The protocol of DECO-MOM: a clinical trial testing the effectiveness of a mobile application for an environmental health intervention among pregnant women.
Environmental toxins are particularly harmful to pregnant women and their fetuses due to the long-term effects of these toxins on children after birth. Environmental health behaviors can prevent and protect mothers and their babies' environmental health. This study presents a protocol for a double-blinded randomized controlled trial to examine the effect of a mobile application named "DECO-MOM" (Deep ECOlogy-MOM) for pregnant women. This application contains content related to environmental perceptions and behaviors according to the revised protection motivation theory. The mobile intervention will be implemented for 4 weeks for 40 pregnant women with a gestational age in the first trimester. As the control group, 40 pregnant women will be recruited at public healthcare centers in Chuncheon and Gongju in South Korea. The hypothesis is that the experimental group will have higher scores for environmental perceptions and behaviors than the control group. An online survey administered before and after the intervention will contain outcome parameters including depression, stress, quality of life, e-learning satisfaction, environmental perceptions, and environmental behaviors. This study will elaborate a guide for an intervention to enhance the effects of the mobile application on strengthening environmental health perceptions, behaviors, e-learning satisfaction, and quality of life and curtailing depression and stress among pregnant women. Trial registration Number: KCT0007725, Registered September 22, 2022. Prospectively registered.


Tat-protein disulfide-isomerase A3: a possible candidate for preventing ischemic damage in the spinal cord.
In the present study, we searched for possible candidates that can prevent ischemic damage in the rabbit spinal cord. For this study, we used two-dimensional gel electrophoresis followed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, in sham- and ischemia-operated animals. As the level of protein disulfide-isomerase A3 (PDIA3) significantly decreased 3 h after ischemia/reperfusion, we further investigated its possible role against ischemic damage using an in vitro spinal cord cell line and in vivo spinal cord ischemic model. The administration of Tat-PDIA3 significantly reduced the hydrogen peroxide-induced formation of reactive oxygen species and cell death, based on terminal deoxynucleotidyl transferase-mediated biotinylated dUTP nick end labeling and a colorimetric WST-1 assay. Further, Tat-PDIA3 significantly ameliorated the ischemia-induced deficits in motor function, based on Tarlov's criteria, 24-72 h after ischemia/reperfusion, as well as the degeneration of motor neurons in the ventral horn 72 h after ischemia/reperfusion. Tat-PDIA3 administration also reduced the ischemia-induced activation of microglia and lipid peroxidation in the motor neurons 72 h after ischemia/reperfusion. PDIA3 also potentially ameliorated the ischemia-induced increase in oxidative markers in serum and decreased the activity of Cu,Zn-superoxide dismutase, Mn-superoxide dismutase, and glutathione peroxidase in spinal cord homogenates, 24 h and 72 h after ischemia/reperfusion. These results suggest that Tat-PDIA3 could be used to protect spinal cord neurons from ischemic damage, due to its modulatory action on the oxidative/anti-oxidative balance. Tat-PDIA3 could be applicable to protects neurons from the ischemic damage induced by thoracoabdominal aorta obstruction.


Lysophosphatidic acid stimulates nuclear and cytoplasmic maturation of golden hamster immature oocytes in vitro via cumulus cells.
Lysophosphatidic acid (LPA), a member of the phospholipid autacoid family, is induced in incubated human follicular fluid by lysophospholipase D. It is well known that LPA functions as a growth factor and the hypothesis that LPA in human follicular fluid takes a part in meiosis of oocytes is quite plausible. We studied the effects of LPA on the maturation of golden hamster immature oocytes in vitro. Hamster oocytes with a germinal vesicle were cultured in Tyrode's albumin lactate pyruvate (TALP) medium with 10(-5) M LPA, 10 ng/ml epidermal growth factor (EGF), 30 ng/ml insulin-like growth factor-1, 1 ng/ml tumor growth factor-alpha or 1 ng/ml basic fibroblast growth factor. The nuclear maturation rates in the LPA and EGF groups were significantly higher than in the control group and the other growth factors did not show any stimulatory effect (LPA group; 74.3% [75/101], EGF group; 82.4% [89/108] vs. control group; 60.2% [59/98], p < 0.05, p < 0.01, respectively). When the cells of cumulus were removed, EGF and LPA did not increase the nuclear maturation rates. Cotreatment EGF and LPA did not significantly enhance the stimulatory effect observed with LPA alone on maturation in vitro. The penetration rate determined by the zona-free hamster oocyte test was significantly higher in the LPA group than in the control group (26.7% vs. 13.2%, p < 0.05) and was comparable with that of oocytes matured in vivo. In conclusion, LPA stimulates the nuclear and cytoplasmic maturation of hamster immature oocytes via cumulus cells.


Contactless conductivity biosensor in microchip containing folic acid as bioreceptor.
We report a glass/PDMS-based microfluidic biosensor that integrates contactless conductivity transduction and folic acid, a target for tumor biomarker, as a bioreceptor. The device presents relevant advantages such as direct determination--dismiss the use of redox mediators as in faradaic electrochemical techniques--and the absence of the known drawbacks related to the electrode-solution interface. Characterizations of the functionalization processes and chemical sensor are described in this communication.


Marked dependence of the cardiac effects of gallopamil on the extracellular K(+)-concentration.
1. In guinea-pig Langendorff hearts, the negative inotropic effect of the calcium antagonist gallopamil is shifted by 15-fold to the left, when the extracellular K(+)-concentration is raised from 2.7 to 8.1 mM. 2. In papillary muscles, the ability of gallopamil to shorten the action potential (AP) markedly depends on K+: 100-fold lower gallopamil concentrations were required at 10.8 mM, compared to 2.7 mM. 3. In isolated myocytes, a change in the holding potential from -90 to -70 mV displaces the gallopamil dose-response curve to block Ca2+ currents leftward by only 6-fold. 4. Tetraethylammonium (TEA, 10 mM) mimics the mitigating effect of low K+ on the gallopamil-induced AP-shortening. Hence, the K(+)-dependence of gallopamil may be comprised of modulation of Ca(2+)-channel and K(+)-channel blocking effects.


Pattern formation in centrosome assembly.
A striking but poorly explained feature of cell division is the ability to assemble and maintain organelles not bounded by membranes, from freely diffusing components in the cytosol. This process is driven by information transfer across biological scales such that interactions at the molecular scale allow pattern formation at the scale of the organelle. One important example of such an organelle is the centrosome, which is the main microtubule organising centre in the cell. Centrosomes consist of two centrioles surrounded by a cloud of proteins termed the pericentriolar material (PCM). Profound structural and proteomic transitions occur in the centrosome during specific cell cycle stages, underlying events such as centrosome maturation during mitosis, in which the PCM increases in size and microtubule nucleating capacity. Here we use recent insights into the spatio-temporal behaviour of key regulators of centrosomal maturation, including Polo-like kinase 1, CDK5RAP2 and Aurora-A, to propose a model for the assembly and maintenance of the PCM through the mobility and local interactions of its constituent proteins. We argue that PCM structure emerges as a pattern from decentralised self-organisation through a reaction-diffusion mechanism, with or without an underlying template, rather than being assembled from a central structural template alone. Self-organisation of this kind may have broad implications for the maintenance of mitotic structures, which, like the centrosome, exist stably as supramolecular assemblies on the micron scale, based on molecular interactions at the nanometer scale.


The development of CNS-active LRRK2 inhibitors using property-directed optimisation.
Mutations in PARK8/LRRK2 are the most common genetic cause of Parkinson's disease. Inhibition of LRRK2 kinase activity has neuroprotective benefits, and provides a means of addressing the underlying biochemical cause of Parkinson's disease for the first time. Initial attempts to develop LRRK2 inhibitors were largely unsuccessful and highlight shortcomings intrinsic to traditional, high throughput screening methods of lead discovery. Recently, amino-pyrimidine GNE-7915 was reported as a potent (IC50=9 nM) selective (1/187 kinases), brain-penetrant and non-toxic inhibitor of LRRK2. The use of in silico modelling, extensive in vitro assays and resource-efficient in vivo techniques to produce GNE-7915, reflects a trend towards the concerted optimisation of potency, selectivity and pharmacokinetic properties in early-stage drug development.


Marcus inverted region of charge transfer from low-dimensional semiconductor materials.
A key process underlying the application of low-dimensional, quantum-confined semiconductors in energy conversion is charge transfer from these materials, which, however, has not been fully understood yet. Extensive studies of charge transfer from colloidal quantum dots reported rates increasing monotonically with driving forces, never displaying an inverted region predicted by the Marcus theory. The inverted region is likely bypassed by an Auger-like process whereby the excessive driving force is used to excite another Coulomb-coupled charge. Herein, instead of measuring charge transfer from excitonic states (coupled electron-hole pairs), we build a unique model system using zero-dimensional quantum dots or two-dimensional nanoplatelets and surface-adsorbed molecules that allows for measuring charge transfer from transiently-populated, single-charge states. The Marcus inverted region is clearly revealed in these systems. Thus, charge transfer from excitonic and single-charge states follows the Auger-assisted and conventional Marcus charge transfer models, respectively. This knowledge should enable rational design of energetics for efficient charge extraction from low-dimensional semiconductor materials as well as suppression of the associated energy-wasting charge recombination.


Correction: Effectiveness of Mobile App-Assisted Self-Care Interventions for Improving Patient Outcomes in Type 2 Diabetes and/or Hypertension: Systematic Review and Meta-Analysis of Randomized Controlled Trials.
[This corrects the article DOI: 10.2196/15779.].


[Bronchiolitis obliterans organizing pneumonia and bronchogenic carcinoma coexisting in different parts of the lungs].
Bronchiolitis obliterans organizing pneumonia (BOOP) coexisting with nonsmall cell lung cancer in a separate part of the lungs is rare. We report the case of a man diagnosed with BOOP by video-assisted thoracoscopic lung biopsy; the patient also had adenocarcinoma in a different part of the lungs. The BOOP was treated with corticosteroids and the carcinoma was surgically resected. Outcome and clinical course were good after both procedures. The possibility of BOOP associated with bronchogenic carcinoma at a distant part of the lungs, although rare, must be taken into account in the differential diagnosis of radiographic alterations that may present in either of the 2 diseases.


