Genome-wide comparative analysis of RNA-binding Glycine-rich protein family genes between Gossypium arboreum and Gossypium raimondii.
RB-GRP (RNA-binding Glycine-rich protein gene) family belongs to the fourth subfamily of the GRP (Glycine-rich protein gene) superfamily, which plays a great role in plant growth and development, as well as in abiotic stresses response, while it has not been identified in cotton. Here, we identified 37 and 32 RB-GRPs from two cotton species (Gossypium arboreum and Gossypium raimondii, respectively), which were divided into four distinct subfamilies based on the presence of additional motifs and the arrangement of the glycine repeats. The distribution of RB-GRPs was nonrandom and uneven among the chromosomes both in two cotton species. The expansion of RB-GRP gene family between two cultivars was mainly attributed to segmental and tandem duplication events indicated by synteny analysis, and the tandem duplicated genes were mapped into homologous collinear blocks, indicated that they shared a common ancestral gene in both species. Furthermore, most RB-GRPs in two cotton species undergone stronger negative selective pressure by evolutionary analysis of RB-GRP orthologous genes. Meanwhile, RB-GRPs participated in different abiotic stresses (Abscisic acid, salt and Polyethylene glycol) responses and tissues at different developmental stages between two cotton species were showed by gene expression analysis. This research would provide insight into the evolution and function of the RB-GRPs in Gossypium species.


Observation of the Superconducting Proximity Effect from Surface States in SmB_{6}/YB_{6} Thin Film Heterostructures via Terahertz Spectroscopy.
The ac conduction of epitaxially grown SmB_{6} thin films and superconducting heterostructures of SmB_{6}/YB_{6} are investigated via time-domain terahertz spectroscopy. A two-channel model of thickness-dependent bulk states and thickness-independent surface states accurately describes the measured conductance of bare SmB_{6} thin films, demonstrating the presence of surface states in SmB_{6}. While the observed reductions in the simultaneously measured superconducting gap, transition temperature, and superfluid density of SmB_{6}/YB_{6} heterostructures relative to bare YB_{6} indicate the penetration of proximity-induced superconductivity into the SmB_{6} overlayer; the corresponding SmB_{6}-thickness independence between different heterostructures indicates that the induced superconductivity is predominantly confined to the interface surface state of the SmB_{6}. This study demonstrates the ability of terahertz spectroscopy to probe proximity-induced superconductivity at an interface buried within a heterostructure, and our results show that SmB_{6} behaves as a predominantly insulating bulk surrounded by conducting surface states in both the normal and induced-superconducting states in both terahertz and dc responses, which is consistent with the topological Kondo insulator picture.


Immunocytochemical stem cell markers can predict clinical stage of breast cancer.
We present a computational-statistical algorithm that, from data on the staining degree of immunocytochemical markers: i) evaluates the ability of the considered immuno-panel in predicting the breast cancer stage; ii) makes the accurate identification of breast cancer stage possible; iii) provides the best stage prognosis compatible with the considered sample; and iv) does so through the use of the minimum number of markers minimizing time and resource costs. After running the algorithm on two data sets [triple-negative breast cancer, (TNBC), and estrogen receptor-negative breast cancer, (ERNBC)], we conclude that EpCAM and β1 integrin are enough to accurately predict TNBC stage, being ALDH1, CD24, CD61, and CK5 the necessary markers to exactly predict ERNBC stage.


Developmental coupling of expression of the Igh-linked minor antigen H-40 to membrane immunoglobulin expression.
C.B-20 (Ighb) but not BALB/c (Igha) mice are able to reject BCL1, a spontaneous B cell leukemia of BALB/c origin. The protective immune response is directed toward the minor histocompatibility (H) antigen, H-40, which can be detected by cytotoxic T lymphocytes and is expressed on surface (s) immunoglobulin positive tumor cells including BCL1 as well as sIg+ lymphoblasts activated by lipopolysaccharide. The fact that only sIg+ tumor cells and lymphoblasts express H-40 suggests that sIg itself may be a component involved in CTL recognition of this antigen. However, this possibility was ruled out by demonstrating that removal of sIg from target cells did not prevent H-40-specific CTL recognition. To determine whether H-40 expression was coordinately regulated with that of membrane Ig, we determined whether H-40- sIg- cells acquire H-40 when induced to express sIg. We also transfected a functional mu c and nu region gene into a sIg- lymphoma so that it acquired a sIg+ phenotype. In neither case did such sIg+ cells acquire H-40. Together, these data indicate that H-40 is expressed on B cells representing a particular stage of differentiation that is coincidental with sIg. We previously showed that H-40 and Igh loci are linked on the 12th murine chromosome. In this study we further localized H-40 to a point beyond Aat (formerly Pre-1) near Lm-1, a locus previously described to encode minor H-antigens expressed on lymphomyeloid cells. Thus, H-40 and Lm-1 may represent a gene cluster encoding antigens expressed on subsets of lymphoid and myeloid cells.


The effect of felodipine on cold-induced digital vasospasm.
Felodipine, a calcium antagonist with pronounced vascular selectivity, was given to 10 patients with cold-induced, digital vasospasm. Placebo and increasing doses of felodipine (2.5, 5, and 10 mg b.i.d.) were given for 2 weeks each. There was a significant decrease in systemic, but not in digital, blood pressure and a significant increase in heart rate during felodipine treatment. The subjective rating of symptoms improved significantly on all doses. No significant effect on cold-induced digital vasospasm during local cooling to 15 and 10 degrees C was registered. Typical side effects of calcium-entry blockers were reported. Moreover, two postmenopausal women reported recurrence of menstrual bleeding and one woman reported vaginal hemorrhagic discharge during treatment. In conclusion, felodipine, although causing a significant, symptomatic relief, had no significant effect on cold-induced digital vasospasm when objective measures were used.


A new dual-ligand DUT-52-type metal-organic framework for ratiometric luminescence detection of aqueous-phase Cu2+ and Cr2O72.
Metal-organic frameworks (MOFs) are a unique class of multifunctional hybrid crystals that have been successfully utilized in diverse ranges of applications. However, since MOFs are prone to aqueous degradation, the development of stable luminescent MOF platforms in aqueous media is still a huge challenge. Here, a novel dual-ligand Eu3+/DUT-52-COOH composite is prepared based on the luminescent DUT-52 prototype structure via a dual-ligand strategy and a post-synthetic modification (PSM) method. The functionalized Eu3+/DUT-52-COOH material exhibits dual emission and good photothermal stability in aqueous media. Thus, Eu3+/DUT-52-COOH is developed as a ratiometric luminescent sensor to achieve highly selective and sensitive detection of Cu2+ and Cr2O72- in aqueous solutions and has a low detection limit of 3.43 μM and 25.7 nM, respectively. This work is one of the few cases of detecting Cu2+ and Cr2O72- in aqueous media based on a DUT-52, and the detection signals can be observed by the bare eye without using sophisticated analytical instruments. The possible sensing mechanism is discussed in detail. The results obtained in this project may provide broad prospects for developing smart sensing systems to accomplish highly efficient, easily operable and quantitative intelligent recognition of Cu2+ and Cr2O72-.


A canonical neural mechanism for behavioral variability.
The ability to generate variable movements is essential for learning and adjusting complex behaviours. This variability has been linked to the temporal irregularity of neuronal activity in the central nervous system. However, how neuronal irregularity actually translates into behavioural variability is unclear. Here we combine modelling, electrophysiological and behavioural studies to address this issue. We demonstrate that a model circuit comprising topographically organized and strongly recurrent neural networks can autonomously generate irregular motor behaviours. Simultaneous recordings of neurons in singing finches reveal that neural correlations increase across the circuit driving song variability, in agreement with the model predictions. Analysing behavioural data, we find remarkable similarities in the babbling statistics of 5-6-month-old human infants and juveniles from three songbird species and show that our model naturally accounts for these 'universal' statistics.


Small bowel obstruction due to incarcerated sciatic hernia: ultrasound diagnosis.
A 71-year-old woman presented with vomiting, abdominal pain and vague right gluteal discomfort. Abdominal ultrasound showed ascites and dilated small bowel loops with peristaltic movement, while transgluteal ultrasound revealed entrapped ascites beneath gluteal muscles and an oedematous, immobile bowel loop trapped between the sacrum and iliac bone with barely visible colour Doppler flow suggestive of an incarcerated sciatic hernia. CT demonstrated similar findings and subsequent surgery confirmed the diagnosis. To our knowledge, this is the first report of a pre-operative diagnosis of incarcerated sciatic hernia on ultrasound.


