAT. IgE hypersensitivity in atopic dogs of Northern Italy is usually associated with indoor allergens, primarily house dust mites. Among the outdoor allergens, an important role was played by Rumex acetosa. Polysensitization also commonly occurs. Therefore, since the numerous factors affect the IgE positivity in CAD, specific panels for geographical areas should be considered and re-evaluated at time intervals.


Summary results of the 1996 Population By-census.
"This article presents the salient features and trends of the population of Hong Kong based on the results of the 1996 Population By-census." Information is included on population size, age and sex structure, marital status, educational attainment, labor force, occupations, industry, households, and housing.


["Delayed" modernization: spatial aspects of marital fertility decline in the federal provinces of Tyrol and Vorarlberg in the 1960s and 1970s].
"This study treats the decline of marital fertility in all of the 374 municipalities ('Gemeinden') of the Alpine area of western Austria (the Federal Provinces of the Tyrol and Vorarlberg). For each municipality Coale's Index of marital fertility (I(g)) is calculated for the years 1961-1971-1981. Particular attention is drawn to the geographical variation of the I(g)-values. A five-stage model is used to describe time-lag effects in the spatial fertility decline." It is found that "although there was a significant overall reduction in marital fertility of about 50%, most regional differences observed in 1961 can also be found in 1981." Economic, social, and religious factors related to these fertility trends are noted (SUMMARY IN ENG)


Drug intake and plasma concentrations in acute asthma.
Drug intake and plasma concentrations of theophylline and beta-agonists were recorded in 19 patients with acute asthma (peak expiratory flow rate less than 50% of predicted normal value and heart rate greater than 100 beats/min). 10 of the patients arrived at the hospital twice; accordingly 29 cases of acute asthma were studied. The results show that few patients overdosed their medicine before arrival at the hospital. On the contrary, they were often undertreated. This was verified both by plasma concentrations and drug intake reported by the patients. There was a poor correlation between plasma concentrations and drug intake in 14% of the 29 patient admissions.


The effect of radiotherapy, and radiotherapy combined with bisphosphonates or RANK ligand inhibitors on bone quality in bone metastases. A systematic review.
The role of radiotherapy in stabilizing metastatic bones is unclear. This systematic review assessed the effects of (1) radiotherapy, (2) radiotherapy combined with bisphosphonates, and (3) radiotherapy combined with RANK ligand (RANKL) inhibitors on bone quality and bone strength in bone metastases originating from solid tumors. Pubmed, EMBASE and the Cochrane Library were searched. Any type of study design and type and dose of radiotherapy, bisphosphonates and RANKL inhibitors were allowed. 39 articles were identified. Animal studies showed that radiotherapy had similar effects on bone quality and strength as receiving no treatment, whereas adding bisphosphonates to radiotherapy restored bone quality and strength. In patient studies, bone density increased after radiotherapy and radiotherapy combined with bisphosphonates. However, due to the often non-optimal study design and study quality, it was unclear whether this increase could be attributed to these treatments. There was insufficient evidence to assess the additional effect of bisphosphonates or RANKL inhibitors. Despite the clinical experience that radiotherapy is an effective treatment for bone metastases, there was no sufficient evidence for a positive effect on bone quality and fracture risk. Animal studies showed that adding bisphosphonates to radiotherapy restored bone quality and strength, whereas this was not proven in patients. There were no studies addressing the adjunct effect of RANKL inhibitors to radiotherapy. Although associated with several methodological, practical and ethical challenges, randomized controlled trials are needed.


Evaluation of nipple discharge cytology and diagnostic value of red blood cells in cases with negative cytology: a cytohistologic correlation.
To evaluate the sensitivity and specificity of nipple discharge cytology and to determine the diagnostic value of the presence of red blood cells (RBCs) in cases with negative cytology. Samples were received either as air-dried or alcohol-fixed slides. All cytology cases were reported by cytopathologists in the Hammersmith Pathology Department. We identified 98 consecutive female patients with nipple discharge cytology in the Hammersmith and Charing Cross hospitals during the period of May 2007 to May 2009. The cytodiagnoses were as follows: 86 cases had negative cytology, 9 cases were C3 (atypia but likely benign), and 3 cases were suspicious for or consistent with malignancy. Thirty of these cases had subsequent biopsy and showed: 9 benign cases, 3 cases with atypical papilloma and 3 cases with a malignant diagnosis (in situ and/or invasive ductal carcinoma). All suspicious and malignant cases with available macroscopic description (whether positive or negative on nipple discharge cytology) were blood stained and on microscopy contained RBCs. Nipple discharge cytology is a useful method in the diagnosis of malignant and suspicious cases. Further evaluation is needed to assess the value of the presence of RBCs in cases with negative cytology and its correlation with a subsequent diagnosis of malignancy.


Development of public health nursing competencies: an oral history.
This paper identifies the external and internal forces that led to the initiation and completion of a set of Public Health Nursing (PHN) competencies by nursing representatives from the Quad Council (QC) organizations: the Association of Community Health Nursing Educators, the American Public Health Association/Public Health Nursing Section, the Association of State and Territorial Directors of Nursing, and the American Nurses Association Congress on Nursing Practice and Economics. Discussion on the need for competencies began in 1988 with the Institute of Medicine report, The Future of Public Health, which cited a widening gap between the education and practice of public health (PH). PH leaders promptly responded by initiating many interactions to improve academic programs and enhance workforce development, including the development of competencies for PH professionals. PHN responded through the Quad Council of Public Health Nursing Organizations, which completed development of a set of national PHN competencies in 2003. The unfolding of that process is reported from the content-specific oral histories of five PHN leaders who served on the QC and participated in developing the PHN competencies.


