Comparison of quality of life, work productivity and medical resource utilization of peginterferon alpha 2a vs the combination of interferon alpha 2b plus ribavirin as initial treatment in patients with chronic hepatitis C.
The on-treatment impact of interferon-based therapies on quality of life (QOL), work productivity, and medical resource utilization has not been systematically studied. We evaluated the effects of treatment with peginterferon alpha (pegIFNalpha) 2a monotherapy and the combination of interferon alpha (IFNalpha) 2b plus ribavirin (RBV) on health-related QOL, work productivity and resource utilization. A total of 412 patients with hepatitis C infection were randomized to open-label treatment with either pegIFNalpha 2a (n = 206) or IFNalpha 2b/RBV (n = 206). PegIFNalpha 2a was administered subcutaneously at a dose of 180 microg once weekly for 48 weeks; and IFNalpha 2b/RBV at doses of 3 MU thrice weekly subcutaneously and 1000-1200 mg/day orally. Outcome measures included the SF-36 Health Survey Questionnaire and additional generic and specific scales. During treatment, for all SF-36 summary and Hepatitis Quality of Life Questionnaire (HQLQ)-specific scales, the pegIFNalpha 2a group experienced less impairment than did the IFNalpha 2b/RBV patients. The between-treatment differences were significant for many of the scores particularly in the first 24 weeks of treatment. Across all measures of work functioning and productivity at each visit, patients randomized to pegIFNalpha 2a treatment showed less impairment relative to the group treated with IFNalpha 2b/RBV. Hence treatment with pegIFNalpha 2a relative to IFNalpha 2b/RBV minimizes the adverse impact of therapy on health-related QOL. Patients randomized to pegIFNalpha 2a had improved work productivity, less activity impairment, decreased need for prescription drugs to treat adverse effects, and better adherence to therapy.


The epigenetic state of IL-4-polarized macrophages enables inflammatory cistromic expansion and extended synergistic response to TLR ligands.
Prior exposure to microenvironmental signals could fundamentally change the response of macrophages to subsequent stimuli. It is believed that T helper-2 (Th2)-cell-type cytokine interleukin-4 (IL-4) and Toll-like receptor (TLR) ligand-activated transcriptional programs mutually antagonize each other, and no remarkable convergence has been identified between them. In contrast, here, we show that IL-4-polarized macrophages established a hyperinflammatory gene expression program upon lipopolysaccharide (LPS) exposure. This phenomenon, which we termed extended synergy, was supported by IL-4-directed epigenomic remodeling, LPS-activated NF-κB-p65 cistrome expansion, and increased enhancer activity. The EGR2 transcription factor contributed to the extended synergy in a macrophage-subtype-specific manner. Consequently, the previously alternatively polarized macrophages produced increased amounts of immune-modulatory factors both in vitro and in vivo in a murine Th2 cell-type airway inflammation model upon LPS exposure. Our findings establish that IL-4-induced epigenetic reprogramming is responsible for the development of inflammatory hyperresponsiveness to TLR activation and contributes to lung pathologies.


Scutellaria radix Extract as a Natural UV Protectant for Human Skin.
Ultraviolet (UV) radiation induces oxidative injury and inflammation in human skin. Scutellaria radix (SR, the root of Scutellaria baicalensis Georgi) contains flavonoids with high UV absorptivity and antioxidant properties. The purpose of this study was to examine the potential use of SR extract as an additive in cosmetic products for UV protection. SR extract and its butanol (BuOH) fraction strongly absorbed UV radiation and displayed free radical scavenging activity against 2,2-diphenyl-1-picrylhydrazyl radials and 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) radicals. They also attenuated the UV-induced death of HaCaT cells. Sunscreen creams, with or without supplementation of SR extract BuOH fraction, were tested in vivo in human trials to evaluate potential skin irritation and determine the sun protection factor (SPF). Both sunscreen creams induced no skin irritation. A sunscreen cream containing 24% ZnO showed an SPF value of 17.8, and it increased to 22.7 when supplemented with 5% SR extract BuOH fraction. This study suggests that SR-derived materials are useful as safe cosmetic additives that provide UV protection.


Nonsteroid anti-inflammatory drugs prevent the recurrence of heterotopic ossification after excision.
The prophylactic effect of nonsteroid anti-inflammatory drugs on the recurrence of high-grade periarticular heterotopic ossification after resection was studied in ten patients operated on for loosening of one or both components of a cemented total hip prosthesis. These drugs, given at a standard dosage for 1-3 weeks after surgery, prevented the recurrence of heterotopic ossification. In some patients the range of motion of their joint increased following surgery, while it remained unaffected in the majority. At follow-up 2-5 years after surgery, all patients walked well and there were no clinical or radiographs signs of loosening of the prosthetic components. It is concluded that treatment with NSAIDs following resection of periarticular heterotopic ossification prevents recurrence.


Failure of exogenous prostacyclin to change placental and fetal blood flow in preeclampsia.
Seven patients with acute preeclampsia and six with superimposed preeclampsia were infused intravenously with incremental doses of prostacyclin (up to 8 ng/min/kg during 80 minutes). Prostacyclin infusion was accompanied by significant decreases in maternal blood pressure and consistent rises in maternal plasma or urinary 6-keto-prostaglandin F1 alpha, but it caused no changes in maternal or fetal pulse rate or uterine contractility. Moreover, prostacyclin did not change the placental and umbilical blood flow, which were measured before and at the end of infusion. All women experienced facial flushing and two complained of headache during infusion. There was no difference in prostacyclin effects between women with acute or superimposed preeclampsia. These results may be taken as evidence that intravenous prostacyclin is not a specific therapy to increase placental or umbilical blood flow in preeclampsia.


Continued erlotinib maintenance and salvage radiation for solitary areas of disease progression: a useful strategy in selected non-small cell lung cancers?
Advanced non-small cell lung cancer (NSCLC) is a common and lethal malignancy that has rarely benefited from chemotherapy. Erlotinib is highly effective in NSCLC patients selected by clinical characteristics and/or the presence of epidermal growth factor receptor-sensitizing mutations. However, the way to delay or bypass erlotinib resistance is not systematically addressed. Different erlotinib-failure modes have been reported in NSCLC, and strategies to prolong erlotinib efficacy are perhaps adaptable to them. We report the feasibility and efficacy of continued erlotinib maintenance and local salvage radiation to overcome erlotinib resistances in selected NSCLC patients. Thirty of 52 consecutive erlotinib-treated advanced NSCLC from the NYU Langone Medical Center and the Arnau de Vilanova Hospital of Lleida responded initially to erlotinib. Twenty-six patients eventually showed a generalized-progression to erlotinib, and four progressed in solitary tumor sites. These four patients were treated with continued erlotinib maintenance and local salvage radiation. The progression-free survival (PFS) was statistically similar in patients with oligo or generalized-progression to erlotinib. However, all four cases with solitary-progression did benefit from continued erlotinib maintenance and salvage radiation with 41-140 % prolongation of PFS. It was reflected in an improved overall survival when they were compared with patients with generalized-progression (76.4 vs. 19.9 months; p = 0.018). Continued erlotinib maintenance and local salvage radiation is feasible and could contribute to a better outcome in selected NSCLC patients with solitary-progression to erlotinib. Prospective randomized trials of this strategy are warranted.


Effect of folic and folinic acid on cytopenia occurring during co-trimoxazole treatment of Pneumocystis carinii pneumonia.
12 AIDS/ARC patients with or suspected of Pneumocystis carinii pneumonia were treated with co-trimoxazole and received supplementary folic or folinic acid to avoid peripheral blood cytopenia. Most patients developed decreased numbers of neutrophils and hemoglobin while receiving co-trimoxazole. Supplementary folate/folinate could not abolish the drug-induced cytopenia. Routine prescription of folinic acid is not recommended. Folic acid is cheap and may be beneficial and should be prescribed.


A 3D-bioprinted scaffold with doxycycline-controlled BMP2-expressing cells for inducing bone regeneration and inhibiting bacterial infection.
Large bone defects face a high risk of pathogen exposure due to open wounds, which leads to high infection rates and delayed bone union. To promote successful repair of infectious bone defects, fabrication of a scaffold with dual functions of osteo-induction and bacterial inhibition is required. This study describes creation of an engineered progenitor cell line (C3H10T1/2) capable of doxycycline (DOX)-mediated release of bone morphogenetic protein-2 (BMP2). Three-dimensional bioprinting technology enabled creation of scaffolds, comprising polycaprolactone/mesoporous bioactive glass/DOX and bioink, containing these engineered cells. In vivo and in vitro experiments confirmed that the scaffold could actively secrete BMP2 to significantly promote osteoblast differentiation and induce ectopic bone formation. Additionally, the scaffold exhibited broad-spectrum antibacterial capacity, thereby ensuring the survival of embedded engineered cells when facing high risk of infection. These findings demonstrated the efficacy of this bioprinted scaffold to release BMP2 in a controlled manner and prevent the occurrence of infection; thus, showing its potential for repairing infectious bone defects.


Dose-effect of polystyrene microplastics on digestive toxicity in chickens (Gallus gallus): Multi-omics reveals critical role of gut-liver axis.
Microplastic pollution seriously threatens the health and safety of humans and wildlife. Avian is one of the main species endangered by microplastics. However, the damage mechanism of microplastics to the digestive system of avian is not clear. The gut-liver axis is a bidirectional channel that regulates the exchange of information between the gut and the liver and is also a key target for tissue damage caused by pollutants. This study aimed to elucidate the digestive toxicity of microplastics in avian and the key role of the gut-liver axis in it. We constructed an exposure model for microplastics in environmental concentrations and toxicological concentrations in chickens and reveal the digestive toxicity of polystyrene microplastics (PS-MPs) in avian by 16S rRNA, transcriptomics and metabolomics. PS-MPs changed the death mode from apoptosis to necrosis and pyroptosis by upregulating Caspase 8, disrupting the intestinal vascular barrier, disturbing the intestinal flora and promoting the accumulation of lipopolysaccharide. Harmful flora and metabolites were translocated to the liver through the liver-gut axis, eliciting hepatic immune responses and promoting hepatic lipid metabolism disorders and apoptosis. Liver injury involves multiple molecular effects of mitochondrial dynamics disturbance, oxidative stress, endoplasmic reticulum stress, and cell cycle disturbance. Furthermore, metabolomics suggested that caffeine and melanin metabolites may be potential natural resistance substances for microplastics. Taken together, our data demonstrate the digestive damage of PS-MPs in avian, revealing a critical role of the liver-gut axis in it. This will provide a reference for protecting the safety of avian populations.