[Meta-analysis of laboratory index of Tripterygium Glycosides Tablets in treatment of rheumatoid arthritis].
The aim of this study was to systematically evaluate the clinical efficacy of Tripterysium Glycosides Tablets( TGT) alone or in combination with methotrexate( MTX) in the treatment of rheumatoid arthritis( RA) based on the laboratory index criteria and to provide a basis for the clinical application of TGT against RA. Six databases including CNKI,Wan Fang,VIP,PubMed,EMbase and Cochrane were retrieved for randomized controlled trials( RCT) about TGT alone or combination with MTX in the treatment of RA.Then risk assessment tools were used for quality evaluation of the studies,and data extraction and analysis were conducted by using Rev Man 5.3 software for Meta-analysis. A total of 1 709 articles were retrieved,and finally 25 studies were included,with a total sample size of 2 507 cases. Meta-analysis results showed that between TGT alone and TGT alone,MDESR=-2. 66,95%CI[-8.17,2.86],P = 0.35; MDCRP=-2.38,95%CI[-9.01,4.24],P = 0.48; between TGT combined with MTX and MTX alone,MDESR= 8.74,95%CI[6.72,10.76],P<0.000 01; MDCRP= 5.37,95%CI[3.71,7.03],P<0.000 01; SMDRF= 1.05,95%CI[0.51,1.60],P = 0.000 1.The effect of TGT on decreasing CRP and ESR in RA patients was similar to the MTX. In addition,TGT combined with MTX were more effective in decreasing CRP,ESR,RF than MTX alone. However,due to the potential bias in the included studies,more and high-quality randomized controlled trials would be needed to improve the level of evidence.


Spatiotemporal Analysis of the Prevalence and Pattern of Multimorbidity in Older Chinese Adults.
Multimorbidity presents an enormous problem to societal and healthcare utilization under the context of aging population in low- and middle-income countries (LMICs). Currently, systematic studies on the profile of multimorbidity and its characteristics among Chinese elderly are lacking. We described the temporal and spatial trends in the prevalence of multimorbidity and explored chronological changes of comorbidity patterns in a large elderly population survey. Data were extracted from the Chinese Longitudinal Healthy Longevity Study (CLHLS) conducted between 1998 and 2018 in a random selection of half of the counties and city districts. All the elderly aged 65 and older were included in the survey of eight waves. We used 13 investigated chronic diseases to measure the prevalence of multimorbidity by means of geography, subpopulation, and chronological changes. The patterns of multimorbidity were assessed by computing the value of relative risk (RR indicates the likelihood of certain diseases to be associated with multimorbidity) and the observed-to-expected ratio (O/E indicates the likelihood of the coexistence of a multimorbidity combination). From 1998 to 2018, the prevalence of multimorbidity went from 15.60 to 30.76%, increasing in the fluctuation across the survey of eight waves (p for trend = 0.020). Increasing trends were observed similarly in a different gender group (p male = 0.009; p female = 0.004) and age groups among female participants (p ~80 = 0.009; p 81-90 = 0.004; p 91-100 = 0.035; p 101~ = 0.018). The gap in the prevalence of multimorbidity between the north and the south was getting narrow across the survey of eight waves. Hypertension was the highest prevalent chronic condition while diabetes was most likely to coexist with other chronic conditions in the CLHLS survey. The most frequently occurring clusters were hypertension and heart disease, hypertension and cataract, and hypertension and chronic lung disease. And, the cancer, TB, and Parkinson's disease cluster took the domination of O/E rankings over time, which had a higher probability of coexistence in all the multimorbidity combinations. The prevalence of multimorbidity has been increasing nationwide, and more attention should be paid to a rapid growth in the southern part of China. It demands the effective diagnosis and treatment adopted to the highly prevalent comorbidities, and strategies and measures were adjusted to strongly relevant clusters.


Impact of using national v. international definitions of underweight, overweight and obesity: an example from Kuwait.
To compare the classification of overweight, obesity and underweight using international v. national approaches in Kuwaiti adolescents. Assessment of underweight, overweight and obesity using a national approach (based on Kuwaiti reference data for BMI-for-age) was compared with assessments obtained using three international approaches: the Cole et al. and International Obesity Task Force (IOTF) definitions of thinness and of overweight and obesity (Cole-IOTF); WHO 2007; and US Centers for Disease Control and Prevention (CDC) 2000 reference data and definitions. The degree of agreement between the different methods was assessed using the weighted κ statistic (κw). Two randomly selected public intermediate schools in Kuwait City. A total of 499 10-14-year-old Kuwaiti adolescents. Prevalence of overweight and obesity using Kuwaiti reference data (36·7 %; 95 % CI 32·4, 41·1) was significantly lower than that obtained using international approaches - Cole-IOTF (44·7 %; 95 % CI 40·3, 49·2), CDC 2000 (44·9 %; 95 % CI 40·5, 49·4) and WHO 2007 (50·5 %; 95 % CI 46·0, 55·0) (P < 0·01). All three international approaches showed almost perfect agreement: IOTF v. WHO (κw = 0·82; 95 % CI 0·79, 0·85) and IOTF v. CDC (κw = 0·90; 95 % CI 0·87, 0·92). However, Kuwaiti reference data showed the lowest agreement with the three international approaches, the poorest being with WHO 2007 (κw = 0·54; 95 % CI 0·49, 0·59). Caution should be exercised when using recently collected national reference data and definitions while assessing underweight, overweight and obesity for clinical and public health applications.


Regulation of STUB1 expression and its biological significance in mouse Sertoli cells.
STIP1 Homology and U-Box Containing Protein 1 (STUB1), a ubiquitin E3 ligase initially involved in immune responses, has recently emerged as a pleiotropic regulator of different biological systems, including skeletal and male reproduction systems. On the latter, a homozygous mutation in the STUB1 gene has been identified in patients with hypogonadism. However, the pattern of expression and biological actions of STUB1 in testis remains so far unexplored. Herein, we report analyses on the testicular expression of STUB1 in human testes with impaired spermatogenesis and paracrine regulation of STUB1 expression in mouse testis development and the direct effects of ablation STUB1 on Sertoli cell (SC) functions. STUB1 was expressed abundantly in pachytene spermatocytes and SCs, and weakly in spermatogonia and differentiating spermatids in normal human testis. In contrast, Sertoli-specific expression of STUB1 was significantly decreased in the human testes with impaired spermatogenesis. Throughout postnatal development of mouse testis, however, STUB1 was expressed exclusively in the nuclei of the functionally mature SCs. The adjacent germ cell (GC)-derived IL-1α overtly regulated STUB1 expression through promoting the ETS domain transcription factor Elk-1 (ELK1)-mediated transactivation. Importantly, ablation of endogenous STUB1 caused lipid accumulation and senescence in GC co-incubated SCs. Together with previous reports on the stimulatory effects of IL-1α on cell senescence, our findings suggest that STUB1 may serve as an important negative feedback signaling to modulate the magnitude of GCs-derived IL-1α, which is normally maintained at low levels within testis.


Crystalline polymorphism and molecular structure of sodium pravastatin.
In this work different crystallization processes of sodium pravastatin are explored and a new polymorph is obtained. The analytical results of powder X-ray diffraction (PXRD) and thermal analysis for this new polymorph indicate that it is different from the polymorphs previously reported. This new crystal form shows different physical-chemical properties than the previous forms, such as crystallographic structure, thermal behavior, and melting point, 181.5 degrees C. Besides, all crystallization processes previously reported use an aprotic solvent as antisolvent. However, we propose a new crystallization process for sodium pravastatin that uses only protic solvents, overcoming industrial scaling and environmental problems. Variable-temperature PXRD experiments show a transformation between different crystal forms in the range of 80-120 degrees C. Solid-state 13C NMR, reported in this work for the first time, and Fourier transform infrared (FT-IR) studies of some polymorphs show some differences in intermolecular interactions, especially with carboxylate and hydroxyl groups. Quantum mechanical calculations of the pravastatin molecule are also presented for the first time, obtaining a molecular structure similar to the experimental structure existing within the crystal lattice of the tert-octylamonium salt of pravastatin.