Identification of Vertebral Fractures by Convolutional Neural Networks to Predict Nonvertebral and Hip Fractures: A Registry-based Cohort Study of Dual X-ray Absorptiometry.
Background Detection of vertebral fractures (VFs) aids in management of osteoporosis and targeting of fracture prevention therapies. Purpose To determine whether convolutional neural networks (CNNs) can be trained to identify VFs at VF assessment (VFA) performed with dual-energy x-ray absorptiometry and if VFs identified by CNNs confer a similar prognosis compared with the expert reader reference standard. Materials and Methods In this retrospective study, 12 742 routine clinical VFA images obtained from February 2010 to December 2017 and reported as VF present or absent were used for CNN training and testing. All reporting physicians were diagnostic imaging specialists with at least 10 years of experience. Randomly selected training and validation sets were used to produce a CNN ensemble that calculates VF probability. A test set (30%; 3822 images) was used to assess CNN agreement with the human expert reader reference standard and CNN prediction of incident non-VFs. Statistical analyses included area under the receiver operating characteristic curve, two-tailed Student t tests, prevalence- and bias-adjusted κ value, Kaplan-Meier curves, and Cox proportional hazard models. Results This study included 12 742 patients (mean age, 76 years ± 7; 12 013 women). The CNN ensemble demonstrated an area under the receiver operating characteristic curve of 0.94 (95% confidence interval [CI]: 0.93, 0.95) for VF detection that corresponded to sensitivity of 87.4% (534 of 611), specificity of 88.4% (2838 of 3211), and prevalence- and bias-adjusted κ value of 0.77. On the basis of incident fracture data available for 2813 patients (mean follow up, 3.7 years), hazard ratios adjusted for baseline fracture probability were 1.7 (95% CI: 1.3, 2.2) for CNN versus 1.8 (95% CI: 1.3, 2.3) for expert reader-detected VFs for incident non-VF and 2.3 (95% CI: 1.5, 3.5) versus 2.4 (95% CI: 1.5, 3.7) for incident hip fracture. Conclusion Convolutional neural networks can identify vertebral fractures on vertebral fracture assessment images with high accuracy, and these convolutional neural network-identified vertebral fractures predict clinical fracture outcomes. © RSNA, 2019 Online supplemental material is available for this article.


[Z-DNA and autoimmune derangement].
The Z conformation of DNA seems closely related to postulated pathogenetic mechanisms of autoimmune complaints like systemic lupus erythematosus (SLE). The following findings are of importance: 1. Z DNA occurs under physiological conditions. 2. Z DNA is likely to be a target of polymerases. 3. Z DNA is immunogen. 4. Antibodies to Z DNA have been detected in both, murine and human SLE.


Studies of native glycogen isolated from synchronized Tetrahymena pyriformis (HSM).
Native glycogen was isolated from Tetrahymena pyriformis (HSM) by isopycnic centrifugation in cesium chloride density gradients. A density of 1.62 to 1.65 was isopycnic for glycogen. Most of the banded glycogen existed as 35 to 40 mmicro particles which had a sedimentation coefficient of 214. These particles were composed of aggregates of 2 to 3 mmicro spherical particles. Extraction of glycogen with hot alkali reduced the sedimentation coefficient of native glycogen from 214 to 64.7 and the particle diameter from approximately 40 to 20 mmicro and smaller. Cell division was synchronized by a repetitive 12-hour temperature cycle, and glycogen was measured at several times during the cell cycle. The temperature cycle consisted of 9.5 hours at 12 degrees C and 2.5 hours at 27 degrees C. Approximately 90 per cent of the cells divided during the last 1.5 hours of the warm period. The carbohydrate/protein ratio of cells at the end of the cold period was 0.27 and was reduced slightly during the warm period. Glucose was incorporated into glycogen during both periods, although the rate of incorporation was greater during the warm period. No preferential incorporation on the basis of particle size was noted. Incorporation was measured in both native glycogen and KOH-extracted glycogen. Tetrahymena glycogen is compared with rat liver glycogen previously isolated by similar procedures, and the significance of using combined rate-zonal and isopycnic centrifugation for isolating native glycogen is discussed.


Should we be targeting sleep architecture to more effectively treat schizophrenia?
The sleep architecture (or sleep kinetics) of schizophrenia is different from that of other mental illnesses, including major depressive disorder. However, clinicians rarely consider these parameters in clinical settings during treatment. This article discusses the use of polysomnography to characterize the sleeping patterns of patients diagnosed with schizophrenia and the positive influence of clozapine on sleep in patients with schizophrenia.