Genetic alterations by human papillomaviruses in oncogenesis.
The integration sites in the cellular genome of human papillomavirus are located in chromosomal regions always associated with oncogenes or other known tumor phenotypes. Two regions, 8q24 and 12q13, are common to several cases of cervical carcinoma and can have integrated more than one type of papillomavirus DNA. These two chromosomal regions contain several genes implicated in oncogenesis. These observations strongly imply that viral integration sites of DNA tumor viruses can be used as the access point to chromosomal regions where genes implicated in the tumor phenotype are located, a situation similar to that of non-transforming retroviruses.


Treatment of delayed- and non-union of fractures using pulsed electromagnetic fields.
A prospective series of 32 consecutive patients, with 33 long-bone fractures suffering from delayed- or non-union were treated by pulsed electromagnetic fields (PEMF) or by PEMF with surgery. The management regime for the PEMF treatment was simpler and less rigid than that reported by Bassett et al. and our stimulation waveform was also different. Nineteen fractures (100%) treated with surgery and PEMF united within nine months of the commencement of PEMF treatment. Fourteen fractures were treated with PEMF alone. Twelve (86%) united within ten months and two failed to unite. The results of this study suggest that the stimulating waveform is less critical than is claimed by Bassett et al. and that a simpler and easier management regime for PEMF treatment can be just as effective. Alternatively PEMF may have no effect on fracture healing.


Immune responses in the haemolymph and antimicrobial peptide expression in the abdomen of Apis mellifera challenged with Spiroplasma melliferum CH-1.
Spiroplasma melliferum generally parasitizes honeybees and is one of main pathogens causing 'bee creeping disease' in China. Spiroplasma melliferum can be spread through honeybee pollination, which causes severe economic losses to apiculture. The design of this study was based on previous studies that utilized an in vitro bioassay to investigate the effects of S. melliferum CH-1 infection. We identified invasive S. melliferum CH-1 within Apis mellifera using transmission electron microscopy and investigated the immune response of honeybees infected with S. melliferum CH-1 by assaying the cellular immune response of the haemocytes, the plasma level of phenoloxidase activity and the transcript levels of 5 antimicrobial peptides, including the Abaecin, Apidaecin, Defensin 1, Defensin 2, and Hymenoptaecin gene products. The percentage of granulocytes in the haemolymph of infected honeybees was significantly higher than those of the controls during the early phase of infection, but the percentage of plasmatocytes was significantly higher than those of the controls at the fifth day post-infection. The phenoloxidase activity of the infected honeybees reached a maximum at the second day, and then decreased continuously. Moreover, the transcript levels of the 5 evaluated antimicrobial peptide genes were significantly increased during the early phase of infection and all 5 antimicrobial peptides were significantly decreased during the middle phase of infection. During the late phase of infection, only Defensin 2 and Hymenoptaecin showed significantly increased transcription. These results suggest that the honeybee immune responses could be activated by S. melliferum CH-1 during the early phase of infection and that S. melliferum CH-1 is also capable of circumventing the host defensive mechanisms to complete its life cycle within the honeybee during the middle phase of infection.


Constraints on the evolution of attractive traits: genetic (co)variance of zebra finch bill colour.
We estimated the heritability and genetic correlation between male and female bill colour in a laboratory population of zebra finches (Taeniopygia guttata) in order to examine the potential genetic constraints on the evolution of a sexually dimorphic trait. The heritability estimates of bill colour from regressions of offspring on single parents ranged from h2 = 0.34 to 0.73 and all but one of these estimates were significantly greater than zero. The restricted maximum likelihood heritability estimates for full- and half-siblings were significant for females (h2 = 0.48) but not significant for males (h2 = 0.45). The maximum likelihood estimates indicate that there is little dominance genetic variance for bill colour. The large genetic correlation between male and female bill colour (rg = 0.91) combined with opposing selection on male and female bill colour indicates that the evolution to sex-specific optima may proceed very slowly.


Protocol for the Production of a Vaccine Against Argentinian Hemorrhagic Fever.
Argentinian hemorrhagic Fever (AHF) is a febrile, acute disease caused by Junín virus (JUNV), a member of the Arenaviridae. Different approaches to obtain an effective antigen to prevent AHF using complete live or inactivated virus, as well as molecular constructs, have reached diverse development stages. This chapter refers to JUNV live attenuated vaccine strain Candid #1, currently used in Argentina to prevent AHF. A general standardized protocol used at Instituto Nacional de Enfermedades Virales Humanas (Pergamino, Pcia. Buenos Aires, Argentina) to manufacture the tissue culture derived Candid #1 vaccine is described. Intermediate stages like viral seeds and cell culture bank management, bulk vaccine manufacture, and finished product processing are also separately presented in terms of Production and Quality Control/Quality Assurance requirements, under the Adminitracion Nacional de Medicamentos, Alimentos y Tecnología Medica (ANMAT), the Argentine national regulatory authority.


HIV treatment scale-up: a critical step to controlling HIV epidemic in a resource-limited country.
The study was conducted to determine the trend in HIV treatment coverage among people living with HIV and to evaluate effectiveness of the national antiretroviral treatment (ART) programme in reducing new infections in a mixed HIV epidemic nation, Nigeria. Ecological cross-sectional study. The study utilized national HIV programme service data and National HIV/AIDS and Reproductive Health Survey (NARHS) data for 36 states and Federal Capital Territory from 2012 to 2015 in Nigeria. Chi-squared test for trend was conducted to determine differences in ART coverage across the years. We correlated 2015 ART coverage with HIV prevalence Annual Rate of Reduction (ARR) between 2012 and 2015. A linear regression model was fitted to predict the HIV prevalence ARR in relation to ART coverage and adjusted for the effect of socio-behavioral interventions (coverage of condom-use among male). Nigeria has recorded steady progress with HIV treatment coverage with an annual rate of progress of 18.25%, P < 0.001; however, huge gaps still exist. Females and adults had higher odds of receiving ART. HIV prevalence annual reduction rate was higher for states that had higher ART coverage (r = 0.4; P = 0.02). Our analysis indicated that a 10% increase in ART coverage was associated with a 4% increase in the annual rate of reduction for HIV prevalence (adjusted β = 0.4; 95% confidence interval: 0.1-0.8; P = 0.01). Regardless of the low ART coverage, our analysis supports the evidence base to inform accelerated access to HIV treatment for population Nigeria and other similar resource-limited settings to make ending HIV by 2030 a reality.


Activation of the food-derived mutagen 2-amino-3-methylimidazo[4, 5-f]quinoline by human-liver microsomes.
The ability of human-liver microsomes to metabolically activate the food-derived heterocyclic amine, 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), and the model mutagen, 2-aminofluorene (AF), has been investigated using Salmonella typhimurium TA98. In 6 subjects tested the number of revertants produced by 0.1 micrograms IQ per mg microsomal protein varied from 11, 830 +/- 320 to 42, 830 +/- 290 (mean +/- SD). With the same livers and a dose of 10 micrograms AF per plate the number of revertants varied from 15,770 +/- 1600 to 29,380 +/- 810 per mg microsomal protein. Metyrapone and alpha-naphthoflavone caused differential inhibition of the mutagenesis of both IQ and AF indicating the involvement of different forms of cytochrome P450 in the metabolic activation of these amines in human-liver microsomes. In presence of human-liver microsomes IQ produced no detectable increase in mutations at the hypoxanthine phosphoribosyl transferase locus in lymphocytes and caused no increase in micronuclei formation at realistic exposure levels.


More mind wandering, fewer original ideas: be not distracted during creative idea generation.
Several studies suggest that mind wandering (MW) benefits creativity when the MW occurs in the incubation period of creative problem solving. The aim of present study was to examine the effects of MW that occurs in the course of creative idea generation. Participants received an Alternative Uses Task (AUT) and were asked to generate ideas for 20min. Their MW frequencies as time passed were measured by means of probe-caught MW. Comparisons of the AUT performances of high and low MW groups revealed that greater MW was associated with lower fluency and originality scores on the AUT. Furthermore, the high MW group showed greater MW as time passed, while the low MW group's MW was steady during the course of idea generation. Accordingly, the originality of idea generation decreased with time passing for the high MW group but was steady for the low MW group. The findings suggest that the MW during the course of creative idea generation is negatively related to creativity, perhaps because the control processes involved in idea generation are impaired by the mind wandering.


Single-Port Robotic-Assisted Laparoscopic Sacrocolpopexy With Magnetic Retraction: A Video Demonstration.
Abdominal sacrocolpopexy is the gold standard for treatment of apical prolapse.1 Minimally invasive surgery offers many advantages over the open approach, including incision size, blood loss, postoperative pain while maintaining similar long-term outcomes.2,3 OBJECTIVE: To assess the safety and feasibility of performing a magnetic-assisted single-port robotic sacrocolpopexy (MARS). Prior to surgery, a magnetic controller was secured to the surgical bed. The Hassan technique was used to place a 25 mm SP port through a single 2.5 cm supra-umbilical incision. A 12 mm assistant port was placed 10 cm lateral to the SP port on the right side, this additional trocar placement may be obviated by using a gel-point for both ports. The SP robot was docked on the right side of the bed. The magnet was clipped onto the sigmoid mesentery and the outer magnet was repositioned to retract the sigmoid laterally. The sacral promontory was exposed, and the peritoneal incision was carried down to the vagina. The magnet was repositioned, and the bladder was reflected off the anterior vagina. The posterior dissection was carried out to reveal the posterior vagina. "Y" mesh was placed, appropriately tensioned, secured to the sacral promontory and retroperitonealized. Cystoscopy was performed. The magnet was removed from the sigmoid colon, and all incisions were closed. A 66-year-old G2P2 female, BMI 25, status-post prior abdominal hysterectomy presented with symptomatic stage IV prolapse. Surgery was uneventful with an operative time of 247 minutes and an estimated blood loss of 10cc. The patient was discharged the following day. At 3 months postoperatively, she had anatomic and symptomatic resolution of her prolapse. Using magnetic assistance, MARS can be offered to women who want a durable option for prolapse repair with improved cosmesis compared to conventional methods and may offer cosmetic benefits when paired with a concurrent hysterectomy.