The development and use of a molecular model for soybean maturity groups.
Achieving appropriate maturity in a target environment is essential to maximizing crop yield potential. In soybean [Glycine max (L.) Merr.], the time to maturity is largely dependent on developmental response to dark periods. Once the critical photoperiod is reached, flowering is initiated and reproductive development proceeds. Therefore, soybean adaptation has been attributed to genetic changes and natural or artificial selection to optimize plant development in specific, narrow latitudinal ranges. In North America, these regions have been classified into twelve maturity groups (MG), with lower MG being shorter season than higher MG. Growing soybean lines not adapted to a particular environment typically results in poor growth and significant yield reductions. The objective of this study was to develop a molecular model for soybean maturity based on the alleles underlying the major maturity loci: E1, E2, and E3. We determined the allelic variation and diversity of the E maturity genes in a large collection of soybean landraces, North American ancestors, Chinese cultivars, North American cultivars or expired Plant Variety Protection lines, and private-company lines. The E gene status of accessions in the USDA Soybean Germplasm Collection with SoySNP50K Beadchip data was also predicted. We determined the E allelic combinations needed to adapt soybean to different MGs in the United States (US) and discovered a strong signal of selection for E genotypes released in North America, particularly the US and Canada. The E gene maturity model proposed will enable plant breeders to more effectively transfer traits into different MGs and increase the overall efficiency of soybean breeding in the US and Canada. The powerful yet simple selection strategy for increasing soybean breeding efficiency can be used alone or to directly enhance genomic prediction/selection schemes. The results also revealed previously unrecognized aspects of artificial selection in soybean imposed by soybean breeders based on geography that highlights the need for plant breeding that is optimized for specific environments.


NAP1L1 accelerates activation and decreases pausing to enhance nucleosome remodeling by CSB.
Cockayne syndrome protein B (CSB) belongs to the SWI2/SNF2 ATP-dependent chromatin remodeler family, and CSB is the only ATP-dependent chromatin remodeler essential for transcription-coupled nucleotide excision DNA repair. CSB alone remodels nucleosomes ∼10-fold slower than the ACF remodeling complex. Strikingly, NAP1-like histone chaperones interact with CSB and greatly enhance CSB-mediated chromatin remodeling. While chromatin remodeling by CSB and NAP1-like proteins is crucial for efficient transcription-coupled DNA repair, the mechanism by which NAP1-like proteins enhance chromatin remodeling by CSB remains unknown. Here we studied CSB's DNA-binding and nucleosome-remodeling activities at the single molecule level in real time. We also determined how the NAP1L1 chaperone modulates these activities. We found that CSB interacts with DNA in two principle ways: by simple binding and a more complex association that involves gross DNA distortion. Remarkably, NAP1L1 suppresses both these interactions. Additionally, we demonstrate that nucleosome remodeling by CSB consists of three distinct phases: activation, translocation and pausing, similar to ACF. Importantly, we found that NAP1L1 promotes CSB-mediated remodeling by accelerating both activation and translocation. Additionally, NAP1L1 increases CSB processivity by decreasing the pausing probability during translocation. Our study, therefore, uncovers the different steps of CSB-mediated chromatin remodeling that can be regulated by NAP1L1.


Conformation of the signal recognition particle in ribosomal targeting complexes.
The bacterial signal recognition particle (SRP) binds to ribosomes synthesizing inner membrane proteins and, by interaction with the SRP receptor, FtsY, targets them to the translocon at the membrane. Here we probe the conformation of SRP and SRP protein, Ffh, at different stages of targeting by measuring fluorescence resonance energy transfer (FRET) between fluorophores placed at various positions within SRP. Distances derived from FRET indicate that SRP binding to nontranslating ribosomes triggers a global conformational change of SRP that facilitates binding of the SRP receptor, FtsY. Binding of SRP to a signal-anchor sequence exposed on a ribosome-nascent chain complex (RNC) causes a further change of the SRP conformation, involving the flexible part of the Ffh(M) domain, which increases the affinity for FtsY of ribosome-bound SRP up to the affinity exhibited by the isolated NG domain of Ffh. This indicates that in the RNC-SRP complex the Ffh(NG) domain is fully exposed for binding FtsY to form the targeting complex. Binding of FtsY to the RNC-SRP complex results in a limited conformational change of SRP, which may initiate subsequent targeting steps.


Altered immune function of monocytes in different stages of patients with acute on chronic liver failure.
The aim of this study was to investigate the characteristics of the immune function of monocytes in different stages of the patients with acute on chronic liver failure (ACLF). Human leucocyte antigen (HLA)-DR and Toll-like receptor 4 (TLR-4) expression on monocytes in early and late stages of acute on chronic liver failure were detected by flow cytometry. The secretion function of monocytes was measured by cytometric bead array. Compared with healthy controls, the levels of HLA-DR expression on monocytes in patients with chronic hepatitis B, liver cirrhosis and acute on chronic liver failure were gradually decreased, especially in the late stage of acute on chronic liver failure (P < 0.001). TLR-4 expression on monocytes in patients with liver cirrhosis and acute on chronic liver failure were higher than the healthy controls. The concentrations of interleukin (IL)-1beta, tumour necrosis factor (TNF)-alpha and IL-12p70 in early-stage ACLF were significantly higher compared with healthy controls and lower in late-stage ACLF (P < 0.01, 0.05). However, a significantly lower amount of IL-10 was found on monocytes in early-stage ACLF than that of late-stage ACLF and healthy controls (P < 0.01). Monocyte HLA-DR expression in patients who died was significantly lower compared with patients who survived in the early and late stages of ACLF (P < 0.01). The dynamic detection of HLA-DR expression or cytokines secreted from monocytes could contribute to the estimation of the status of the immune function of patients with acute on chronic liver failure.


Recovery From Substance Abuse Among Zimbabwean Men: An Occupational Transition.
Substance abuse is a rising global problem, associated with medical, psychiatric, family, occupational, legal, political, financial, and spiritual problems. Recovery is an important area of consideration in occupational therapy's quest to promoting health and well-being. This narrative inquiry explored the journey of recovery from substance abuse among young adult Zimbabwean men. Three men were purposively selected to participate in in-depth narrative interviews about their occupations during recovery. Data were analyzed using a narrative analysis. Explanatory stories and three superordinate themes illustrated how substance abuse was associated with both positive and negative outcomes. The recovery process emerged as an ongoing occupational transition, influenced by occupational identity and involving changes in occupational participation. Recovery from substance abuse can be conceptualized as an occupational transition. Ongoing participation in "healthy" and meaningful occupations is key factor in this process. Construction of a positive occupational identity is also central.


Two forkhead transcription factors regulate the division of cardiac progenitor cells by a Polo-dependent pathway.
The development of a complex organ requires the specification of appropriate numbers of each of its constituent cell types, as well as their proper differentiation and correct positioning relative to each other. During Drosophila cardiogenesis, all three of these processes are controlled by jumeau (jumu) and Checkpoint suppressor homologue (CHES-1-like), two genes encoding forkhead transcription factors that we discovered utilizing an integrated genetic, genomic, and computational strategy for identifying genes expressed in the developing Drosophila heart. Both jumu and CHES-1-like are required during asymmetric cell division for the derivation of two distinct cardiac cell types from their mutual precursor and in symmetric cell divisions that produce yet a third type of heart cell. jumu and CHES-1-like control the division of cardiac progenitors by regulating the activity of Polo, a kinase involved in multiple steps of mitosis. This pathway demonstrates how transcription factors integrate diverse developmental processes during organogenesis.


Negative spin polarization of Mn2VGa probed by tunnel magnetoresistance.
The ferrimagnetic Heusler compound Mn(2)VGa is predicted to have a pseudogap in the majority spin channel, which should lead to a negative tunnel magnetoresistance (TMR). We synthesized epitaxial Mn(2)VGa thin films on MgO(001) substrates by dc and rf magnetron co-sputtering, resulting in nearly stoichiometric films. XRD analysis revealed a mostly B2 ordered structure for the films deposited at substrate temperatures of 350, 450, and 550 °C. Magnetic tunnel junctions with MgO barriers and CoFe counter-electrodes were fabricated. After post-annealing at up to T(a) = 425 °C negative TMR was obtained around zero bias, providing evidence for inverted spin polarization. The band structures of both electrodes were computed within the coherent potential approximation and used to calculate the TMR(V) characteristics, which were in good agreement with our experimental findings.