Development of a rotavirus vaccine: clinical safety, immunogenicity, and efficacy of the pentavalent rotavirus vaccine, RotaTeq.
Initial approaches for rotavirus vaccines were based on the classical "Jennerian" approach and utilized simian and bovine rotavirus strains, which provided cross-protection against human rotavirus strains but did not cause illness in infants and young children because of their species-specific tropism. The demonstrated efficacy of these vaccines was not consistent across studies. Thus, human-animal reassortants containing an animal rotavirus backbone with human rotavirus surface G and/or P proteins were developed, which demonstrated more consistent efficacy than that observed with the non-reassortant rotavirus strains. The pentavalent rotavirus vaccine, RotaTeq, contains 5 human-bovine reassortant rotaviruses consisting of a bovine (WC3) backbone with human rotavirus surface proteins representative of the most common G (G1, G2, G3, G4) or P (P1A[8]) types worldwide. The present review focuses on the development of the pentavalent rotavirus vaccine RotaTeq. Results of a large-scale Phase III clinical study showed that three doses of RotaTeq were immunogenic, efficacious, and well tolerated with no increased clinical risk of intussusception. RotaTeq was efficacious against rotavirus gastroenteritis of any severity (74%) and severe disease (98-100%), using a validated clinical scoring system. Reductions in rotavirus-associated hospitalizations and emergency department (ED) visits, for up to 2 years post-vaccination, were 95% in Europe, 97% in the United States, and 90% in the Latin American/Caribbean regions. RotaTeq was recently shown to be up to 100% effective in routine use in the US in reducing hospitalizations and ED visits and 96% effective in reducing physician visits. Additional studies in 8 different locations in the US have shown 85-95% reduction in rotavirus-associated hospitalizations and/or ED visits in the first 2-2.5 years of routine use.


BOS MOrth cases prize 2008.
This paper describes the clinical orthodontic treatment of two cases that were successfully entered for the 2008 intercollegiate MOrth cases prize. The first case describes the management of a 12-year-old female with an increased overjet treated using a Dynamax functional appliance followed by fixed appliances. The second case involves the management of a class II division I malocclusion complicated by an unerupted maxillary central incisor and a mandibular first molar of poor prognosis.


Electrolytic deposition of lithium into calcium phosphate coatings.
Lithium ions stimulate the Wnt signaling pathway and the authors previously demonstrated that lithium enhances the proliferation of tissue cultured human mesenchymal stem cells. The aim of this study was to prepare and characterize a calcium phosphate/lithium coating by means of electrolytic deposition. It was hypothesized that the hybrid coatings would enhance the proliferation of MG63 osteoblast-like cells in vitro. Calcium phosphate coatings were electrolytically deposited in electrolytes containing 0, 0.5 and 5g/L lithium chloride, respectively. They were characterized by scanning electron microscopy, X-ray diffraction, and Fourier transform infrared spectroscopy. The coating thickness, lithium content and release profile were also measured. The cell attachment and cell-doubling index of MG63 cells on these coatings were determined through a Cell Counting Kit-8. Lithium inhibited calcium phosphate deposition in a dose-dependent manner. Both crystallinity and thickness of the coatings were reduced with increasing lithium concentration in the electrolyte. The incorporation of lithium was 2.2 and 5.5microg/mg, respectively. The hybrid coatings demonstrated a burst lithium release within half an hour upon immersion into simulated physiological solution. Both attachment and early proliferation of MG63 cells on these hybrid coatings were enhanced. These results suggest that lithium can be effectively incorporated into calcium phosphate coatings. The incorporation of lithium interferes with calcium phosphate deposition; however, it enhances the biocompatibility of the coatings.


Biochemical Adaptations in a Slow and a Fast Plantarflexor Muscle of Rats Housed in Small Cages.
Chronic unloading and restricted activity are distinctly different processes, i.e., unloading completely removes the load on postural muscles, whereas restricted activity allows for loading of postural muscles. There are limited data available on the effects of restricted activity on skeletal muscles. Thus the effects of restricted activity on the properties of the slow soleus and fast plantaris muscles in rats were examined. Eight-week-old rats were housed for 21 d in normal-sized (control group) or in small-sized (restricted group) cages. Decreased mRNA levels of peroxisome proliferator-activated receptor γ coactivator-1α (81 and 85% of control values) and reduced succinate dehydrogenase activity (85 and 88% of control values) were observed in the soleus and the plantaris muscles of the restricted group, respectively. Increased mRNA levels of forkhead box-containing protein O1 (128% of control values), decreased muscle weight (74% of control values), and reduced cross-sectional areas of type IIA (89% of control values) and type IIB (80% of control values) fibers were observed in the plantaris muscle of the restricted group. Restricted activity decreased the mRNA levels of peroxisome proliferator-activated receptor γ coactivator-1α and increased the mRNA levels of forkhead box-containing protein O1, which are associated with reduced oxidative capacity and atrophy, respectively, in the muscles. The plantaris muscle was more affected by restricted activity than the soleus muscle, most likely reflecting a greater relative change in the normal activity pattern in the fast than slow plantarflexor muscle. Takemura A, Roy RR, Edgerton VR, Ishihara A. Biochemical adaptations in a slow and a fast plantarflexor muscle of rats housed in small cages.


Role of the gap junction in ischemic preconditioning in the heart.
The gap junction plays roles not only in electrical coupling of cardiomyocytes but also in intercellular transport of biologically active substances. Furthermore, the gap junction participates in decision making on cell survival versus cell death in various types of cells, and a part of reperfusion injury in the heart has been indicated to be gap junction mediated. The contribution of gap junction communication (GJC) and/or mitochondrial "hemichannels" to protective signaling during the trigger phase of ischemic preconditioning (IPC) is suggested by observations that IPC failed to protect the heart when GJC was blocked during IPC. Although ischemia suppresses both electrical and chemical GJC, chemical GJC persists for a considerable time after electrical GJC is lost. IPC facilitates the ischemia-induced suppression of chemical GJC, whereas IPC delays the reduction of electrical GJC after ischemia. The inhibition of GJC during sustained ischemia and reperfusion by GJC blockers mimics the effect of IPC on myocardial necrosis. IPC induces distinct effects on the interaction of connexin-43 with protein kinases, and the phosphorylation of connexin-43 at Ser368 by PKCepsilon is a primary mechanism of inhibition of chemical GJC by IPC. Several lines of evidence support the notion that the modulation of GJC is a part of the mechanism of IPC-induced protection against myocardial necrosis and arrhythmias, though what percentage of IPC protection is attributable to the inhibition of GJC during ischemia-reperfusion still remains unclear.