Changes in nuclear chromatin related to apoptosis or necrosis induced by the DNA topoisomerase II inhibitor fostriecin in MOLT-4 and HL-60 cells are revealed by altered DNA sensitivity to denaturation.
The antitumor drug fostriecin (phosphotrienin, FST) has been reported to exert its cytostatic and cytotoxic effects via inhibition of DNA topoisomerase II. The sensitivity of human lymphocytic leukemic MOLT-4 and promyelocytic HL-60 leukemic cells to a wide range of FST concentrations was studied by analyzing the cell cycle-specific effects and changes in nuclear chromatin induced by this inhibitor. The latter was evaluated by assaying the sensitivity of DNA in situ to acid-induced denaturation cytofluorimetrically, with the use of the metachromatic fluorochrome acridine orange (AO), which differentially stains double-stranded and denatured DNA. The cytostatic effects were observed soon after addition of FST (at concentrations of 1-30 microM for MOLT-4 cultures and 1-5 microM for HL-60 cultures) as a perturbation of cell progression through S and G2 phases of the cell cycle. Cell progression through the cycle was halted at greater than 30 microM FST in MOLT-4 cultures and at greater than 5 microM in HL-60 cultures; the effect was instantaneous and affected all phases of the cycle, so that no changes in the cell cycle distribution were apparent with increasing length of exposure to the drug. Instead, at these high FST concentrations, immediate cytotoxic effects became evident, manifesting either as cell apoptosis or necrosis. Apoptosis was observed only in the case of HL-60 cells, at FST concentrations of 5-100 microM, and was characterized by markedly increased sensitivity of DNA to denaturation combined with a decrease in overall DNA stainability, either with the DNA-specific dye DAPI or with AO, indicative of the activation of endogenous nucleases. Necrotic cell death was observed at FST concentrations of 1 mM and at greater than 30 microM for HL-60 and MOLT-4 cells, respectively: in both cases the overall DNA stainability, with either DAPI or AO, was unchanged compared to the control, but their DNA was very sensitive to denaturation. Interestingly, DNA in G2 and late S phase MOLT-4 cells, which were undergoing necrotic death, was much more sensitive to denaturation than was DNA in G1 cells of this lineage. The data indicate that chromatin changes induced by DNA topoisomerase II inhibitors in cells that undergo apoptotic or necrotic death can be conveniently monitored by the assay of DNA in situ sensitivity to denaturation.


STING mediates neurodegeneration and neuroinflammation in nigrostriatal α-synucleinopathy.
In idiopathic Parkinson's disease (PD), pathologic αSyn aggregates drive oxidative and nitrative stress that may cause genomic and mitochondrial DNA damage. These events are associated with activation of the cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) immune pathway, but it is not known whether STING is activated in or contributes to α-synucleinopathies. Herein, we used primary cell cultures and the intrastriatal αSyn preformed fibril (αSyn-PFF) mouse model of PD to demonstrate that αSyn pathology causes STING-dependent neuroinflammation and dopaminergic neurodegeneration. In microglia-astrocyte cultures, αSyn-PFFs induced DNA double-strand break (DSB) damage response signaling (γH2A.X), as well as TBK1 activation that was blocked by STING inhibition. In the αSyn-PFF mouse model, we similarly observed TBK1 activation and increased γH2A.X within striatal microglia prior to the onset of dopaminergic neurodegeneration. Using STING-deficient (Stinggt) mice, we demonstrated that striatal interferon activation in the α-Syn PFF model is STING-dependent. Furthermore, Stinggt mice were protected from α-Syn PFF-induced motor deficits, pathologic αSyn accumulation, and dopaminergic neuron loss. We also observed upregulation of STING protein in the substantia nigra pars compacta (SNpc) of human PD patients that correlated significantly with pathologic αSyn accumulation. STING was similarly upregulated in microglia cultures treated with αSyn-PFFs, which primed the pathway to mount stronger interferon responses when exposed to a STING agonist. Our results suggest that microglial STING activation contributes to both the neuroinflammation and neurodegeneration arising from α-synucleinopathies, including PD.


Minmax designs for planning the second phase in a two-phase case-control study.
Two-phase designs, in which a subsample with validation or complete information data is sampled stratified both on outcome and covariate from a first-phase study with incomplete data, have been proposed over 10 years ago and have been proven to result in efficient estimates with respect to standard designs. The efficiency depends, however, on the sampling fractions within each stratum. Our aim is to present a strategy for obtaining an optimized design, i.e. sampling fractions, that makes use of available phase-one data of an existing case-control study considered as the first-phase sample when the focus is on estimating a parameter vector. No global optimal design exists and local optimal designs depend on scenarios comprising the true disease model and the association between the phase-one and phase-two information. We develop an admissibility test that rejects scenarios inconsistent with the phase-one data and, for the selected scenarios, determine a minmax D- or A-optimal design that protects against worst-case scenarios. This work is applied on two examples.


Publisher Correction: Harnessing innate immunity in cancer therapy.
An Amendment to this paper has been published and can be accessed via a link at the top of the paper.


Simultaneous Anterior Posterior Approach for Single-Position Lateral Lumbar Interbody Fusion with Robotic Assistance: Technical Guidelines and Early Outcomes.
Lumbar lateral interbody fusion (LLIF) is traditionally performed in 2 stages: placing the interbody cage in the lateral decubitus position, then placing the percutaneous pedicle screw in the prone position. Performing interbody fusion and posterior fixation simultaneously could improve operative efficiency and clinical outcomes associated with longer operative times. We describe the operative steps and report clinical and radiographic outcomes associated with a simultaneous anterior and posterior approach (SAPA) for LLIF. Patients who underwent SAPA LLIF performed by a single surgeon over 1 year were retrospectively reviewed. Demographic, clinical, and radiographic data were analyzed, an operative guideline was created, and a learning curve was constructed using operative times. SAPA LLIF was performed in 11 patients. Three patients experienced transient postoperative femoral nerve plexopathy with symptoms of ipsilateral hip flexion weakness and/or anterior thigh numbness; there were no other complications in the cohort. Radiographically, patients achieved significant increases in disc height (8.3 mm vs. 13.5 mm, P = 0.002) and foraminal height (20.2 mm vs. 25.3 mm, P = 0.0001). Patients showed significant improvements in Oswestry Disability Index (52 vs. 27.8, P = 0.002) and Patient-Reported Outcome Measurement Information System Physical Function (32.6 vs. 39, P = 0.048) and Pain Interference (64.9 vs. 59.6, P = 0.001) at 3 months. A downward trend in operative time was observed for 1-level SAPA LLIF. SAPA LLIF is a safe approach for LLIF that results in favorable clinical outcomes. This technique can potentially improve operative efficiency further along the course of a surgeon's learning curve.


PCSK9 deficiency results in a specific shedding of excess LDLR in female mice only: Role of hepatic cholesterol.
PCSK9 promotes the lysosomal degradation of cell surface LDL receptor (LDLR). We analyzed how excess LDLR generated by PCSK9 deficiency is differently handled in male and female mice to possibly unveil the mechanism leading to the lower efficacy of PCSK9 mAb on LDL-cholesterol levels in women. Analysis of intact or ovariectomized PCSK9 knockout (KO) mice supplemented with placebo or 17β-estradiol (E2) demonstrated that female, but not male mice massively shed the soluble ectodomain of the LDLR in the plasma. Liver-specific PCSK9 KO or alirocumab-treated WT mice exhibit the same pattern. This shedding is distinct from the basal one and is inhibited by ZLDI-8, a metalloprotease inhibitor pointing at ADAM10/ADAM17. In PCSK9 KO female mice, ZLDI-8 raises by 80 % the LDLR liver content in a few hours. This specific shedding is likely cholesterol-dependent: it is prevented in PCSK9 KO male mice that exhibit low intra-hepatic cholesterol levels without activating SREBP-2, and enhanced by mevalonate or high cholesterol feeding, or by E2 known to stimulate cholesterol synthesis via the estrogen receptor-α. Liver transcriptomics demonstrates that critically low liver cholesterol in ovariectomized female or knockout male mice also hampers the cholesterol-dependent G2/M transition of the cell cycle. Finally, higher levels of shed LDLR were measured in the plasma of women treated with PCSK9 mAb. PCSK9 knockout female mice hormonally sustain cholesterol synthesis and shed excess LDLR, seemingly like women. In contrast, male mice rely on high surface LDLR to replenish their stocks, despite 80 % lower circulating LDL.


Response format changes the reading the mind in the eyes test performance of autistic and non-autistic adults.
Recognizing and understanding the perspectives of others-also called theory of mind-is important for effective communication. Studies have found that some autistic individuals have greater difficulty with theory of mind compared to non-autistic individuals. One purported theory of mind measure is the Reading the Mind in the Eyes Test (RMET). This test presents participants with photographs of pairs of eyes and asks them to identify the emotion displayed by each pair of eyes from four choices. Some researchers have argued that the multiple-choice format of the RMET may not be an accurate measure of theory of mind, as participants could simply be guessing or using a process of elimination to select the correct answer. Participants may also be disadvantaged if they are not familiar with the specific emotion words used in the multiple-choice answers. We examined whether a free-report (open-ended) format RMET would be a more valid measure of theory of mind than the multiple-choice RMET. Autistic and non-autistic adults performed better on the multiple-choice RMET than the free-report RMET. However, both versions successfully differentiated autistic and non-autistic adults, irrespective of their level of verbal ability. Performance on both versions was also correlated with another well-validated adult measure of theory of mind. Thus, the RMET's multiple-choice format does not, of itself, appear to underpin its ability to differentiate autistic and non-autistic adults.


Effect of adding anionic surfactant on the stability of Pickering emulsions.
We investigated the structure and stability of dodecane-in-water emulsions stabilised by partially hydrophobised silica particles after dilution of the emulsions in solutions of sodium dodecyl sulfate and sodium chloride. The emulsions were stable to coalescence on dilution in salt solutions, but did cream over time. The rate and extent of creaming gradually decreased as the salt concentration in the diluted emulsion increased. Dilution in low concentrations of the anionic surfactant did not affect the emulsion stability to coalescence or alter the creaming behaviour of the emulsion. At surfactant concentrations above the critical micelle concentration, however, the rate and extent of creaming and flocculation of the drops were enhanced.


Towards an understanding of tensile deformation in Ti-based bulk metallic glass matrix composites with BCC dendrites.
The microstructure and tension ductility of a series of Ti-based bulk metallic glass matrix composite (BMGMC) is investigated by changing content of the β stabilizing element vanadium while holding the volume fraction of dendritic phase constant. The ability to change only one variable in these novel composites has previously been difficult, leading to uninvestigated areas regarding how composition affects properties. It is shown that the tension ductility can range from near zero percent to over ten percent simply by changing the amount of vanadium in the dendritic phase. This approach may prove useful for the future development of these alloys, which have largely been developed experimentally using trial and error.