Effects of Distigmine on the Mechanical Activity of Urinary Bladder Smooth Muscle.
Distigmine bromide (distigmine) is a reversible carbamate cholinesterase (ChE) inhibitor. Its principle clinical application is in the treatment of myasthenia gravis. Distigmine is also used as a remedy for dysuria and glaucoma. Its effectiveness in the management of dysuria has been demonstrated in several clinical reports. Distigmine may improve (enhance) urinary bladder smooth muscle (UBSM) contraction during micturition by inhibiting acetylcholine (ACh) decomposition. However, the pharmacological effects of distigmine on UBSM have not been adequately studied so far. In this review article, we summarize the reported effects of distigmine on the contractile responses elicited by exogenous and endogenous ACh in isolated UBSM preparations. We also discuss the effects of distigmine on the UBSM basal tone and the contractile response of UBSM to ATP, which is co-released with ACh from parasympathetic nerve terminals.


Loss of connexin36 in rat hippocampus and cerebellar cortex in persistent Borna disease virus infection.
Neonatal Borna disease virus (BDV) infection of the Lewis rat leads to progressive degeneration of dentate gyrus granule cells, and cerebellar Purkinje neurons. Our aim here was to clarify whether BDV interfered with the formation of electrical synapses, and we, therefore, analysed expression of the neuronal gap junction protein connexin36 (Cx36) in the Lewis rat hippocampal formation, and cerebellar cortex, 4 and 8 weeks after neonatal infection. Semiquantitative RT-PCR, revealed a BDV-dependent decrease in Cx36 mRNA in the hippocampal formation 4 and 8 weeks post-infection (p.i.), and in the cerebellar cortex 8 weeks p.i. Correspondingly, immunofluorescent staining revealed reduced Cx36 immunoreactivity in both dentate gyrus, and ammons horn CA3 region, 4 and 8 weeks post-infection. In the cerebellar cortex, Cx36 immunoreactivity was detected only 8 weeks post-infection in the molecular layer, where it was down regulated by BDV. Our findings demonstrate, for the first time, distinct BDV-dependent reductions in Cx36 mRNA and protein in the rat hippocampal formation and cerebellar cortex, suggesting altered neuronal network properties to be an important feature of persistent viral brain infections.


Primary Osteosarcoma of the Breast Arising in an Intraductal Papilloma.
Primary osteosarcoma of the breast is extremely rare, and an osteosarcoma arising from an intraductal papilloma is exceptional. A 72-year-old Saudi Arabian woman presented with a solid, bone-containing breast mass that was diagnosed as primary osteosarcoma of the breast on biopsy. She had a history of untreated intraductal papilloma. Treatment was completed with a modified mastectomy after excluding extramammary metastases. However, she subsequently developed multiple recurrent lesions at the same site. Primary osteogenic sarcomas of the breast are very rare. Although the main treatment is resection the optimal management remains uncertain and prognosis is poor.


The anticoccidial effects of amprolium, dinitolmide and monensin against Eimeria maxima, E, brunetti and E. acervulina with particular reference to oocyst sporulation.
Chicks infected with the Weybridge strains of Eimeria maxima and E. acervulina were not protected by the normal levels of amprolium, but the sporulation of the oocysts was inhibited. With higher drug concentrations, fewer oocysts were produced. E brunetti was not so markedly affected, although oocyst sporulation was reduced by the higher dosage levels. The effects were not enhanced by the inclusion of ethopabate. With dinitolmide the phenomenon was not so marked, although oocysts of E. maxima and E. acervulina were reduced in numbers by the normal drug concentration and sporulation was reduced when this level was increased. Much higher drug levels were required to obtain these effects with E. brunetti. Monensin at 120 ppm affected neither oocyst numbers nor their sporulation in any of the species tested. The significance of the effects of anticoccidial drugs on gametogony and sporogony is discussed.


New cases of myopia in children.
To report the percentage of new cases of myopia in 4927 children aged 5 to 16 years who participated in the Collaborative Longitudinal Evaluation of Ethnicity and Refractive Error Study between 1989 and 2009. A multicenter, longitudinal, observational, volunteer study of refractive error and ocular development in children from 5 racial/ethnic groups in which the participants were children who were not myopic (right eye cycloplegic auto refraction of less myopia/more hyperopia than -0.75 diopters [D] in both principal meridians) at study entry. A new case was a diagnosis of myopia (right eye cycloplegic auto refraction of -0.75 D or more myopia in both principal meridians) after study entry. Of the 4556 children entering the study who were not myopic, 749 (16.4%) received a diagnosis of myopia after study entry. Among these 749 children, the ages of the participants at diagnosis varied from 7 to 16 years, with the largest number diagnosed at age 11 years(136 participants [18.2%]). New cases of myopia occurred in 27.3% of Asians, 21.4% of Hispanics, 14.5% of Native Americans, 13.9% of African Americans, and 11% of whites. Female participants had more new cases than did male participants (18.5% vs 14.5%). Normal-birth weight children had more new cases than did low-birth weight children (16.9% vs 15.5%). Sixteen percent of children enrolled in the Collaborative Longitudinal Evaluation of Ethnicity and Refractive Error Study developed myopia during their school-aged years. The percentage increased yearly until age 11 years, after which it decreased. New cases of myopia varied by ethnic/racial group.


Increases of amphiregulin and transforming growth factor-alpha in serum as predictors of poor response to gefitinib among patients with advanced non-small cell lung cancers.
Serum levels of amphiregulin and transforming growth factor-alpha (TGF-alpha), which were identified previously to be expressed at high levels in non-small cell lung cancer (NSCLC) with poor response to gefitinib, were examined by ELISA using blood samples taken from 50 patients with advanced NSCLCs. Of 14 cases that revealed above the cutoff line for amphiregulin in serum, 12 responded poorly to gefitinib, whereas 18 of the 36 cases showing below the cutoff revealed partial response (PR) or stable disease (SD; P = 0.026). Thirteen of 15 patients who were positive for TGF-alpha responded poorly to gefitinib, whereas 18 of the 35 patients with negative TGF-alpha levels turned out to be relatively good responders (P = 0.014). Of 22 patients with positive values for either or both markers, 19 were poor responders. On the other hand, among 28 patients negative for both markers, 17 were classified into the PR or SD groups (P = 0.001). Gefitinib-treated NSCLC patients whose serum amphiregulin or TGF-alpha was positive showed a poorer tumor-specific survival (P = 0.037 and 0.002, respectively, by univariate analysis) compared with those whose serum amphiregulin or TGF-alpha concentrations were negative. Multivariate analysis showed an independent association between positivity for TGF-alpha and shorter survival times among NSCLC patients treated with gefitinib (P = 0.034). Amphiregulin or TGF-alpha positivity in NSCLC tissues was significantly higher in male, nonadenocarcinomas, and smokers. Our data suggest that the status of amphiregulin and TGF-alpha in serum can be an important predictor of the resistance to gefitinib among patients with advanced NSCLC.


Acceptability of a school-based intervention for the prevention of adolescent obesity.
This article describes the development and pilot testing of a computer-based, multiple-behavior obesity prevention program for adolescents. Using the Transtheoretical Model as a framework, this intervention offers individualized feedback based on readiness to engage in physical activity, to consume fruits and vegetables, and to limit television viewing. Focus groups and interviews with students, teachers, school administrators, and experts guided the development. Forty-five students participated in a baseline intervention session and completed a 16-item acceptability measure. Ratings were positive, with item means ranging from 3.60-4.75 on a 5-point scale. Student responses to open-ended questions aided in the enhancement of the intervention, for which an effectiveness trial begins in September 2006. This formative work demonstrated the acceptability of this school-based intervention approach, which can be promoted and prescribed by school nurses. Further, if found effective, it can be disseminated as an efficient, low-cost, population-based approach designed to address the epidemic of obesity.


Strength exercise weakens aerobic exercise-induced cognitive improvements in rats.
Aerobic exercise improves cognitive function and adult hippocampal neurogenesis. However, the effects of aerobic exercise combined with strength exercise on cognitive function and adult hippocampal neurogenesis are still unknown. In this study, we established exercise paradigms in rats to mimic aerobic exercise combined with low- and high-intensity strength exercise. We found that aerobic exercise improved spatial learning and memory as well as adult hippocampal neurogenesis, whereas strength exercise suppressed aerobic exercise-induced cognitive improvements and adult hippocampal neurogenesis in an intensity-dependent manner. Furthermore, the levels of β-hydroxybutyrate (β-HB) and its downstream effector brain-derived neurotrophic factor (BDNF) were increased in the aerobic exercise group, and strength exercise impaired the aerobic exercise-induced increases in β-HB and BDNF mRNA levels. Taken together, these results demonstrated that strength exercise weakened aerobic exercise-induced cognitive improvements and adult hippocampal neurogenesis in rats.