The brain in late-onset glycogenosis II: a structural and functional MRI study.
Late-onset glycogenosis type II (GSD II) is a rare, multisystem disorder mainly affecting limb and respiratory muscles due to acid alpha glucosidase deficiency. Despite evidence at autopsy of glycogen accumulation in the brain, no study exploring brain functions is yet available. Our objective in this study was to assess brain changes in late-onset GSD II. Each patient underwent a standardized neuropsychological assessment, regional grey-matter (GM) atrophy, and resting-state functional magnetic resonance imaging (RS-fMRI). Functional connectivity maps of the salience (SN) and default-mode (DMN) networks were considered. A group of age- and gender-matched healthy controls was enrolled for MRI comparisons. P values family-wise error (FWE) cluster level corrected inferior to 0.05 were considered. Nine GSD II patients (age 46.6 ± 8.0; 55% male) were recruited. No significant GM atrophy was found in patients compared with controls (n = 18; age 48.0 ± 9.8,;40% male). Functional connectivity within the SN was selectively reduced in patients, and cingulate gyrus and medial frontal cortex were mainly involved. Accordingly, patients had significant impairment of executive functions (as measured by Wisconsin Card Sorting test), whereas other cognitive domains were within mean normal ranges. Our findings extend the clinical spectrum of GSD II by indicating that brain changes occur in this muscular disorder. Above all, these results should lead to better examinations of therapeutic approaches and perspectives for the affected patients. Further studies evaluating in depth these issues are warranted.


Spin textures and Larmor precession of holes modulated by the spin-orbit coupling confined in the two-dimensional Si x Ge1-x mixed-alloy quantum well system.
We theoretically study the spin textures of holes confined in the two-dimensional (2D) [Formula: see text] quantum well (QW) system. We particularly focus on the spin-orbit interaction (SOI) caused by the bulk-inversion-asymmetry (BIA) and explore the effective magnetic field (EMF) generated by the combination of the SOI couplings. For the study of the semiconductor mixed-alloy (MA) system, we propose the extended [Formula: see text] perturbation approach including possible perturbation terms crossing with the SOI couplings up to the second order ones. We then study the distribution and orientation of the EMF and investigate how the EMF changes the spin textures of the heavy-mass holes (HHs), light-mass holes (LHs) and separated holes (SHs), respectively. Finally, we study the Larmor spin precession of these holes having the characteristic spin textures driven by the SOI couplings.


The Patient's Point of View: COVID-19 and Neuroendocrine Tumor Disease.
The assessment of cancer patient care during the COVID-19 pandemic has been mainly reported from a physician's perspective. Patients with rare tumor entities such as neuroendocrine tumors (NET), which require a complex and specialized care infrastructure, were highly affected by the COVID-19 crisis. Using a structured questionnaire consisting of a general section on the disease and a special COVID-19 section to record medical care, vaccination behavior as well as social and psycho-emotional parameters were collected from NET patients. The survey was distributed via direct medical contact and via the patient organization NETZWERK NeT. A total of 684 patients participated in the survey and 79.2% (n = 542) of the participants answered the questionnaire completely (54 questions). Patient characteristics were comparable to those in large NET registries. The majority of participants were patients with pancreatic and small bowel NET on somatostatin analogue (SSA) therapy. Medical care under COVID-19 was adequate and appointment cancellations and postponements were not common. Nevertheless, the majority of patients were worried about adequate treatment for their tumor disease during the crisis. Most of the participants considered themselves to be at risk of severe COVID-19 infection and were therefore very concerned. This was accompanied by an extremely high vaccination readiness rate of 90%. Increased distress in the social and psycho-emotional domains in the course of the crisis reflected a need for optimization in the medical care of NET patients, although the rate of COVID-19 positive participants was low (3.7%). Therefore, patient-reported measurements are required to identify and address all areas of medical care. Overall, our survey provides an essential contribution to the care of NET patients during the COVID-19 pandemic from the patient's perspective.


The CHILD-syndrome--congenital hemidysplasia with ichthyosiform erythroderma and limb defects. A case report.
A presentation of a 3-year-old girl with a congenital hemidysplasia of the left side together with ichtyosiform erythroderma, the so-called CHILD-syndrome. A short review of the syndrome is given.


Pharmacokinetic Interaction Between Isavuconazole and a Fixed-Dose Combination of Lopinavir 400 mg/Ritonavir 100 mg in Healthy Subjects.
This phase 1, open-label study evaluated the pharmacokinetic effects of coadministration of the antifungal agent, isavuconazole (administered as its water-soluble prodrug isavuconazonium sulfate), with the antiretroviral agent lopinavir/ritonavir in healthy adults. In part 1, 13 subjects were randomized to 2 arms to receive multiple doses of oral isavuconazole 100 mg either alone or with lopinavir/ritonavir 400/100 mg. In part 2, a different group of 55 subjects were randomized to 3 arms to receive multiple doses of oral isavuconazole 200 mg, either alone or with lopinavir/ritonavir 400/100 mg, or to receive oral lopinavir/ritonavir 400/100 mg alone. Mean area under the concentration-time curve (AUC) following the last dose (AUCτ ) and Cmax of isavuconazole increased by 113% and 96% in part 1 and by 96% and 74% in part 2 in the presence vs absence of lopinavir/ritonavir, respectively. Mean AUCτ and Cmax of lopinavir were 27% and 23% lower, and mean AUCτ and Cmax of ritonavir were 31% and 33% lower in the presence vs absence of isavuconazole, respectively. Mild to moderate gastrointestinal disorders were the most common adverse events experienced. These findings indicate that coadministration of lopinavir/ritonavir with isavuconazole can decrease the exposure of lopinavir/ritonavir and increase the exposure of isavuconazole. Patients should be monitored for reduced antiviral efficacy if these agents are coadministered.


Eosinophilic cystitis complicated with cystitis glandularis: a case report.
Eosinophilic cystitis (EC) is a rare inflammatory disease characterized by the gathering and infiltration of numerous eosinophilia (EOS) in the bladder wall. Because of Few cases of EC have been reported globally, the epidemiology of EC is not well known. We report herein the details of one very scarce case of large tumor-like eosinophilic cystitis complicated with cystitis glandularis (CG) diagnosed by biopsy. A 45-year-old Chinese man was referred to our hospital for the treatment of right lumbago and odynuria. Ultrasound examination indicated the low echo on the right portion wall and the neck of the bladder. Computed tomography showed a remarkable enhancing large mass that measured 5.0 cm × 2.3 cm located on the right portion of the bladder with undefined margin. For further treatment, diagnostic transurethral resection of the bladder was performed, the postoperative histopathological diagnosis was EC complicated with CG. After transurethral resection, antibiotics, glucocorticoids, and antihistamines were treated. The patient recovered uneventfully and was discharged on postoperative day 8 without evidence of recurrence followed-up for 6 months. Large tumor-like eosinophilic cystitis complicated with cystitis glandularis is rare, malignant tumors need to be ruled out. We deem that prompt biopsy led to the exact diagnosis, appropriate treatment led to better prognosis.


Identification and characterization of a thermostable GH11 xylanase from Paenibacillus campinasensis NTU-11 and the distinct roles of its carbohydrate-binding domain and linker sequence.
An extracellular thermostable xylanase (XynNTU) from Paenibacillus campinasensis NTU-11, consisted of a glycoside hydrolase (GH) family 11 catalytic domain, a Gly/Pro-rich linker sequence (LS) and a family 6 carbohydrate-binding module (CBM6), was identified and expressed in E. coli BL21. The purified XynNTU had a specific activity of 2750 U/mg and an optimal activity at 60 °C and pH 7.0, and retained a residual activity of 58.4% after incubation (60 °C, 48 h). Two truncated mutants, CBM6-truncated form XynNTU-CDLS, CBM6 and linker-truncated form XynNTU-CD, possessed similar values of optimum pH and temperature as the native XynNTU. XynNTU-CD displayed a lower thermostability than XynNTU, whereas for XynNTU-CDLS, more than 90% of residual activity was remained (60 °C, 48 h), indicating that this enzyme presented a higher thermostability than that of the majority of reported GH11 xylanases. Furthermore, XynNTU and two mutants maintained more than 70% of residual activity at pH values of 5-9. Kinetic measurements suggested that CBM6 had a crucial function in the ability of the enzyme to bind and hydrolyze xylan substrates, while LS had a relatively mild influence. Collectively, a noticeable thermostability and a high specific activity of XynNTU and its truncated form XynNTU-CDLS highlights their potentials for diverse industrial applications.


Clinical and radiographic behaviour of 290 dental implants with a surface treated with hydrofluoric acid and passivated with hydrofluoric and nitric acid: early loading results after 2 years.
This work presents the results of clinical and radiological behaviour, for 2 years, of 290 implants treated with a first etching with HF and a second etching with HF and HNO3 acids and that were loaded 8 weeks after insertion. It is a prospective study on 290 implants placed in 56 patients with an age range from 28 to 81. The selection was previously made through radiological study with panoramic and tomographic radiographs, followed by the implantological treatment with prosthetic loading and clinical (15 days, 1, 3 , 6, 12, 18 and 24 months) and radiological control (12 and 24 months). During the healing period, 11 implants failed, resulting in a CSR of 96.21%. After prostheses placement at 2 months, 4 implants were retired, successfully remaining 275 implants. The following and favourable results after the prosthetic loading of 179 implants (CSR of 98.56%), attest that early loading may and must be applied, after rigorous planning and case selection.


Pregnancies following conservative treatment of malignant ovarian tumors.
Sixteen patients with malignant ovarian tumors were treated conservatively; 1 had a serous cystadenoma of low potential malignancy; 6 had a mucinous cystadenoma of low potential malignancy; 2 had a pure dysgerminoma; 2 had a mature solid teratoma; 3 had a mucinous cystadenocarcinoma; and 2 had an endodermal sinus tumor. Postoperative chemotherapy was given in 12 cases and 1 patient with a pure dysgerminoma had radiotherapy. Eighteen pregnancies occurred in 13 patients. One full-term and one 8 month premature infant died in utero, and 2 infants had malformations; the other 14 infants are all well. The patient with moderately differentiated mucinous cystadenocarcinoma who delivered a premature infant and 2 patients with endodermal sinus tumors died of recurrence.


