A novel role of CD30L/CD30 signaling by T-T cell interaction in Th1 response against mycobacterial infection.
A CD30 ligand (CD30L, CD153) is a type II membrane-associated glycoprotein belonging to the TNF family. To illustrate the potential role of CD30L in CD4(+) Th1 cell responses, we investigated the fate of Ag-specific CD4(+) T cells in CD30L-deficient (CD30L(-/-)) mice after Mycobacterium bovis bacillus Calmette-Guérin (BCG) infection. The number of bacteria was significantly higher in organs of CD30L(-/-) mice than in wild-type (WT) mice 4 wk postinfection. The numbers of purified protein derivative- or Ag85B-specific-IFN-gamma-producing-CD4(+) T cells in spleen, lung, or peritoneal exudate cells were significantly fewer in CD30L(-/-) mice than in WT mice. During the infection, CD30L was expressed mainly by CD44(+)CD3(+)CD4(+) T cells but not by CD3(+)CD8(+) T cells, B cells, dendritic cells, or macrophages. Costimulation with agonistic anti-CD30 mAb or coculturing with CD30L-transfected P815 cells restored IFN-gamma production by CD4(+) T cells from BCG-infected CD30L(-/-) mice. Coculturing with CD30L(+/+)CD4(+) T cells from BCG-infected WT mice also restored the number of IFN-gamma(+)CD30L(-/-)CD4(+) T cells. When transferred into the CD30L(+/+) mice, Ag-specific donor CD30L(-/-) CD4(+) T cells capable of producing IFN-gamma were restored to the compared level seen in CD30L(+/+) CD4(+) T cells on day 10 after BCG infection. When naive CD30L(+/+) T cells were transferred into CD30L(-/-) mice, IFN-gamma-producing-CD4(+) Th1 cells of donor origin were normally generated following BCG infection, and IFN-gamma-producing-CD30L(-/-)CD4(+) Th1 cells of host origin were partly restored. These results suggest that CD30L/CD30 signaling executed by CD30(+) T-CD30L(+) T cell interaction partly play a critical role in augmentation of Th1 response capable of producing IFN-gamma against BCG infection.


Biophysical and structural characterization of polyethylenimine-mediated siRNA delivery in vitro.
The goals of this study were as follows: 1) to evaluate the efficacy of different polyethylenimine (PEI) structures for siRNA delivery in a model system, and 2) to determine the biophysical and structural characteristics of PEI that relate to siRNA delivery. Biophysical characterization (effective diameter and zeta potential), cytotoxicities, relative binding affinities and in vitro transfection efficiencies were determined using nano-complexes formed from PEI's of 800, 25,000, (both branched) and 22,000 (linear) molecular weights at varying N:P ratios and siRNA concentrations. The HR5-CL11 cell line stably expressing luciferase was used as a model system in vitro. Successful siRNA delivery was observed within a very narrow window of conditions, and only with the 25,000 branched PEI at an N:P ratio of 6:1 and 8:1 and with 200 nM siRNA. While the zeta potential and size of PEI:siRNA complexes correlated to transfection efficacy in some cases, complex stability may also affect transfection efficacy. The ability of PEI to transfer functionally active siRNA to cells in culture is surprisingly dependent on its biophysical and structural characteristics when compared to its relative success and ease of use for DNA delivery.


Student mentoring to enhance graduates' employability potential.
This paper considers whether the adoption of a subject-specific, classroom-based, voluntary extra-curricular student mentoring scheme could provide an effective mechanism and andragogic approach to enhance higher education students' employability potential pre-graduation. Over the three-year pilot, 26 more advanced (second to fourth year) undergraduate students actively mentored nearly 400 first year undergraduate students during workshops delivered annually within forensic and policing focused courses. In total, 17 mentors anonymously completed online, post-scheme surveys. Survey data was quantitatively analysed to evaluate the scheme, establish which skills and attributes mentors had developed and investigate whether mentors could appropriately identify example skills within professional terminology used during employer recruitment. In addition, this paper reflects on the implementation of remote student mentoring during the COVID-19 pandemic and its adoption within a blended learning framework. The results from this research strongly support mentoring as an effective mechanism to develop undergraduate employability skills, significantly developing mentors' self-confidence and self-efficacy in their interpersonal and communication skills. Although mentors were aware of university graduate attributes and thought they could evidence these with appropriate examples, in practice this was not necessarily the case. As a result, a framework is proposed to enable mentors to identify their skills and how they may align with competencies sought by relevant forensic and policing employers. However, other andragogic practices may need to be implemented to maximise the potential for successful graduate employment.


Conjunctival Microangiopathy in Diabetes Mellitus Assessed with Optical Coherence Tomography Angiography.
To detect and quantify conjunctival microangiopathy with optical coherence tomography angiography (OCTA). Imaging was performed in the temporal and nasal quadrant of the conjunctiva using a Heidelberg Spectralis spectral domain-OCT in OCTA mode adding a 25D lens to the standard 30° fundus lens. Images were acquired within a 10° × 5° cube at the limbus. Binary images were analyzed using ImageJ (Fiji software version 2.0) and an average relative conjunctival vessel density was assessed. Thirty-two patients with diabetes mellitus type 1 and 2 and 42 healthy individuals were included. Vessel density in healthy individuals was 16.7 ± 5.2% in the nasal and 17.9 ± 6.4% in the temporal quadrant. In patients with diabetes without retinopathy, vessel density was 16.3 ± 6.7% in the nasal and 15.3 ± 7.3% in the temporal conjunctiva. In patients with diabetic retinopathy, vessel density was 13.7 ± 4.3% in the nasal and 15.2 ± 6.5% in the temporal conjunctiva. There were statistically significant higher values in both nasal and temporal measurements among healthy individuals than in patients with diabetic retinopathy (P = 0.03 and P = 0.01, respectively). Patients with diabetic retinopathy exhibit reduced vessel density, which may suggest diabetic microangiopathy in the conjunctiva. Anterior segment OCTA may detect conjunctival microangiopathy in patients with visual axis opacifications, where retinal OCTA is not possible. The findings of this study bridge the gap between experimental anterior segment OCTA imaging and clinical screening for diabetic complications.


Primary support optimization of large-span and shallow buried hard rock tunnels based on the active support concept.
Considering the large-span underground excavation subway station of Qingdao Metro Line 6 of China for analysis, it is necessary to optimize the traditional support system by investigating relevant codes and other tunnel projects. Based on the active support concept, a high prestressed rock bolt support system is proposed, and the optimization direction is defined to apply a high prestress force to rock bolts, increasing the appropriate spacing between supporting arches and strengthening support at key parts such as the large arch foot area, sidewalls and junctions. Numerical calculations and field monitoring are performed to analyze and evaluate the new support system. Numerical simulation results show that the new support system can effectively improve the stress state of the surrounding rock; the tensile stress area markedly decreases in size or disappears; and the plastic area also decreases in size. Field monitoring results show that the settlement of the arch crown is concentrated at 2-5 mm and the deformation rates are less than 0.5 mm/day. The supporting arches, shotcrete and rock bolts are all less than the yield strength and a high safety reserve. These results verify the safety and rationality of the proposed support system, which can be used as a reference for similar projects.


Maffucci's syndrome.
A case is reported of Maffucci's Syndrome with multiple enchondromata involving the left ring finger and subcutaneous haemangiomata in the left thenar eminence, treated by surgical excision.


Myelinated afferents signal the hyperalgesia associated with nerve injury.
Pain to light touching of the skin is a hallmark sign of causalgia. The purpose of this study was to determine whether myelinated or unmyelinated afferent fibers signal this hyperalgesia. Sensory testing was performed in 17 patients with long-standing hyperalgesia after nerve injury. The patients underwent a differential ischemic block of nerve function of the involved area. At a time when touch sensation in adjacent normal skin was eliminated, but when sensibility to warming and cooling stimuli was unaffected, the hyperalgesia to mechanical stimuli was abolished in 15 of the subjects. In 2 of these 15 patients, a differential local anesthetic block of the injured nerve was performed proximal to the site of injury. When temperature sensibility was absent, but when touch sensation was intact, hyperalgesia was present. In a third study, latency measurements in response to 400 micron stepped displacement stimuli were made in two patients who had hyperalgesia on the foot. The mean latency for detection of pain in the hyperalgesic region was 414 +/- 18 msec, compared to 458 +/- 16 msec for the detection of touch to the same stimuli applied to the opposite normal foot. These 3 lines of evidence indicate that myelinated primary afferents, perhaps A beta fibers, signal the hyperalgesic pain in causalgia. These fibers may be sensitized A beta nociceptors or low-threshold mechanoreceptors.


Numerical modelling of the memory effect in wet scrubbers.
Polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) can be absorbed in and desorbed from polypropylene (PP) tower packings in wet scrubbers utilized in waste incineration lines. This behaviour, also known as the memory effect, has been modelled using a gas phase-PP surface equilibrium and a numerical solid phase diffusion model describing the transport of PCDD/Fs inside the PP. The diffusivities and gas-PP partition coefficients of TCDD/F to HxCDD/Fs in PP have been estimated using the numerical model. Two incineration lines were modelled. In the first line, the absorption and desorption in PP test rods was followed before and after installation of a fabric filter that was placed before a wet scrubber. In the second incineration line, the accumulation of PCDD/Fs in a wet scrubber during start up periods and the subsequent decline during the following three months was modelled and compared to continuous two-week gas measurements after the scrubber. The obtained diffusivities in PP range from 10(-13) m(2)/s for TCDD to 10(-16) m(2)/s for HxCDD. Lower chlorinated homologues with a distinctive change in concentrations during the desorption period (e.g. TCDF) are easier to model, and show the best agreement between the two incineration lines.


Microencapsulation of endophytic LAB (KCC-41) and its probiotic and fermentative potential for cabbage kimchi.
The aim of the present study was to isolate novel lactic acid bacteria (LAB) from hairy vetch forage crop and characterize their probiotic and fermentative potential for preparing Korean cabbage kimchi. First, functional characterization of isolated strains such as antagonistic property, auto-aggregation, antibiotic susceptibility, and extracellular enzyme production was performed. The isolated Lactobacillus plantarum KCC-41 strain was able to inhibit pathogenic fungal spore formation. It showed susceptibility to common commercial antibiotics drugs. The selected LAB strain was then subjected to microencapsulation with alginate biopolymer. Its ability to survive in in vitro simulated gastro-intestinal fluid was evaluated. It was also used in the fermentation of cabbage kimchi samples. The encapsulated KCC-41 strain could effectively lead to kimchi fermentation in terms of reducing its pH and dominating bacterial count. It also significantly increased organic acid production than non-encapsulated LAB (KCC-41) for cabbage kimchi samples.