[Antibiotic concentration in postoperative wound fluid during short-term prevention with cephalosporins].
Antibiotic concentrations were measured in wound fluid from Redon-drains and in serum during short-time prophylaxis in orthopaedic surgery. 1. Chephaloridine and cephazolin concentrations in wound fluid rose to therapeutic levels. 3 h after i.v. application of 1 g concentrations in wound fluid and in serum were nearly identical. 6 and 12 h after application the concentrations in wound fluid were significantly higher than those in the serum. 2. At the end of the 12-h interval of administration the mean concentrations of both antibiotics as well in wound fluid as in serum remained at therapeutic levels. 3. For reasons of their good diffusion into the wounds both cephaloridine and cefazolin should be appropriate for short-time prophylaxis in orthopaedic surgery.


Renal Calculus in Floating-Harbor Syndrome: A Case Report.
Floating-Harbor syndrome is a rare condition marked by short stature and delayed bone age, characteristic facial features, and speech impairment. Floating-Harbor syndrome commonly results from a sporadic genetic mutation. Renal abnormalities have rarely been encountered. We report the first patient with Floating-Harbor syndrome who spontaneously passed a renal calculus consisting of calcium oxalate monohydrate and calcium oxalate dihydrate. A renal ultrasound showed echotexture within the renal pyramids, hydronephrosis, and a cyst. Pediatric nurse practitioners should be alert to the unique features associated with Floating-Harbor syndrome and be prepared to monitor and treat the renal abnormalities that may accompany this uncommon condition.


Local control and failure patterns after intensity modulated radiotherapy with reduced target volume delineation after induction chemotherapy for patients with T4 nasopharyngeal carcinoma.
The delineation of target volume after induction chemotherapy(IC) for nasopharyngeal carcinoma(NPC) is currently controversial. In this study, we aimed to analyze the long-term local control(LC) and failure patterns of T4 NPC treated with reduced target volume radiotherapy after IC. From September 2007 to January 2013, 145 patients with T4 NPC were retrospectively reviewed. All patients received at least 1 cycle of IC followed by intensity modulated radiotherapy(IMRT). The gross tumor volume(GTV) was delineated according to the post-IC images for intracavity tumors and lymph nodes. The LC and overall survival (OS) rates were calculated using the Kaplan-Meier method. The location and extent of local failures were transferred to the pretreatment planning computed tomography (CT) for dosimetric analysis. With a median follow-up time of 95 months (range, 16-142 months), 23 local failures were found. The estimated 10-year LC and OS rates were 81.1%and 54.8% respectively. Among the 20 local failures with available diagnostic images, 18(90%) occurred within the 95% isodose lines and were considered in-field failures and 2(10%) were marginal. There was no outside-field failure. In-field failure was the major pattern of local failure for T4 NPC. IMRT with reduced target volume after IC seems to be feasible. Further researches exploring optimal volume and radiation dose for local advanced NPC in the era of IC are warranted.


Developing the marine medicine syllabus for medical sciences students: a multiphase design study.
Marine medicine is one of the medical fields that deals with the health and safety of people related to the sea but the marine medicine syllabus for education to the students is not specified yet. The present study aimed to develop the marine medicine syllabus to medical sciences students education. This study was conducted in three phases. First, a literature review was conducted to find the concepts and topics related to marine medicine. Second, a content analysis research method was conducted. Data collection was done first by using semi-structured interviews with the 12 experts in marine medicine. Sampling was purposeful and continued until data saturation was reached. The information obtained from the interviews was analyzed by conventional content analysis with Geranheim's method. The found topics in the literature review and content analysis of interviews were combined and formed the initial draft of the marine medicine syllabus, which was validated with the Delphi method in the third phase. The Delphi was conducted in two rounds and the panel consisted of 18 experts in the field of marine medicine. After the completion of each round, the items that had less than 80% consensus among the participants were removed and the remaining topics after round two formed the final syllabus of the marine medicine. The findings showed that the marine medicine syllabus should include an overview of marine medicine, health at sea, common physical diseases and injuries at sea, subsurface medicine and hyperbaric, safety action in marine incidents, medical care at sea, psychology at sea and medical examinations of people working at sea main topics and their sub topics. Marine medicine is an extent and specialized medical field which has been neglected and it is necessary to teach this lesson to medical sciences students with the syllabus found in the present study.


Elevated hCG can be a benign finding in perimenopausal and postmenopausal women.
In a perimenopausal or postmenopausal woman, an elevation in human chorionic gonadotropin (hCG) can raise the concern of malignancy or even pregnancy, but it can also be a benign physiologic finding due to production in the pituitary gland in this patient population. Diagnosing the underlying cause of hCG elevation can be challenging, especially if a pituitary source is not considered. Pituitary hCG production remains largely underrecognized and can lead to unnecessary testing, harmful therapy such as chemotherapy, or delay in receiving appropriate care for other unrelated diseases. It is therefore important to establish guidelines to aid medical evaluation.


Aspiration in patients with head and neck cancer and tracheostomy.
Tracheopulmonary aspiration is a common occurrence in patients with dysphagia associated with head and neck cancer. We performed quantitative scintigraphic analysis of tracheopulmonary aspiration in 125 patients with head and neck cancer; 58 of these patients had a tracheostomy. Tracheopulmonary aspiration occurred in 58% of patients with a tracheostomy and in 23% of patients without a tracheostomy. In six of seven patients with a tracheostomy, tracheopulmonary aspiration significantly increased when the obturator was removed and, in these patients, occlusion of the tracheostomy tube during feedings eliminated or reduced the complication. Our studies suggest that aspiration can be monitored accurately and conveniently by scintigraphy, and that this technique is useful in the evaluation and management of dysphagia in debilitated patients.


Impairment of sexual activity before and after endoscopic totally extraperitoneal (TEP) hernia repair.
In patients with inguinal hernias, sexual activity may be impaired due to hernia-related pain. Surgical repair may improve these complaints but can also lead to similar symptoms as a long-term complication of the operation. Endoscopic hernia repair is associated with less postoperative pain and earlier return to normal activities, but its effect on pain-related sexual function is unknown. In this study, the incidence and effect of pain related to sexual activity are evaluated before and after endoscopic totally extraperitoneal (TEP) hernia repair. A hospital-based questionnaire study of pain-related sexual dysfunction was conducted in November 2009 in 500 male patients ≥18 years, who underwent TEP repair of a primary hernia between March 2006 and December 2008. The response rate was 77.2%. Pain of any severity during sexual activity was reported by 124 patients (32.1%) preoperatively and 35 patients (9.1%) postoperatively. Only 2.3% of the 262 patients with no history of preoperative pain experienced moderate to severe (VAS 4-10) pain postoperatively. Pain impaired sexual function in 63 patients (16.3%) preoperatively and in 18 patients (4.7%) postoperatively. The majority of patients who reported pain during sexual activity preoperatively (n = 102, 82.3%) had no pain postoperatively. The frequency of moderate to severe painful sexual activity decreased from 21.2% (preoperatively) to 3.4% after TEP repair (P < 0.001), and the frequency of moderate to severely impaired sexual function decreased from 6.0 to 1.0% (P < 0.001). The preoperative presence of pain during sexual activity and chronic non-hernia-related pain syndromes were predictive for the occurrence of postoperative pain. Painful sexual activity, present in one third of patients with inguinal hernias, improved in the majority of patients following TEP hernia repair. Postoperatively, moderate to severe painful sexual activity occurred in 2.3% of the patients with no history of preoperative complaints.


Performance of a continuous flow microbial reverse-electrodialysis electrolysis cell using a non-buffered substrate and catholyte effluent addition.
A continuous flow microbial reverse-electrodialysis electrolysis cell (MREC) was operated under non-buffered substrate with various flow rates of catholyte effluent into anode chamber to investigate the effects on the hydrogen gas production. Adding the catholyte effluent to the anolyte influent resulted in increased salt concentration in the anolyte influent. The increasing anolyte influent salt concentration to 0.23M resulted in improved hydrogen gas production, Coulombic recovery, yield, and hydrogen production rate to 25±1.4mL, 83±5%, 1.49±0.15mol-H2/mole-COD, 0.91±0.03m3-H2/m3-Van/day, respectively. These improvements were attributed to the neutral pH rather than increase in anolyte conductivity as there was no significant improvement in the reactor performance when the NaCl was directly added to the reactor. These results show that addition of catholyte effluent into the anode chamber improved the MREC performance.


Hydroxylated metabolites of the polybrominated diphenyl ether mixture DE-71 are weak estrogen receptor-alpha ligands.
Polybrominated diphenyl ethers (PBDEs) are widely found in the environment and are suspected endocrine disruptors. We previously identified six hydroxylated metabolites of PBDE (OH-PBDEs) in treated mice. We tested the hypothesis that OH-PBDEs would interact with and alter activity of estrogen receptor-alpha (ER-alpha). We tested estrogenicity using two assays: 3H-estradiol (3H-E2) displacement from recombinant ER-alpha and induction of reporter gene (ERE-luciferase) in cultured cells. We incubated the PBDE mixture DE-71 with rat liver microsomes and tested the resultant metabolite mixture for estrogenic activity. We also determined relative estrogenic potential of individual hydroxylated PBDE congeners. Reporter gene activity was increased by DE-71 that had been subjected to microsomal metabolism. DE-71 did not displace E2 from ER-alpha, but all six of the OH-PBDE metabolites did. para-Hydroxylated metabolites displayed a 10- to 30-fold higher affinity for ER-alpha compared with ortho-hydroxylated PBDEs, and one produced a maximal effect 30% higher than that produced by E2. Coadministration of E2 and DE-71, or certain of its metabolites, yielded reporter activity greater than either chemical alone. Two ortho-OH-PBDEs were antiestrogenic in the reporter assay. The observations--that the DE-71 mixture did not displace 3H-E2 from ER-alpha while the hydroxylated metabolites did-suggest that the weak estrogenic effects of DE-71 are due to metabolic activation of individual congeners. However, the behavior of DE-71 and its metabolites, when co-administered with E2, suggest a secondary, undetermined mechanism from classical ER-alpha activation.


Epigenetic regulation of ageing: linking environmental inputs to genomic stability.
Ageing is affected by both genetic and non-genetic factors. Here, we review the chromatin-based epigenetic changes that occur during ageing, the role of chromatin modifiers in modulating lifespan and the importance of epigenetic signatures as biomarkers of ageing. We also discuss how epigenome remodelling by environmental stimuli affects several aspects of transcription and genomic stability, with important consequences for longevity, and outline epigenetic differences between the 'mortal soma' and the 'immortal germ line'. Finally, we discuss the inheritance of characteristics of ageing and potential chromatin-based strategies to delay or reverse hallmarks of ageing or age-related diseases.