Differential involvement of IFN-beta in Toll-like receptor-stimulated dendritic cell activation.
Toll-like receptor (TLR) can activate dendritic cells (DC) through common signaling pathways requiring a cytoplasmic adapter, MyD88. However, the signaling is differentially regulated among TLR family members. TLR4 can activate MyD88-deficient bone marrow-derived DC (BMDC), and lead to induction of IFN-inducible genes and up-regulation of co-stimulatory molecules such as CD40, implying that the MyD88-independent signaling pathway functions downstream of TLR4. Because these effects can also be induced by type I IFN, we have analyzed whether type I IFN is involved in TLR4-induced responses. In response to lipopolysaccharide (LPS), IFN-beta gene expression was augmented in both wild-type and MyD88-deficient BMDC. Expression of all IFN-inducible genes except immune-responsive gene 1 (IRG1) was abolished and CD40 up-regulation was decreased in LPS-stimulated BMDC lacking either IFN-alpha/beta receptor (IFN-alpha/betaR) or signal transducer and activator of transcription 1 (STAT-1). Similar to the LPS response, TLR9 signaling can also induce expression of IFN-beta and IFN-inducible genes, and up-regulation of CD40. However, all these effects were MyD88 dependent. Thus, in TLR4 signaling, IFN-beta expression can be induced either by the MyD88-dependent or -independent pathway, whereas, in TLR9 signaling, it is dependent on MyD88. In CpG DNA-stimulated DC, expression of IFN-inducible genes except IRG1 was dependent on type I IFN signaling as in LPS-stimulated DC. However, in contrast to TLR4 signaling, TLR9 signaling requires type I IFN signaling for CD40 up-regulation. Taken together, this study demonstrates differential involvement of type I IFN in TLR4- and TLR9-induced effects on DC.


Clinical predictors of shockable versus non-shockable rhythms in patients with out-of-hospital cardiac arrest.
To identify factors associated with a non-shockable rhythm as first recorded heart rhythm. Patients ≥18 years old suffering out-of-hospital cardiac arrest between 2001 and 2012 were identified in the population-based Danish Cardiac Arrest Registry. Danish administrative registries were used to identify chronic diseases (within 10 years) and drug prescriptions (within 180 days). A multivariable logistic regression model, including patient related and cardiac arrest related characteristics, was used to estimate odds ratios (OR) for factors associated with non-shockable rhythm. A total of 29,863 patients were included: 6600 (22.1%) patients with a shockable rhythm and 23,263 (77.9%) patients with a non-shockable rhythm. A non-shockable rhythm was associated with female gender, arrest in private home, unwitnessed arrest, no bystander CPR, and longer time to first rhythm analysis compared to patients with shockable rhythm. In the adjusted multivariable regression model, pre-existing non-cardiovascular disease and drug prescription were associated with a non-shockable rhythm e.g. chronic obstructive lung disease (OR 1.44 [95% CI: 1.32-1.58]); and the prescription for antidepressants (OR 1.49 [95% CI: 1.35-1.65]), antipsychotics (OR 2.30 [95% CI: 1.96-2.69]) analgesics (OR 1.32 [95% CI: 1.23-1.41]), corticosteroids (OR 1.64 [95% CI: 1.44-1.85]), and antibiotics (OR 1.59 [95% CI: 1.40-1.81]). In contrast, the prescription of cardiovascular drugs and a history of cardiovascular disease e.g. ischemic heart disease was associated with a lower risk of non-shockable rhythm (OR 0.66 [95% CI: 0.60-0.71]). This study demonstrate that non-cardiovascular disease and medication prescription are associated with a non-shockable rhythm while cardiovascular disease and medication prescription are associated with a shockable rhythm as first recorded rhythm in patients with OHCA.


Studying in vitro metabolism of the first and second generation of antisense oligonucleotides with the use of ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry.
The aim of the present investigation was the analysis and identification of antisense oligonucleotide metabolism products after incubation with human liver microsomes regarding four different oligonucleotide modifications. Separation and detection methods based on the use of liquid chromatography coupled with quadrupole time-of-flight mass spectrometry were developed for this purpose. Firstly, the optimization of mass spectrometer parameters was done to select those which ensure the highest possible sensitivity of oligonucleotide analysis. This step was conducted for two chromatographic modes-ion pair chromatography and hydrophilic interaction liquid chromatography-due to their common application in oligonucleotide analysis. Based on sensitivity results, ion pair chromatography coupled with mass spectrometry was selected for the separation of model oligonucleotide mixtures in order to verify its selectivity for N-deleted metabolite separation. Next, the developed method was applied in the examination of oligonucleotides in vitro metabolism. First, wide optimization of incubation parameters was conducted including the concentration of the reaction buffer components. Obtained results indicated that both 3'-exonucleases and 5'-exonucleases contributed to the biotransformation of oligonucleotides. Moreover, it may be concluded that the number of metabolites depends on oligonucleotide modification and consequently its resistance to enzymatic attack. Thus, the number of the oligonucleotide metabolites decreased with the decrease of the resultant polarity of oligonucleotide caused by chemical modification. Graphical abstract.