Formation of vinylogous compounds in model Maillard reaction systems.
The thermal degradation over temperature and time of selected amino acids (Asp, Gln, and Glu) in the presence of reducing sugars was investigated in low moisture model systems. Copyrolysis of glucose-Asp mixtures led to the release of acrylic acid, attaining >5 mmol/mol Asp at 230 degrees C after 5 min. Spurious amounts of 3-butenamide were detected upon heating Gln together with a carbonyl source. Apparently, intramolecular cyclization is favored to procure 2-pyrrolidinone, reaching levels >3 mmol/mol above 230 degrees C. 2-Pyrrolidinone was also formed in comparable amounts in pyrolyzed sugar-Glu mixtures, indicating that the Maillard reaction may be an important contributor to the formation of 2-pyrrolidinone in certain cooked foods. The chemical route to acrylic acid and 3-butenamide is probably analogous to that described for acrylamide recently. Evidence is also presented that acrylic acid may be an intermediate in the formation of acrylamide, and yields could be augmented by coincubation of fructose-Asp with certain amino acids such as Gln, reaching approximately 5% of the yield obtained by the Asn route. A computational study to determine the reactivity of the vinylogous products indicated a reduced ability of 3-butenamide as compared to acrylamide to form stable intermediates by Michael nucleophilic addition. Acrylamide and acrylic acid exhibited a similar theoretical reactivity potential toward nucleophiles. No information is as yet available on the occurrence of acrylic acid in cooked foods. Extensive toxicological evaluation indicates that acrylic acid is of no concern at the amounts to be expected in foods.


Mantle-zone lymphoma. An immunohistologic study.
Mantle-zone lymphoma (MZL) is a histologically distinctive variant of follicular lymphocytic lymphoma which is characterized by a proliferation of atypical small lymphoid cells as wide mantles around benign-appearing germinal centers. Immunoperoxidase stains were performed on fixed and processed lymph nodes from four patients with MZL. Three cases were of the intermediate lymphocytic type, and one was of the small cleaved lymphocytic type. In all cases, the small lymphoid cells of the mantle zones did not stain. A monoclonal population (IgM, lambda) of plasma cells and large lymphoid cells was demonstrated predominantly in the paracortical areas in one case. In all cases, small numbers of plasma cells and large lymphoid cells in the follicle centers stained in a polyclonal pattern, confirming the benign nature of the centers. These findings suggest that follicular lymphomas of the mantle-zone type are exceptions to the theory that follicular B-cell lymphomas are derived from follicular center cells. Apparently, the lymphoid cells of MZL home to the mantle zones of secondary follicles, where they surround, proliferate, and eventually obliterate residual benign germinal centers.


Optical linear frequency sweep based on a mode-spacing swept comb and multi-loop phase-locking for FMCW interferometry.
We report on the generation of a highly coherent broadband optical linear frequency sweep (LFS) using mode-spacing swept comb and multi-loop composite optical phase-locked loop (OPLL). We exploit a specially designed agile opto-electronic frequency comb as a sweeping reference, whose mode-spacing is capable of arbitrary frequency sweep while preserving a stable phase and power distribution per mode. By locking a continuous-wave (CW) laser to any of its modes using composite OPLL with a large loop bandwidth, it allows the extraction of the optical LFS at high-order modes in a coherent manner with a multiplied sweep range and rate. With such capability, only intermediate frequency LFS with smaller bandwidth is required to yield a broadband LFS while inheriting the coherence and precision from the comb. We achieve optical LFS of 60 GHz at 6 THz/s sweep rate with a nine-folded sweep bandwidth of the driving signal. Fourier transform-limited spatial resolution at more than 80 times of the intrinsic coherence length of the CW laser is demonstrated in an OFMCW interferometry, verifying the high coherence with more than 4 orders of magnitude improvement in spatial resolution. The characteristics in terms of agility, coherence, and precision are discussed together with the potential limitations. The proposed method is capable of generating arbitrary frequency-modulated optical waveforms with a multiplied bandwidth, showing attractive potential in future metrology applications.


Delivery of drugs, growth factors, genes and stem cells via intrapericardial, epicardial and intramyocardial routes for sustained local targeted therapy of myocardial disease.
Local myocardial delivery (LMD) of therapeutic agents is a promising strategy that aims to treat various myocardial pathologies. It is designed to deliver agents directly to the myocardium and minimize their extracardiac concentrations and side effects. LMD aims to enhance outcomes of existing therapies by broadening their therapeutic window and to utilize new agents that could not be otherwise be implemented systemically. Areas covered: This article provides a historical overview of six decades LMD evolution in terms of the approaches, including intrapericardial, epicardial, and intramyocardial delivery, and the wide array of classes of agents used to treat myocardial pathologies. We examines delivery of pharmaceutical compounds, targeted gene transfection and cell implantation techniques to produce therapeutic effects locally. We outline therapeutic indications, successes and failures as well as technical approaches for LMD. Expert opinion: While LMD is more complicated than conventional oral or intravenous administration, given recent advances in interventional cardiology, it is safe and may provide better therapeutic outcomes. LMD is complex as many factors impact pharmacokinetics and biologic result. The choice between routes of LMD is largely driven not only by the myocardial pathology but also by the nature and physicochemical properties of the therapeutic agents.


Adenosine A2A analogue ATL-146e reduces systemic tumor necrosing factor-alpha and spinal cord capillary platelet-endothelial cell adhesion molecule-1 expression after spinal cord ischemia.
Inflammation is likely a major contributor to spinal cord reperfusion injury after aortic reconstruction. Systemic 4-(3-[6-amino-9-(5-ethylcarbamoyl-3,4-dihydroxy-tetrahydro-furan-2-yl)-9H-purin-2-yl]-prop-2-ynyl)-cyclohexanecarboxylic acid methyl ester (ATL-146e), a selective adenosine A(2A) agonist, has been shown to reduce paralysis after spinal cord ischemia. We hypothesized that ATL-146e reduces cytokine production during spinal cord reperfusion, curtailing inflammation and decreasing spinal cord capillary platelet-endothelial cell adhesion molecule-1 (PECAM-1) expression. New Zealand White rabbits sustained spinal cord ischemia with 45-minute cross-clamping of the infrarenal aorta. One group of animals received intravenous ATL-146e at 0.06 microg/kg/min for 3 hours during reperfusion, beginning after 30 minutes of ischemia. A second group received saline solution vehicle alone for 3 hours, serving as an ischemic control. A third group served as sham-operated animals, undergoing laparotomy with anesthesia. Serum was assayed with enzyme-linked immunosorbent assay for tumor necrosing factor-alpha (TNF-alpha). Animals were allowed to recover for 48 hours and were evaluated for hind-limb motor function with the Tarlov (0 to 5) scoring system. At necropsy, animals from each group yielded spinal cords for immunohistochemical staining for PECAM-1. Data are expressed as mean +/- standard error of the mean, with statistical analysis with Student t test and Kruskal-Wallis nonparametric test. Markedly improved Tarlov scores were seen in rabbits with ATL-146e (P <.001) during spinal cord reperfusion as compared with ischemic control animals. A significant reduction was found in TNF-alpha in the sera of rabbits with ATL-146e infusion (P <.01) as compared with ischemic control animals. Significantly reduced endothelial PECAM-1 staining intensity (P <.05) was seen in microscopic spinal cord sections from rabbits with ATL-146e. ATL-146e, an adenosine A(2A) agonist, reduces spinal cord reperfusion injury. The mechanism of the protection may involve a reduction in circulating TNF-alpha during a critical 3-hour reperfusion interval and reduction in spinal cord endothelial PECAM-1 upregulation.