Effect of Supplementation of Nano Zinc Oxide on Nutrient Retention, Organ and Serum Minerals Profile, and Hepatic Metallothionein Gene Expression in Wister Albino Rats.
A study was conducted to validate the effects of nano form of zinc (NZn) on nutrient digestibility, zinc retention, organ and serum zinc profile, and hepatic metallothionein gene expression in Wistar albino rats (WAR). Nano zinc (NZn) was synthesized through chemical method, by using 0.45 M zinc nitrate [Zn(NO3)2.6H2O] and 0.9 M sodium hydroxide (NaOH). The NZn particle in its oxide form was characterized by TEM-EDAX and XRD, and found to be in nano range (below 100 nm. Zinc was supplemented to the Wistar albino rats (WAR) through synthetic semi-purified diet either without Zn, or as inorganic zinc (IZn; 25 mg/kg), or as synthesized NZn (25, 12.5, 6.25, 3.125 or 50 mg/kg DM) for 60 days. The zinc content was observed to be significantly (P < 0.05) higher in liver, bone, kidney, and serum due to NZn supplementation where NZn-50 had highest zinc content and control had the least, without affecting Fe, Mn, and Cu. NZn at 12.5 mg/kg group rats were either comparable or better than IZn at 25 mg/kg in terms of zinc retention, CP digestibility, zinc level in serum, liver, bone, and kidney suggesting its better bioavailability simultaneously also reduced fecal excretion of zinc to the environment. Metallothionein mRNA expression was upregulated in NZn at 25 mg/kg and NZn at 50 mg/kg than IZn at 50 mg/kg. Thus, in WAR, NZn at half of the ICAR recommendation (25 mg/kg DM) is as effective as inorganic zinc at 100% of recommended dose.


Heterocyclic aromatic amines in meat: Formation mechanisms, toxicological implications, occurrence, risk evaluation, and analytical methods.
Heterocyclic aromatic amines (HAAs) are detrimental substances can develop during the high-temperature cooking of protein-rich foods, such as meat. They are potent mutagens and carcinogens linked to an increased risk of various cancers. HAAs have complex structures with nitrogen-containing aromatic rings and are formed through chemical reactions between amino acids, creatin(in)e, and sugars during cooking. The formation of HAAs is influenced by various factors, such as food type, cooking temperature, time, cooking method, and technique. HAAs exert their toxicity through mechanisms like DNA adduct formation, oxidative stress, and inflammation. The research on HAAs is important for public health and food safety, leading to risk assessment and management strategies. It has also led to innovative approaches for reducing HAAs formation during cooking and minimizing related health risks. Understanding HAAs' chemistry and formation is crucial for developing effective ways to prevent their occurrence and protect human health. The current review presents an overview about HAAs, their formation pathways, and the factors influencing their formation. Additionally, it reviews their adverse health effects, occurrence, and the analytical methods used for measuring them.


The Impact of Food Processing on the Structure and Hypoglycemic Effect of Oat β-glucan.
The impact of food processing including baking, steaming and bread making, on the structure and hypoglycemic effect of oat β-glucan was studied. The structural analysis revealed the β-D-glucopyranosyl units of β-glucan was unchanged in aforementioned processing. The baking processing endowed β-glucan with increased molecular weight (Mw) and viscosity, which enhanced the capacity of β-glucan to delay starch digestion in vitro, such as the rapidly-digestible starch content decreased, the slowly-digestible and resistant starch content increased, and the glycemic index (GI) value decreased. Meanwhile, the inhibitory activity of β-glucan against α-glucosidase and α-amylase was enhanced by baking processing. By contrast, during steaming and bread making processing, β-glucan showed decreased Mw and viscosity, which accelerated starch digestion in vitro and reduced the inhibitory activity of β-glucan against α-glucosidase and α-amylase. Apart from that, baking processing promoted the physiological and antioxidant properties of β-glucan, but the properties decreased during steaming and bread making processing. The results suggest that oat raw materials can be treated with dry heat and high temperature, avoiding moist heat and fermentation treatments to maximize the hypoglycemic effect of β-glucan.


Predicting peak oxygen uptake from 6-min walk test performance in male patients with left ventricular systolic dysfunction.
In patients with left ventricular systolic dysfunction (LVSD), peak oxygen uptake (pVO2) has strong predictive power for mortality, and can be used to guide management. However, many patients cannot tolerate standard test protocols. The 6-min walk test (6-MWT) is often used to estimate functional capacity due to its simplicity, cost effectiveness and familiarity to patients with LVSD. The relationship between 6-MWT performance and pVO2 is not certain, but if closely related could allow substitution of an expensive and cumbersome test for a cheaper and more familiar one. 120 male patients with LVSD (LVEF <40%; (mean+/-S.D.) age 68+/-13 years; BMI 28+/-5) performed, in random order, a maximal incremental treadmill exercise test with metabolic gas exchange measurements to derive peak oxygen consumption (pVO2 = 19.8+/-5.8 mL.kg(-1).min(-1)), and a standardised 6-MWT (308+/-142 m; r = 0.44; P = 0.00001). In multivariate models including demographic data, resting blood pressure and heart rate, spirometry, routine blood samples, and walk distance, five variables were independently predictive of peak oxygen consumption. pVO2 = 11.92 + (1.48 x FEV1 (L)) + (1.12 x haemoglobin (g dl(-1))) + (0.016 x distance walked (m)) - (0.33 x BMI) - (0.11 x age (years)). This equation accounted for 48% of the variation in pVO2. Using these five simple variables, peak oxygen consumption can be estimated with moderate accuracy. In clinical practice, however, when an estimate of peak oxygen consumption is required, incremental exercise testing with metabolic gas exchange measurements cannot be avoided in male patients with LVSD. Further work is needed to assess the relation between estimated pVO2 and outcome.


A new endogenous retroviral sequence is expressed in skin of patients with psoriasis.
The origin of psoriasis, a chronic inflammatory skin disease involving keratinocyte proliferation, immune disturbances and complex inheritance, remains unknown. Human endogenous retroviruses (HERVs) are part of the normal human genome and their participation in the pathogenesis of various human diseases with complex genetic traits has been proposed. A possible role of HERVs in the induction of psoriasis was suggested many years ago. However, to date no study has searched for HERV expression in psoriasis. To determine firstly, which HERV families are expressed in the psoriatic lesion and secondly, whether specific variants can be detected. HERV expression was analysed at the mRNA level after degenerated reverse transcription-polymerase chain reaction (RT-PCR) of retroviral pol sequences followed by sequencing. Screening for a specific variant was performed by RT-PCR on lesional and nonlesional psoriatic skin and compared with normal and atopic dermatitis skin. We report the expression of three HERV families in psoriatic lesions, namely HERV-W, K and E. We then partially characterized a new endogenous retroviral variant, which was related to the ERV-9/HERV-W family. This sequence contains at least two open reading frames that could encode for a gag protein and a retroviral protease. The expression of this sequence was detected in 29 of 43 lesional psoriasis skin samples and rarely in normal (two of 21) or atopic dermatitis (three of 14) skin samples. In psoriatic lesions, HERV sequences of the W, K and E families are expressed and a new variant of the ERV-9/HERV-W family has been characterized. The possible role of HERV-related sequences in the pathogenesis of psoriasis is under investigation.


Cyclic Phosphine Oxides and Phosphinamides from Di-Grignard Reagents and Phosphonic Dichlorides: Modular Access to Annulated Phospholanes.
The reaction between 1,4-di-Grignard reagents and phosphonous(III) dichlorides is a classical method for the direct synthesis of phospholanes. Reported here is an extension of this approach to the preparation of value-added, annulated phospholane oxides, achieved through the combination of carbocyclic-fused di-Grignard reagents and readily available phosphonic(V) dichlorides. The procedure is amenable to (benz)annulation at both the 2,3- and 3,4-positions of the phospholane ring, and a variety of aliphatic, cyclic and aryl P-electrophiles are tolerated in reasonable to excellent yields.


Fiber-packed channel bioreactor for microfluidic protein digestion.
The fabrication and performance of a fiber-packed channel bioreactor in microchip along with its application in protein analysis were reported. The feasibility and performance of the unique microfluidic bioreactor were demonstrated by the tryptic digestion of myoglobin (MYO) and BSA. The on-chip digestion was carried out at a flow rate of 2.0 microL/min and the digestion time was significantly reduced to less than 5 s. The digests were identified by MALDI-TOF MS with sequence coverages of 66% (MYO) and 40% (BSA) that were comparable to those obtained by the conventional in-solution tryptic digestion. The present fiber-based microchip bioreactor provides a promising platform for the high-throughput protein identification.


The recognition of partially visible natural objects in the presence and absence of their occluders.
The visual system is adept at compensating for the missing information in scenes that results from occlusion, but how this is done is not fully understood. In particular, the role of the occluding object in visual processing and its effect on the subsequent recognition of the occluded object is unclear. We report three human behavioral experiments suggesting that the recognition of partially visible objects is facilitated when the missing object information is replaced by an occluder rather than simply removed. Furthermore, we provide EEG evidence suggesting that the processes responsible for facilitated recognition occur relatively early in the visual stream.


Activation of basophils by the double-stranded RNA poly(A:U) exacerbates allergic inflammation.
It is commonly acknowledged that asthma is exacerbated by viral infections. On the other hand, basophil infiltration of lung tissues has been evidenced postmortem in cases of fatal disease, raising the question of a possible link between these two observations. Herein, we addressed the relationship between asthma exacerbation by viral infection and basophil activation and expansion by investigating how stimulation with the dsRNA polyadenylic/polyuridylic acid [poly(A:U)] affected basophil activities and recruitment in an allergic airway inflammation model. The effect of dsRNA on basophils was assessed by measuring the cytokine levels produced upon stimulation. We used an OVA-induced experimental model of allergic asthma. Airway hyperreactivity, recruitment of infiltrating cells, and cytokine production were determined in the lung of mice having received poly(A:U), as compared with untreated controls. The exacerbating effect of basophils was assessed both by adoptive transfer of poly(A:U)-treated basophils and by their in vivo depletion with Ba103 antibody. We found that in vitro treatment with poly(A:U) increased basophil functions by inducing TH 2-type cytokine and histamine production, whereas in vivo treatment increased peripheral basophil recruitment. Furthermore, we provide the first demonstration for increased infiltration of basophils in the lung of mice suffering from airway inflammation. In this model, disease symptoms were clearly exacerbated upon adoptive transfer of basophils exposed to poly(A:U), relative to their unstimulated counterpart. Conversely, in vivo basophil depletion alleviated disease syndromes, thus validating the transfer data. Our findings provide the first evidence for airway inflammation exacerbation by basophils following dsRNA stimulation.