The influences of recovery on low back pain development: A theoretical model.
Psychologically and physically straining work conditions increase the risk of low back pain (LBP) development. According to recent recovery theories, leisure time recovery can counteract the negative influences of work stress on health. Similarly, a recent empirical work has indicated a moderating role of recovery on the link between stress and health issues. In this paper, a theoretical model is deduced to integrate the moderating effects of recovery on work stress and LBP development. Based on theoretical and empirical results, 2 separate recovery paths are distinguished: on the one hand, recovery can prevent the experience of stress because a well-recovered person can cope more easily with work demands; while on the other hand, recovery refills the depleted resources after confrontation with work strain and reduces stress experiences. Given that work strains is a main risk factor for LBP development, recovery in leisure time seems to be a highly relevant aspect, which has not been investigated to date in the field of LBP.


Regulation of gene expression and cellular localization of prostaglandin synthase by oestrogen and progesterone in the ovine uterus.
Expression of the gene for prostaglandin synthase (PGS) was examined in whole endometrial tissue derived from ewes during the oestrous cycle (Days 4-14), on Day 15 of pregnancy and following ovariectomy and treatment with ovarian steroid hormones. Whilst no significant differences were seen in PGS mRNA concentrations analysed by Northern blot analysis in endometrial tissue during the oestrous cycle or in early pregnancy, treatment of ovariectomized (OVX) ewes with oestradiol-17 beta markedly reduced endometrial PGS mRNA concentration. There was no difference in PGS mRNA concentration in ewes treated with progesterone, either alone or in conjunction with oestrogen, from that in OVX controls. In contrast, differences in immunolocalization of PGS observed in uterine tissue from OVX-steroid-treated ewes were much more marked and reflected similar changes seen previously in the immunocytochemical distribution of endometrial PGS during the oestrous cycle. In OVX ewes and those treated with oestrogen, immunocytochemical staining for PGS was seen in stromal cells, but little immunoreactive PGS was located in the endometrial epithelial cells. However, in ewes treated with progesterone alone or with oestrogen plus progesterone, PGS was found in luminal and glandular epithelial cells and in stromal cells. Intensity of immunostaining for PGS in endothelial cells and myometrium did not differ between the treatments. Thus, whilst oestrogen lowers PGS mRNA in the endometrium, presumably in stroma, it may also increase the stability of the enzyme itself in the stromal cells. Although oestradiol-17 beta has no effect on PGS in endometrial epithelium, progesterone stimulates the production of PGS in endometrial epithelial cells without altering the overall abundance of PGS mRNA in the endometrium as a whole. Conceptus-induced changes in PGF-2 alpha release by ovine endometrium would not appear to be mediated via effects on PGS gene expression or protein synthesis.


Molecular approximation between residue 10 of secretin and its receptor demonstrated by photoaffinity labeling.
Using photoaffinity labeling, we have previously explored the molecular approximations between multiple positions of secretin and its receptor. Interestingly, the amino-terminal secretin probe incorporating a photolabile residue in position 1 labels the top of the sixth transmembrane domain of the receptor, whereas other probes with photolabile residue in positions 6, 12, 13, 14, 18, 22, and 26 all label the long amino-terminal domain of the secretin receptor. Recently, we have developed a secretin probe that incorporated a radioiodinatable photolabile p-(4-hydroxybenzoyl)phenylalanine in position 10 and demonstrated that it efficiently labeled the secretin receptor in a saturable and specific manner. In this work, we attempted to further map its domain of labeling by cyanogen bromide (CNBr) cleavage of the wild-type and mutant receptors. Surprisingly, this position 10 probe labeled the top of the sixth transmembrane domain of the receptor, a domain labeled by the position 1 probe. These data provide an important constraint for modeling the agonist-bound G protein-coupled secretin receptor and should add substantially to our current understanding of the molecular basis of ligand binding of this important receptor.


Dynamics of pattern coarsening in a two-dimensional smectic system.
We have followed the coarsening dynamics of a single layer of cylindrical block copolymer microdomains in a thin film. This system has the symmetry of a two-dimensional smectic. The orientational correlation length of the microdomains was measured by scanning electron microscopy and found to grow with the average spacing between +/-1/2 disclinations, following a power law xi2(t) approximately t(1/4). By tracking disclinations during annealing with time-lapse atomic force microscopy, we observe dominant mechanisms of disclination annihilation involving tripoles and quadrupoles (three and four disclinations, respectively). We describe how annihilation events involving multiple disclinations result in similarly reduced kinetic exponents as observed here. These results map onto a wide variety of physical systems that exhibit similarly striped patterns.


Prognostic relevance of CD56 expression in multiple myeloma: a study including 107 cases treated with high-dose melphalan-based chemotherapy and autologous stem cell transplant.
CD56 is a neural adhesion molecule and expressed in 70-80% cases of multiple myeloma (MM). Lack of CD56 expression has shown to be a poor prognosis in MM patients treated with conventional chemotherapy, but its prognostic relevance in MM treated with high dose chemotherapy and autologous stem cell transplant (ASCT) is not known. CD56 expression was evaluated by immunohistochemistry on bone marrow paraffin embed specimens from 107 MM cases undergoing Melphalan-based high dose therapy and ASCT. CD56 was expressed by the myeloma cells in 71% of the patients. CD56 negative myeloma was associated with bone lesions (p = 0.032), but there was no association with any other biological or genetic risk factors including deletions 13q, p53 and IgH translocations, as evaluated by fluorescence in situ hybridization (FISH). There was no significant difference between CD56 positive and CD56 negative myeloma for progression free or overall survival (p = 0.28 and p = 0.67, respectively). In contrast to reports of CD56 in myeloma treated with conventional chemotherapy, CD56 negativity was not found to confer a poor prognosis in these patients, suggesting Melphalan-based high-dose chemotherapy and ASCT may overcome the adverse influence of CD56 negative myeloma.