Inhibition of plasminogen activator inhibitor-1 expression in vascular smooth muscle cells by protoporphyrins through a heme oxygenase-independent mechanism.
Heme oxygenase-1 (HO-1), a rate-limiting enzyme in heme catabolism, has been shown to play a regulatory role in the expression of plasminogen activator inhibitor-1 (PAI-1), a risk factor for vascular disease. Accordingly, we examined the effect of protoporphyrins, both HO inhibitors and activators, on PAI-1 expression in human vascular smooth muscle cells (VSMCs). Tin-protoporphyrin (SnPP) markedly inhibited the transforming growth factor beta1 (TGFbeta1)-induced expression of PAI-1 protein. Protoporphyrins, whether they are inhibitors or activators of HO, produced a similar inhibitory effect. However, SnPP had no effect on the level of PAI-1 mRNA transcripts. Knockdown of human HO-1 with a specific siRNA did not reduce the PAI-1 protein level in TGFbeta1-treated cells. In addition, the proteasome inhibitor lactacystin reversed the inhibitory effect of SnPP on PAI-1 protein expression. Both cobalt-protoporphyrin (CoPP) and CoCl2 markedly induced HO-1 expression. However, CoPP did not affect PAI-1 gene expression, whereas CoCl2 upregulated PAI-1 mRNA in a dose-dependent manner. Our results demonstrate that protoporphyrins can block the TGFbeta1-mediated induction of PAI-1 protein in VSMCs and that this inhibitory effect is independent of HO activity.


Resistive and New Optical Switching Memory Characteristics Using Thermally Grown Ge0.2Se0.8 Film in Cu/GeSex/W Structure.
It is known that conductive-bridge resistive-random-access-memory (CBRAM) device is very important for future high-density nonvolatile memory as well as logic application. Even though the CBRAM devices using different materials, structures, and switching performance have been reported in Nanoscale Res. Lett., 2015, however, optical switching characteristics by using thermally grown Ge0.2Se0.8 film in Cu/GeSex/W structure are reported for the first time in this study. The Cu/GeSex/W memory devices have low current compliances (CCs) ranging from 1 nA to 500 μA with low voltage of ±1.2 V, high resistance ratio of approximately 10(3), stable endurance of >200 cycles, and good data retention of >7 × 10(3) s at 85 °C. Multi-steps of RESET phenomena and evolution of Cu filaments' shape under CCs ranging from 1 nA to 500 μA have been discussed. Under external white-light illumination with an intensity of 2.68 mW/cm(2) (wavelength ranges from 390 to 700 nm), memory device shows optical switching with long read pulse endurance of >10(5) cycles. This CBRAM device has optically programmed and electrically erased, which can open up a new area of research field for future application.


The 6-plus-person lift transfer technique compared with other methods of spine boarding.
To achieve full spinal immobilization during on-the-field management of an actual or potential spinal injury, rescuers transfer and secure patients to a long spine board. Several techniques can be used to facilitate this patient transfer. To compare spinal segment motion of cadavers during the execution of the 6-plus-person (6+) lift, lift-and-slide (LS), and logroll (LR) spine-board transfer techniques. Crossover study. Laboratory. Eight medical professionals (1 woman, 7 men) with 5 to 32 years of experience were enlisted to help carry out the transfer techniques. In addition, test conditions were performed on 5 fresh cadavers (3 males, 2 females) with a mean age of 86.2 +/- 11.4 years. Three-dimensional angular and linear motions initially were recorded during execution of transfer techniques, initially using cadavers with intact spines and then after C5-C6 spinal segment destabilization. The mean maximal linear displacement and angular motion obtained and calculated from the 3 trials for each test condition were included in the statistical analysis. Flexion-extension angular motion, as well as anteroposterior and distraction-compression linear motion, did not vary between the LR and either the 6+ lift or LS. Compared with the execution of the 6+ lift and LS, the execution of the LR generated significantly more axial rotation (P = .008 and .001, respectively), more lateral flexion (P = .005 and .003, respectively), and more medial-lateral translation (P = .003 and .004, respectively). A small amount of spinal motion is inevitable when executing spine-board transfer techniques; however, the execution of the 6+ lift or LS appears to minimize the extent of motion generated across a globally unstable spinal segment.


Development of a hyper-adhesive and attenuated Edwardsiella ictaluri strain as a novel immersion vaccine candidate in yellow catfish (Pelteobagrus fulvidraco).
Edwardsiella ictaluri, a Gram-negative intracellular pathogen, is the causative agent of enteric septicemia in channel catfish, and catfish aquaculture in China suffers heavy economic losses due to E. ictaluri infection. Vaccination is an effective control measure for this disease. In this study, an attenuated E. ictaluri strain was acquired through deletion mutation of the T3SS protein eseJei, and the ΔeseJei strain fails to replicate in the epithelioma papillosum of carp cells. The type 1 fimbria plays a pivotal role in the adhesion of E. ictaluri, and it was found in this study that deletion of -245 to -50 nt upstream of fimA increases its adhesion to around five times that of the WT strain. A hyper-adhesive and highly attenuated double mutant (ΔeseJeiΔfimA-245--50 strain) was constructed, and it was used as a vaccine candidate in yellow catfish via bath immersion at a dosage of 1 × 105 CFU/mL. It was found that this vaccine candidate can stimulate protection when challenged with E. ictaluri HSN-1 at 5 × 107 CFU/mL (∼20 × LD50). The survival rate was 83.61% for the vaccinated group and 33.33% for the sham-vaccinated group. The RPS (relative percent of survival) of the vaccination trial reached 75.41%. In conclusion, the ΔeseJeiΔfimA-245--50 strain developed in this study can be used as a vaccine candidate. It excels in terms of ease of delivery (via bath immersion) and is highly efficient in stimulating protection against E. ictaluri infection.


Vascularization of conjunctival autografts in pterygium surgery: comparison of fibrin glue with sutures.
To monitor the development of graft vascularization after pterygium excision with conjunctival autograft transplantation (CAT) using indocyanine green angiography (ICGA) and to compare the graft vascularization between 2 different fixation techniques (fibrin glue and sutures). A total of 26 eyes of 26 patients with primary pterygium were randomly assigned after pterygium excision as having either fibrin glue (13 eyes) or Vicryl sutures (13 eyes) for CAT. Anterior segment ICGA findings were evaluated postoperatively at 1, 7, and 15 days and the percentages of graft vascularization in both groups were compared using pixel analysis software program. The mean ± SD age of patients in the suture and fibrin glue groups was 52.1 ± 12.7 years and 57.1 ± 9.82 years, respectively. There was no statistically significant difference between the groups regarding age, sex, or follow-up (p<0.05 for all). Also, the mean intraoperative defect size was not significantly different between the groups, which was measured as 20.11 ± 10.44 mm2 in the suture group and 23.44 ± 12.34 mm2 in the fibrin glue group (p = 0.343). The mean percentage of vascularized graft area at postoperative day 1 and 7 was 18.1 ± 7.8% and 25.3 ± 8.6% in the suture group and 34.8 ± 10.2% and 66.1 ± 17.8% in the fibrin glue group. The difference between the groups was statistically significant (p<0.01 for both). At postoperative day 15, all grafts were 100% perfused in both groups. Fibrin glue fixation of conjunctival autografts led to more vascularization in the early postoperative period than suture fixated grafts, which in turn may have significance in terms of graft health and pterygium recurrence.


Enhanced expression of the proto-oncogenes fos and raf in the rhabdomyosarcoma cell line BA-HAN-1C after differentiation induction with retinoic acid and N-methylformamide.
BA-HAN-IC is a clonal rat rhabdomyosarcoma cell line consisting of proliferating mononuclear tumor cells, some of which spontaneously fuse to form terminally differentiated post-mitotic myotubes. Exposure of BA-HAN-IC cells to retinoic acid (RA) or N-methylformamide (NMF) resulted in a significant inhibition of proliferation (p less than 0.001) and in cellular differentiation, as evidenced by a significant increase in the creatine kinase (CK) activity (p less than 0.05) and the number of terminally differentiated post-mitotic myotubes (p less than 0.001). Furthermore, between 5% (NMF) and 30% (RA) of the mononuclear tumor cells exhibited ultrastructural features of rhabdomyogenic differentiation, not observed in their mononuclear counterparts under standard growth conditions. Although BA-HAN-IC cells responded to both inducers of differentiation, differences in time course and magnitude of both increase of differentiation and growth inhibition were observed. These effects of RA and NMF were preceded by a marked enhancement of c-raf expression which became evident 6 and 12 hr after exposure to RA and NMF, respectively, and which persisted throughout the observation period of 5 days. Furthermore, a transient expression of c-fos could be observed 15 and 30 min after exposure to RA. Our results suggest that c-raf expression might be implicated in the differentiation process of BA-HAN-IC tumor cells.


The diurnal course of leaf gas exchange of the C4 species Amaranthus retroflexus under field conditions in a 'cool' climate: Comparison with the C3 species Glycine max and Chenopodium album.
The gas exchange of leaves of Amaranthus retroflexus (C4) measured under fluctuating environmental conditions in an experimental garden in Würzburg was compared with that of Glycine max and Chenopodium album (C3). Consistent with previous observations, Amaranthus had higher leaf diffusion resistance than the C3 species and low internal air space carbon dioxide concentration. Due to high photosynthetic capacity, Amaranthus fixed as much carbon during the light as the C3 species, even at low temperatures and low light intensities. Low rates of dark respiration of leaves potentially enhances the ability of Amaranthus to grow rapidly after establishment in a disturbed habitat. The data suggest that some populations of Amaranthus retroflexus are adapted to cool climate conditions but are also able to exploit high temperature situations.


Non-equivalence of impulse blockade and denervation in the production of membrane changes in rat skeletal muscle.
1. A complete and long lasting blockade of nerve impulses was established in the sciatic nerve of rats, by implanting silastic cuffs of critical internal diameters. Either marcaine-impregnated or plain cuffs were used. The contralateral sciatic nerve was sectioned. 2. At various days after the initial procedures, the extensor digitorum longus muscles of the two sides were examined with intracellular electrodes. 3. Decrease in resting membrane potential, fibrillatory activity and resistance of the action potential to tetrodotoxin developed not only in the denervated but also in the impulse-blocked muscles. In the latter, the fibres were normally innervated since they displayed miniature end-plate potentials and were excitable by nerve stimulation distal to the blocking cuff. 4. However, all of the above mentioned denervation-like changes were significantly less pronounced in the blocked muscles than in the denervated ones. 5. It is concluded that in addition to loss of nerve impulses, some other neural factor must be taken into account to explain the origin of muscle changes induced by denervation. The possible relation of this additional factor with nerve degeneration is discussed.