The sternum: An important review area when reporting pre-surgical staging breast MRI studies.
Identification and assessment of extramammary findings on contrast-enhanced breast MRI scans is particularly important in the setting of newly diagnosed invasive cancer as metastatic lesions may be encountered in the liver, lungs, pleural cavity or bones. Establishing that stage IV disease is present has a profound effect on patient management. The sternum is routinely included on breast MRI studies and can be an early site for breast cancer metastases. These appear as enhancing lesions with high signal on fat-suppressed T2-weighted images. However, incidental benign lesions, notably haemangiomas, may also be encountered, and careful analysis is required to avoid false-positive results. Clinical context is important with a much lower likelihood of malignancy in the setting of routine screening of young women with no personal history of breast cancer. This pictorial essay illustrates findings encountered with lesions in the sternum and offers insights into how to interpret and manage them.


Hematopoietic stem cell transplantation for primary immunodeficiency disease.
Hematopoietic stem cell transplantation is the definitive therapy for a variety of rare primary cellular immunodeficiency syndromes diagnosed in children. All primary immunodeficiencies benefit from early diagnosis and transplantation before the development of serious infections, which contribute to a significant increased risk of mortality following transplant. In the absence of a matched sibling, parental haplocompatible, matched unrelated donor and cord blood stem cells have all been utilized with varying degrees of success and immune reconstitution. The role of pretransplant conditioning in patients with SCID disease in terms of its effects upon T- and B-cell immune reconstitution and late effects is still under debate and will require further study.


Silk fibroin hydrogels induced and reinforced by acidic calcium phosphate - A simple way of producing bioactive and drug-loadable composites for biomedical applications.
Silk fibroin (SF) hydrogels have attracted extensive interest in biomedical applications due to their biocompatibility and wide availability. However, their generally poor mechanical properties limit their utility. Here, injectable, ready-to-use SF-based composites, simultaneously induced and reinforced by acidic calcium phosphates, were prepared via a dual-paste system requiring no complex chemical/physical treatment. The composite was formed by mixing a monocalcium phosphate monohydrate paste with a β-tricalcium phosphate/SF paste. The conformational transition of SF in an acidic environment forms continuous networks, and the acidic calcium phosphate, brushite and monetite, formed simultaneously in the networks during mixing. The composites displayed a partly elastomeric compression behavior, with mechanical properties increasing with an increasing calcium phosphate and β-sheet content at the lower calcium phosphate contents evaluated (22.2-36.4 wt%). While the stiffness was still relatively low, the materials presented a high elasticity and ductility, and no failure at stresses in the range of failure stresses of trabecular bone. Furthermore, the calcium phosphate confers bioactivity to the material, and the composites with a promising in vitro cell response also showed potential as drug vehicles, using vancomycin as a model drug. These dual-paste systems exhibit potential utility in biomedical applications, such as bone void fillers and drug vehicles.


Position Effect of Fatty Acid Modification on the Cytotoxicity and Antimetastasis Potential of the Cytotoxic Peptide Lycosin-I.
Peptide modification with fatty acids is an effective method to improve peptide performance. We previously investigated the fatty acid modification of R-lycosin-I, a cytotoxic peptide derived from lycosin-I from the venom of the spider Lycosa singoriensis. In this study, we further investigated the position effects of fatty acid modification of lycosin-I. Dodecanoic acid was covalently coupled to the α/ε-amino group of one of the seven Lys residues of lycosin-I, generating eight different lipopeptides. Although all the lipopeptides had significantly improved cytotoxicity compared with lycosin-I, they displayed different cytotoxic potencies and profiles, which might be explained by multifactors including charge, size, helicity, hydrophobicity, and so forth. Of the eight lipopeptides, L-C12 demonstrated highest cytotoxicity and antimetastasis activity in two-dimensional cells, tumor spheroids, subcutaneous transplantation mouse models, and experimental melanoma metastasis mouse models. Collectively, our finding indicated that fatty acid modification position plays important roles in physiochemical parameters and biological activities of cytotoxic peptides.


Three-dimensional replica of a life-sized model of aortic arch aneurysm for preoperative assessments.
In the treatment of extended distal aortic arch aneurysms with open stent grafting, detailed preoperative minute evaluation is essential to determine the optimal operative strategy and reduce the incidence of complications. We describe a three-dimensional replica of a life-sized aortic arch aneurysm model for aiding preoperative assessments. Life-sized replicas of an aortic arch aneurysm were made for 4 patients who underwent total aortic arch replacement with open stent-grafting. These replicas were used to determine the curve of the CLATE, a newly developed open stent delivery system (Senko Medical Instrument Mfg, Co, Ltd, Tokyo, Japan), and the depth of the open stent grafting. The replica and the CLATE system were also used to obtain informed consent from the patients. Surgeons could simulate the operative procedure precisely. Insertion of the graft was smooth in all patients. Use of the replica made it easier for the patients to understand the form and site of the aneurysm, as well as the operative procedure. The combination of the three-dimensional replica and the CLATE system may be useful for both surgeons and patients in the treatment of extended distal aortic arch aneurysms.


Learning Acoustic Assessment of Voice: An Action Research-Based SoTL Project.
The purpose of this action research, scholarship of teaching and learning study was to develop and integrate effective, student-informed teaching methods for voice acoustics instruction in a graduate speech-language pathology voice disorders course. An online focus group was used to determine what aspects of voice acoustics to include in the course as well as how these aspects were to be covered. A blend of face-to-face, technology-assisted, and practice-based teaching/learning activities resulted from the focused group and were employed in the course. An open-ended application question was used to measure student learning regarding application of voice acoustics to the understanding of human voice. A summative assessment of student recall and application of voice acoustics to speech-language pathology practice was also administered. Results showed significant, positive change pre- to post-course on the open-ended application question. Results of the summative assessment revealed that the largest distribution of student scores was in the 90%-100% range. While individual classes in different programs will differ, this project provides instructors with a baseline format from which to work to tailor acoustics instruction in their own classrooms.


A health screening and promotion clinic to improve metabolic monitoring for patients prescribed antipsychotic medication.
We sought to determine whether the introduction of a health screening and promotion clinic might serve as a useful addition to existing services for patients prescribed antipsychotic medication. In particular, we wished to assess whether such a clinic might improve adherence to best practice guidelines. We also wished to determine the level of patient interest in such a clinic and how readily this service might be provided within the constraints of existing clinical resources. We conducted an audit of outpatient records before and following the introduction of a health screening and promotion clinic. Of the eligible patients, 73% attended the clinic. The proportion of patients who had fasting blood tests within the previous 12 months increased from 45% at baseline to 85% at follow-up (χ 2 = 14.1, p < 0.001). The proportion of patients with appropriate physical observations completed increased from 5% at baseline to 80% at follow-up (χ 2 = 46.0, p < 0.001). We found that the introduction of a health screening and promotion clinic improved adherence to best practice guidelines. This service was well received and readily provided within the constraints of existing resources. Ultimately, the structure of services to screen and advise patients prescribed antipsychotic medication will be determined by local resource considerations and configuration of services.


Fracture of the tibial tubercle following anterior cruciate ligament reconstruction.
A case is presented of a traumatic avulsion fracture of part of the tibial tubercle after harvesting of the central third of the patellar tendon, with bone blocks, for anterior cruciate ligament (ACL) reconstruction. The literature is reviewed. This injury has not been reported previously.


Assessing autism at its social and developmental roots: A review of Autism Spectrum Disorder studies using functional near-infrared spectroscopy.
We review a relatively new method for studying the developing brain in children and infants with Autism Spectrum Disorder (ASD). Despite advances in behavioral screening and brain imaging, due to paradigms that do not easily allow for testing of awake, very young, and socially-engaged children-i.e., the social and the baby brain-the biological underpinnings of this disorder remain a mystery. We introduce an approach based on functional near-infrared spectroscopy (fNIRS), which offers a noninvasive imaging technique for studying functional activations by measuring changes in the brain's hemodynamic properties. This further enables measurement of brain activation in upright, interactive settings, while maintaining general equivalence to fMRI findings. We review the existing studies that have used fNIRS for ASD, discussing their promise, limitations, and their technical aspects, gearing this study to the researcher who may be new to this technique and highlighting potential targets for future research.


Association of elimination dysfunction and body mass index.
The reported prevalence of mild and severe obesity among US children is 30% and 15%, respectively. Childhood obesity likely relates to alterations in diet that also may cause constipation. We investigated the relationship between obesity and various forms of elimination dysfunction. The data of 251 patients who were diagnosed as having elimination dysfunction were analyzed retrospectively. Each patient's age, weight, height and diagnosis were evaluated and body mass index (BMI) was calculated. The percentile BMI was then analyzed based on diagnosis. BMI percentile> or =85% was defined as mild obesity and BMI percentile> or =95% was defined as severe obesity. The patients were divided into four groups based on diagnosis: constipation (n=70), enuresis+constipation (n=21), daytime incontinence (n=96) and nocturnal enuresis (n=64). The mean age of the patients was 9 years (range: 4-18 years). In the group with enuresis and constipation, 8/21 (38%) were mildly and 5/21 (24%) severely obese. Of patients with daytime incontinence, 36/70 (51%) were mildly and 22 (31%) severely obese, and of those with nocturnal enuresis alone, 35 (55%) were mildly and 20/64 (31%) severely obese. Of children with voiding dysfunction, 62-86% are also obese. This is almost double the rate in the normal population. These conditions may have a common etiology.


Adverse perinatal outcomes of chlamydia infections: an ongoing challenge.
Chlamydia trachomatis is one of the most common sexually transmitted diseases in the world, but there are limited data on its impact on perinatal outcomes. Our objective was to investigate the association between chlamydia infections and adverse perinatal outcomes. This is a retrospective analysis of the United States Centers for Disease Control and Prevention natality live birth database for the years 2016-2019. The rates of adverse perinatal outcomes were compared between patients with a chlamydia infection during pregnancy and patients without such infection, using Pearson's chi-square test with the Bonferroni adjustment. A multivariate logistic regression was then used to adjust outcomes for potential confounders. Chlamydia infections were associated with small, but statistically significant, increased odds of preterm birth (<37 weeks), early preterm birth (<32 weeks), low birthweight (<2,500 g), congenital anomalies, low 5-min Apgar score (<7), neonatal intensive care unit admission, immediate neonatal ventilation, prolonged (>6 h) neonatal ventilation, and neonatal antibiotic treatment for suspected sepsis. Chlamydia infections during pregnancy are associated with adverse perinatal outcomes. These results call for increased education regarding the potential risks of pregnancies with a chlamydia infection, as well as for increased antenatal surveillance and post-natal pediatric assessment in these pregnancies.