Stickler Syndrome: A Review of Clinical Manifestations and the Genetics Evaluation.
Stickler Syndrome (SS) is a multisystem collagenopathy frequently encountered by ophthalmologists due to the high rate of ocular complications. Affected individuals are at significantly increased risk for retinal detachment and blindness, and early detection and diagnosis are critical in improving visual outcomes for these patients. Systemic findings are also common, with craniofacial, skeletal, and auditory systems often involved. SS is genotypically and phenotypically heterogenous, which can make recognizing and correctly diagnosing individuals difficult. Molecular genetic testing should be considered in all individuals with suspected SS, as diagnosis not only assists in treatment and management of the patient but may also help identify other at-risk family members. Here we review common clinical manifestation of SS and genetic tests frequently ordered as part of the SS evaluation.


Capillaroscopic skin ulcer risk index: a new prognostic tool for digital skin ulcer development in systemic sclerosis patients.
Digital ulcerations are one of the most frequent manifestations of microangiopathy in patients with systemic sclerosis (SSc; scleroderma). The early detection of SSc patients who are at high risk to develop digital ulcers could allow a preventive treatment of these complications with reduction of morbidity and social costs. The aim of our study was to develop a capillaroscopic skin ulcer risk index (CSURI) that can predict the onset of new digital ulcers by using nailfold videocapillaroscopy (NVC) in patients with SSc. We performed NVC in 120 consecutive unselected patients with SSc (13 men, 107 women, mean +/- SD age 56.1 +/- 13.4 years, mean +/- SD SSc duration 44.7 +/- 60.7 months) to assess the total number of capillaries in the distal row (N), maximum loop diameter (D), number of megacapillaries (M), and the M:N ratio. Within 3 months since NVC examination, 35 of 120 patients experienced digital ulcers. A significant association between ischemic lesions and the M:N ratio, N, and D was observed; the combination of these parameters allowed us to develop the CSURI, which is characterized by the formula D x M:N(2). A receiver operating characteristic curve analysis showed an area under the curve of 0.926 for ulcer appearance, with specificity and sensitivity of 85.9% and 94.3%, respectively, at the cutoff value of 2.94. Interestingly, 33 of 35 patients with new skin ulcers had a CSURI >2.94, but only 2 of 35 had a CSURI < or =2.94. The proposed CSURI may represent a novel tool with the ability to predict the development of digital ulcers in patients with scleroderma.


Imaging features of posttransplantation lymphoproliferative disorder in pancreas transplant recipients.
The purpose of this study was to describe the imaging features of posttransplant lymphoproliferative disorder (PTLD) in pancreas transplant recipients. The prominent image finding of PTLD in pancreas transplant recipients is diffuse allograft enlargement, an appearance that may be indistinguishable from the image findings of acute pancreatitis or transplant rejection. However, failure of response to immunosuppressive therapy, presence of intraallograft or extraallograft focal masses, or organomegaly may suggest the diagnosis of PTLD.


Strandwise translocation of a DNA glycosylase on undamaged DNA.
Base excision repair of genotoxic nucleobase lesions in the genome is critically dependent upon the ability of DNA glycosylases to locate rare sites of damage embedded in a vast excess of undamaged DNA, using only thermal energy to fuel the search process. Considerable interest surrounds the question of how DNA glycosylases translocate efficiently along DNA while maintaining their vigilance for target damaged sites. Here, we report the observation of strandwise translocation of 8-oxoguanine DNA glycosylase, MutM, along undamaged DNA. In these complexes, the protein is observed to translocate by one nucleotide on one strand while remaining untranslocated on the complementary strand. We further report that alterations of single base-pairs or a single amino acid substitution (R112A) can induce strandwise translocation. Molecular dynamics simulations confirm that MutM can translocate along DNA in a strandwise fashion. These observations reveal a previously unobserved mode of movement for a DNA-binding protein along the surface of DNA.


A Review on the Role of Ethylenediaminetetraacetic Acid (EDTA) in the Treatment and Understanding of Psoriasis.
Psoriasis is a long-term, autoimmune inflammatory condition characterized by red, scaly plaques that can range from a few patches to total skin coverage. Over the past 60 years, and more recently, the metal-chelating agent ethylenediaminetetraacetic acid (EDTA) has proven increasingly useful in the treatment and understanding of psoriasis and related conditions. This review will analyze the current role and effectiveness of EDTA in clinical and non-clinical studies designed to improve the diagnosis and treatment of psoriasis in patients. Currently, EDTA demonstrates great medical benefit in the treatment of psoriasis as an antioxidant and as an inhibitor of beta-lipoprotein production. EDTA additionally functions well in research applications due to its ability to maintain red blood cell structural integrity. The authors find that the perceived impact of EDTA in the understanding and combating of psoriasis to be greatly underestimated and is therefore in need of increased awareness and attention by healthcare professionals, dermatologists, and clinical researchers.