Nerve Fibers in the Tumor Microenvironment as a Novel Biomarker for Oncological Outcome in Patients Undergoing Surgery for Perihilar Cholangiocarcinoma.
Perihilar cholangiocarcinoma (pCCA) is a biliary tract cancer with a dismal prognosis, with surgery being the only chance of cure. A characteristic aggressive biological feature of pCCA is perineural growth which is defined by the invasion of cancer cells to nerves and nerve fibers. Recently, nerve fiber density (NFD) was linked to oncological outcomes in various malignancies; however, its prognostic role in pCCA remains to be elucidated. Data of 101 pCCA patients who underwent curative-intent surgery between 2010 and 2019 were included in this study. Extensive group comparisons between patients with high and low NFD were carried out, and the association of cancer-specific survival (CSS) and recurrence-free survival with NFD and other clinicopathological characteristics was assessed using univariate and multivariable cox regression models. Patients with high NFD showed a median CSS of 90 months (95% CI: 48-132, 3-year CSS = 77%, 5-year CSS = 72%) compared to 33 months (95% CI: 19-47, 3-year CSS = 46%, 5-year CSS = 32%) in patients with low NFD (p = 0.006 log rank). Further, N1 category (HR = 2.84, p = 0.001) and high NFD (HR = 0.41, p = 0.024) were identified as independent predictors of CSS in multivariable analysis. Patients with high NFD and negative lymph nodes showed a median CSS of 90 months (3-year CSS = 88%, 5-year CSS = 80%), while patients with either positive lymph nodes or low NFD displayed a median CSS of 51 months (3-year CSS = 59%, 5-year CSS = 45%) and patients with both positive lymph nodes and low NFD a median CSS of 24 months (3-year CSS = 26%, 5-year CSS = 16%, p = 0.001 log rank). NFD has been identified as an important novel prognostic biomarker in pCCA patients. NFD alone and in combination with nodal status in particular allows to stratify pCCA patients based on their risk for inferior oncological outcomes after curative-intent surgery.


Epidemiology of prehospital emergency medical service use in Korean children.
The aim of this study was to elucidate the epidemiology of pediatric patients transported by the National 119 Rescue Services in Korea. We enrolled all pediatric patients (<16 years old) who used the National 119 Rescue Services in Korea between January 2006 and December 2008, and analyzed the 119 ambulance patient care record databases. The total number of the cases was 238,644 for 3 years. The median age was 6 years old and 59.0% were male, and the 2- to 5-year-old group was the largest (31.0%). The peak transport times were in the afternoon (from 12:00 p.m. to 17:59 p.m., 36.3%), on Saturday and Sunday (15.9% and 15.7%), and in summer (June to August, 27.3%). The ratio of disease versus injury as the cause of the transports was 42.3% vs. 57.7%. Among the 16 metropolitan cities and provinces, Gyeonggi (25.7%), Seoul (17.6%), and Incheon (7.0%) account for almost half of the all transported children. Regarding the annual transport rates per 100,000 children standardized by age, and gender to the Korean child population, Jeju was the largest (1,650.2) followed by Gangwon (1,201.3), and Jeonnam (1,178.1). This report presents comprehensive epidemiologic data of pediatric patients transported by 119 rescue services in Korea.


Hyperammonemia crisis following parturition in a female patient with ornithine transcarbamylase deficiency.
Ornithine transcarbamylase deficiency (OTCD) is an X-linked disorder, with an estimated prevalence of 1 per 80000 live births. Female patients with OTCD develop metabolic crises that are easily provoked by non-predictable common disorders, such as genetic (private mutations and lyonization) and external factors; however, the outcomes of these conditions may differ. We resuscitated a female patient with OTCD from hyperammonemic crisis after she gave birth. Hyperammonemia after parturition in a female patient with OTCD can be fatal, and this type of hyperammonemia persists for an extended period of time. Here, we describe the cause and treatment of hyperammonemia in a female patient with OTCD after parturition. Once hyperammonemia crisis occurs after giving birth, it is difficult to improve the metabolic state. Therefore, it is important to perform an early intervention before hyperammonemia occurs in patients with OTCD or in carriers after parturition.


Detection of terminal transferase in acute myeloid leukemia by flow cytometry.
The purpose of this study was twofold: (1) to develop an optimized, reliable method for the flow cytometric analysis of the intranuclear DNA polymerase, terminal deoxynucleotidyl transferase (TdT) in acute myeloid leukemia, and (2) to establish the usefulness of a novel, fluorescein-isothiocyanate conjugated monoclonal anti-TdT antibody (HT-6) in double-fluorescence staining for surface antigens in the characterization of leukemic cells. Inclusion of an aldehyde blocking buffer in the staining protocol reduced background fluorescence sufficiently to allow for the detection of the low-level fluorescent TdT+ myeloblasts. When admixed to normal peripheral blood mononuclear cells, 0.4-0.5% of HLA-DR+ or myeloid surface antigen+, TdT+ double-stained myeloblasts could be reliably detected above background levels. Flow cytometric TdT measurements using the HT-6 antibody in 55 patients with TdT+ acute lymphocytic or myelocytic leukemia or blast crisis of chronic myelogenous leukemia were equal or superior to the results obtained with a mixture of monoclonal anti-TdT antibodies (anti-HTDT-Mix) and comparable to those obtained by the conventional slide method employing polyclonal rabbit anti-human TdT antiserum. This flow cytometric TdT determination in combination with surface antigen staining using a novel anti-TdT monoclonal antibody (HT-6) allows for the recognition of minimal leukemic blast cells during clinical remission in acute myeloid leukemia.


Mass spectrometry in newborn and metabolic screening: historical perspective and future directions.
The growth of mass spectrometry (MS) in clinical chemistry has primarily occurred in two areas: the traditional clinical chemistry areas of toxicology and therapeutic drug monitoring and more recent, human genetics and metabolism, specifically inherited disorders of intermediary metabolism and newborn screening. Capillary gas chromatography and electrospray tandem MS are the two most common applications used to detect metabolic disease in screening, diagnostics and disease monitoring of treated patients. A few drops of blood from several million newborn infants are screened annually throughout the world making this the largest application of MS in medicine. Understanding the technique, how it grew from a few dozen samples per week in the early 1990s to increasing daily volume today will provide important information for new tests that either expand newborn screening or screening in other areas of metabolism and endocrinology. There are numerous challenges to the further expansion of MS in clinical chemistry but also many new opportunities in closely related applications. The model of newborn screening and MS in medicine may be useful in developing other applications that go beyond newborns and inherited metabolic disease. As MS continues to expand in clinical chemistry, it is clear that two features will drive its success. These features are excellent selectivity and multiple analyte or profile analysis; features recognized in the 1950s and remain true today.


Visual-Auditory Integration and High-Variability Speech Can Facilitate Mandarin Chinese Tone Identification.
Previous studies have demonstrated that tone identification can be facilitated when auditory tones are integrated with visual information that depicts the pitch contours of the auditory tones (hereafter, visual effect). This study investigates this visual effect in combined visual-auditory integration with high- and low-variability speech and examines whether one's prior tonal-language learning experience shapes the strength of this visual effect. Thirty Mandarin-naïve listeners, 25 Mandarin second language learners, and 30 native Mandarin listeners participated in a tone identification task in which participants judged whether an auditory tone was rising or falling in pitch. Moving arrows depicted the pitch contours of the auditory tones. A priming paradigm was used with the target auditory tones primed by four multimodal conditions: no stimuli (A-V-), visual-only stimuli (A-V+), auditory-only stimuli (A+V-), and both auditory and visual stimuli (A+V+). For Mandarin naïve listeners, the visual effect in accuracy produced under the cross-modal integration (A+V+ vs. A+V-) was superior to a unimodal approach (A-V+ vs. A-V-), as evidenced by a higher d prime of A+V+ as opposed to A+V-. However, this was not the case in response time. Additionally, the visual effect in accuracy and response time under the unimodal approach only occurred for high-variability speech, not for low-variability speech. Across the three groups of listeners, we found that the less tonal-language learning experience one had, the stronger the visual effect. Our study revealed the visual-auditory advantage and disadvantage of the visual effect and the joint contribution of visual-auditory integration and high-variability speech on facilitating tone perception via the process of speech symbolization and categorization. https://doi.org/10.23641/asha.21357729.