Targeting receptor-activator of nuclear kappaB ligand in aneurysmal bone cysts: verification of target and therapeutic response.
Aneurysmal bone cyst (ABC) is a benign tumor of bone presenting as a cystic, expansile lesion in both the axial and appendicular skeleton. Axial lesions demand special consideration, because treatment-related morbidity can be devastating. In similar lesions, such as giant cell tumor of bone (GCTB), the receptor-activator of nuclear kappaB ligand (RANKL)-receptor-activator of nuclear kappaB (RANK) signaling axis is essential to tumor progression. Although ABC and GCTB are distinct entities, they both contain abundant multinucleated giant cells and are osteolytic characteristically. We hypothesize that ABCs express both RANKL and RANK similarly in a cell-type specific manner, and that targeted RANKL therapy will mitigate ABC tumor progression. Cellular expression of RANKL and RANK was determined in freshly harvested ABC samples using laser confocal microscopy. A consistent cell-type-specific pattern was observed: fibroblastlike stromal cells expressed RANKL strongly whereas monocyte/macrophage precursor and multinucleated giant cells expressed RANK. Relative RANKL expression was determined by quantitative real-time polymerase chain reaction in ABC and GCTB tissue samples; no difference in relative expression was observed (P > 0.05). In addition, we review the case of a 5-year-old boy with a large, aggressive sacral ABC. After 3 months of targeted RANKL inhibition with denosumab, magnetic resonance imaging demonstrated tumor shrinkage, bone reconstitution, and healing of a pathologic fracture. Ambulation, and bowel and bladder function were restored at 6 months. Denosumab treatment was well tolerated. Post hoc analysis demonstrated strong RANKL expression in the pretreatment tumor sample. These findings demonstrate that RANKL-RANK signal activation is essential to ABC tumor progression. RANKL-targeted therapy may be an effective alternative to surgery in select ABC presentations.


Impact of lowering the US maximum contaminant level on arsenic exposure: Differences by race, region, and water arsenic in NHANES 2003-2014.
Our objective was to evaluate regional and sociodemographic inequalities in water arsenic exposure reductions associated with the US Environmental Protection Agency's Final Arsenic Rule, which lowered the arsenic maximum contaminant level to 10 μg/L in public water systems. We analyzed 8544 participants from the 2003-14 National Health and Nutrition Examination Survey (NHANES) reliant on community water systems (CWSs). We estimated arsenic exposure from water by recalibrating urinary dimethylarsinate (rDMA) to remove smoking and dietary contributions. We evaluated mean differences and corresponding percent reductions of urinary rDMA comparing subsequent survey cycles to 2003-04 (baseline), stratified by region, race/ethnicity, educational attainment, and tertile of CWS arsenic assigned at the county level. The overall difference (percent reduction) in urine rDMA was 0.32 μg/L (9%) among participants with the highest tertile of CWS arsenic, comparing 2013-14 to 2003-04. Declines in urinary rDMA were largest in regions with the highest water arsenic: the South [0.57 μg/L (16%)] and West [0.46 μg/L, (14%)]. Declines in urinary rDMA levels were significant and largest among Mexican American [0.99 μg/L (26%)] and Non-Hispanic White [0.25 μg/L (10%)] participants. Reductions in rDMA following the Final Arsenic Rule were highest among participants with the highest CWS arsenic concentrations, supporting legislation can benefit those who need it the most, although additional efforts are still needed to address remaining inequalities in CWS arsenic exposure.


Genes, nitric oxide and malaria in African children.
The unresolved and complex relationship between nitric oxide and falciparum malaria is reflected in recent genetic and immunohistochemical studies in African children. Different genetic associations, perhaps geographically distinctive, are seen between genetic variants of the inducible nitric oxide gene and various disease manifestations in African populations. The picture might not be complete without considering the emerging roles of carbon monoxide, another endogenous gaseous mediator with similar effects to those of nitric oxide. Only when genetic comparisons from across tropical Africa are examined, in conjunction with the newly recognized complexities in the events of systemic inflammation, will this relationship be understood.


Nitric oxide synthase containing neurons in the ventral lateral geniculate of the rat project to the optic pretectal nuclei.
We combined fluorescent tracing with immunohistochemistry to examine nitric oxide synthase (NOS) containing neurons in the rat ventral lateral geniculate nucleus (vLGN). NOS immunopositive neurons in vLGN had a similar appearance to previously described NADPH-d positive neurons. The majority (96%) of the NOS immunopositive neurons in vLGN projected to the pretectal nuclei and these represented 16% of all the vLGN neurons that project to the pretectal nuclei. No NOS immunopositive neurons projected to the superior colliculus. Co-localization of NADPH-d and gamma-aminobutyric acid (GABA) has been reported in vLGN neurons but we found few cells containing both NOS and GABA.


Sodium imaging of human brain at 7 T with 15-channel array coil.
Signal-to-noise ratio (SNR) is a major challenge to sodium magnetic resonance imaging. Phased array coils have been shown significantly improving SNR in proton imaging over volume coils. This study investigates SNR advantage of a 15-channel array head coil (birdcage volume coil for transmit/receive and 15-channel array insert for receive-only) in sodium imaging at 7 T. Phantoms and healthy human brains were scanned on a whole-body 7 T magnetic resonance imaging scanner using a customer-developed pulse sequence with the twisted projection imaging trajectory. Noise-only images were acquired with blanked radiofrequency excitations for noise measurement on a pixel basis. SNR was calculated on the root of sum-of-squares images. When compared with the volume coil, the 15-channel array produced SNR more than doubled at the periphery and slightly increased at the center of the phantoms and human brains. Decorrelation of noise across channels of the array coil extended the SNR-doubled region into deep area of the brain. The spatial modulation of element sensitivities on the sum-of-squares combined image was removed by performing self-calibrated sensitivity encoding parallel image reconstruction and uniform image intensity across entire field of view was attained. The 15-channel array coil is an efficient tool to substantially improve SNR in sodium imaging on human brain.


Modified constraint-induced therapy in subacute stroke: a case report.
To determine the efficacy of a modified constraint-induced therapy (CIT) protocol administered to a patient with subacute stroke. Multiple-baseline, before-after trial. Subacute outpatient clinic. A 68-year-old woman who had a left anterior cerebral artery infarct 5 months before study entry and who exhibited learned nonuse of the affected upper limb. Thirty minutes of structured physical therapy and 30 minutes of occupational therapy 3 times a week for 10 weeks, each session emphasizing affected arm use. During the same period, her unaffected arm and hand were restrained 5d/wk during 5 hours initially identified as a time of frequent use. The Fugl-Meyer Assessment of Motor Recovery (FMA), Action Research Arm Test (ARA), Wolf Motor Function Test (WMFT), and Motor Activity Log (MAL). The patient exhibited substantial improvements on the FMA and ARA. She also improved on the WMFT in her ability to perform tasks and in the time taken to complete the tasks. Amount and quality of arm use also improved, as measured by the MAL. Modified CIT may be an efficacious method of improving function and use of the affected arms of patients with learned nonuse.


Effect of smoking, hypertension and lifestyle factors on kidney cancer - perspectives for prevention and screening programmes.
Renal cell carcinoma (RCC) incidence has doubled over the past few decades. However, death rates have remained stable as the number of incidental renal mass diagnoses peaked. RCC has been recognized as a European health care issue, but to date, no screening programmes have been introduced. Well-known modifiable risk factors for RCC are smoking, obesity and hypertension. A direct association between cigarette consumption and increased RCC incidence and RCC-related death has been reported, but the underlying mechanistic pathways for this association are still unclear. Obesity is associated with an increased risk of RCC, but interestingly, improved survival outcomes have been reported in obese patients, a phenomenon known as the obesity paradox. Data on the association between other modifiable risk factors such as diet, dyslipidaemia and physical activity with RCC incidence are conflicting, and potential mechanisms underlying these associations remain to be elucidated.


Pseudo-likelihood based logistic regression for estimating COVID-19 infection and case fatality rates by gender, race, and age in California.
In emerging epidemics, early estimates of key epidemiological characteristics of the disease are critical for guiding public policy. In particular, identifying high-risk population subgroups aids policymakers and health officials in combating the epidemic. This has been challenging during the coronavirus disease 2019 (COVID-19) pandemic because governmental agencies typically release aggregate COVID-19 data as summary statistics of patient demographics. These data may identify disparities in COVID-19 outcomes between broad population subgroups, but do not provide comparisons between more granular population subgroups defined by combinations of multiple demographics. We introduce a method that helps to overcome the limitations of aggregated summary statistics and yields estimates of COVID-19 infection and case fatality rates - key quantities for guiding public policy related to the control and prevention of COVID-19 - for population subgroups across combinations of demographic characteristics. Our approach uses pseudo-likelihood based logistic regression to combine aggregate COVID-19 case and fatality data with population-level demographic survey data to estimate infection and case fatality rates for population subgroups across combinations of demographic characteristics. We illustrate our method on California COVID-19 data to estimate test-based infection and case fatality rates for population subgroups defined by gender, age, and race/ethnicity. Our analysis indicates that in California, males have higher test-based infection rates and test-based case fatality rates across age and race/ethnicity groups, with the gender gap widening with increasing age. Although elderly infected with COVID-19 are at an elevated risk of mortality, the test-based infection rates do not increase monotonically with age. The workforce population, especially, has a higher test-based infection rate than children, adolescents, and other elderly people in their 60-80. LatinX and African Americans have higher test-based infection rates than other race/ethnicity groups. The subgroups with the highest 5 test-based case fatality rates are all-male groups with race as African American, Asian, Multi-race, LatinX, and White, followed by African American females, indicating that African Americans are an especially vulnerable California subpopulation.


Synergistic effects of PI3K inhibition and pioglitazone against acute promyelocytic leukemia cells.
Although pioglitazone, a well-known anti-diabetic agent, has recently established itself as a pillar of cancer treatment, its therapeutic value could be attenuated by the aberrant activation of the PI3K/Akt pathway. To evaluate whether the PI3K/Akt suppression in leukemic cells could potentiate the anti-leukemic effects of pioglitazone. To assess the anti-leukemic effects of PI3K/Akt inhibitors on anti-leukemic effects of pioglitazone, we used MTT and trypan blue assays. Flow cytometric analysis and qRT-PCR were also applied to evaluate cell cycle and apoptosis. The resulting data revealed that upon PPARγ stimulation in different leukemic cell lines using pioglitazone, the survival and the proliferative capacity of the cells were significantly halted. Then, we evaluated the impact of the PI3K/Akt axis on the effectiveness of the drug in the most sensitive leukemic cell line; NB4 cells. Our results showed that treatment of NB4 cells with the PI3K inhibitors increased the sensitivity of leukemic cells to pioglitazone to the degree that even lower concentrations of the agent succeeded to induce apoptotic as well as the anti-proliferative effects. Moreover, it seems that PI3K inhibition could potentiate the anti-leukemic effect of pioglitazone through induction of p21-mediated sub-G1 cell cycle arrest and altering the balance between the pro-and anti-apoptotic genes. This study sheds light on the significance of the PI3K/Akt pathway in APL cell sensitivity to pioglitazone and proposed that the presence of the PI3K inhibitor in the therapeutic regimen containing pioglitazone could be promising in the treatment of this malignancy.