Misinterpretations of P-values and statistical tests persists among researchers and professionals working with statistics and epidemiology.
The aim was to investigate inferences of statistically significant test results among persons with more or less statistical education and research experience. A total of 75 doctoral students and 64 statisticians/epidemiologist responded to a web questionnaire about inferences of statistically significant findings. Participants were asked about their education and research experience, and also whether a 'statistically significant' test result (P = 0.024, α-level 0.05) could be inferred as proof or probability statements about the truth or falsehood of the null hypothesis (H0) and the alternative hypothesis (H1). Almost all participants reported having a university degree, and among statisticians/epidemiologist, most reported having a university degree in statistics and were working professionally with statistics. Overall, 9.4% of statisticians/epidemiologist and 24.0% of doctoral students responded that the statistically significant finding proved that H0 is not true, and 73.4% of statisticians/epidemiologists and 53.3% of doctoral students responded that the statistically significant finding indicated that H0 is improbable. Corresponding numbers about inferences about the alternative hypothesis (H1) were 12.0% and 6.2% about proving H1 being true and 62.7 and 62.5% for the conclusion that H1 is probable. Correct inferences to both questions, which is that a statistically significant finding cannot be inferred as either proof or a measure of a hypothesis' probability, were given by 10.7% of doctoral students and 12.5% of statisticians/epidemiologists. Misinterpretation of P-values and statistically significant test results persists also among persons who have substantial statistical education and who work professionally with statistics.


Mercury and other trace elements in a pelagic Arctic marine food web (Northwater Polynya, Baffin Bay).
Total mercury (THg), methylmercury (MeHg) and 22 other trace elements were measured in ice algae, three species of zooplankton, mixed zooplankton samples, Arctic cod (Boreogadus saida), ringed seals (Phoca hispida) and eight species of seabirds to examine the trophodynamics of these metals in an Arctic marine food web. All samples were collected in 1998 in the Northwater Polynya (NOW) located between Ellesmere Island and Greenland in Baffin Bay. THg and MeHg were found to biomagnify through the NOW food web, based on significant positive relationships between log THg and log MeHg concentrations vs. delta15N muscle and liver . The slope of these relationships for muscle THg and MeHg concentrations (slope=0.197 and 0.223, respectively) were similar to those reported for other aquatic food webs. The food web behavior of THg and delta15N appears constant, regardless of trophic state (eutrophic vs. oligotrophic), latitude (Arctic vs. tropical) or salinity (marine vs. freshwater) of the ecosystem. Rb in both liver and muscle tissue and Zn in muscle tissue were also found to biomagnify through this food web, although at a rate that is approximately 25% of that of THg. A number of elements (Cd, Pb and Ni in muscle tissue and Cd and Li in seabird liver tissue) were found to decrease trophically through the food web, as indicated by significantly negative relationships with tissue-specific delta15N. A diverse group of metals (Ag, Ba, La, Li, Sb, Sr, U and V) were found to have higher concentrations in zooplankton than seabirds or marine mammals due to bioconcentration from seawater. The remaining metals (As, Co, Cu, Ga, Mn, Mo and Se in muscle tissue) showed no relationship with trophic position, as indicated by delta15N values, although As in liver tissue showed significant biomagnification in the seabird portion of the food web.


Exploitation of pulsed flows for on-line dispersive liquid-liquid microextraction: Spectrophotometric determination of formaldehyde in milk.
Formaldehyde is often added to foods as a preservative, but it is highly toxic to humans, having been identified as a carcinogenic substance. It has also been used for the adulteration of milk in order to diminish the bacteria count and increase the shelf life of the product. Herein, we present a green dispersive liquid-liquid microextraction procedure in a flow-batch system for the determination of formaldehyde in milk. Pulsed flows were exploited for the first time to improve the dispersion of the extractant in the aqueous phase. The Hantzsch reaction was used for the derivatization of formaldehyde and the product was extracted with the ionic liquid (IL) trihexyltetradecylphosphonium chloride with methanol as the disperser. The flow-batch chamber was made of stainless steel with the facility for resistive heating to speed up the derivatization reaction. Spectrophotometric measurements were directly carried out in the organic phase using an optical fiber spectrophotometer. The limit of detection and coefficient of variation were 100 μg L(-1) and 3.1% (n=10), respectively, with a linear response from 0.5 to 5.0 mg L(-1), described by the equation A=0.088+0.116CF (mg L(-1)) in which A is absorbance and CF is formaldehyde concentration in mg L(-1). The estimated recoveries of formaldehyde from spiked milk samples ranged from 91% to 106% and the slopes of the analytical curves obtained with reference solutions in water or milk were in agreement, thus indicating the absence of matrix effects. Accuracy was demonstrated by the agreement of the results with those achieved by the reference fluorimetric procedure at the 95% confidence level. The proposed procedure allows for 10 extractions per hour, with minimized reagent consumption (120 μL of IL and 3.5 μL acetylacetone) and generation of only 6.7 mL waste per determination, which contribute to the eco-friendliness of the procedure.


MUC1 membrane trafficking: protocols for assessing biosynthetic delivery, endocytosis, recycling, and release through exosomes.
MUC1 is normally apical in polarized epithelial cells but is aberrantly localized in tumor cells. To better understand the mechanism of this altered localization as well as the normal functions of MUC1, we are focused on characterizing the features of MUC1 that regulate the membrane trafficking of this mucin-like transmembrane protein. Previous studies using heterologous expression of MUC1 in CHO and MDCK cells revealed that trafficking to the cell surface as well as endocytosis and recycling is modulated by glycosylation, palmitoylation, and docking of adaptor protein complexes. Protocols for assessing MUC1 trafficking have utilized membrane-impermeant cell surface biotinylation and subsequent stripping with reducing reagents, such as MESNA. The cumulative data have been used for computer modeling and calculation of rate constants. As MUC1 is released through trafficking to exosomes, we have devised protocols for the affinity isolation of MUC1-containing lipid rafts from nanovesicular subpopulations to perform proteomic mapping of protein constituents in these sorting platforms. Our studies to date have shown that plasma membranous MUC1 traffics via lipid raft-associated pathways to exosomes, which are independent of caveolin-1 or dynamin, but dependent on flotillin.


Synthesis and Characterization of the High-Pressure Nickel Borate γ-NiB4O7.
γ-NiB4O7 was synthesized in a high-pressure/high-temperature experiment at 5 GPa and 900 °C. The single-crystal structure analysis yielded the following results: space group P6522 (No. 179), a = 425.6(2), c = 3490.5(2) pm, V = 0.5475(2) nm3, Z = 6, and Flack parameter x = -0.010(5). Second harmonic generation measurements confirmed the acentric crystal structure. Furthermore, γ-NiB4O7 was characterized via vibrational as well as single-crystal electronic absorption spectroscopy, magnetic measurements, high-temperature X-ray diffraction, differential scanning calorimetry, and thermogravimetry. Density functional theory-based calculations were performed to facilitate band assignments to vibrational modes and to evaluate the elastic properties and phase stability of γ-NiB4O7.


Kraepelinian and non-Kraepelinian schizophrenia subgroup differences in cerebral metabolic rate.
We studied two subtypes of schizophrenia. the Kraepelinian subtype (n = 10) characterized by an unremitting and severe course and the non-Kraepelinian subtype (n = 17) characterized by a remitting course and some periods of self-care. Patients were assessed with positron emission tomography (PET) with 18F-deoxyglucose (FDG) and high-resolution magnetic resonance imaging (MRI). A group of 32 age- and sex-matched normal volunteers served as comparison subjects. During the FDG tracer uptake period, patients performed a serial verbal learning task. MR images were segmented into gray, white and cerebrospinal fluid regions, and warped to average normal coordinates. PET images were coregistered to the MR images and similarly warpedfor analysis. Kraepelinian subtype patients were characterized by lower metabolic rates in the temporal lobe and cingulategyrus. and lower fronto/occipital ratios than non-Kraepelinian subtype patients. Exploratory statistical probability mapping alsorevealed lower metabolic rates in the right striatum in Kraepelinian versus non-Kraepelinian patients. These differences couldnot be attributed to differences in age, symptom severity, task performance during FDG uptake, or severity of involuntary movements. Factor analysis of the cortical surface identified significantly lower temporal lobe metabolic rates in Kraepelinian patients than non-Kraepelinian patients. A combined frontal/temporal deficit or greater cortical change may be associated with poorer longitudinal course.


Effects of selective and nonselective beta-agonists on plasma potassium and norepinephrine.
The effects of graded infusions of the beta-agonists isoproterenol (nonselective), l-prenalterol (beta 1-selective), and salbutamol (beta 2-selective) on plasma potassium and norepinephrine were compared in subjects with borderline hypertension. Potassium levels fell with all three agonists, and norepinephrine levels rose with isoproterenol and salbutamol. These effects on potassium and norepinephrine were closely correlated and occurred at the same dose ranges as the cardiovascular responses. The fall in plasma potassium was probably caused by activation of beta-receptors, mainly on skeletal muscle, with subsequent stimulation of active sodium-potassium transport across the cellular membrane. The rise in plasma norepinephrine may have been due to activation of beta-receptors on sympathetic nerve endings. Activation of these presynaptic receptors is known to enhance the release of norepinephrine during nerve stimulation. For a given increase in heart rate and cardiac contractility, as measured by the heart rate-corrected duration of total electromechanical systole, which are mainly beta 1-responses, the effects on potassium and norepinephrine were in the order: salbutamol greater than isoproterenol greater than prenalterol. beta-Blockade with propranolol (nonselective), 80 mg four times a day, or atenolol (beta 1-selective), 100 mg once a day, antagonized the hypokalemic effect of isoproterenol as well as the rise in norepinephrine, but when isoproterenol was infused in doses high enough to overcome the blockade of the heart rate response, the effects on norepinephrine and potassium were abolished by propranolol and not by atenolol. Thus, the receptors in question appear to be of the beta 2-subtype.(ABSTRACT TRUNCATED AT 250 WORDS)


A case of percutaneous transluminal renal angioplasty for partial coverage of a renal artery by a stent graft after endovascular aneurysm repair.
An elderly woman was admitted to our hospital for evaluation of an abdominal aortic aneurysm (AAA) and we decided to treat her AAA with endovascular aneurysm repair. Her renal function became worse after the operation and a renogram suggested flow disturbance of her right renal artery. We performed angiography and checked her right renal artery using intravascular ultrasound. The ultrasound revealed thrombus formation and severe stenosis caused by the stent graft. We performed percutaneous transluminal renal angioplasty at the ostium of her right renal artery. After this procedure, her renal function rapidly improved.