Biosensors based detection of novel biomarkers associated with COVID-19: Current progress and future promise.
The pandemic situation of COVID-19 has caused global alarm in health care, devastating loss of lives, strangled economy, and paralysis of normal livelihood. The high inter-individual transmission rate created havoc in the global community. Although tremendous efforts are pitching in from across the globe to understand this disease, the clinical features seemed to have a wide range including fever, cough, and fatigue are the prominent features. Congestion, rhinorrhea, sore throat, and diarrhea are other less common features observed. The challenge of this disease lies in the difficulty in maneuvering the clinical course causing severe complications. One of the major causative factors for multi-organ failure in patients with severe COVID-19 complications is systemic vasculitis and cytokine-mediated coagulation disorders. Hence, effective markers trailing the disease severity and disease prognosis are urgently required for prompt medical treatment. In this review article, we have emphasized currently identified inflammatory, hematological, immunological, and biochemical biomarkers of COVID-19. We also discussed currently available biosensors for the detection of COVID-19-associated biomarkers & risk factors and the detection methods as well as their performances. These could be effective tools for rapid and more promising diagnoses in the current pandemic situation. Effective biomarkers and their rapid, scalable, & sensitive detection might be beneficial for the prevention of serious complications and the clinical management of the disease.


The 10-year incidence of hypertension across blood pressure categories in a population-based cohort in southwestern Sweden.
To explore the determinants of incident hypertension, and especially the impact of baseline blood pressure categories, in a representative Swedish population. A 10-year longitudinal study of residents aged 30-74. Blood pressures were measured and categorized according to ESH guidelines with optimal blood pressure < 120/80 mmHg, normal 120-129/80-84 mmHg, and high normal 130-139/85-89 mmHg. Incident hypertension was defined as ongoing treatment or three consecutive blood pressure readings ≥ 140/ ≥ 90 mmHg (one or both) at follow-up, while those with ≥ 140 and/or ≥ 90 mmHg at only one or two visits were labelled as unstable. After excluding subjects with hypertension, ongoing blood pressure lowering medication or a previous CVD event at baseline, 1099 remained for further analyses. Sixteen (2.6%) subjects with optimal baseline blood pressure had hypertension at follow up. Corresponding numbers for subjects with normal, high normal and unstable blood pressure were 55 (19.4%), 50 (39.1%) and 46 (74.2%), respectively. Compared with subjects in optimal group those in normal, high normal and unstable blood pressure categories had significantly higher risk to develop manifest hypertension with odds ratios OR and (95% CI) of 7.04 (3.89-12.7), 17.1 (8.88-33.0) and 84.2 (37.4-190), respectively, with adjustment for age, BMI and family history for hypertension. The progression to hypertension was also independently predicted by BMI (p < 0.001), however, not by age. Subjects with high normal or unstable blood pressure should be identified in clinical practice, evaluated for global hypertension risk and offered personalized advice on lifestyle modification for early prevention of manifest hypertension and cardiovascular disease.


Long-term effect of physical activity on health-related quality of life among menopausal women: a 4-year follow-up study to a randomised controlled trial.
The aim of the study was to explore the long-term effects of physical activity intervention on quality of life (QoL) 4 years after an original randomised controlled trial (RCT). Cohort study after an RCT. 95 of the 159 women from the original RCT participated in weight, height and waist circumference measurements, performed the UKK 2 km Walk Test and completed the SF-36 Health Survey questionnaire. Multilevel mixed regression models were performed in order to compare the original and current group in an RCT setting. There were 159 participants in the original RCT; 2.5 years later, 102 of the women responded to a questionnaire and 4-year after the trial, there were 95 respondents. The inclusion criteria in the original RCT were: being symptomatic, experiencing daily hot flushes, age between 40 and 63 years, not using hormone therapy now or in the past 3 months, sedentary lifestyle and having last menstruated 3-36 months earlier. Health-related QoL as measured with the SF-36 instrument. Women in the intervention group had a significantly higher probability of improved physical functioning (OR 1.41; 95% CI 1.00 to 1.99) as compared with women in the control group. In addition, women in the intervention group had higher odds of good role functioning (OR 1.21; 95% CI 0.88 to 1.67), physical health (OR 1.33; 95% CI 0.96 to 1.84) and general health (OR 1.14; 95% CI 0.81 to 1.62), relative to women in the control group, although the differences did not reach statistical significance. Women in the intervention group showed positive long-term effects on physical and mental dimensions of QoL after 4 years. ISRCTN54690027.


Cystoscopic removal of transvaginal mesh: Long-term outcomes.
This study's aim is to evaluate the long-term quality of life and functional outcomes following cystoscopic excision of stress urinary incontinence (SUI) and pelvic organ prolapse (POP) mesh extruded into the urinary tract in women. A retrospective chart review was performed of all cases of cystoscopic removal of extruded mesh at our high-volume tertiary care centre between April 2013 and August 2021. Postoperative patient-reported outcomes were collected via questionnaires: Urogenital Distress Inventory Short Form (UDI-6), EQ-5D-5L Visual analogue scale, ICIQ-Satisfaction (ICIQ-S) and additional questions regarding postoperative sexual function. During the study period, 27 women with a median age of 61 years (45-87) underwent cystoscopic mesh removal surgery using either Ho-YAG laser (56%) or bipolar loop resection (44%). The most common presentation of mesh extrusion was recurrent urinary tract infections (67%). Other presenting complaints were pain (41%), urinary urgency ± incontinence (41%) and voiding difficulties (18%). Long-term follow-up outcomes from 20 patients (median follow-up: 24 months) showed that mesh removal was rated successful by 80%, and 100% would choose to have the surgery again if in the same situation. Recurrent SUI was reported by 45% of respondents, and urinary urge incontinence was found in 50%. For patients who answered the sexual function questions, 50% reported improved sexual function postmesh removal (6/12). Cystoscopic removal of extruded female SUI and POP mesh is associated with high patient satisfaction and low morbidity in appropriately selected patients at 2-year median follow-up. A patient-centred shared decision-making process is essential in counselling patients regarding options and expected outcomes following mesh removal surgery.


Prevalence and acceptability of public health initiatives in licensed premises.
To determine the prevalence and acceptability of public health initiatives in licensed premises. Licensees/managers of all 333 licensed premises in the Hunter Region of NSW were interviewed to assess the practice of, and interest in undertaking public health initiatives relating to: responsible service of alcohol; environmental tobacco smoke; healthy-food choices; skin, breast and cervical cancer prevention; and the prevention of HIV/AIDS. Ninety eight percent of contacted premises participated in the study. Approximately two-thirds of premises reported having a responsible service of alcohol policy and training their staff in responsible service. One third of premises reported the provision of healthy food choices and smoke-free areas. Initiatives concerned with the prevention of cancer and HIV/AIDS were practised by less than 25% of premises. Between 41% and 85% of premises expressed an interest in undertaking all but two initiatives. Almost all interested premises accepted the offer of resources to facilitate adoption of public health initiatives. The study suggests that licensed premises are already involved in a number of public health initiatives, and that they appear willing to consider the introduction of a wide range of such initiatives. The prevalence of public health initiatives in licensed premises, and the extent of interest expressed by licensees/managers in undertaking such initiatives suggests that both a need and an opportunity exist for public health and other agencies to be more actively involved in disseminating appropriate services in this setting.


Carbon dioxide assimilation and stomatal response of afroalpine giant rosette plants.
Maximal rates of CO2 assimilation of 8-11 μmol m-2 s-1 at ambient CO2 concentration were measured for Dendrosenecio keniodendron, D. brassica, Lobelia telekii and L. keniensis during the day in the natural habitat of these plants at 4,200 m elevation on Mt. Kenya. Even at these maximal rates, the CO2 uptake of all species was found to correspond to the linear portion of the CO2 response curve, with a calculated stomatal limitation for CO2 diffusion of 42%. Photosynthesis was strongly reduced at temperatures above 15° C. In contrast to this sensitivity to high temperatures, frozen leaves regained full photosynthetic capacity immediately after thawing. Stomata responded to dry air, but not to low leaf water potentials which occurred in cold leaves and at high transpiration rates. During the day reduced rates of CO2 uptake were associated with reduced light interception due to the erect posture of the rosette leaves and with high temperatures. Stomata closed at vapour pressure deficits which were comparable in magnitude to those characteristic of many lowland habitats (40 mPa Pa-1).


Nonlinear Relation Between Burst Dorsal Root Ganglion Stimulation Amplitude and Behavioral Outcome in an Experimental Model of Painful Diabetic Peripheral Neuropathy.
Dorsal root ganglion stimulation (DRGS) has recently emerged as a neuromodulation modality in the treatment of chronic neuropathic pain. The objective of this study was to compare the efficacy of different Burst-DRGS amplitudes in an experimental model of painful diabetic peripheral neuropathy (PDPN). Diabetes mellitus was induced in female Sprague-Dawley rats by intraperitoneal injection of streptozotocin (STZ, n = 28). Animals were tested for mechanical hypersensitivity (von Frey paw withdrawal test) before, and four weeks after STZ injection. PDPN rats (n = 13) were implanted with a unilateral bipolar electrode at the L5 DRG. Animals received Burst-DRGS at 0%, 10%, 33%, 50%, 66%, and 80% of motor threshold (MT) in a randomized crossover design on post-implantation days 2-7 (n = 9). Mechanical hypersensitivity was assessed before stimulation onset, 15 and 30 min during stimulation, and 15 and 30 min after stimulation. Burst-DRGS at amplitudes of 33%, 50%, 66%, and 80% MT resulted in significant attenuation of STZ-induced mechanical hypersensitivity at 15 and 30 min during stimulation, as well as 15 min after cessation of stimulation. No effect on mechanical hypersensitivity was observed for Burst-DRGS at 0% MT and 10% MT. Optimal pain relief and highest responder rates were achieved with Burst-DRGS at 50-66% MT, with an estimated optimum at 52% MT. Our findings indicate a nonlinear relationship between Burst-DRGS amplitude and behavioral outcome, with an estimated optimal amplitude of 52% MT. Further optimization and analysis of DRGS driven by insights into the underlying mechanisms related to the various stimulation paradigms is warranted.