Comparison of Perineal Sonographically Measured and Functional Urodynamic Urethral Length in Female Urinary Incontinence.
Objectives. To detect the anatomical insufficiency of the urethra and to propose perineal ultrasound as a useful, noninvasive tool for the evaluation of incontinence, we compared the anatomical length of the urethra with the urodynamic functional urethral length. We also compared the urethral length between continent and incontinent females. Methods. 149 female patients were enrolled and divided into four groups (stress, urge, or mixed incontinence; control). Sonographically measured urethral length (SUL) and urodynamic functional urethral length (FUL) were analyzed statistically. Standardized and internationally validated incontinence questionnaire ICIQ-SF results were compared between each patient group. Results. Perineal SUL was significantly longer in incontinent compared to continent patients (p < 0.0001). Pairwise comparison of each incontinent type (stress, urge, or mixed incontinence) with the control group showed also a significant difference (p < 0.05). FUL was significantly shorter in incontinent patients than in the control group (p = 0.0112). But pairwise comparison showed only a significant difference for the stress incontinence group compared with the control group (p = 0.0084) and not for the urge or mixed incontinent group. No clear correlation between SUL, FUL, and ICIQ-SF score was found. Conclusions. SUL measured by noninvasive perineal ultrasound is a suitable parameter in the assessment of female incontinence, since incontinent women show a significantly elongated urethra as a sign of tissue insufficiency, independent of the type of incontinence.


Microfluidic Migration and Wound Healing Assay Based on Mechanically Induced Injuries of Defined and Highly Reproducible Areas.
All cell migration and wound healing assays are based on the inherent ability of adherent cells to move into adjacent cell-free areas, thus providing information on cell culture viability, cellular mechanisms and multicellular movements. Despite their widespread use for toxicological screening, biomedical research and pharmaceutical studies, to date no satisfactory technological solutions are available for the automated, miniaturized and integrated induction of defined wound areas. To bridge this technological gap, we have developed a lab-on-a-chip capable of mechanically inducing circular cell-free areas within confluent cell layers. The microdevices were fabricated using off-stoichiometric thiol-ene-epoxy (OSTEMER) polymer resulting in hard-polymer devices that are robust, cost-effective and disposable. We show that the pneumatically controlled membrane deflection/compression method not only generates highly reproducible (RSD 4%) injuries but also allows for repeated wounding in microfluidic environments. Performance analysis demonstrated that applied surface coating remains intact even after multiple wounding, while cell debris is simultaneously removed using laminar flow conditions. Furthermore, only a few injured cells were found along the edge of the circular cell-free areas, thus allowing reliable and reproducible cell migration of a wide range of surface sensitive anchorage dependent cell types. Practical application is demonstrated by investigating healing progression and endothelial cell migration in the absence and presence of an inflammatory cytokine (TNF-α) and a well-known cell proliferation inhibitor (mitomycin-C).


Pre-eclampsia, severe pre-eclampsia and hemolysis, elevated liver enzymes and low platelets syndrome: what is new?
Pre-eclampsia and eclampsia have been known to us for centuries. Significant improvements have been made in our knowledge of the disease, however, delivery remains the only effective form of treatment. There is widespread variation of practice in the management of hypertensive disease in pregnancy, which may lead to substandard care. The use of aspirin in preventing pre-eclampsia, the lack of correlation between urinary protein and adverse outcome, and the ineffectiveness of corticosteroids in the management of hemolysis and elevated liver enzymes and low platelets syndrome are a few of the developments that will alter the way this condition is managed. This article aims to provide a general overview of pre-eclampsia, eclampsia and hemolysis, hemolysis and elevated liver enzymes and low platelets syndrome supported by the latest evidence, which will help the care provider adopt a focused approach and use the latest knowledge to understand and manage this old condition.


An ATP-Binding Cassette Transporter, ABCB19, Regulates Leaf Position and Morphology during Phototropin1-Mediated Blue Light Responses.
Blue light regulates multiple processes that optimize light capture and gas exchange in plants, including chloroplast movement, changes in stomatal conductance, and altered organ positioning. In Arabidopsis (Arabidopsis thaliana), these processes are primarily modulated by the blue light phototropin photoreceptors phot1 and phot2. Changes in leaf positioning and shape involve several signaling components that include NON-PHOTOTROPIC HYPOCOTYL3, PHYTOCHROME KINASE SUBSTRATE, ROOT PHOTOTROPISM2, and alterations in localized auxin streams. Direct phosphorylation of the auxin transporter ATP-BINDING CASSETTE subfamily B19 (ABCB19) by phot1 in phototropic seedlings suggests that phot1 may directly regulate ABCB19 to adjust auxin-dependent leaf responses. Here, abcb19 mutants were analyzed for fluence and blue light-dependent changes in leaf positioning and morphology. abcb19 displays upright petiole angles that remain unchanged in response to red and blue light. Similarly, abcb19 mutants develop irregularly wavy rosette leaves that are less sensitive to blue light-mediated leaf flattening. Visualization of auxin distribution, measurement of auxin transport in protoplasts, and direct quantification of free auxin levels suggest these irregularities are caused by misregulation of ABCB19-mediated auxin distribution in addition to light-dependent auxin biosynthesis.


Enlarging cystic lymphangioma of the mediastinum in an adult: is this a neoplastic lesion related to the recently discovered PIK3CA mutation?
Cystic lymphangioma, a lymphatic system malformation, is usually observed in infants and children and is rarely found in adults. It most commonly occurs in the cervicofacial region, followed by the axilla. Mediastinal cystic lymphangioma is rare, accounting for 1.8% of all mediastinal cysts. Herein, we present an exceedingly rare adult case of mediastinal cystic lymphangioma that had increased in size over a 5-year period. Although fluid collection might be an alternative explanation for this increase in size, this lymphangioma might harbor a neoplastic nature related to the recently discovered PIK3CA mutation.