Report on the GHPP-BloodTrain online workshop on "Authorisation and Licensing of Blood Establishments - Review of quality documentation of blood and blood components", 5th-8th of July 2021.
The GHPP BloodTrain team developed an e-learning concept in response to the COVID-19 travel restrictions, providing training formats with virtual stages that can be completed during the pandemic (and beyond) and on-site stages, where practical exercises and case reports in smaller groups can lead to a deeper understanding of the content. The virtual training workshop on "Authorisation and Licensing of Blood Establishments", hosted by the PEI GHPP BloodTrain from the 5th to the 8th of July 2021, was the first application of this concept. The number of participants could be substantially increased compared to an on-site event thanks to the virtual setting. Participants came mainly from national regulatory authorities and national blood transfusion services. There were also some Ministry of Health representatives from 19 countries from the WHO regions of AFRO, EMRO, and from Indonesia in attendance. The virtual workshop focused on reviewing and evaluating the quality documentation required for approval of processes used by blood establishments to prepare blood components. Presentations were given by members of the GHPP BloodTrain team as well as by representatives of the German Red Cross. The program was complemented by contributions from the WHO HQ and presentations on country-specific experiences from Ghana and Zimbabwe.


A review on deep learning MRI reconstruction without fully sampled k-space.
Magnetic resonance imaging (MRI) is an effective auxiliary diagnostic method in clinical medicine, but it has always suffered from the problem of long acquisition time. Compressed sensing and parallel imaging are two common techniques to accelerate MRI reconstruction. Recently, deep learning provides a new direction for MRI, while most of them require a large number of data pairs for training. However, there are many scenarios where fully sampled k-space data cannot be obtained, which will seriously hinder the application of supervised learning. Therefore, deep learning without fully sampled data is indispensable. In this review, we first introduce the forward model of MRI as a classic inverse problem, and briefly discuss the connection of traditional iterative methods to deep learning. Next, we will explain how to train reconstruction network without fully sampled data from the perspective of obtaining prior information. Although the reviewed methods are used for MRI reconstruction, they can also be extended to other areas where ground-truth is not available. Furthermore, we may anticipate that the combination of traditional methods and deep learning will produce better reconstruction results.


Synthesis of a C-glycoside analogue of beta-D-galactosyl hydroxynorvaline and its use in immunological studies.
A C-linked isostere of beta-D-galactosylated hydroxynorvaline has been prepared in eight steps from per-O-benzylated galactopyranolactone. Addition of a homoallylic Grignard reagent to the lactone, reduction of the resulting hemiacetal with triethylsilane, and a Wittig reaction with Garner's aldehyde were key steps in this synthesis. The C-linked building block was then incorporated at position 264 into the fragment CII(256--270) from typeII collagen by solid-phase synthesis using a combination of the tert-butoxycarbonyl (Boc) and 9-fluorenylmethoxycarbonyl (Fmoc) protective group strategies. Deprotection of the benzylated C-linked galactosyl moiety was achieved simultaneously with cleavage of the glycopeptide from the solid phase by using triethylsilyl trifluoromethanesulfonate in TFA. Helper T-cell hybridomas obtained in a mouse model for rheumatoid arthritis responded to the C-linked glycopeptide when presented by classII MHC molecules. However, 10- to 20-fold higher concentrations were required as compared to when O-linked beta-D-galactosylated hydroxynorvaline or hydroxylysine (Hyl) were present at position 264 of CII(256--270). Thus, replacement of a single oxygen atom by a methylene group in the carbohydrate moiety of a glycopeptide antigen had a substantial influence on the T-cell response. This reveals that T cells are able to recognize the carbohydrate moiety of glycopeptide antigens with high specificity. Finally, the results suggest that structural modifications of beta-D-Gal-Hyl(264) in CII(256--270) may give altered peptide ligands that can be used for induction of tolerance in autoimmune rheumatoid arthritis.


Factors modifying the association between hormone-replacement therapy and breast cancer risk.
Hormone-replacement therapy (HRT) is an established risk factor for breast cancer. HRT users are different from non-users with respect to socio-economic and other characteristics. There may be women where the HRT-related risk could be modulated by other factors. We conducted a population-based case-control study with 688 breast cancer cases and 724 controls to characterize HRT users and to estimate odds ratios (OR) and 95% confidence intervals (CI) for HRT use and potentially risk modifying factors. In women aged 50 years and older, 58% of controls and 61% of cases ever used HRT. Among women in natural menopause, HRT use for 10 years and more years was associated with an increased breast cancer risk (OR 1.79, 95% CI, 1.12-2.87), but not among women in surgical menopause (OR 0.61, 95% CI, 0.09-4.17). In the subgroup of women with a positive family history of breast cancer, each year of HRT use increased the risk by 1.22 (95% CI, 1.02-1.47). Another subgroup comprised women with at least 10 diagnostic mammograms (OR 4.04, 95% CI, 1.10-14.81 for using HRT 10 or more years). Long-term HRT use was associated with a breast cancer risk in women with natural menopause. Our findings suggest that this risk may be increased in women with a positive family history of breast cancer and in women who received frequent diagnostic mammographic screens.


Dichlorodiphenyltrichloroethane inhibits soil ammonia oxidation by altering ammonia-oxidizing archaeal and bacterial communities.
Dichlorodiphenyltrichloroethane (DDT), a persistent organic pollutant, has known effects on natural microbes. However, its effects on soil ammonia-oxidizing microbes, significant contributors to soil ammoxidation, remain unexplored. To address this, we conducted a 30-day microcosm experiment to systematically study the effects of DDT contamination on soil ammonia oxidation and the communities of ammonia-oxidizing archaea (AOA) and ammonia-oxidizing bacteria (AOB). Our findings revealed that DDT inhibited soil ammonia oxidation in the early stage (0-6 days), but it gradually recovered after 16 days. The copy numbers of amoA gene of AOA decreased in all DDT-treated groups from 2 to 10 days, while that of AOB decreased from 2 to 6 days but increased from 6 to 10 days. DDT influenced the diversity and community composition of AOA but had no significant effect on AOB. Further, the dominant AOA communities comprised uncultured_ammonia-oxidizing_crenarchaeote and Nitrososphaera sp. JG1: while the abundance of the latter significantly and negatively correlated with NH 4+-N (P ≤ 0.001), DDT (0.001 < P ≤ 0.01), and DDD (0.01 < P ≤ 0.05) and positively correlated with NO3--N (P ≤ 0.001), that of the former significantly and positively correlated with DDT (P ≤ 0.001), DDD (P ≤ 0.001), and NH 4+-N (0.01 < P ≤ 0.05) and negatively correlated with NO3--N (P ≤ 0.001). Among AOB, the dominant group was the unclassified Nitrosomonadales in Proteobacteria, which showed significant negative correlation with NH 4+-N (0.01 < P ≤ 0.05) and significant positive correlation with NO3--N (0.001 < P ≤ 0.01). Notably, among AOB, only Nitrosospira sp. III7 exhibited significant negative correlations with DDE (0.001 < P ≤ 0.01), DDT (0.01 < P ≤ 0.05), and DDD (0.01 < P ≤ 0.05). These results indicate that DDT and its metabolites affect soil AOA and AOB, consequently affecting soil ammonia oxidation.


Nuclear pore complex assembly through the cell cycle: regulation and membrane organization.
In eukaryotes, all macromolecules traffic between the nucleus and the cytoplasm through nuclear pore complexes (NPCs), which are among the largest supramolecular assemblies in cells. Although their composition in yeast and metazoa is well characterized, understanding how NPCs are assembled and form the pore through the double membrane of the nuclear envelope and how both processes are controlled still remains a challenge. Here, we summarize what is known about the biogenesis of NPCs throughout the cell cycle with special focus on the membrane reorganization and the regulation that go along with NPC assembly.


Quantitative interpretation of lumbar muscle myoelectric signals during rapid cyclic attempted trunk flexions and extensions.
The quantitative relationship between lumbar myoelectric signals (MES) and rapidly varying isometric trunk muscle forces was investigated. Ten young adult males were asked to cycle harmonically between attempted trunk flexion and attempted trunk extension in an upright position at rates of 0.33, 0.67 and 1.0 Hz to peak efforts of 20, 40 and 60% of maximum voluntary exertion levels. The forces voluntarily exerted against a load cell were measured and used along with acquired kinematic data to calculate the time course of the net sagittal moment at the level of the third lumbar vertebra during task performances. A 22 muscle double linear programming biomechanical model was used to predict the lumbar trunk muscle contraction forces from the calculated moments. Rectified and bidirectionally low-pass filtered myoelectric activities were acquired at the L3 level from four abdominal muscles and four back muscles. The processed MES were found to be well correlated (r > 0.90) with predicted muscle forces when the MES were time-shifted to account for electromechanical delay as well as the dynamic phase shift between muscle electrical activity and contraction force. Mean time shifts that maximized the linear MES-force relationship ranged from 111 to 218 ms, were greater for the trunk extensors than the trunk flexors and generally exhibited lateral symmetry. The corresponding approximate phase angles averaged 20 degrees at the slowest rate and 50 degrees at the fastest rate. MES-force phase angles decreased as effort level was increased indicating that the dynamic MES-force relationship is nonlinear. These results illustrate the importance of accounting for the phase lag between muscle electrical activity and force when using MES to quantify muscle loads during rapidly varying exertions.


Mental morbidity in industrial workers of khetri copper complex.
There is dearth of researches pertaining to prevalence of mental morbidity in Industrial setups, particularly in our country.They are important as psychological ill health of workers may adversely effect the productivity in developing country like India.Khetri Copper Complex in Rajasthan was selected for present study. Aims were to determine the period prevalence of mental morbidity among workers and role of sociodemographic, psychological variables in such disorders. 330 workers were randomly selected from various departments. Each worker was given specially designed proforma and Goldberg's General Health Questionnaire. Workers scoring 12 or more were given "A standardised psychiatric interview schedule" suspected cases were examined by senior consultants to assign them diagnostic categories (I.C.D.-9).Period Prevalence in this study was 186.66/1000. As regards diagnostic categories, 75% were neurotic and 12.5% psychotics. Role of socio demographic, psychological and psychiatric variables in the development of these disorders has been discussed.Findings of this study are in expected direction and results obtained can be easily explained in terms of formulations given by other researchers in this field.Recommendation and plans for further research are discussed.