Mathematics competitions: an integral part of the educational process.
For a century and a half, the scene of mathematics competitions underwent a remarkable transformation from isolated and geographically scattered events to a full-scale and a full-featured vibrant global ecosystem comprising an impressive variety of competitions, school students, university students, teachers, mentors, scientists, schools, universities, research institutions, journals, websites, civil society organizations, educational authorities, parents, etc. The evolution, the current state, the functioning of this ecosystem as well as its role for the identification and development of talent, its impact on the educational process, and the institutions involved with it, is briefly reflected on. Some relatively new online competitions are presented that cultivate the use of dynamic geometry software systems for a deeper understanding of mathematical facts and phenomena, and for finding approximate numerical solutions to problems that are not part of a typical school curriculum, but often arise from real-life practice.


Cardioprotection after angiotensin II type 1 blockade involves angiotensin II type 2 receptor expression and activation of protein kinase C-epsilon in acutely reperfused myocardial infarction in the dog. Effect of UP269-6 and losartan on AT1 and AT2-receptor expression and IP3 receptor and PKCepsilon proteins.
To determine whether cardioprotection after chronic angiotensin II (Ang II) type 1 (AT(1)) receptor blockade involves Ang II type 2 (AT(2)) receptor expression and protein kinase C-epsilon (PKC(epsilon)) activation, we measured in vivo haemodynamics and left ventricular (LV) remodelling and dysfunction (echocardiogram/ Doppler) and ex vivo AT(1)/AT(2)-receptor expression, IP(3)R (1, 4, 5-inositol trisphosphate type 2 receptor) and PKC(epsilon) proteins in dogs with acutely reperfused (90 minutes ischaemia, 90 minutes reperfusion) myocardial infarction (MI) following seven days of AT(1)-receptor blockade with oral losartan or UP269-6. The animals were randomised to sham; sham + losartan or UP269-6; MI alone; MI + losartan; MI + UP269-6. More marked AT(1)-receptor blockade with UP269-6 (greater inhibition of Ang II pressor responses) was associated with a smaller increase in preload, less systolic and diastolic dysfunction, less infarct expansion, and smaller LV diastolic and systolic volumes. However, both AT(1)-receptor antagonists decreased infarct size. Importantly, MI decreased AT(1)-receptor and AT(2)-receptor expression while MI after AT(1)-receptor antagonism increased AT(1)-receptor (mRNA, not protein) and AT(2)-receptor (mRNA and protein) expression as well as IP(3)R and PKC(epsilon) proteins and cyclic guanosine 3', 5' monophosphate (cGMP). These results suggest that cardioprotection induced by chronic AT(1)-receptor antagonism involves enhanced AT(2)-receptor expression and possibly downstream signalling through IP(3)R, PKC(epsilon) and cGMP.


Disulfiram attenuates MCMV-Induced pneumonia by inhibition of NF-κB/NLRP3 signaling pathway in immunocompromised mice.
Cytomegalovirus (CMV) pneumonia in immunocompromised individuals is associated with damaging hyperinflammation and leads to high morbidity and mortality. It is urgently needed to develop new strategies to treat CMV-induced pneumonia. As disulfiram (DSF) reportedly inhibits inflammatory responses in different disease models, its therapeutic effects in CMV-induced pneumonia are proposed. In this study, we demonstrated that DSF effectively attenuated pulmonary injury and improved survival in murine CMV (MCMV) pneumonia model. DSF treatment inhibited lung inflammatory responses, e.g. reducing pro-inflammatory cytokines, upregulating anti-inflammatory cytokine, and lowering the accumulation of leukocytes in the lung. Similar to the in vivo results, DSF attenuated inflammatory responses and modulated NF-κB/NLRP3 inflammasome activation in MCMV-infected BMDMs. Furthermore, DSF reduced pulmonary fibrosis and viral loads in MCMV pneumonia mice and BMDMs. The mechanism of anti-inflammatory effects of DSF may due to its regulating NF-κB signaling and NLRP3 inflammasome activation. Collectively, our results suggest that DSF-mediated anti-hyperinflammatory effects have potentials for therapy of human CMV pneumonia.


Which will carry more weight when CTR > 0.5, solid component size, CTR, tumor size or SUVmax?
This study was conducted to explore the clinical significance of the maximum standard uptake value (SUVmax) in the clinical stage IA lung adenocarcinoma with tumor size ≤ 2 cm and consolidation to tumor ratio (CTR) > 0.5. We retrospectively reviewed non-small cell lung cancer patients who underwent surgeries between January 2014 and March 2017. Clinical stage IA lung adenocarcinoma patients with tumor of size ≤ 2 cm and CTR > 0.5 were enrolled. The patients were divided into two groups: part-solid and pure-solid based on whether CTR = 1.0 or not. Nodules with any amount of solid or micropapillary components were regarded as the high-risk subtype. Time-dependent ROC curve was used to determine the best cut-off value. Finally, we analyzed the relationship between SUVmax, high-risk subtypes, node metastasis and 5-year relapse-free survival and overall survival. Totally, 270 patients were included. The distribution of pathological subtypes (p < 0.001), SUVmax (p < 0.001), and pathological N stage (p < 0.001) were different between the two groups. Multivariable analysis indicated that SUVmax could predict high-risk subtypes in cases of part-solid nodules (p < 0.001) and both high-risk subtypes (p = 0.022) and node metastasis (p < 0.001) in cases of pure-solid ones. SUVmax ≥ 2.6 and SUVmax ≥ 5.1 were strongly associated with 5-year relapse-free survival (p < 0.001) and 5-year overall survival (p < 0.001) among all the patients, respectively. Part-solid nodules with 0.5 < CTR < 1 and pure-solid nodules in lung adenocarcinoma show different clinicopathological characteristics, especially in SUVmax. SUVmax is significantly associated with high-risk subtypes, node metastasis, 5-year relapse-free survival and overall survival.


Protein recognition of hetero-/homoleptic ruthenium(II) tris(bipyridine)s for α-chymotrypsin and cytochrome c.
We examined the relationship between the structures of hetero-/homoleptic ruthenium(II) tris(bipyridine) metal complexes (Ru(II)(bpy)(3)) and their binding properties for α-chymotrypsin (ChT) and cytochrome c (cyt c). Heteroleptic compound 1a binds to both ChT and cyt c in 1:1 ratio, whereas homoleptic 2 forms 1:2 protein complex with ChT but 1:1 complex with cyt c. These results suggest that the structure of the recognition cavity in Ru(II)(bpy)(3) can be designed for shape complementarity to the targeted proteins. In addition, Ru(II)(bpy)(3) complexes were found to be potent inhibitors of cyt c reduction and to permeate A549 cells.


A Specialized Mechanism of Translation Mediated by FXR1a-Associated MicroRNP in Cellular Quiescence.
MicroRNAs predominantly decrease gene expression; however, specific mRNAs are translationally upregulated in quiescent (G0) mammalian cells and immature Xenopus laevis oocytes by an FXR1a-associated microRNA-protein complex (microRNP) that lacks the microRNP repressor, GW182. Their mechanism in these conditions of decreased mTOR signaling, and therefore reduced canonical (cap-and-poly(A)-tail-mediated) translation, remains undiscovered. Our data reveal that mTOR inhibition in human THP1 cells enables microRNA-mediated activation. Activation requires shortened/no poly(A)-tail targets; polyadenylated mRNAs are partially activated upon PAIP2 overexpression, which interferes with poly(A)-bound PABP, precluding PABP-enhanced microRNA-mediated inhibition and canonical translation. Consistently, inhibition of PARN deadenylase prevents activation. P97/DAP5, a homolog of canonical translation factor, eIF4G, which lacks PABP- and cap binding complex-interacting domains, is required for activation, and thereby for the oocyte immature state. P97 interacts with 3' UTR-binding FXR1a-associated microRNPs and with PARN, which binds mRNA 5' caps, forming a specialized complex to translate recruited mRNAs in these altered canonical translation conditions.


Mechanistic insights into copper-catalyzed Sonogashira-Hagihara-type cross-coupling reactions: sub-mol% catalyst loadings and ligand effects.
An efficient catalytic system for Sonogashira-Hagihara-type reactions displaying ligand acceleration in the copper-catalyzed formation of C(sp²)-C(sp) bonds is described. The structure of the ligand plays a key role for the coupling efficiency. Various copper sources show excellent catalytic activity, even in sub-mol% quantities. A wide variety of substituents is tolerated in the substrates. Mechanistic details have been revealed by kinetic measurements and DFT calculations.


A social approach to the validation of traditional veterinary remedies--the Anthra project.
Anthra, an organization of women veterinary scientists working in the field of livestock production and development, has been involved since 1996 in a research project to document and validate local ethnoveterinary and animal management practices carried out by livestock-rearing communities in different parts of the states of Andhra Pradesh and Maharashtra in India. Communal knowledge and innovation are an integral part of the day-to-day healing and management practices of farmers in all areas and over 80% of farmers continue to use these because they are easily and quickly available, especially in remote villages. However, this knowledge is today rapidly being lost. Farmers, both men and women, have expressed a keen desire to increase their own knowledge of these systems. This paper outlines the validation framework evolved by Anthra, wherein farmers using these medicines are actively participating in an evaluation process. Major findings are that local practices are effective, participating farmers use them confidently and other farmers are keen to use and increase their knowledge of them.


COVID-19 vaccine hesitancy in periconceptional and lactating women: a systematic review and meta-analysis protocol.
The pandemic of COVID-19 disease has caused severe impact globally. Governments consider vaccination as an effective measure to control pandemic. However, many people have been hesitant to receive COVID-19 vaccine, particularly periconceptional and lactating women. Although research has indicated that pregnant women with COVID-19 are at a higher risk of adverse pregnancy and birth outcomes, as well as severe illness. There appears to be a lack of systematic and comprehensive evidence of the prevalence and determinants of COVID-19 vaccine hesitancy among periconceptional and lactating women. As a result, it has been essential to investigate periconceptional and lactating women's vaccination views and behaviours. This study will review articles on vaccine hesitancy among periconceptional and lactating women to assess the impact of the COVID-19 vaccine hesitancy during the pandemic. We will systematically search observational studies from 1 November 2019 to 30 October 2021 in the following databases: Web of Science, PubMed, EMBASE, MEDLINE, Cochrane Library, EBSCO, WHO COVID-19 Database, CNKI and WanFang Database. The following medical subject headings and free-text terms will be used: "COVID-19 vaccines" AND "female" AND "vaccine hesitancy". Eligibility criteria are as follows: population (women of reproductive age); exposure (currently pregnant, lactational or trying to get pregnant); comparison (general women who are not in preconception, gestation or lactation) and outcome (the rate of COVID-19 vaccine hesitancy). Article screening and data extraction will be undertaken independently by two reviewers, and any discrepancy will be resolved through discussion. We will use I2 statistics to assess heterogeneity and perform a meta-analysis when sufficiently homogeneous studies are provided. We will explore the potential sources of heterogeneity using subgroup and meta-regression analysis. This study will use published data, so ethical approval is not required. The findings will be disseminated by publication in peer-reviewed journal(s). CRD42021257511.