Main component assay of pharmaceuticals by capillary electrophoresis: considerations regarding precision, accuracy, and linearity data.
Capillary electrophoresis has been successfully employed to determine the level of drugs in a variety of pharmaceutical preparations. A large number of reports have shown agreement between CE results and HPLC data or with label claim. Currently the use of CE for main component assays constitutes 26% of the routine usage of CE within drug companies and is the most frequent application. The choice between adopting CE or HPLC for a particular application is very dependent upon the relative merits of each technique to the individual assay. Often, CE can have advantages in terms of reduced sample pretreatment, consumable costs, and analysis time. The ability to separate a wide range of solutes using a single set of operating conditions is a strong advantage of CE. This paper extensively reviews the literature reports of the use of CE for main peak assay and indicates the validation performance data achieved. The specific requirements relating to optimized accuracy and precision in CE assay are discussed in some detail. The use of an appropriate internal standard to improve performance for precision, accuracy, and linearity, and to reduce the impact of sample matrix effects, is experimentally shown by results from the analysis of levothyroxine samples. The applications are subdivided into those samples analyzed by free solution capillary electrophoresis (FSCE) at low or high pH or those separated by micellar electrokinetic capillary electrophoresis (MECC).


Simultaneous interferometric measurement of linear coefficient of thermal expansion and temperature-dependent refractive index coefficient of optical materials.
Characterizing the thermal properties of optical materials is necessary for understanding how to design an optical system for changing environmental conditions. A method is presented for simultaneously measuring both the linear coefficient of thermal expansion and the temperature-dependent refractive index coefficient of a sample interferometrically in air. Both the design and fabrication of the interferometer is presented as well as a discussion of the results of measuring both a steel and a CaF2 sample.


Phone-based interventions to control gestational weight gain: a systematic review on features and effects.
Objective: The aim of this study was to summarize the evidence regarding the effects and the features of phone-based interventions to control gestational weight gain (GWG).Methods: We included studies that evaluated the effects of phone-based interventions on controlling GWG. The characteristics of studies, effects, and features of interventions were extracted.Results: A total of 12 studies met the inclusion criteria. Outcomes were categorized into three groups (GWG control, proportion of women returning to pre-pregnancy weight, and proportion of women who exceeded the Institute of Medicine recommendations for GWG). Although most studies (66%) showed a statistically significant positive effect of phone-based interventions on the GWG control, the effects on the other outcome categories were found to be inconsistent. While the included studies used phone call and short messaging service (SMS), no study used the other functions of telephones and mobile phones such as video call, internet access, social networks, and smartphone applications. Regarding the functionalities, phone calls were used to provide guidance for healthy weight gain and communication with healthcare providers. SMS provided reminders, educational materials, and guidance.Conclusion: Phone-based interventions can help pregnant women control GWG by providing guidance, reminders, and educational materials. When these interventions use multiple functionalities, they are more effective in controlling GWG.


Smoke-free Ordinances and Youth Tobacco Use in Kentucky.
Determine associations of strength of local smoke-free laws and urban/rural location with cigarette and smokeless tobacco use among high school students in grades 10 and 12. Secondary data analysis from the 2004-2018 biennial Kentucky Incentives for Prevention Survey. Public high schools in Kentucky. N = 353502 10th/12th graders. County-level smoke-free law status from the Kentucky Center for Smoke-free Policy; Rural Urban Continuum Codes; self-reported last 30-day alcohol, marijuana, cigarette, and smokeless tobacco use. Generalized estimating equations modeling assessed the association of law status and urban/rural location with tobacco use across cohorts, controlling for demographics and other substance use. Students in counties with a comprehensive smoke-free law were 23% less likely to smoke cigarettes and 16% less likely to use smokeless, compared to those in counties without a law. Students in counties with moderate/weak laws did not differ in likelihood of use for either product, compared to those in counties without a law. Students in urban counties were 14% less likely to smoke, but there was no difference in likelihood of smokeless use by urban/rural location. Comprehensive smoke-free laws are associated with a lower likelihood of youth cigarette and smokeless use. Rural youth may be at increased risk of cigarette smoking relative to youth in urban areas.


Cloning, expression and characterization of 3-hydroxyisobutyrate dehydrogenase from Pseudomonas denitrificans ATCC 13867.
The gene encoding an NAD(+)-dependent, 3-hydroxyisobutyrate dehydrogenase (3HIBDH-IV) from Pseudomonas denitrificans ATCC 13867 was cloned and expressed in Escherichia coli BL 21 (DE3) and characterized to understand its physiological relevance in the degradation of 3-hydroxypropionic acid (3-HP). The deduced amino acid sequence showed high similarity to other 3-hydroxyisobutyrate dehydrogenase isozymes (3HIBDHs) of P. denitrificans ATCC 13867. A comparison of 3HIBDH-IV with its relevant enzymes along with molecular docking studies suggested that Lys171, Asn175 and Gly123 are important for its catalytic function on 3-hydroxyacids. The recombinant 3HIBDH-IV was purified to homogeneity utilizing a Ni-NTA-HP resin column in high yield. 3HIBDH-IV was very specific to (S)-3-hydroxyisobutyrate, but also catalyzed the oxidation of 3-HP to malonate semialdehyde. The specific activity and half-saturation constant (K m) for 3-HP at 30°C and pH 9.0 were determined to be 17 U/mg protein and 1.0 mM, respectively. Heavy metals, such as Ag(+) and Hg(2+), completely inhibited the 3HIBDH-IV activity, whereas dithiothreitol, 2-mercaptoethanol and ethylenediaminetetraacetic acid increased its activity 1.5-1.8-fold. This paper reports the characteristics of 3HIBDH-IV as well as its probable role in 3-HP degradation.