Alkaline subcritical-water treatment and alkaline heat treatment for the increase in biodegradability of newsprint waste.
This work describes two alkaline semicontinuous processes for the conversion of refractory organic materials into biodegradable substances. Newsprint was used as a lignocellulosic waste. Methane conversion efficiencies and cellulose removals were investigated for the two following processes: alkaline subcritical-water treatment (ASWT) coupled with methane fermentation and alkaline heat treatment (newsprint heated with steam in an autoclave; AHT) coupled with methane fermentation with a neutral subcritical-water treatment (NSWT) recycle. Results showed that for ASWT coupled with methane fermentation higher methane conversion efficiencies and higher cellulose removals were achieved as HRT increased. At HRT = 20 days, average CH4 conversion efficiency and average cellulose removal reached 26% and 44%, respectively. After a final HRT of 40 days, average CH4 conversion efficiency and average cellulose removal reached 50% and 60%, respectively. On the other hand, for AHT coupled with methane fermentation, methane conversion efficiencies did not show a greater improvement using this pretreatment process. Average conversion reached 9% with an average cellulose removal of 20%. In order to improve the yield of the reactor, approximately one-third of the effluent was recycled using NSWT (150 degrees C; neutral pH). Methane conversion efficiency of this process increased as more recycles were performed. For the fifth operation, the total average methane conversion efficiency was 44% with a total average cellulose removal of 55%.


The serum NT-proBNP is associated with all-cause mortality in geriatric hip fracture: a cohort of 1354 patients.
Geriatric hip fracture patients often have increased N-terminal prohormone of brain natriuretic peptide (NT-proBNP) levels. This study found a curved association between preoperative NT-proBNP level and all-cause mortality. There was an inflection point of NT-proBNP 781 ng/L in the saturation effect. Thus, NT-proBNP was a valuable indicator of all-cause mortality. To explore the relationship between N-terminal prohormone of brain natriuretic peptide (NT-proBNP) level and all-cause mortality in geriatric hip fractures and evaluate the possible predictive role of NT-proBNP level. Consecutive older adult patients with hip fractures were screened between January 2015 and September 2019. Demographic and clinical characteristics of the patients were collected. Linear and nonlinear multivariate Cox regression models were used to identify the association between NT-proBNP levels and mortality. All analyses were performed using EmpowerStats and the R software. One thousand three hundred fifty-four patients were included in the study. The mean follow-up was 34.35 ± 15.82 months. Four hundred twenty-nine (31.68%) patients died due to all-cause mortality. The preoperative NT-proBNP was median 337.95 (range 16.09-20,123.00) ng/L. Multivariate Cox regression models showed a nonlinearity association between NT-proBNP levels and mortality in elderly hip fractures. An NT-proBNP of 781 ng/L was an inflection point in the saturation effect. When < 781 ng/L, NT-proBNP was associated with mortality (hazard ratio [HR] = 1.12, 95% confidence interval [CI]: 1.06-1.18, P < 0.0001), whereas at > 781 ng/L, NT-proBNP was not associated with mortality (HR = 1.00, 95% CI: 0.98-1.01, P = 0.4718). In the stratification analysis, the result was stable. The NT-proBNP levels were nonlinearly associated with mortality in elderly hip fractures, and NT-proBNP of 781 ng/L was a valuable indicator of all-cause mortality. ChiCTR2200057323.


Urinary uroplakin expression in cyclophosphamide-induced rat cystitis model.
Cyclophosphamide (CYP) induces urothelial injury and causes excretion of cellular exudates at 24 h, followed by rapid restoration at 72 h. We investigated the role of urinary uroplakin II (UPII) levels in a CYP-induced cystitis model. For the purpose of this study, 10 controls and 26 CYP-injected female Sprague Dawley rats were killed at 24 h and 72 h postinjection. The vesical weight, severity of hematuria, and expression of UPII in the urinary bladder and urine were measured. CYP decreased the level of vesical UPII messenger RNA at 24 h, followed by rapid recovery at 72 h. Contrary to the negligible levels of urinary UPII and hematuria in controls, CYP treatment abruptly increased the excretion of urinary UPII at 24 h. The excretion had subsided at 72 h. Similarly, severe hematuria was observed at 24 h, with improvement at 72 h. However, some rats still exhibited hematuria at 72 h. CYP caused increase in vesical weight. The vesical weight at 24 h after CYP injection was negatively correlated with the vesical UPII level. Rats with significant hematuria demonstrated higher urinary UPII levels than those with insignificant hematuria. Vesical UPII could be an important barrier for early CYP-related injury, while the levels of urinary UPII may be associated with the severity of hematuria during dynamic periods in the urothelium.


A Time Off Incentive Was Not Associated with Influenza Vaccination Acceptance among Healthcare Workers.
Objectives. The national influenza vaccination rate among healthcare workers (HCWs) remains low despite clear benefits to patients, coworkers, and families. We sought to evaluate formally the effect of a one-hour time off incentive on attitudes towards influenza vaccination during the 2011-2012 influenza season. Methods. All HCWs at the Philadelphia Veterans Affairs (VA) Medical Center were invited to complete an anonymous web-based survey. We described respondents' characteristics and attitudes toward influenza vaccination and determined the relationship of specific attitudes with respondents' acceptance of influenza vaccination, using a 5-point Likert scale. Results. We analyzed survey responses from 154 HCWs employed at the Philadelphia VA Medical Center, with a response rate of 8%. Among 121 respondents who reported receiving influenza vaccination, 34 (28%, 95% CI 20-37%) reported agreement with the statement that the time off incentive made a difference in their decision to accept influenza vaccination. Conclusions. Our study provides evidence that modest incentives such as one-hour paid time off will be unlikely to promote influenza vaccination rates within medical facilities. More potent interventions that include mandatory vaccination combined with penalties for noncompliance will likely provide the only means to achieve near-universal influenza vaccination among HCWs.


Switchable Anion Exchange in Polymer-Encapsulated APbX3 Nanocrystals Delivers Stable All-Perovskite White Emitters.
We report a one-step synthesis of halide perovskite nanocrystals embedded in amphiphilic polymer (poly(acrylic acid)-block-poly(styrene), PAA-b-PS) micelles, based on injecting a dimethylformamide solution of PAA-b-PS, PbBr2, ABr (A = Cs, formamidinium, or both) and "additive" molecules in toluene. These bifunctional or trifunctional short chain organic molecules improve the nanocrystal-polymer compatibility, increasing the nanocrystal stability against polar solvents and high flux irradiation (the nanocrystals retain almost 80% of their photoluminescence after 1 h of 3.2 w/cm2 irradiation). If the nanocrystals are suspended in toluene, the coil state of the polymer allows the nanocrystals to undergo halide exchange, enabling emission color tunability. If the nanocrystals are suspended in methanol, or dried as powders, the polymer is in the globule state, and they are inert to halide exchange. By mixing three primary colors we could prepare stable, multicolor emissive samples (for example, white emitting powders) and a UV-to-white color converting layer for light-emitting diodes entirely made of perovskite nanocrystals.


Safety of switching between rituximab biosimilars in onco-hematology.
Comparable clinical efficacy and safety of the reference rituximab (MABTHERA) and its biosimilars has been established in randomized trials. However, safety concerns are often raised when switching from reference to biosimilar products and between different biosimilars. In this prospective observational study we aimed at evaluating the safety of switching between reference and biosimilar rituximab (TRUXIMA and RIXATHON) at Trento General Hospital (Italy). All patients (n = 83) with Non Hodgkin's Lymphoma (NHL, n = 72) and Chronic Lymphocytic Leukemia (CLL, n = 11) who received rituximab between March 2018 and March 2019 were asked to take part in the study. In 2017 and 2018 two tenders were carried out and two different biosimilars became available in the hospital, these were used sequentially. Thus, patients with or without previous treatments with the originator rituximab either received a biosimilar or were switched between different biosimilars. The incidence of adverse events in these groups of patients is described. The study population received 465 rituximab infusions and all received biosimilars. Fifty patients (60%) experienced at least one switch between different biosimilars or between rituximab originator and biosimilar, whereas 33 (40%) received one of the two biosimilars and one patient received reference rituximab. Adverse events (n = 146) were reported in 71 patients (84.5%). Treatment-related grade 3-4 events were reported in 5 patients (5.9%), whereas grade 1 rituximab related infusion events were observed in 6 patients (7.1%). No safety signal emerged in association with the use of a specific biosimilar nor with the practice of switching. Adverse events were similar, in terms of seriousness and frequency, to those described in the literature, providing further support to the clinical safety of rituximab biosimilars.


Cardiopulmonary response to exercise in patients with neuromuscular diseases.
In order to evaluate the possible effects of respiratory muscle training in patients with neuromuscular disease, we examined the cardiopulmonary response in 13 patients and 17 healthy controls by recording flow volume curves, ECG and alveolar carbon dioxide levels and collecting mixed expiratory air in Douglas bags. The cardiopulmonary response of our patients was not significantly different from that of the controls, and therefore we see no reason to avoid muscle training in patients with such disease.