Comparison of donor scores in bilateral lung transplantation-A large single-center analysis.
Objectifying donor lung quality is difficult and currently there is no consensus. Several donor scoring systems have been proposed in recent years. They all lack large-scale external validation and widespread acceptance. A retrospective evaluation of 2201 donor lungs offered to the lung transplant program at the Medical University of Vienna between January 2010 and June 2018 was performed. Five different lung donor scores were calculated for each offer (Oto, ET, MALT, UMN-DLQI, and ODSS). Prediction of organ utilization, 1-year graft survival, and long-term outcome were analyzed for each score. 1049 organs were rejected at the initial offer (group I), 209 lungs declined after procurement (group II), and 841 lungs accepted and transplanted (group III). The Oto score was superior in predicting acceptance of the initial offer (AUC: 0.795; CI: 0.776-0.815) and actual donor utilization (AUC: 0.660; CI: 0.618-0.701). Prediction of 1-year graft survival was best using the MALT score, Oto score, and UMN-DLQI. Stratification of early outcome by MALT was significant for length of mechanical ventilation (LMV), PGD3 rates, ICU stay and hospital stay, and in-hospital-mortality, respectively. To the best of our knowledge, this study is the largest validation analysis comparing currently available donor scores. The Oto score was superior in predicting organ utilization, and MALT score and UMN-DLQI for predicting outcome after lung transplantation.


Tranexamic acid in epistaxis: a systematic review.
The role of tranexamic acid in the management of epistaxis remains unclear. There is uncertainty about its safety and about the contraindications for its use. We performed a systematic review of the use of systemic and topical tranexamic acid in epistaxis and a comparative review of its use in other specialties. This review assesses and summarises the existing evidence for the efficacy and safety of tranexamic acid in the management of epistaxis. Systematic review. MEDLINE and EMBASE were searched for 'epistaxis' and equivalent MESH terms, combined with the Boolean operator 'OR' and 'tranexamic acid'. The Cochrane library and society guidelines were reviewed for evidence regarding the use of tranexamic acid in other specialties. All five relevant RCTs were included in the review and were evaluated according to the recommendations of the Cochrane Handbook for Systematic Reviews. Three RCTS pertained to spontaneous epistaxis; of these, one trial found no benefit of oral tranexamic acid in acute epistaxis, one trial found no significant benefit of topical tranexamic acid, but the largest of the trials showed significant benefit of topical tranexamic acid in acute epistaxis management. Two RCTs examined oral tranexamic acid for prophylaxis of recurrent epistaxes in patients with hereditary haemorrhagic telangiectasia; both showed significant reduction in severity and frequency. Tranexamic acid, as a WHO 'essential medicine', is a powerful, readily available tool, the use of which in epistaxis has been limited by uncertainty over its efficacy and its safety profile. This systematic review summarises the existing evidence and extrapolates from the wealth of data for other specialties to address the clinical question - does TXA have a role in epistaxis management?


Quantitative determination of major capsaicinoids in serum by ELISA and time-resolved fluorescent immunoassay based on monoclonal antibodies.
To monitor capsaicinoids in serum on-site, three new monoclonal antibodies (mAbs) were firstly proposed using a conjugate of 4-[(4-hydroxy-3-methoxybenzyl) amino]-4-oxobutanoic acid as the immunogen. Among them, the YQQD8 mAb showed the highest sensitivity and cross-reactivity to major capsaicinoids, such as capsaicin, dihydrocapsaicin and N-vanillylnonanamide. A competitive indirect enzyme-linked immunosorbent assay (icELISA) and a time-resolved fluorescent immunochromatographic assay (TRFICA) were established based on this mAb. The linear range was 1.1-27.0ngmL(-1) for icELISA and 1.9-62.5ngmL(-1) for TRFICA and the limit of detection (LOD) of TRFICA was 1.5ngmL(-1). To decrease the interference of sample components and increase accuracy, serum samples were diluted four times before assays. As a result, the linear range of serum samples was 4.6-107.9ngmL(-1) for icELISA and 7.6-250.0ngmL(-1) for TRFICA. Both icELISA and TRFICA showed good recoveries (91.0-112.8% for icELISA and 87.6-111.5% for TRFICA) and concordant results in spiked experiments. Overall, this is the first report of immunoassay based on the mAbs for quantitative determination of major capsaicinoids, and the results demonstrate that both methods can meet the demands of rapid on-site assay for capsaicinoids in serum samples.


[Protective ventilation reduces postoperative pulmonary complications - Contra].
Protective ventilation is a treatment strategy for patients with ARDS. The main goals are the prevention of de-recruitment and overinflation and hence development of VILI. Therefore, protective ventilation is an individualised therapy by adjusting PEEP and Vt in respect to patient' own volume-pressure-curve. Nowadays the term "protective ventilation" is reduced to ventilation with Vt 6 ml/kg only. Although protective ventilatory strategies are used in patients with severe pulmonary impairment there is a trend to transfer this strategy to healthy humans undergoing surgery. In ventilated patients with healthy lungs a ventilation with Vt higher than 17 ml/kg seems to increase the risk for development of VILI. Nevertheless, many studies show a association between application of protective intraoperative ventilatory strategies and a reduced rate of postoperative pulmonary complications. However, "protective ventilation" has not been standardised yet, and the adequate Vt and PEEP in an individual patient undergoing surgery has still to be clarified. Therefore, due to inconsistent intraoperative ventilation and methodical flaws it remains questionable if a generalized Vt reduction copes this complex topic. One should be aware that reduction of Vt may increase the rate of atelectasis and has been shown to be associated with increased mortality.


Challenges and Advances in Chimeric Antigen Receptor Therapy for Acute Myeloid Leukemia.
The advent of chimeric antigen receptor (CAR) T-cell therapy has led to dramatic remission rates in multiple relapsed/refractory hematologic malignancies. While CAR T-cell therapy has been particularly successful as a treatment for B-cell malignancies, effectively treating acute myeloid leukemia (AML) with CARs has posed a larger challenge. AML not only creates an immunosuppressive tumor microenvironment that dampens CAR T-cell responses, but it also lacks many unique tumor-associated antigens, making leukemic-specific targeting difficult. One advantage of CAR T-cell therapy compared to alternative treatment options is the ability to provide prolonged antigen-specific immune effector and surveillance functions. Since many AML CAR targets under investigation including CD33, CD117, and CD123 are also expressed on hematopoietic stem cells, CAR T-cell therapy can lead to severe and potentially lethal myeloablation. Novel strategies to combat these issues include creation of bispecific CARs, CAR T-cell "safety switches", TCR-like CARs, NK CARs, and universal CARs, but all vary in their ability to provide a sustained remission, and consolidation with an allogeneic hematopoietic cell transplantation (allo-HCT) will be necessary in most cases This review highlights the delicate balance between effectively eliminating AML blasts and leukemic stem cells, while preserving the ability for bone marrow to regenerate. The impact of CAR therapy on treatment landscape of AML and changing scope of allo-HCT is discussed. Continued advances in AML CAR therapy would be of great benefit to a disease that still has high morbidity and mortality.


Understanding stakeholder participation in research as part of sustainable development.
Participation is often presented as a 'good' thing and a fairer way to represent views and opinions outside narrow confines of interest and expertise. However, the roots of participatory approaches within research contexts are deep and numerous twists and turns demonstrate a confused and possibly confusing morphology with significant gaps and weaknesses. In this paper 'via the medium' of the POINT (Policy Influence of Indicators) research project we trace elements of the recent history of group participation in sustainable development and the emergence of focus on four areas, most significantly how participatory methods are used. In the absence of strong evidence to contrary we suggest that the issue of how participants engage in participation remains a significant weakness for the field. In order to counter the apparent gap we suggest that a certain degree of structure and process can provide the oeuvre of participatory approaches with a higher degree of transparency in the research process and, by focus on the use of a method called Triple Task, group participatory events can be encouraged to yield greater insights into the workings of groups of all kinds.


Difficult-to-treat pediatric obsessive-compulsive disorder: feasibility and preliminary results of a randomized pilot trial of D-cycloserine-augmented behavior therapy.
This study examined the feasibility and preliminary effectiveness of d-cycloserine (DCS)-augmented cognitive behavioral therapy (CBT) for children and adolescents with difficult-to-treat Obsessive Compulsive Disorder, in a double-blind randomized controlled pilot trial (RCT). Seventeen children and adolescents (aged 8-18 years) with a primary diagnosis of OCD, which was deemed difficult-to-treat, were randomly assigned to either nine sessions of CBT including five sessions of DCS-augmented exposure and response prevention (ERP) [ERP + DCS] or nine sessions of CBT including five sessions of placebo-augmented ERP [ERP + PBO]. Weight-dependent DCS or placebo doses (25 or 50 mg) were taken 1 hour before ERP sessions. At posttreatment, both groups showed significant improvements with 94% of the entire sample classified as responders. However, a greater improvement in the ERP + DCS relative to the ERP + PBO condition was observed at 1-month follow-up on clinician-rated obsessional severity and diagnostic severity, and parent ratings of OCD severity. There were no changes across time or condition from 1- to 3-month follow-up. In this preliminary study, DCS-augmented ERP produced significant improvements in OCD severity from posttreatment to 1-month follow-up, relative to a placebo control condition, in severe and difficult-to-treat pediatric OCD. The significant effect on obsessional severity suggests that DCS augmentation might be associated with enhanced modification of obsessional thoughts during ERP, and warrants further investigation.


The effect of stimulation frequency and calcium concentration on maintenance of developed tension in isolated heart muscle preparations.
The ability of isolated cardiac muscle preparations to maintain force of contraction was assessed at different extracellular Ca2+ concentrations and at various stimulation frequencies. Preparations were incubated in Krebs-Henseleit buffer at 32 degrees C and electrically stimulated at frequencies between 0.25 and 3.0 Hz. Extra-cellular Ca2+ was maintained at given concentrations between 0.8 and 2.4 mM, a range that included the plasma-ionized Ca2+ levels determined for rat and guinea pig. Developed tension of atrial or papillary muscle preparations of guinea pig heart was more stable at higher stimulation frequencies. Rat atria and ventricular strips were more stable at 0.25 than at 0.5 or 1.0 Hz, and the stability increased at 2.0 and 3.0 Hz. Guinea pig atrial muscle was maintained for a longer time at higher media Ca2+ concentrations; however, no such effect was observed with rat atrial tissue. Thus, the decrementing at developed tension in isolated cardiac muscle preparations is dependent on stimulation frequency and Ca2+ concentrations and can be retarded by selection of appropriate incubation conditions.