Full-dose ifosfamide can be safely administered to outpatients.
This report compares a traditional full-dose ifosfamide administration modality (24-hr hyperhydration and mesna infusion) with a simplified 9-hr hyperhydration and mesna infusion for use in outpatients. Acute ifosfamide toxicity was the same, suggesting that ifosfamide could be safely administered to outpatients, reducing the currently-recommended prolonged hyperhydration and mesna uroprotection, thus resulting in shorter hospital stays and consequently lower costs.


In-vitro evaluation of a ciprofloxacin and azithromycin sinus stent for Pseudomonas aeruginosa biofilms.
Chronic rhinosinusitis (CRS) is a chronic inflammatory disease characterized by persistent inflammation and bacterial infection. Ciprofloxacin and azithromycin are commonly prescribed antibiotics for CRS, but the ability to provide targeted release in the sinuses could mitigate side effects and improve drug concentrations at the infected site. This study was aimed to evaluate the efficacy of the novel ciprofloxacin-azithromycin sinus stent (CASS) in vitro. The CASS was created by coating ciprofloxacin (hydrophilic, inner layer) and azithromycin (hydrophobic, outer layer) onto a biodegradable poly-l-lactic acid (PLLA) stent. In-vitro evaluation included: (1) assessment of drug-coating stability within the stent using scanning electron microscopy (SEM); (2) determination of ciprofloxacin and azithromycin release kinetics; and (3) assessment of anti-biofilm activities against Pseudomonas aeruginosa. The ciprofloxacin nanoparticle suspension in the inner layer was confirmed by zeta potential. Both ciprofloxacin (60 µg) and azithromycin (3 mg) were uniformly coated on the surface of the PLLA stents. The CASS showed ciprofloxacin/azithromycin sustained release patterns, with 80.55 ± 11.61% of ciprofloxacin and 93.85 ± 6.9% of azithromycin released by 28 days. The CASS also significantly reduced P aeruginosa biofilm mass compared with bare stents and controls (relative optical density units at 590-nm optical density: CASS, 0.037 ± 0.006; bare stent, 0.911 ± 0.015; control, 1.000 ± 0.000; p < 0.001; n = 3). The CASS maintains a uniform coating and sustained delivery of ciprofloxacin and azithromycin, providing anti-biofilm activities against P aeruginosa. Further studies evaluating the efficacy of CASS in a preclinical model are planned.


Platelet rich plasma in treatment of musculoskeletal pathologies.
Over the past two decades, platelet rich plasma (PRP) has been available as a biological treatment for healing or regeneration of impaired or non-functional tissues. This manuscript highlights PRP application in the treatment of musculoskeletal pathologies. Data in relation to PRP were gathered using PubMed and Medline database from 1994 to 2019, including in vivo animal experiments and clinical studies. PRP appears to promote pain relief and improvement in joint function and it usage has gained popularity for the treatment of musculoskeletal diseases. Nevertheless, limitations in current studies also need to be taken into account in view of the short term effects of PRP therapy and follow-up studies are needed to confirm the long-term efficacy of PRP. Growing interest in the use of this therapeutic modality for the treatment of musculoskeletal diseases gives new opportunities for further clinical studies on the efficacy of this bioproduct, including the more standardised PRP lysate which contains all the active principles of native PRP, and will become highly popular in regenerative medicine.


Circulating cell-free fetal DNA in maternal serum appears to originate from cyto- and syncytio-trophoblastic cells. Case report.
Circulating cell-free fetal DNA in maternal serum offers an early and non-invasive method for prenatal diagnosis, but the origin of this DNA is still unknown. We report the absence of the SRY gene in maternal serum of a pregnant woman despite male genitalia at ultrasound. The karyotype was 45,X after direct trophoblast analysis and 45,X/46,Xidic(Yp) after culture and in all fetal tissues studied. Due to the absence of the SRY sequence in maternal blood and in the cytotrophoblast, we presume that free fetal DNA in this case originates from trophoblastic cells. As the case presented here is exceptional, it only has a minor impact on the accuracy of fetal sex determination by maternal serum analysis, but highlights the importance of and the necessity for the complementary ultrasonographic control.


Substance P in rat brain synaptosomes.
1. Rat brain synaptosomes were incubated under different conditions to study the release of substance P (SP). 2. Potassium ions and electrical field stimulation induced a loss of SP from synaptosomes. The release of SP by potassium in high concentrations (23.8 mM) was shown to be calcium dependent. 3. Substance P was retained in synaptosomes during incubation in 0.32 M sucrose at +4 degrees C up to 120 min. During incubation at 30 degrees C the SP content fell initially (30 min) but was gradually restored (120 min). 4. If these pre-incubated synaptosomes were reincubated for 45 min at 30 degrees C in potassium free Krebs-Ringer-phosphate buffer a further rise in their SP content occurred which was taken as indication that SP is being synthesized in synaptosomes. 5. The newly synthesized SP is presumably stored by binding to phosphatidyl serine until a sudden release is initiated by depolarization.


A meta-analysis on the efficacy and tolerability of natalizumab in relapsing multiple sclerosis.
Natalizumab is a new humanized monoclonal antibody used in multiple sclerosis (MS). The aim of this meta-analysis was to evaluate the efficacy and tolerability of this drug in relapsing MS. PubMed, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials were searched for studies that investigated the efficacy and/or tolerability of natalizumab in MS. Data were collected from 1966 to 2008 (up to October). THE SEARCH TERMS WERE: "multiple sclerosis" or "MS" and "natalizumab". "Mean change in Expanded Disability Status Scale (EDSS)", "number of patients with at least one relapse", and "number of patients with at least one new gadolinium (Gd)-enhancing lesion" were the key outcomes of interest for assessment of efficacy. "Any adverse events", "serious adverse events", "death", and "withdrawal because of adverse events" were the key outcomes for tolerability. Among existing trials, four randomized placebo controlled clinical trials met our criteria and were included. Pooled relative risk for at least one relapse in four trials including all doses was 0.7, with a non-significant RR (95% CI: 0.42-1.17, p = 0. 17). Summary RR for at least one relapse in two trials in which doses of 3 mg/kg or 6 mg/kg or 300 mg every 4 weeks were administered gave a value of 0.5 asa significant RR (95% CI: 0.42-0.61, p < 0.0001). The summary RR for at least one new Gd-enhancing lesion was 0.22, a non-significant RR (95% CI: 0.05-1.01, p = 0.051). Three deaths were reported in the natalizumab group. Comparing adverse events between natalizumab and placebo yielded a non-significant RR of 0.99 (95% CI: 0.96-1.01, p = 0.34) for any adverse events (n = 3), and a significant RR of 0.39 (95% CI: 0.29-0.52, p < 0.0001) for serious adverse events (n = 2). The summary RR for withdrawal due to adverse events by natalizumab vs. placebo therapy between two trials was 1.43, a non-significant RR (95% CI: 0.68-3.02, p = 0.35). It seems that using 3 or 6 mg/kg every 4 weeks is the best method of administration of natalizumab for preventing relapse and occurrence of new Gd-enhancing lesions. The current data on the efficacy and safety of natalizumab are insufficient to reach a convincing conclusion and thus further clinical trials are still needed.


COVID-19 or clinical amyopathic dermatomyositis associated rapidly progressive interstitial lung disease? A case report.
Coronavirus disease 2019 (COVID-19) has reach pandemic proportions globally. For patients with symptoms of fever and cough accompanied by rapid lung damage progression, COVID-19 needs to be distinguished from interstitial lung disease (ILD) attributed to connective tissue disease (CTD), especially dermatomyositis (DM)/clinical amyopathic dermatomyositis (CADM) associated rapidly progressive interstitial lung disease (RP-ILD). We report a case of a woman observed with fever, cough, and rapid lung damage during the epidemic. The patient had a suspicious epidemiological history, and her chest CT scans showed lung damage similar to that caused by COVID-19, but anti-Ro52 antibody was strongly positive. She was diagnosed with CADM associated RP-ILD and died 1 month later. During the COVID-19 epidemic, it is critical to carefully assess patients with CTD related ILD, especially RP-ILD associated with CADM. Repeated nucleic acid tests for COVID-19 are necessary to achieve accurate case diagnosis. High-resolution CT (HRCT) of the chest is presently deemed an inefficient technique to distinguishing between COVID-19 and CADM associated RP-ILD. The characteristic rashes of dermatomyositis require careful observation and can often provide diagnostic clues. For patients with CADM, a high titers of anti-Ro52 antibody may be related to the pathogenesis of RP-ILD, suggesting a poor prognosis.


Clinical manifestation for immunoglobulin A deficiency: a systematic review and meta-analysis.
Immunoglobulin A deficiency (IgAD) is a common disease with an unknown genetic defect, characterized by the decreased or absent IgA with other isotypes normal, normal subclasses, and specific antibodies. Patients with this disorder represent a spectrum of clinical manifestations including infections, autoimmune disorders, malignancy, and allergic diseases. The current study aimed to evaluate their prevalence and categorized them. We searched PubMed, Web of Science, and Scopus databases to find eligible studies from the earliest available date to January 2022 with standard keywords. Pooled estimates of clinical manifestations prevalence and the corresponding 95% confidence intervals were calculated using random-effects models. The most prevalent clinical manifestations belonged to infection (64.8%) followed by allergic diseases (26.16%) and autoimmunity (22.0%), respectively. In selective IgA deficiency patients as the largest group of IgAD in current study, celiac disease (6.57%), Inflammatory bowel disease (4.01%), and rheumatoid arthritis (3.80%) were the most prevalent autoimmunity. Meanwhile, the most frequent infection was respiratory tract infection, fungal infection, and gastrointestinal infection at 50.74%, 18.48%, and 15.79%, respectively. In addition, the pooled prevalence of asthma, allergic rhinitis, and allergic conjunctivitis were 19.06%, 15.46%, and 11.68%, respectively which were reported as the most widespread allergic diseases. Our results showed that apart from undiagnosed IgAD patients, IgAD patients represent a wide range of clinical manifestations. Infection, allergy, and autoimmunity are the most common clinical manifestations. The concurrent presence of IgA and IgG subtypes deficiency could be associated with increased susceptibility to infection. Considering the probability of developing new clinical complications during follow-up, periodic assessments of IgAD patients should be inspected.