The Influence of Taoism on Employee Low-Carbon Behavior in China: The Mediating Role of Perceived Value and Guanxi.
We established a dual-pathway model in which Taoism at work can shape employee low-carbon behavior via two mediating mechanisms: perceived value as a psychological mediator and guanxi as a social mediator. Data were collected from 788 Chinese enterprises employees. Our results confirm the direct positive effect of Taoism on employee low-carbon behavior and the partial mediating effects of perceived value and co-worker guanxi. However, supervisor-subordinate guanxi does not mediate the relationship between Taoism and employee low-carbon behavior. Despite the key role of employee low-carbon behavior, the individual-level antecedent to employees' pro-environmental behavior remains underexplored. This study examines the influence of Taoism (an individual-level cultural value) on employee low-carbon behavior in the Chinese context. Theoretical and managerial implications were discussed.


Cimetidine pharmacokinetics in patients with Zollinger-Ellison syndrome.
Although most patients with Zollinger-Ellison syndrome can be effectively treated with histamine H2-receptor antagonists, many patients require large doses of drug to inhibit gastric acid secretion adequately. The purpose of the present study was to compare the pharmacokinetics of a 1200-mg oral dose of cimetidine in 9 patients with Zollinger-Ellison syndrome requiring more than 2.4 g/day of cimetidine with 5 age-matched normal volunteers receiving intravenous pentagastrin infusions. Poor responsiveness to cimetidine in patients with Zollinger-Ellison syndrome has several different causes. The concentration of cimetidine in the blood required to inhibit gastric acid secretion by 50% was markedly increased in 3 of the patients with Zollinger-Ellison syndrome, suggesting parietal cell resistance. One patient showed a substantial decrease in cimetidine absorption and 4 patients had delayed cimetidine absorption. Thus 7 of the 9 patients with Zollinger-Ellison syndrome who required more than 2.4 g/day of cimetidine to inhibit gastric acid secretion had abnormal cimetidine pharmacokinetics.


Efficacy and tolerance of atrisin in degenerative and inflammatory joint disorders.
In a randomized multi-centre clinical trial the efficacy and tolerance of a herbal product Atrisin three capsules/day was evaluated in 65 patients (31 male, 34 female) suffering from osteoarthritis and rheumatoid arthritis, during a period of 2 months. Assessment of pain and functional disability were made on a 10 cm horizontal visual analogue scale. The severity of osteoarthritis was evaluated by Lequesne's index.Spontaneous pain showed significant improvement. Similarly there was progressive and significant reduction in the Lequesne's functional index. At the completion of the study patients taking Atrisin were using less NSAIDs. Atrisin was tolerated well by the patients and there were no adverse cardiovascular or gastric effects reported. There was feeling of general well-being and compliance by the patients.


Pharyngeal airway changes associated with maxillary distraction osteogenesis in adult cleft lip and palate patients.
To investigate 1) the changes in pharyngeal airway sizes associated with maxillary distraction osteogenesis and 2) the correlations between maxillary skeletal variables and the pharyngeal airway in adult patients with cleft lip and palate. The study was carried out in 14 adult subjects with cleft lip and palate. Predistraction records were taken at a mean age of 22.7 ± 4.6 years. All patients had placement of a rigid external distraction device (RED I; KLS Martin, Tuttlingen, Germany) after Le Fort I osteotomy. Lateral cephalograms were assessed before surgery and at short-term follow-up (8.0 ± 6.4 months). The cephalometric skeletal and pharyngeal airway variables were statistically evaluated by use of the Wilcoxon signed-rank test. Spearman ρ correlation was performed to check the correlations between maxillary skeletal and pharyngeal variables. The maxillary movement was 8.7 mm (P < .01). The maxillary depth angle (+7.9°) and effective maxillary length (9.4 mm) increased significantly (P < .01) after distraction, whereas the palatal plane angle remained unchanged. Anterior nasal spine (8.2 mm) and Posterior nasal spine (6.9 mm) moved anteriorly. The overjet increased (9.5 mm) significantly (P < .01). Posterior, superoposterior, and middle airway spaces increased significantly, with mean differences of 7.5 mm, 5.1 mm, and 3.3 mm, respectively. The soft palate moved anteriorly, with the greatest movement at its superior point. Significant positive correlations were observed for the posterior and superoposterior airway spaces and maxillary movement. PNS changes showed the highest correlation with posterior airway changes. The significant anterior movement of the maxilla resulted in significant increases in posterior, superoposterior, and middle airway spaces. The posterior airway space showed the highest significant positive correlation with the movement of PNS. The posterior and superoposterior airway spaces also showed significant positive correlations with the maxillary skeletal variables.


Competency in infection prevention: a conceptual approach to guide current and future practice.
Professional competency has traditionally been divided into 2 essential components: knowledge and skill. More recent definitions have recommended additional components such as communication, values, reasoning, and teamwork. A standard, widely accepted, comprehensive definition remains an elusive goal. For infection preventionists (IPs), the requisite elements of competence are most often embedded in the IP position description, which may or may not reference national standards or guidelines. For this reason, there is widespread variation among these elements and the criteria they include. As the demand for IP expertise continues to rapidly expand, the Association for Professionals in Infection Control and Epidemiology, Inc, made a strategic commitment to develop a conceptual model of IP competency that could be applicable in all practice settings. The model was designed to be used in combination with organizational training and evaluation tools already in place. Ideally, the Association for Professionals in Infection Control and Epidemiology, Inc, model will complement similar competency efforts undertaken in non-US countries and/or international organizations. This conceptual model not only describes successful IP practice as it is today but is also meant to be forward thinking by emphasizing those areas that will be especially critical in the next 3 to 5 years. The paper also references a skill assessment resource developed by Community and Hospital Infection Control Association (CHICA)-Canada and a competency model developed by the Infection Prevention Society (IPS), which offer additional support of infection prevention as a global patient safety mission.


Development and Validation of Benzophenone Derivatives in Packaged Cereal-Based Foods by Solid-Liquid Extraction and Ultrahigh-Performance Liquid Chromatography-Tandem Mass Spectrometry.
We established and validated a sensitive multi-residue analytical method for identifying benzophenone (BP) and nine BP derivatives (2,4-dihydroxybenzophenone [BP-1], 2,2′,4,4′-tetrahydroxydroxybenzophenone, 2-hydroxy-4-methoxy benzophenone, 2,2′-dihydroxy 4-methoxy benzophenone, 2-hydroxybenzophenone [2-OHBP], 4-hydroxybenzophenone, 4-methylbenzophenone [4-MBP], methyl-2-benzoylbenzoate, and 4-benzoylbiphenyl). Solid−liquid extraction pretreatment and ultra-high-performance liquid chromatography−tandem mass spectrometry (UHPLC−MS/MS) were employed in an analysis of 85 packaged cereal-based food samples (25 pastry, 50 rice, and 10 noodle samples). The method had satisfactory linearity (R2 ≥ 0.995), low limits of detection (pastry: 0.02−4.2 ng/g; rice and noodle: 0.02−2 ng/g), and favorable precision, with within-run and between-run coefficient of variation ranges of 1−29% and 1−28%, respectively. BP and 4-MBP were detected in 100% of the pastry samples, and BP-1 and 2-OHBP were found in 76% and 56% of the pastry samples, respectively. BP and 2-OHBP were found in 92% and 38% of the rice samples, respectively. BP was found in 50% of the noodle samples. BP contributed the most to the total level of BPs in pastries, with significantly higher mean ± standard deviation (range) levels for pastries (26.8 ± 32.6 [1.8−115.4] ng/g) than rice (1.2 ± 2.0 [0.4−13.4] ng/g) and noodles (0.7 ± 0.7 [0.4−1.9] ng/g); p < 0.0001). The trace levels of 4-MBP identified in the samples demonstrate the need for the development of analytical methods with high sensitivity and specificity; the proposed method satisfies this need.


Radio waves from grains in HII regions.
A mechanism is described whereby the optical radiation from stars embedded in dust-filled HII regions may be converted to microwave and longwave radio emissions.


Novel pathogenic CERKL variant in Iranian familial with inherited retinal dystrophies: genotype-phenotype correlation.
Inherited retinal dystrophies (IRDs) include a large chronic heterogeneity genetic disease. While many disease-causing pathogenic variants were involved in the progression of IRD, the Ceramide Kinase Like (CERKL) gene variant in Iranian patients is not well characterized. In this study, a consanguineous Iranian family with three generations was recruited whom presented with the clinical diagnosis of autosomal recessive IRD. By targeted next-generation sequencing (TGS) and Sanger sequencing, the proband was found to have a novel, pathological homozygous deletion variant c.560_568del (p.187_190del) of the CERKL gene (NM_001030311.2) that co-segregated with the disease in all affected family members. The Cerkl is highly expressed in the later four developmental retinal stages, playing a vital role in retina degeneration. Therefore, the identification of a novel, homozygous deletion CERKL variant c.560_568del (p.187_190del) in an IRD familial cohort descent provides insights into the molecular pathogenesis of IRD and facilitates genetic counseling and disease prediction.


Allogeneic HCT for adults with B-cell precursor acute lymphoblastic leukemia harboring IKZF1 gene mutations. A study by the Acute Leukemia Working Party of the EBMT.
The presence of IKZF1 gene mutations is associated with poor prognosis of B-cell precursor acute lymphoblastic leukemia (BCP-ALL). The goal of this retrospective study was to evaluate outcome of allogeneic hematopoietic cell transplantation (allo-HCT) in this population. Ninety-five patients transplanted in first (n = 75) or second (n = 20) complete remission (CR) from either HLA-matched sibling (n = 32), unrelated (n = 47) or haploidentical (n = 16) donor were included in the analysis. The probabilities of the overall survival (OS) and leukemia-free survival (LFS) at 2 years were 55% and 47%, respectively. Relapse incidence (RI) was 32% while non-relapse mortality (NRM), 21%. The incidence of grade II-IV acute graft-versus-host disease (GVHD) and chronic GVHD was 34% and 30%, respectively. The probability of GVHD and relapse-free survival (GRFS) was 35%. In a multivariate analysis positive minimal residual disease (MRD) status was associated with decreased chance of LFS (HR = 3.15, p = 0.004) and OS (HR = 2.37, p = 0.049) as well as increased risk of relapse (HR = 5.87, p = 0.003). Disease stage (CR2 vs. CR1) affected all, LFS, OS, GRFS, RI, and NRM. Results of allo-HCT for patients with BCP-ALL and IKZF1 mutations are generally improving, however, individuals with detectable MRD have poor prognosis and require additional intervention prior to transplantation.