Prospective cohort study of ultrasound surveillance of regional lymph nodes in patients with intermediate-risk cutaneous melanoma.
For patients with intermediate-thickness melanoma, surveillance of regional lymph node basins by clinical examination alone has been reported to result in a larger number of lymph nodes involved by melanoma than if patients had initial sentinel node biopsy and completion dissection. This may result in worse regional control. A prospective study of both regular clinical examination and ultrasound surveillance was conducted to assess the effectiveness of these modalities. Between 2010 and 2014, patients with melanoma of thickness 1·2-3·5 mm who had under-gone wide local excision but not sentinel node biopsy were recruited to a prospective observational study of regular clinical and ultrasound nodal surveillance. The primary endpoint was nodal burden within a dissected regional lymph node basin. Secondary endpoints included locoregional or distant relapse, progression-free and overall survival. Ninety patients were included in the study. After a median follow-up of 52 months, ten patients had developed nodal relapse as first recurrence, four had locoregional disease outside of an anatomical nodal basin as the first site of relapse and six had relapse with distant disease. None of the patients who developed relapse within a nodal basin presented with unresectable nodal disease. The median number of involved lymph nodes in patients undergoing lymphadenectomy for nodal relapse was 1 (range 1-2; mean 1·2). This study suggests that ultrasound surveillance of regional lymph node basins is safe for patients with melanoma who undergo a policy of nodal surveillance.


Sepsis after elective surgery - Incidence, aetiology and outcome.
Sepsis requiring admission to intensive care (ICU) is a rare complication of elective surgery, but is associated with high morbidity and mortality. The aim of this study was to describe the incidence and outcome of sepsis following elective surgery. This was a retrospective, observational study where all admissions to Icelandic ICUs during calendar years 2006, 2008, 2010, 2012, 2014 and 2016 were screened, identifing patients with sepsis following elective surgery (ACCP/SCCM criteria). The number of elective operations performed at the largest center (Landspitali) during the study years were collected. Descriptive statistics were used to assess the incidence and outcome of patients with sepsis after elective surgery. During the study years, 88 patients were admitted to Icelandic ICUs with sepsis following elective surgery. Of those, 80 were operated at Landspitali, where the incidence of sepsis was 0.19% per elective procedure, highest following pancreaticoduodenectomies (14%, CI 6-25) and esophagectomies (13%, CI 4-27), but the greatest number of patients (30% (26/88)) developed sepsis after a colorectal procedure. The most common infection sources were the abdomen (65% (57/88)) and lungs/mediastinum (22% (19/88)), frequently polymicrobial (58% (36/62) of patients with cultures). The incidence of insufficient empirical antibiotics was high (50% (30/60)). The median ICU and hospital length-of-stay were 5.5 and 26 days and the 28-day and 1-year mortality rates were 16% (14/88) and 41% (36/87), respectively. Incidence of sepsis following elective surgery is low in Iceland but mortality is high. Initial antimicrobial therapy needs careful consideration in these hospital-acquired, often polymicrobial infections.


Effects of classroom cleaning on student health: a longitudinal study.
School districts across the world have been grappling with how to keep their schools open, students healthy, and prevent the spread of viruses in their communities. The aims of this study included assessing both (1) the effectiveness of enhanced classroom cleaning and disinfecting protocol on surface biocontamination and (2) the associations between surface biocontamination and student absence due to illnesses. Cleaning effectiveness was assessed using quantitative adenosine triphosphate (ATP) measurements during a 10-week study period in a sample of 34 public schools (15,814 students), of a district located in the Western US. The schools were randomly assigned to 17 intervention schools implementing enhanced cleaning and disinfecting protocol and 17 control schools cleaning as usual. General estimating equations (GEEs) were used for modeling associations between ATP levels and weekly aggregates of student absences due to respiratory and gastrointestinal illnesses, which were recorded by the schools according to district wide protocol. The weekly average ATP levels on logarithmic scale were 5.02 (SD 0.53) and 5.26 (SD 0.48) in the intervention and control schools, respectively, where the difference is statistically significant (p < 0.001). The probability of weekly absence due to gastrointestinal illness was significantly associated with ATP levels (parameter estimate 1.16, 95% CI 1.01-1.34, per unit (log) increase of weekly average ATP), where the model accounts for student level, gender, ethnic group, and socioeconomic status as well as for school level attendance, total absence ratio, and ventilation adequacy in classrooms. Associations were not found between ATP levels and weekly probability of any absence, or absence due to respiratory illness. Enhanced cleaning resulted in a significantly lower level of biocontamination on desktops in the intervention group. In addition, a statistically significant association was established between ATP levels on classroom desks and probability of absence due to gastrointestinal illness. We found that enhanced cleaning protocol, including bi-weekly cleaning of classroom desks, as well as training of custodians and teachers, monitoring of effectiveness, and feedback, yielded a moderate but statistically significantly lower level of biocontamination on desktops, indicated by quantitative ATP monitoring. Within the range of weekly average desktop ATP levels observed, the probability of reported absence due to gastrointestinal illness is estimated to increase from 0.021 to 0.026. Based on the results, enhanced surface cleaning and monitoring its effectiveness is a possible district, state, or even national level policy to support healthy school environments.


Pertussis antitoxin decay after vaccination with DTPa. Response to a first booster dose 3 1/2-6 1/2 years after the third vaccine dose.
Longitudinal serum samples were collected from 542 children that had participated in a Swedish pertussis vaccine trial 1992-1995 [Gustafsson L, Hallander HO, Olin P, Reizenstein E, Storsaeter J. A controlled trial of a two-component acellular, a five-component acellular, and a whole-cell pertussis vaccine. N Engl J Med 1996;334(6):349-355] and who did not contract pertussis. The sera were analyzed for post vaccination antibody decay and for booster response of anti-PT (IgG antibodies against pertussis toxin), as measured by ELISA. Generally, an initial rapid decay of antitoxin antibody concentration was followed by a slower decay; the change occurring when the geometric mean level of antitoxin concentration reached 8-9 ELISA Units/mL (EU/mL). The time needed to reach this level was 8-9 months after the third dose in a 2, 4, and 6 months schedule. A "best-fit" combined regression model was used to predict when 50% of the children have less than the minimum level of detection of anti-PT (1EU/mL). This occurred about 65 months after dose 3 at an age of 6 years. The anti-PT response to a booster dose was evident but the post-booster geometric mean values decreased with number of years after the third dose and the response appeared later. The results indicate that a pre-school booster might be considered at 6 years of age or earlier.


Adjunctive use of essential oils following scaling and root planing -a randomized clinical trial.
Hitherto no study has been published on the effect of the adjunctive administration of essential oils following scaling and root planing (SRP). This study describes the effect of a mouthrinse consisting of essential oils (Cymbopogon flexuosus, Thymus zygis and Rosmarinus officinalis) following SRP by clinical and microbiological variables in patients with generalized moderate chronic periodontitis. Forty-six patients (aged 40-65 years) with moderate chronic periodontitis were randomized in a double-blind study and rinsed their oral cavity following SRP with an essential oil mouthrinse (n = 23) or placebo (n = 23) for 14 days. Probing depth (PD), attachment level (AL), bleeding on probing (BOP) and modified sulcus bleeding index (SBI) were recorded at baseline and after 3 and 6 months. Subgingival plaque was taken for assessment of major bacteria associated with periodontitis. AL, PD, BOP and SBI were significantly improved in both groups after three (p < 0.001) and 6 months (p ≤ 0.015). AL improved significantly better in the test than in the control group after 3 and 6 months (p < 0.001), so did PD after three months in the tendency (p = 0.1). BOP improved better in the test group after 3 months (p = 0.065). Numbers of Treponema denticola (p = 0.044) and Fusobacterium nucleatum (p = 0.029) decreased more in the test than in the control group after 3 months, those of Tannerella forsythia after 6 months (p = 0.039). Prevotella micra (p < 0.001, p = 0.035) and Campylobacter rectus (p = 0.002 , p = 0.012) decreased significantly in both groups after 3 months. The adjunctive use of a mouthrinse containing essential oils following SRP has a positive effect on clinical variables and on bacterial levels in the subgingival biofilm. 332-12-24092012, DRKS 00009387, German Clinical Trials Register, Freiburg i. Br., 16.09.2015.


Reduced 2-D Frontal Plane Motion During Single-Limb Landing Is Associated With Risk of Future Anterior Cruciate Ligament Graft Rupture After Anterior Cruciate Ligament Reconstruction and Return to Sport: A Pilot Study.
To evaluate the association between 2-D frontal plane movement and second anterior cruciate ligament (ACL) injury risk in young athletes at return to sport (RTS) after ACL reconstruction. Prospective cohort. Forty-nine participants who had ACL reconstruction (mean ± SD age, 16.5 ± 3.0 years) performed a single-leg drop landing from a 31-cm box at the time of their RTS. Frontal plane trunk, pelvis, and knee angles were measured using 2-D video analysis at the point of maximum depth during landing. Summated frontal plane angles were calculated by adding trunk, pelvis, and knee angles. Participants were grouped based on whether or not they sustained an ACL graft rupture over the 24 months after RTS. Seven participants (14%) sustained an ipsilateral graft rupture within 24 months after RTS. Participants who suffered a second ACL injury had a significant reduction in the summated frontal plane angle of the trunk, pelvis, and knee (P = .018) and of the trunk and knee (P = .02) compared to those who did not suffer a second injury. For every 5° increase in the summated trunk, pelvis, and knee angle (odds ratio [OR] = 0.54; 95% confidence interval [CI]: 0.31, 0.94) and the summated trunk and knee angle (OR = 0.48; 95% CI: 0.25, 0.94), the athletes were 46% to 52% less likely to sustain a graft rupture. Athletes who suffered an ACL graft rupture within 24 months of RTS had a more rigid posture when landing compared to their uninjured peers. The results of this pilot study should be replicated in a larger sample to determine whether this method has merit as a screening tool to identify athletes at high risk for second ACL injury. J Orthop Sports Phys Ther 2021;51(2):82-87. Epub 25 Dec 2020. doi:10.2519/jospt.2021.9302.


The organization of n-alkanes in lipid bilayers.
The interaction of n-alkanes (C6--C16) with phosphatidylcholine has been studied by the combined use of differential scanning calorimetry, X-ray diffraction and monolayer techniques. It has been found that the thermal properties and ultrastructure of lipid-alkane vesicles are strongly dependent on the length of the n-alkanes. Long alkanes, such as tetradecane and hexadecane, increase the transition temperature of dimyristoyl phosphatidylcholine and dipalmitoyl phosphatidylcholine, while the X-ray data indicate that these long alkanes align parallel to the lipid acyl chains. In contrast, shorter alkanes, such as hexane and octane, decrease and broaden the thermal transition and electron density profiles show that these alkanes increase bilayer width by partitioning between the apposing monolayers of the bilayer. For lipids in the gel and liquid crystalline states, the short alkanes form an alkane region in the geometric center of the bilayer.


Master regulator activity QTL protocol to implicate regulatory pathways potentially mediating GWAS signals using eQTL data.
Here, we present a protocol to identify transcriptional regulators potentially mediating downstream biological effects of germline variants associated with complex traits of interest, which enables functional hypothesis generation independent of colocalizing expression quantitative trait loci (eQTLs). We describe steps for tissue-/cell-type-specific co-expression network modeling, expression regulator activity inference, and identification of representative phenotypic master regulators. Finally, we detail activity QTL and eQTL analyses. This protocol requires genotype, expression, and relevant covariables and phenotype data from existing eQTL datasets. For complete details on the use and execution of this protocol, please refer to Hoskins et al.1.


Vildagliptin Attenuates Huntington's Disease through Activation of GLP-1 Receptor/PI3K/Akt/BDNF Pathway in 3-Nitropropionic Acid Rat Model.
Vildagliptin (Vilda), a dipeptidyl peptidase-4 (DPP-4) inhibitor, has been highlighted as a promising therapeutic agent for neurodegenerative diseases as Alzheimer's and Parkinson's diseases. Vilda's effect is mostly linked to PI3K/Akt signaling in CNS. Moreover, PI3K/Akt activation reportedly enhanced survival and dampened progression of Huntington's disease (HD). However, Vilda's role in HD is yet to be elucidated. Thus, the aim of the study is to uncover the potentiality of Vilda in HD and unfold its link with PI3K/Akt pathway in 3-nitropropionic acid (3NP) rat model. Rats were randomly assigned into 4 groups; group 1 received saline, whereas, groups 2, 3 and 4 received 3NP (10 mg/kg/day; i.p.) for 14 days, concomitantly with Vilda (5 mg/kg/day; p.o.) in groups 3 and 4, and wortmannin (WM), a PI3K inhibitor, (15 μg/kg/day; i.v.) in group 4. Vilda improved cognitive and motor perturbations induced by 3NP, as confirmed by striatal histopathological specimens and immunohistochemical examination of GFAP. The molecular signaling of Vilda was estimated by elevation of GLP-1 level and protein expressions of survival proteins; p85/p55 (pY458/199)-PI3K, pS473-Akt. Together, it boosted striatal neurotrophic factors and receptor; pS133-CREB, BDNF, pY515-TrKB, which subsequently maintained mitochondrial integrity, as indicated by enhancing both SDH and COX activities, and the redox modulators; Sirt1, Nrf2. Such neuroprotection restored imbalance of neurotransmitters through increasing GABA and suppressing glutamate as well PDE10A. These effects were reversed by WM pre-administration. In conclusion, Vilda purveyed significant anti-Huntington effect which may be mediated, at least in part, via activation of GLP-1/PI3K/Akt pathway in 3NP rat model.


One carbon metabolism in pregnancy: Impact on maternal, fetal and neonatal health.
One carbon metabolism or methyl transfer, a crucial component of metabolism in all cells and tissues, supports the critical function of synthesis of purines, thymidylate and methylation via multiple methyl transferases driven by the ubiquitous methyl donor s-adenosylmethionine. Serine is the primary methyl donor to the one carbon pool. Intracellular folates and methionine metabolism are the critical components of one carbon transfer. Methionine metabolism requires vitamin B12, B6 as cofactors and is modulated by endocrine signals and is responsive to nutrient intake. Perturbations in one carbon transfer can have profound effects on cell proliferation, growth and function. Epidemiological studies in humans and experimental model have established a strong relationship between impaired fetal growth and the immediate and long term consequences to the health of the offspring. It is speculated that during development, maternal environmental and nutrient influences by their effects on one carbon transfer can impact the health of the mother, impair growth and reprogram metabolism of the fetus, and cause long term morbidity in the offspring. The potential for such effects is underscored by the unique responses in methionine metabolism in the human mother during pregnancy, the absence of transsulfuration activity in the fetus, ontogeny of methionine metabolism in the placenta and the unique metabolism of serine and glycine in the fetus. Dietary protein restriction in animals and marginal protein intake in humans causes characteristic changes in one carbon metabolism. The impact of perturbations in one carbon metabolism on the health of the mother during pregnancy, on fetal growth and the neonate are discussed and their possible mechanism explored.


Anterolateral thigh flap pedicle for interposition artery and vein grafts in head and neck reconstruction: a case report.
The selection of receiving vessels is one of the most critical steps in ensuring a successful outcome in microvascular surgery. The use of interposition grafts in microsurgery offers the surgeon valuable options when the free flaps vascular pedicles are too short to be anastomosed directly to the recipient vessels. Here, we present a case in which artery and vein grafts were used in microsurgical reconstruction of an anterior maxillary defect with an iliac free flap. As donor vessels, we used the descending branch of the lateral circumflex femoral artery and one of the two venae commitantes. The flap survived without major or minor complications. The anterolateral thigh flap pedicle allowed us to harvest safe, reliable grafts easily, with a suitable vessel length and diameter.


Significance of risk factors for osteoporosis is dependent on gender and menopause in rheumatoid arthritis.
The aim of our study was to compare the significance of risk factors for osteoporosis according to gender and menopausal state in patients with rheumatoid arthritis (RA). Bone mineral density (dual X-ray absorptiometry), cumulative glucocorticoid dose, age, disease duration, body mass index (BMI) and parameters of disease activity and bone turnover were registered in 343 postmenopausal women, 100 premenopausal women and 108 men with RA. Osteoporosis was found in a significantly higher percentage in postmenopausal women (55.7%) and in men (50.5%) in comparison with premenopausal women (18%; P < 0.001). The following risk factors for osteoporosis were found: older age, low BMI and high cumulative glucocorticoid dose in postmenopausal women, low BMI and high cumulative glucocorticoid dose in men and low BMI in premenopausal women. There is a very high prevalence of osteoporosis not only in postmenopausal women but also in men with RA. Osteoporosis risk factors are strongly dependent from gender and menopausal state.


KGCAK: a K-mer based database for genome-wide phylogeny and complexity evaluation.
The K-mer approach, treating genomic sequences as simple characters and counting the relative abundance of each string upon a fixed K, has been extensively applied to phylogeny inference for genome assembly, annotation, and comparison. To meet increasing demands for comparing large genome sequences and to promote the use of the K-mer approach, we develop a versatile database, KGCAK ( http://kgcak.big.ac.cn/KGCAK/ ), containing ~8,000 genomes that include genome sequences of diverse life forms (viruses, prokaryotes, protists, animals, and plants) and cellular organelles of eukaryotic lineages. It builds phylogeny based on genomic elements in an alignment-free fashion and provides in-depth data processing enabling users to compare the complexity of genome sequences based on K-mer distribution. We hope that KGCAK becomes a powerful tool for exploring relationship within and among groups of species in a tree of life based on genomic data.


Early radiation survey of Iitate village, which was heavily contaminated by the Fukushima Daiichi accident, conducted on 28 and 29 March 2011.
Following the news that the radiation level in Iitate Village, located 25-45 km from the Fukushima Daiichi Nuclear Power Plant, was seriously increased, an urgent field survey was carried out on 28 and 29 March 2011. Radiation levels at 130 locations were measured inside a van that traveled throughout the village using a CsI pocket survey meter and an ionization chamber. Soil samples were also taken at five locations and submitted to gamma ray analysis using a Ge detector. A radiation exposure rate of more than 20 μSv h was observed in the southern part of Iitate Village. Volatile radionuclides such as iodine and cesium were found to be the main components of radioactive contamination. A trace amount of plutonium isotopes originating from the accident was also confirmed in several soil samples, the level of which was less than the global fallout. Based on the measured density of radionuclides at the highest contamination location during the present survey, an exposure rate of about 200 μGy h at 1 m above the ground was estimated at the time of the radioactive deposition on March 15. At this location, the cumulative exposure would reach 50 mGy in the middle of May 2011.


Genetic characterization and improved genotyping of the dysferlin-deficient mouse strain Dysf (tm1Kcam).
Mouse models of dysferlinopathies are valuable tools with which to investigate the pathomechanisms underlying these diseases and to test novel therapeutic strategies. One such mouse model is the Dysf (tm1Kcam) strain, which was generated using a targeting vector to replace a 12-kb region of the dysferlin gene and which features a progressive muscular dystrophy. A prerequisite for successful animal studies using genetic mouse models is an accurate genotyping protocol. Unfortunately, the lack of robustness of currently available genotyping protocols for the Dysf (tm1Kcam) mouse has prevented efficient colony management. Initial attempts to improve the genotyping protocol based on the published genomic structure failed. These difficulties led us to analyze the targeted locus of the dysferlin gene of the Dysf (tm1Kcam) mouse in greater detail. In this study we resequenced and analyzed the targeted locus of the Dysf (tm1Kcam) mouse and developed a novel PCR protocol for genotyping. We found that instead of a deletion, the dysferlin locus in the Dysf (tm1Kcam) mouse carries a targeted insertion. This genetic characterization enabled us to establish a reliable method for genotyping of the Dysf (tm1Kcam) mouse, and thus has made efficient colony management possible. Our work will make the Dysf (tm1Kcam) mouse model more attractive for animal studies of dysferlinopathies.


"Those Who Need It the Most": Equity Framing in 2021 U.S. Print News About Food Assistance.
To understand how equity appeared in news about food assistance from 2021. We assessed a national sample of news articles (N=298) for equity arguments and language about racial and health equity. Only 28% of coverage argued that food assistance programs promote equity. Just 6% mentioned people of color or named racial disparities in food access. Narratives that explain how food assistance programs reduce inequities could deepen their policy appeal and broaden public perceptions around recipients. There are opportunities for news coverage to expand the discussion of how food assistance programs improve racial and health equity outcomes.


[Study on HPLC fingerprint of Swertia mussotii var. mussotii from north-west area of Sichuan Province I].
To constitute HPLC fingerprint of the methanol extract from Swertia mussotii grown in Sichuan Province. RP-HPLC, methanol and water including 0.02% acid as mobile phase, gradient elution, flow rate 1.0 mL x min(-1), the detection wavelength was 260 nm, temperature was 30 degrees C. The RSD values of peak area and retention time of common peaks in precision, repeatability and stability were lower than 5.0%, respectively, similarity was over 0.805 in S. mussotii collected from 10 different habitats. All results above exhibit that this method is simple, practicable, and reliable as a standard method in controlling the quality of S. mussotii.