The pathway of arginine catabolism in Giardia intestinalis.
In Giardia intestinalis, arginine is catabolised by the arginine dihydrolase pathway. The enzymes of the pathway (arginine deiminase, ornithine transcarbamoylase and carbamate kinase) were investigated and their basic kinetic parameters determined. The specific activity of arginine deiminase was 270 +/- 23 nmol min-1 (mg protein)-1; ornithine transcarbamoylase, in the direction of citrulline utilisation 170 +/- 22 nmol min-1 (mg protein)-1, and in the direction of ornithine utilisation 2100 +/- 100 nmol min-1 (mg protein)-1; and carbamate kinase 2100 +/- 400 nmol min-1 (mg protein)-1. The activities of these enzymes are between 10 and 250 fold greater than those reported for the enzymes in Trichomonas vaginalis, the only other parasite in which the arginine dihydrolase pathway has been reported. The flux through the pathway in G. intestinalis, as determined by the liberation of 14CO2 from 1 mM [14C-guanidino]arginine was 30 nmol min-1 (mg protein)-1. This flux was not affected by valinomycin (0.1 microM), nigericin (3 microM), azide (5 mM) or cyanide (1 mM). The flux was only marginally affected by glucose up to 10 mM concentration. Conversely, the flux through glucose metabolism, as determined by the release of 14CO2 from 1 mM [1-14C]glucose was only 2 nmol min-1 (mg protein)-1, and was unaffected by arginine concentrations up to 10 mM. These observations suggest that there is no direct metabolic interface between arginine and glucose catabolism.(ABSTRACT TRUNCATED AT 250 WORDS)


Maternal-placental axis and its impact on fetal outcomes, metabolism, and development.
Maternal obesity could impact offspring's health. During "critical period" such as pregnancy insults have a significant role in developing chronic diseases later in life. Literature has shown that diet can play a major role in essential metabolic and development processes on fetal outcomes. Moreover, the placenta, an essential organ developed in pregnancy, seems to have its functions impaired based on pre-gestational and gestational nutritional status. Specifically, a high-fat diet has been shown as a potential nutritional insult that also affects the maternal-placental axis, which is involved in offspring development and outcome. Moreover, some classes of nutrients are associated with pregnancy complications such as reduced intake of micronutrients and diabetes, preeclampsia, and preterm delivery. Thus, we will summarize the current literature on maternal environment factors that impacts the placental development and consequently the fetal an offspring health, or the maternal-placental axis, and this on fetal outcomes, metabolism, and development.


Degradation of tenascin-C and activity of matrix metalloproteinase-2 are associated with tumor recurrence in early stage non-small cell lung cancer.
To find out an effective prognostic factor for early stage non-small cell lung cancer (NSCLC), we examined the relationship of the degree of tenascin-C (TN-C) degradation in relapsed NSCLC tumors with the prognosis of the patients. The molecular mechanism of TN-C degradation was also evaluated. In 63 stage-1 NSCLC patients, TN-C protein was analyzed by Western blotting, and the activity of matrix metalloproteinase (MMP)-2 was examined by gelatin zymography in 23 stage-1 NSCLC patients. Degradation of TN-C was detected in 12 of 63 patients. TN-C degradation was detected in 9 of 17 patients (52.9%) that showed local and distant cancer recurrences. In short, in 9 of 12 patients (75%) showing TN-C degradation, lung cancer recurrence was recognized. The actual frequency of free-from-recurrence at 4 years was 28.1% in patients with tumors showing TN-C degradation, and actual frequency of free-from-recurrence at 4 years and 10 years was 82.1% and 76.6% in patients without TN-C degradation (P < 0.001). In 23 stage-1 NSCLC patients, in tumors with or without degraded TN-C, the mean ratio of tumor:normal-tissue of activated MMP-2 was 3.5 +/- 0.4 or 1.54 +/- 0.4, respectively. Significantly increased activity of MMP-2 was recognized in tumors showing TN-C degradation (P < 0.001). These results suggest that TN-C degradation is a reliable marker for recurrence potential of stage-1 NSCLC and that MMP-2 may be a protease breaking down TN-C in lung cancer.


High annual variability in reproductive success and survival of an Antarctic seabird, the snow petrel Pagodroma nivea : A 27-year study.
Demographic parameters were estimated for snow petrels Pagodroma nivea nesting at Pointe Géologie Archipelago, Adélie Land, Antarctica between 1963 and 1990; 21 years of data on adult survival and 27 years of data on breeding success are available. The average age of first return and first breeding were 8.1 and 9.9 years respectively and there was no signifcant difference between the sexes. The overall breeding success averaged 51.3% and was very variable between years (21-80%). Breeding failure was mostly due to incubation failure and annual breeding success was negatively correlated with average snow falls in October-November and October-March. Breeding frequency was very low, averaging 52% of seasons during a reproductive lifetime. Good quality sites, with high occupancy rate and high breeding success were few in the study plots. Poor years in 1966-1967, 1976-1977 and 1983-1984, with low breeding success, very low proportions of nets with breeding attempts and high numbers of non-breeders, occurred 1 year after large-scale El Niño Southern Oscillation (ENSO) events. Snow petrels exhibited very low philopatry. Only 45 birds have been recovered in the study plots from a total of 1115 banded fledglings giving an estimated rate of return of 12.9% between fledging and 3 years old. Annual survival between 3 and 10 years was 91.4%. Annual adult survival (93.4%), though variable, was low during poor years of 1977-1978 and 1983-1984. Adult survival of males (94.7%) was not significantly different from that of females (93.9%). Over the study period, the population of Pointe Géologie was stable. Using the estimated parameters, a Leslie model gave a growth rate of 0.948%, which was probably compensated by immigration (5.7% per year). Restricted numbers of good-quality sites at the place of birth could have led young birds to prospect other colonies and could have selected low philopatry. High adult survival, strong site tenacity and capacity to spread breeding over a long lifetime are probably part of the adaptive strategy of this small fulmarine petrel facing highly variable environmental conditions.


Update on ivabradine for heart failure.
Despite dramatic advances in therapy for heart failure (HF) during the past 3 decades, hospitalization and mortality rates remain relatively high. In recent decades, it has become apparent that HF is divisible into two equally lethal but pathophysiologically different sub-classes, the first comprising patients with LV systolic dysfunction [heart failure with reduced ejection fraction (HFrEF)] and the other, approximately equal in size, involving patients with "preserved" systolic function [heart failure with preserved ejection fraction (HFpEF)]. Evidence-based event reducing therapy currently is available only for HFrEF. With the completion of seminal trials of beta blockers, now part of standard therapy for HFrEF, it was apparent that heart rate slowing is an underlying basis of clinical effectiveness of HFrEF therapy. With the discovery of the "f current" that modulates the slope of spontaneous diastolic depolarization of the sino-atrial node, a non-beta blockade approach to heart rate slowing became available. Ivabradine, the first FDA-approved f-current blocker for HFrEF, markedly reduces hospitalizations for worsening heart failure, while also progressively reducing mortality as pre-therapy heart rate increases, and also promotes beneficial left ventricular remodeling, improves health-related quality of life and is effective despite a wide range of comorbidities. The drug is well tolerated and adverse effects are relatively few. Ivabradine represents an important addition to the armamentarium for mitigation of HFrEF.


The effect of age at diagnosis on outcome in rhabdomyosarcoma.
Survival for rhabdomyosarcoma appears to be more favorable in children and adolescents compared with adults. To determine the significance of age at diagnosis as a prognostic indicator in rhabdomyosarcoma, we performed a retrospective analysis of a combined pediatric and adult rhabdomyosarcoma data base. Pertinent prognostic variables, including age, TNM stage, histopathologic subtype, anatomic site, resectability, radiation to the primary site, and dose intensity of chemotherapy, were compared in a Cox proportional hazards model with mortality as the outcome variable. Age at diagnosis (P = 0.0001) and local tumor invasiveness (P < 0.0001), distant parenchymal metastases (P < 0.0001), regional lymph node involvement (P = 0.0027), and histopathologic subtype (P = 0.0446) contributed information to the proportional hazards model. Age at diagnosis is an independent predictor of outcome in patients with rhabdomyosarcoma along with tumor invasiveness, metastases, regional lymph node involvement, and histopathologic subtype.


What is in it for me? Norwegian radiographers and radiation therapists' experiences from obtaining a master's degree.
Radiographers and radiation therapists are essential in providing patients with high-quality diagnostic imaging or therapeutic services. Therefore, radiographers and radiation therapists must get involved in evidence-based practice and research. Even though many radiographers and radiation therapists obtain their master's degrees, little is known about how this degree affects clinical practice or personal and professional growth. We aimed to fill this knowledge gap by investigating Norwegian radiographers' and radiation therapists' experiences when deciding to undertake and complete a master's degree and exploring the impact of the master's degree in clinical practice. Semi-structured interviews were conducted and transcribed verbatim. The interview guide covered five broad areas: 1) the process of achieving a master's degree, 2) the work situation, 3) the value of competencies, 4) the use of competencies and 5) expectations. Data were analyzed using inductive content analysis. The analysis included seven participants (four diagnostic radiographers and three radiation therapists) working at six different departments of varying sizes across Norway. Four main categories emerged from the analysis, of which the categories: Motivation and Management support, were categorized into the theme experiences pre-graduation, whereas the categories Personal gain and Application of skills were categorized into the theme experiences pre-graduation. The fifth category Perception of pioneering embraces both themes. Participants reported great motivation and personal gain, but challenges in management and application of skills post-graduation. The participants perceived themselves as pioneers, as there is a lack of experience with radiographers and radiation therapists undertaking master studies, hence no culture and systems for professional development are established. There is a need for professional development and research culture in the Norwegian Departments of Radiology and Radiation therapy. Radiographers and radiation therapists must take the initiative to establish such. Further research should investigate managers' attitudes and perceptions toward radiographers' master's competencies in the clinic.


Motoric cognitive risk syndrome and incident dementia in older adults from the Québec NuAge cohort.
The co-occurrence of slow walking speed and subjective cognitive complaint (SCC) in non-demented individuals defines motoric cognitive risk syndrome (MCR), which is a pre-dementia stage. There is no information on the association between MCR and incident dementia in Québec's older population. The study aims to examine the association of MCR and its individual components (i.e. SCC and slow walking speed) with incident dementia in community-dwelling older adults living in the province of Québec (Canada). Québec older people population-based observational cohort study with 3 years of follow-up. Community dwellings. A subset of participants (n = 1,098) in 'Nutrition as a determinant of successful aging: The Québec longitudinal study' (NuAge). At baseline, participants with MCR were identified. Incident dementia was measured at annual follow-up visits using the Modified Mini-Mental State (≤79/100) test and Instrumental Activity Daily Living scale (≤6/8) score values. The prevalence of MCR was 4.2% at baseline and the overall incidence of dementia was 3.6%. MCR (Hazard Ratio (HR) = 5.18, with 95% confidence interval (CI) = [2.43-11.03] and P ≤ 0.001) and SCC alone (HR = 2.54, with 95% CI = [1.33-4.85] and P = 0.005) were associated with incident dementia, but slow walking speed was not (HR = 0.81, with 95%CI = [0.25-2.63] and P = 0.736). MCR and SCC are associated with incident dementia in NuAge study participants.