Effect of molecular structure of eco-friendly glycolipid biosurfactants on the adsorption of hair-care conditioning polymers.
Pseudo-binary mixtures of different glycolipids, four different rhamnolipids (RL) and an alkyl polyglucoside (APG), with poly(diallyl-dimethylammonium chloride) (PDADMAC) have been studied in relation to their adsorption onto negatively charged surfaces to shed light on the impact of the molecular structure of surfactants from natural sources (instead of synthetic surfactant, such as sodium laureth sulfate) on the adsorption of hair-conditioning polymers. For this purpose, the self-assembly of such mixtures in aqueous solution and their adsorption onto negatively charged surfaces mimicking the negative charge of damaged hair fibres have been studied combining experiments and self-consistent field (SCF) calculations. The results show that the specific physico-chemical properties of the surfactants (charge, number of sugar rings present in surfactant structure and length of the hydrocarbon length) play a main role in the control of the adsorption process, with the adsorption efficiency and hydration being improved in relation to conventional sulfate-based systems for mixtures of PDADMAC and glycolipids with the shortest alkyl chains. SCF calculations and Energy Dispersive X-Ray Spectroscopy (EDS) analysis on real hair confirmed such observations. The results allow one to assume that the characteristic of the surfactants, especially rhamnolipids, conditions positively the adsorption potential of polyelectrolytes in these model systems. This study provides important insights on the mechanisms underlying the performance of more complex but eco-friendly washing formulations.


Where do health benefits of flavonoids come from? Insights from flavonoid targets and their evolutionary history.
Flavonoid intake is negatively correlated with the incidence of some chronic diseases including cardiovascular diseases, type II diabetes, neurodegenerative diseases, and cancers. Thus, the molecular mechanisms underlying this correlation are of great interest. Although ample attention has been given to the free radical-scavenging potential of flavonoids, the poor bioavailability of exogenous flavonoids suggests that the direct antioxidant activity is unlikely responsible for their favorable effects. This study comprehensively analyzed flavonoid targets. The results show that the main functions of these targets are associated with cancers and cardiovascular and metabolic diseases. Moreover, evolutionary analysis of these targets showed that ~1000 of the targets have homologues in human gut bacterial metagenomes. Clusters of orthologous groups of proteins (COG) analysis indicated that most of these bacterial targets are associated with bacterial metabolism. Given that the metabolism of gut microbiota is coupled with the metabolism of the host, this finding implies that flavonoids exert their benefits by regulating gut microbes. Therefore, the health benefits of flavonoids are well explained by their targets rather than their direct antioxidant potential.


Stroke related to androgen deprivation therapy for prostate cancer: a meta-analysis and systematic review.
Whether androgen deprivation therapy (ADT) leads to stroke morbidity is still unclear because of inconsistent evidence. We performed a systematic review and meta-analysis to evaluate if ADT used in men with prostate cancer (PCa) is associated with stroke. Medline, Embase and Cochrane Library databases up to September 30th 2014 were systematically searched with no date or language restriction, and reports from potentially relevant journals were complementally searched. Both randomized controlled trials and observational studies were included. Two reviewers independently extracted data and assessed study quality. Six observational studies finally met inclusion criteria, with 74,538 ADT users and 85,947 non-ADT users reporting stroke as an endpoint. Although no significant association was observed in pooled estimates, the incidence of stroke in ADT users was 12 % higher than control groups, (HR = 1.12, 95 % confidence interval [CI]: 0.95 to 1.32; P = 0.16). In subgroup-analyses of different ADT types, stroke was found to be significantly associated with gonadotropin-releasing hormone (GnRH) alone (HR = 1.20, 95 % CI: 1.12 to 1.28; P < 0.001), GnRH plus oral antiandrogen (AA) (HR = 1.23, 95 % CI: 1.13 to 1.34; P < 0.001) and orchiectomy (HR = 1.37, 95 % CI: 1.33 to 1. 46; P = 0.001), but not with AA alone (HR = 1.06, 95 % CI: 0.71 to 1.57; P = 0.78). GnRH alone, GnRH plus AA and orchiectomy is significantly associated with stroke in patients with PCa.


A 3-year prospective study of a single-tooth implant--prosthodontic complications.
The objective of this 3-year prospective study was to evaluate a new titanium dental implant system and to identify any mechanical concerns or deficiencies in its design. One periodontist placed 78 single-tooth implants in 59 subjects. One restorative dentist using one dental laboratory fabricated all of the crowns. Each patient then was seen eight times by the authors for clinical, radiographic, and laboratory testing. One of the 78 implants failed to integrate and was removed. There were no structural failures per se, although six of the cemented crowns and six of the restorative posts and cores (abutments) became loose. On a few occasions, the emergence profile was esthetically or functionally unsatisfactory. The manufacturer introduced changes in design and created an adjustable torque wrench, a torque-adjusting beam scale, and die replicas of the abutment posts in response to the identified concerns. The clinical trial helped in the development of an implant system that is user friendly, cost effective, and able to withstand parafunctional forces in the absence of antirotational features.


Altered osteoblast gluconeogenesis in X-linked hypophosphatemic mice is associated with a depressed intracellular pH.
We have studied gluconeogenesis and intracellular pH levels in normal (+/Y) and X-linked hypophosphatemic (Hyp/Y) mice. Compared with +/Y littermates, Hyp/Y mouse osteoblasts showed a higher rate of glucose production from fructose (10-fold), glutamine, and malate, but no significant difference when alpha-ketoglutarate was used as substrate. The activities of the pentose cycle enzymes, glucose-6-phosphate dehydrogenase, and 6-phosphogluconate dehydrogenase, were not different in the two osteoblast preparations. Examination of intracellular pH (pHi) using the double excitation of the pH-sensitive dye 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein acetoxymethyl ester (BCECF-AM) revealed a significantly lower pHi in Hyp/Y mouse osteoblasts compared with +/Y mouse osteoblasts (7.01 +/- 0.03 n = 10 versus 7.15 +/- 0.04 n = 8, respectively; P < 0.05). These results show for the first time that osteoblasts are capable of glucose production and that glucose production is altered in the Hyp/Y mouse osteoblast. As altered gluconeogenesis has been associated with reduced intracellular pH in other systems, a similar mechanism may be operative in the Hyp/Y mouse osteoblast. The observed defects may be intrinsic to the Hyp phenotype as the alterations in intracellular pH and gluconeogenesis persisted in vitro, or they may represent impressed memory from the in vivo state and the presumed circulating factor that influences phosphate transport.


A solid phase extraction procedure for indium prior to its graphite furnace atomic absorption spectrometric determination.
A procedure based on solid phase extraction of indium ions at trace level on Chromosorb 108 resin as bathocuproinedisulfonic acid chelate is presented for its preconcentration. The optimum pH value for quantitative sorption is 8.0-9.0, and desorption can be achieved by using 10.0 ml of 2 M HNO3. The effects of diverse ions on the sorption and recovery of indium have been studied. The capacity of sorbent was 3.78 mg In/g resin. Recoveries for indium from water samples were in the range 95-105%. The accuracy of procedure was confirmed by indium determination in certified reference materials. The method developed was applied with varying results to the analysis of real samples including metallic zinc with satisfactory results.


Pre-surgical assessment of mediastinal lymph node metastases in Stage IA non-small-cell lung cancers.
Evaluation of sensitivity and specificity of CT and fluorodeoxyglucose-positron emission tomography for pre-surgical staging of mediastinal lymph node metastases (N2/N3) of non-small-cell-lung-cancers ≤30 mm. We reviewed a total of 263 patients from a prospective cohort study, who underwent resection including mediastinal lymph nodes, for first primary non-small-cell-lung-cancer ≤30 mm in maximum diameter on pre-surgical CT. Cutoff criteria for short-axis diameter on CT of the largest N2/N3 node of 10, 15, and 20 mm and positron emission uptake of 2.5, 3.0, and 4.0 were evaluated using Area-Under-the-Curve (AUC) assessment. Accuracy criterion was used to determine the optimal cutoffs. Of 263 patients, 9 had nonsolid, 42 part-solid, and 212 solid non-small-cell-lung-cancers. Post-surgically, none of the 51 patients with nonsolid or part-solid cancers had mediastinal lymph node metastases. Among the 212 patients with solid cancers, 23 had N2 node metastases. For the 212 patients with solid cancers, the AUC for CT lymph node measurements was 0.67 (95% CI: 0.57-0.77), significantly higher (p = 0.001) than chance alone, while the AUC for SUVmax measurements, 0.56 (95% CI: 0.48-0.65), was not (p = 0.13). Optimal CT cutoff was >20 mm had low sensitivity of 30.4% (95% CI: 11.6%-49.2%) but high specificity of 99.5% (95% CI: 98.4%-100.0%). Based on these results, clinical Stage IA for non-small-cell-lung-cancers with nonsolid, part-solid, or solid consistency should be based on pre-surgical CT maximum tumor diameter and lymph node short-axis measurements on CT ≤20 mm. Further prospective evaluation of these clinical Stage IA staging criteria is needed.


Polygenic transcriptome risk scores for COPD and lung function improve cross-ethnic portability of prediction in the NHLBI TOPMed program.
While polygenic risk scores (PRSs) enable early identification of genetic risk for chronic obstructive pulmonary disease (COPD), predictive performance is limited when the discovery and target populations are not well matched. Hypothesizing that the biological mechanisms of disease are shared across ancestry groups, we introduce a PrediXcan-derived polygenic transcriptome risk score (PTRS) to improve cross-ethnic portability of risk prediction. We constructed the PTRS using summary statistics from application of PrediXcan on large-scale GWASs of lung function (forced expiratory volume in 1 s [FEV1] and its ratio to forced vital capacity [FEV1/FVC]) in the UK Biobank. We examined prediction performance and cross-ethnic portability of PTRS through smoking-stratified analyses both on 29,381 multi-ethnic participants from TOPMed population/family-based cohorts and on 11,771 multi-ethnic participants from TOPMed COPD-enriched studies. Analyses were carried out for two dichotomous COPD traits (moderate-to-severe and severe COPD) and two quantitative lung function traits (FEV1 and FEV1/FVC). While the proposed PTRS showed weaker associations with disease than PRS for European ancestry, the PTRS showed stronger association with COPD than PRS for African Americans (e.g., odds ratio [OR] = 1.24 [95% confidence interval [CI]: 1.08-1.43] for PTRS versus 1.10 [0.96-1.26] for PRS among heavy smokers with ≥ 40 pack-years of smoking) for moderate-to-severe COPD. Cross-ethnic portability of the PTRS was significantly higher than the PRS (paired t test p < 2.2 × 10-16 with portability gains ranging from 5% to 28%) for both dichotomous COPD traits and across all smoking strata. Our study demonstrates the value of PTRS for improved cross-ethnic portability compared to PRS in predicting COPD risk.