Accumulation of Biological and Behavioral Data of Female Sex Workers Using Respondent-Driven Sampling: Protocol for a Systematic Review.
Respondent-driven sampling (RDS) is a nonprobability sampling technique that allows the extrapolation of its outcome to the target population. This approach is typically used to overcome the difficulties in studying hidden or difficult-to-reach groups. The purpose of this protocol is to generate a systematic review on the accumulation of biological and behavioral data of female sex workers (FSWs) through different surveys that use the RDS method from around the world in the near future. The future systematic review will discuss the initiation, actualization, and problems of RDS during the accumulation of biological and behavioral data of FSWs through surveys from around the world. The behavior and biological data of FSWs will be extracted from peer-reviewed studies published between 2010 and 2022 and that are acquired through RDS. Using PubMed, Google Scholar, the Cochrane database, Scopus, Science Direct, and the Global Health network, all papers that are available will be obtained using the search phrases "respondent-driven" and "Female Sex Workers" OR "FSW" OR "sex workers" OR "SW." According to STROBE-RDS (Strengthening the Reporting of Observational Studies in Epidemiology for Respondent-Driven Sampling) criteria, the data will be retrieved through a data extraction form and will be organized using World Health Organization classifications of areas. The Newcastle-Ottawa Quality Assessment Scale will be used to measure bias risk and overall study quality. The future systematic review that will be generated from this protocol will offer evidence for or against the claim that using the RDS technique to recruit participants from "hidden" or "hard-to-reach" populations is the best strategy. The results will be disseminated through a peer-reviewed publication. Data collection started on April 1, 2023, and the systematic review is expected to be published by December 15, 2023. A minimum set of parameters for specific methodological, analytical, and testing procedures, including RDS methods to evaluate the overall quality of any RDS survey, will be provided by the future systematic review, in accordance with this protocol, to assist researchers, policy makers, and service providers in improving RDS methods for the surveillance of any key population. PROSPERO CRD42022346470; https://tinyurl.com/54xe2s3k. DERR1-10.2196/43722.


Multidisciplinary Treatment of a Giant Maxillofacial Congenital Hemangioma With Multiple Severe Complications.
Giant congenital hemangiomas are rare, especially when combined with multiple complications. This article presents a case of a giant congenital hemangioma of the maxillofacial region in a neonate with combined thrombocytopenia, coagulation dysfunction, and heart failure, which was eventually treated surgically after a multidisciplinary consultation and achieved a good outcome.


An economic model to assess the cost-benefit of BNCT.
We have constructed a formal model on cost-benefit of new technology in health care, and apply it on boron neutron capture therapy (BNCT). We assume that the patient health benefit from getting cured in acute treatment is always higher than the patient utility resulting from any long term treatment or death. This assumption makes it possible to evaluate the monetary cost impacts of a new technology and relate these measures to the patient health benefit.


Relationship of the subscapular nerves to the base of the coracoid.
This study was performed to determine the relation of the subscapular nerves to the medial base of the coracoid when using an arthroscopic approach. Twenty human cadaveric shoulder specimens were dissected, and measurements were taken from the medial base of the coracoid to the innervation points of the upper and lower subscapular nerves. Measurements were obtained with the humerus in both neutral and maximal external rotation. The average distance of the upper subscapular nerve from the coracoid base was 31.6 ± 6.6 mm (range, 22 to 45 mm) in neutral rotation and 24.2 ± 7.4 mm (range, 11 to 35 mm) in external rotation. The lower subscapular nerve's insertion point averaged 42.6 ± 7.6 mm (range, 25 to 55 mm) from the coracoid base in neutral rotation and 33.9 ± 6.9 mm (range, 24 to 45 mm) in external rotation. For both nerves, their distance from the coracoid significantly decreased when the humerus was placed in external rotation. The closest that the innervation point of either the upper or lower subscapular nerve came to the medial aspect of the coracoid was 11 mm. Understanding the relationship of the subscapular nerves to the base of the coracoid allows a safe arthroscopic release of a retracted subscapularis muscle that has formed adhesions to the inferior aspect of the coracoid. Use of an arthroscopic elevator to release adhesions between the subscapularis and the inferior aspect of the coracoid does not appear to risk denervation of the subscapularis muscle.


Three-dimensional numerical evaluation of skin surface thermal contrast by application of hypothermia at different depths and sizes of the breast tumor.
Thermal procedures can provide improvements in the thermal contrast of thermographic images in an attempt to diagnose early cases of breast cancer. This work aims to analyze the thermal contrast of different stages and depths of breast tumors from hypothermia treatment using an active thermography analysis. The influence of variation in metabolic heat generation and adipose tissue composition on thermal contrasts is also analyzed. The proposed methodology was based on the solution of the Pennes equation for a three-dimensional model similar to the real anatomy of the breast by commercial software COMSOL Multiphysics. The thermal procedure consists of three steps: Stationary, hypothermia and thermal recovery. During hypothermia, the boundary condition of the external surface was replaced by a constant temperature of 0, 5, 10, and 15 ∘C, simulating a gel pack, for cooling times of up to 20 min. In the thermal recovery, after the removal of the cooling, the breast was submitted again to the condition of natural convection on the external surface. Thermal contrasts in superficial tumors, for all hypothermia resulted in improvements in thermographs. For smallest tumor, the use of high resolution and sensitive thermal imaging cameras to acquire this thermal change may be necessary. For tumor of diameter of 10 cm, cooling from 0 ∘C can increase the thermal contrast by up to 136% compared to the passive thermography. Analyzes with deeper tumors showed very small temperature variations. Even so, the thermal contrast gain in cooling at 0 ∘C for the tumor with a diameter of 1 cm reached 37% in relation to passive thermography. Thus, this work contributes as an important tool in the analysis of the appropriate use of hypothermia for different cases in early stages of breast cancer, considering that long times are needed to obtain the best thermal contrast.


Public patient views of artificial intelligence in healthcare: A nominal group technique study.
The beliefs of laypeople and medical professionals often diverge with regards to disease, and technology has had a positive impact on how research is conducted. Surprisingly, given the expanding worldwide funding and research into Artificial Intelligence (AI) applications in healthcare, there is a paucity of research exploring the public patient perspective on this technology. Our study sets out to address this knowledge gap, by applying the Nominal Group Technique (NGT) to explore patient public views on AI. A Nominal Group Technique (NGT) was used involving four study groups with seven participants in each group. This started with a silent generation of ideas regarding the benefits and concerns of AI in Healthcare. Then a group discussion and round-robin process were conducted until no new ideas were generated. Participants ranked their top five benefits and top five concerns regarding the use of AI in healthcare. A final group consensus was reached. Twenty-Eight participants were recruited with the mean age of 47 years. The top five benefits were: Faster health services, Greater accuracy in management, AI systems available 24/7, reducing workforce burden, and equality in healthcare decision making. The top five concerns were: Data cybersecurity, bias and quality of AI data, less human interaction, algorithm errors and responsibility, and limitation in technology. This is the first formal qualitative study exploring patient public views on the use of AI in healthcare, and highlights that there is a clear understanding of the potential benefits delivered by this technology. Greater patient public group involvement, and a strong regulatory framework is recommended.


Mapping the Acoustic Soundscape off Vancouver Island Using the NEPTUNE Canada Ocean Observatory.
NEPTUNE Canada is a cabled ocean observatory system containing five nodes located in the northeast Pacific Ocean. Using passive acoustic data recorded at two nodes (Folger Passage Deep and Barkley Canyon Axis) between June 2010 and May 2011, we sought to quantify the levels of vessel traffic and the occurrence of biological sounds to determine the potential impact of anthropogenic sound in masking acoustic communication. The results from a comparison of the relative amplitude and occurrence of low-frequency biotic sounds to broadband sounds resulting from vessel traffic are presented. Additional contributions to the marine soundscape from self-generated instrument noise are discussed.


Isolation and primary structure of adrenocorticotropin from several species of whale.
The isolation of adrenocorticotropin (ACTH) from fin (Balaenoptera physalus), sei (Blaenoptera borelis) and sperm (Physeter catodon) whale pituitaries is described. Their primary structures have been elucidated by the fluorescein isothiocyanate method and revealed to be identical to the structure of the human hormone. Fin whale exhibited an identical steroidogenic activity to that of the porcine hormone.


Hypermethylation trigger of the glutathione-S-transferase gene (GSTP1) in prostate cancer cells.
Understanding what triggers hypermethylation of tumour suppressor genes in cancer cells is critical if we are to discern the role of methylation in the oncogenic process. CpG sites in CpG island promoters, that span most tumour suppressor genes, remain unmethylated in the normal cell, despite the fact that CpG sites are the prime target for de novo methylation by the DNA methyltransferases. The CpG island-associated with the GSTP1 gene is an intriguing example of a CpG rich region which is susceptible to hypermethylation in the majority of prostate tumours and yet is unmethylated in the normal prostate cell. In this study we evaluate a number of factors purported to be involved in hypermethylation to test their role in triggering hypermethylation of GSTP1 in prostate cancer DU145 and LNCaP cells. We find that hypermethylation is not associated with (1) elevated expression of the DNA methyltranferases, or (2) removal of Sp1 transcription factor binding sites in the CpG island or (3) removal of CpG island boundary elements or (4) prior gene silencing. Instead our results support a model that requires a combination of prior gene silencing and random "seeds" of methylation to trigger hypermethylation of the GSTP1 gene in the prostate cancer cell. We propose that the GSTP1 gene is initially silenced in the prostate cancer and random sites of methylation accumulate that result in subsequent hypermethylation and chromatin remodelling.


Polypeptide backbone, C(β) and methyl group resonance assignments of the 24 kDa plectin repeat domain 6 from human protein plectin.
The 500 kDa protein plectin is essential for the cytoskeletal organization of most mammalian cells and it is up-regulated in some types of cancer. Here, we report nearly complete sequence-specific polypeptide backbone, (13)C(β) and methyl group resonance assignments for 24 kDa human plectin(4403-4606) containing the C-terminal plectin repeat domain 6.