Nuclear polymorphism--a prognostic parameter to evaluate local recurrence of female breast cancer.
Between 1980 and 1986 676 patients underwent surgery for primary breast cancer. Of these, 35 patients developed locoregional recurrence. Retrospective analysis of the spontaneous postoperative development revealed 2 groups: group A had subsequent distant metastases, group B was tumor-free after surgical treatment of local recurrence. Analysis of the commonly employed characterization criteria of primary tumors (tumor size, lymph node involvement, estrogen receptors, histologic grading of primary tumors, and excised locoregional recurrence) showed no statistically significant difference between the two groups. However, a more detailed differentiation of the subcriteria for the histologic grading according to Bloom and Richardson revealed a prevalence of anaplastic nuclei in the primary tumors of group A (9/11). Even in this small patient population the parameter of nuclear polymorphism revealed a highly significant statistical difference between the two groups.


Prenatal diagnosis of osteogenesis imperfecta type II by real-time ultrasound.
By comparing fetal femur length to biparietal diameter a fetus at risk for osteogenesis imperfecta type II was diagnosed in the early second trimester of pregnancy. Real-time ultrasound is a reliable non-invasive technique for the prenatal diagnosis of fetal dwarfism syndromes.


Efficacy and safety of entecavir in clinical practice in treatment-naive Caucasian chronic hepatitis B patients.
Entecavir is an effective treatment for chronic hepatitis B. However, data from clinical practice are limited, especially in hepatitis B e antigen (HBeAg)-positive patients. We retrospectively analysed data from 190 nucleos(t)ide-naive chronic hepatitis B patients treated with entecavir (0.5 mg/day) in 25 Spanish centres. Virological response (hepatitis B virus DNA <50 IU/ml by PCR), biochemical response (alanine aminotransferase ≤ 1 × upper limit of normal) and serological response were assessed at weeks 12, 24, 36 and 48. The cohort was 73% male, 84% Caucasian, and 30% HBeAg-positive. Thirty-four per cent of the patients who underwent biopsy had advanced fibrosis/cirrhosis. At baseline, the median hepatitis B virus DNA was 5.94 (interquartile range=4.64-7.39) log10 IU/ml. At week 48, 83% of the patients (61% HBeAg-positive; 92% HBeAg-negative) achieved a virological response and 82% (78% HBeAg-positive; 83% HBeAg-negative) of those with elevated baseline alanine aminotransferase showed a biochemical response. Twenty-six per cent (14/54) of the HBeAg-positive patients lost HBeAg and 22% (12/54) achieved seroconversion to anti-HBe. A significant correlation was observed between virological response at week 12 and the rate of seroconversion to anti-HBe at week 48 (P=0.039). This correlation was also noted at weeks 24, 36 and 48 (P=0.003, 0.002 and 0.017, respectively). Three patients (2%) showed clearance of hepatitis B surface antigen. No resistance to entecavir was observed. Treatment with entecavir was generally well tolerated. No patients discontinued treatment due to adverse events. Entecavir monotherapy in clinical practice was well tolerated and resulted in a rapid and significant reduction in viral load. A virological response at week 12 correlated significantly with the rate of seroconversion to anti-HBe at week 48.


The remarkable genus Coptosapelta (Rubiaceae): pollen and orbicule morphology and systematic implications.
The pollen morphology and distribution of orbicules were investigated in ten species of the genus Coptosapelta (Rubiaceae) using light, scanning electron and transmission electron microscopy. In general, Coptosapelta pollen is three- to five-pororate and suboblate to oblate-spheroidal. The sexine ornamentation varies from psilate to reticulate, and the pollen-wall stratification lacks columellae. 'Droplets' are observed on the inner nexine surface. Distinct orbicules are found in five species. Orbicules are often lobed and appear to be aggregated and embedded in the tapetal remnants of the locule wall. Ultrastructurally, a single, flattened core is frequently observed. Coptosapelta has a unique pollen type within Rubiaceae and does not resemble possibly related genera. Pollen characteristics provide additional evidence supporting earlier findings that Coptosapelta represents an isolated lineage in Rubiaceae.


Early administration of recombinant erythropoietin improves hemoglobin recovery after reduced intensity conditioned allogeneic stem cell transplantation.
The use of recombinant human erythropoietin (rHuEPO) has been controversial after myeloablative allogeneic Stem cell transplantation (allo-SCT). Reduced intensity conditioning regimens (RIC) offer a novel approach that might translate into a different profile of erythropoietic recovery. We treated 20 consecutive patients with rHuEPO early after matched sibling RIC allo-SCT. Conditioning included fludarabine, busulfan and antithymocyte globulin. EPO treatment was analyzed in terms of toxicity, impact on the frequency of Red blood cell transfusions (RBCT) and kinetics of Hemoglobin recovery within the 60 days post-allo-SCT. Results were compared with 27 matched patients who did not receive rHuEPO. In the first 2 months after allo-SCT all patients receiving rHuEPO (100%) achieved an Hb level > 11 g/dl at a median of 30 (15-35) days post-allo-SCT, as compared to only 63% of the patients not receiving rHuEPO (P = 0.007) at a median of 35 (20-55) days (P = 0.03). A total of 70% (95% CI, 50-90) of rHuEPO patients maintained an Hb over 11 g/dl in the second month as compared to only 19% (95% CI, 4-34) in the other group (P = 0.0004). For patients receiving RBCT, the use of rHuEPO was associated with a trend towards reduced RBCT requirements. This pilot study suggests a potential benefit of early administration of rHuEPO after RIC allo-SCT on early erythropoietic recovery.


Testosterone metabolism by homogenates of human prostates with benign hyperplasia: effects of zinc, cadmium and other bivalent cations.
The effects of various quantities of Ba, Be, Ca, Cd, Co, Cu, Mg, Mn, Sr, Zn and EDTA on the formation of 5 alpha-reduced metabolites of testosterone (T) substrate and of 3 alpha-/3 beta-reduced metabolites of 5 alpha-dihydrotestosterone substrates by homogenates of 6 human hyperplastic prostate glands were studied in incubations at pH 7.4 with NADPH-generating system. Effects of these cations and EDTA on the VM and KM of the 5 alpha-reductase and 3 alpha-/3 beta-hydroxysteroid dehydrogenases (-HSD) were also measured. Quantities of 5 alpha-reduced T metabolites were significantly increased by Cd, Cu and Zn supplementations. These increments were shown to result from significant augmentations of the VM but no change in KM of the NADPH-dependent 5 alpha-reductase. Quantities of 3 alpha-reduced DHT metabolites were significantly decreased by Cd and Cu supplementations and resulted from an increase of the KM of the NADPH-dependent 3 alpha-HSD by Cd and both an increase of KM and a decrease of VM by Cu. Quantities of 3 beta-reduced DHT metabolites were significantly decreased by Cd and Cu supplementations. Increase of the KM of the NADPH-dependent 3 beta-HSD by Cd was found significant while Cu both increased the KM and decreased the VM of the enzyme. EDTA-related changes in 5 alpha-reductase activity were shown to result from the EDTA-induced decrease of the pH of the medium. No effect of EDTA was observed on the activities of both 3 alpha/3 beta-HSD.


Clinical factors associated with in-hospital death in pediatric surgical patients admitted to the neonatal intensive care unit: a 15-year single tertiary center experience.
The purpose of this study was to explore clinical characteristics and primary surgical diagnoses associated with in-hospital death in pediatric surgical patients admitted to the neonatal intensive care unit (NICU) of a tertiary hospital. This retrospective study includes all patients admitted to our NICU for pediatric surgical diseases between January 2001 and December 2015. Univariate and multivariate binary logistic regression were performed to assess independent factors associated with in-hospital death. A total of 440 cases were included and 334 (83.5%) patients underwent one or more surgeries. Thirty six patients (8.2%) died while hospitalized in the NICU. The 5 most common surgical diagnoses were intestinal atresia/stenosis, anorectal malformation, congenital diaphragmatic hernia (CDH), esophageal atresia, and urinary system disorder. Necrotizing enterocolitis (NEC) had the highest mortality rate. Using logistic regression, in-hospital death was predicted by extremely low birth weight (ELBW) (odds ratio (OR)=6.594; P=0.006), CDH (OR=13.954; P<0.001), and NEC (OR=8.991; P=0.049). This study describes CDH, NEC, and ELBW are independent predictive factors associated with in-hospital death of pediatric surgical patients in our NICU. Novel approaches for those conditions are required to improve the survival. Prognostic LEVELS OF EVIDENCE: II.


The preventative effect of bone marrow-derived mesenchymal stem cell exosomes on urethral stricture in rats.
Urethral stricture (US) is a major challenge in urology and there is an urgent need for effective therapies for its treatment. Exosomes derived from bone marrow mesenchymal stem cells (BMSCs-Exos) have been shown to be effective in preventing scar and fibrosis formation after tissue injury. However, the potential utility of BMSCs-Exos in the prevention of US remains unknown. We hypothesized that local administration of BMSCs-Exos may influence urethral healing and scar formation in a rat model of US. A previously established model of rat US was used in this study. Sprague Dawley rats were randomly assigned into sham, US, and US + BMSCs-Exos groups. Micro-ultrasound assessment, histopathology, immunohistochemistry, and gene expression analysis were performed at four weeks post-surgery. US rats exhibited thick urethral walls with a narrowed lumen, when compared with sham rats. However, these changes were suppressed in the US + BMSCs-Exos group. The preventative effects of BMSCs-Exos on US formation were also apparent histologically. US + BMSCs-Exos rats demonstrated decreased expression of several fibrosis-related genes in urethral tissues, including Col I, fibronectin, and elastin, when compared with US rats. BMSCs-Exos treatment also led to an increase in the expression of angiogenesis-related genes in these tissues, including VEGF, eNOS, and bFGF. Our findings therefore demonstrate that the local administration of BMSCs-Exos prevents urethral stricture formation by regulating fibrosis and angiogenesis. These findings provide a basis for an innovative strategy involving the clinical application of exosomes to counteract US formation.


Stomach cancer and occupational exposure to asbestos: a meta-analysis of occupational cohort studies.
A recent Monographs Working Group of the International Agency for Research on Cancer concluded that there is limited evidence for a causal association between exposure to asbestos and stomach cancer. We performed a meta-analysis to quantitatively evaluate this association. Random effects models were used to summarise the relative risks across studies. Sources of heterogeneity were explored through subgroup analyses and meta-regression. We identified 40 mortality cohort studies from 37 separate papers, and cancer incidence data were extracted for 15 separate cohorts from 14 papers. The overall meta-SMR for stomach cancer for total cohort was 1.15 (95% confidence interval 1.03-1.27), with heterogeneous results across studies. Statistically significant excesses were observed in North America and Australia but not in Europe, and for generic asbestos workers and insulators. Meta-SMRs were larger for cohorts reporting a SMR for lung cancer above 2 and cohort sizes below 1000. Our results support the conclusion by IARC that exposure to asbestos is associated with a moderate increased risk of stomach cancer.