Depression and older people.
Nearly a third of older people admitted for acute hospital care experience depression. Rates of depression are even higher in care homes. The purpose of this article is to raise awareness among nurses of this debilitating condition and its potentially fatal consequences, and to suggest interventions that can bring about improvement. Although challenging for nurses, detecting and treating depression can bring enormous benefits for older people and, in some cases, can mean the difference between life and death.


[Evidence of pregnancy in blood stains].
Evidence of pregnancy in blood traces is important for proving murder of the newborn child by the mother or illegal abortion. By immunoprecipitation in a semi-solid medium (by double radial immunodiffusion, counter-current immunoelectrophoresis), using antiserum of their own production, the authors proved in blood traces a specific gestational product--SP1 (Schwangerschaftspezifisches beta-1-Glykoprotein, PS-beta-G, TSG, PAPP-C). The authors examined a total of 172 blood traces on cloth from pregnancies of different stages (37 from the first trimester, 34 from the beginning of the second half of pregnancies and 101 at term) as extracts from the blood stain or particles of the blood stains on a slide. The reliability was 91--95%. Hitherto used methods were based on detection of choriogonadotropic hormone. Detection of SP1 can be considered reliable evidence of pregnancy. It was possible to detect it in blood traces starting with the fourth month of pregnancy.


Parent-of-origin effects on schizophrenia-relevant behaviours of type III neuregulin 1 mutant mice.
A robust, disease-relevant phenotype is paramount to the validity of genetic mouse models, which are an important tool in understanding complex diseases. Recent evidence from genome-wide association studies suggests the genetic contribution of parents to offspring is not equivalent. Despite this, few studies to date have examined the potential impact of parent genotype (i.e. origin of mutation) on the offspring of disease-relevant genetic mouse models. To elucidate the potential impact of the sex of the mutant parent on offspring phenotype, we characterized male and female offspring of an established schizophrenia mouse model, which had been generated using two different breeding schemes, in a range of disease-relevant behaviours. We compared heterozygous type III neuregulin 1 mutant (type III Nrg1+/-) and wild type-like control (WT) offspring from mutant father x WT mother pairings with offspring from mutant mother x WT father pairings. Offspring were tested in schizophrenia-relevant paradigms including the elevated plus maze (EPM), fear conditioning (FC), prepulse inhibition (PPI), social interaction (SI), and open field (OF). We found type III Nrg1+/- males from mutant fathers, but not mutant mothers, showed deficits in contextual fear-associated memory and exhibited increased social interaction, compared to their WT littermates. Type III Nrg1+/- females across breeding colonies only exhibited a subtle change to their acoustic startle response and sensorimotor gating. These results suggest a paternal-dependent transmission of genetically induced behavioural characteristics. Though the mechanisms governing this phenomenon are unclear, our results show that parental origin of mutation can alter the behavioural phenotype of genetic mouse models. Thus, researchers should carefully consider their breeding scheme when dealing with genetic mouse models of diseases such as schizophrenia.


Real-time observation of the thermo-optical and heat dissipation processes in microsphere resonators.
This work reports the real-time observation of the thermo-optical dynamics in silica microsphere resonators based on the dispersive time stretch technique. In general, the thermo-optical dynamics of silica microsphere resonators, including the thermal refraction and thermal expansion, can be characterized by the resonance wavelength shift, whose duration is at the millisecond timescale. However, this fast wavelength shift process cannot be directly captured by conventional spectroscopy, and only its transmission feature can be characterized by a fast-scanning laser and an intensity detector. With the advance of the time-stretch spectroscopy, whose temporal resolution is up to tens of nanoseconds, the thermo-optical dynamics can be observed in a more straight-forward way, by utilizing the pump-probe technology and mapping the resonance wavelength to the time domain. Here, the thermo-optical dynamics are explored as a function of the power and the scanning rate of the pump laser. Theoretical simulations reproduce the experimental results, revealing that the thermo-optical dynamics of silica microsphere resonators is dominated by the fast thermo-optical effect and the slow heat dissipation process to the surroundings, which leads to gradual regression of the resonance wavelength. This work provides an alternative solution for studying the thermo-optical dynamics in whispering gallery mode microresonators, which would be crucial for future applications of microresonator photonic systems.


Origin of renal proximal tubular injuries by Fe(III)-nta chelate.
Interaction between apo-transferrin and several iron(III) chelates has been investigated in terms of the capillary electrophoresis method. Based on the results, it has been clarified that (i) a binuclear iron(III) unit with an oxo-bridge is necessary for the facile transfer of an iron atom from the iron(III) chelate to apo-transferrin, and (ii) the renal proximal tubular injuries by Fe(III)-nitrilotriacetate (Fe-nta) should be due to the unique binuclear structure of this complex, which gives a peroxide adduct of the binuclear Fe-nta in the presence of glutathione cycle and oxygen.


Astrocytes in the nucleus of the solitary tract are activated by low glucose or glucoprivation: evidence for glial involvement in glucose homeostasis.
Glucose homeostasis is maintained through interplay between central and peripheral control mechanisms which are aimed at storing excess glucose following meals and mobilizing these same stores during periods of fasting. The nucleus of the solitary tract (NST) in the dorsal medulla has long been associated with the central detection of glucose availability and the control of glucose homeostasis. Recent evidence has emerged which supports the involvement of astrocytes in glucose homeostasis. The aim of the present study was to investigate whether NST-astrocytes respond to physiologically relevant decreases in glucose availability, in vitro, as well as to the presence of the glucoprivic compound 2-deoxy-D-Glucose. This report demonstrates that some NST-astrocytes are capable of responding to low glucose or glucoprivation by increasing cytoplasmic calcium; a change that reverses with restoration of normal glucose availability. While some NST-neurons also demonstrate an increase in calcium signaling during low glucose availability, this effect is smaller and somewhat delayed compared to those observed in adjacent astrocytes. TTX did not abolish these hypoglycemia mediated responses of astrocytes, suggesting that NST-astrocytes may be directly sensing low glucose levels as opposed to responding to neuronal detection of hypoglycemia. Thus, chemodetection of low glucose by NST-astrocytes may play an important role in the autonomic regulation of glucose homeostasis.


High-average-power femtosecond laser at 258 nm.
We present an ultrafast fiber laser system delivering 4.6 W average power at 258 nm based on two-stage fourth-harmonic generation in beta barium borate (BBO). The beam quality is close to being diffraction limited with an M2 value of 1.3×1.6. The pulse duration is 150 fs, which, potentially, is compressible down to 40 fs. A plain BBO and a sapphire-BBO compound are compared with respect to the achievable beam quality in the conversion process. This laser is applicable in scientific and industrial fields. Further scaling to higher average power is discussed.


Transdifferentiation of adipose-derived stem cells into hepatocytes: a new approach.
Several studies have demonstrated techniques in differentiating human adipose-derived stem cells (hADSCs) into hepatocytes. Unfortunately, transdifferentiation is inefficient, and the function of these induced hepatocyte-like cells (which we termed 'iHeps') is low compared with that of real hepatocytes. We aimed to identify transcriptional deficiencies in iHeps that are critical to hepatocyte development, which may provide insights into improving the efficiency of transdifferentiation. hADSCs were differentiated into iHeps, and iHeps were assayed for hepatocyte-like activity. iHeps were then screened for expression of several growth factors, receptors and transcription factors (TFs) critical to liver development using reverse transcription-polymerase chain reaction (RT-PCR). Deficient TFs were transduced into hADSCs and hepatocyte function was reassessed after hepatic differentiation. Differentiation of hADSCs into iHeps resulted in the upregulation of hepatic proteins. However, the levels of expression of hepatocyte-specific proteins in these iHeps were well below those of Huh 7.5 hepatoma cells, used in comparison. Five developmental TFs were notably absent on the RT-PCR screen. Lentiviral transduction of these TFs into hADSCs followed by culture in hepatocyte induction medium resulted in increased albumin expression compared with untransduced hADSCs treated in a parallel fashion. These five missing TFs are known to regulate hepatocyte differentiation and some are required to establish the competence of the foregut endoderm. Presumably due to their mesenchymal lineage, hADSCs do not express these endodermal TFs and are not fully competent to respond to critical developmental signals. Supplementation of these TFs may induce competency and enhance the differentiation of hADSCs into hepatocytes.


Combined UV-C/H2O2-VUV processes for the treatment of an actual slaughterhouse wastewater.
In this study, a three-factor, three-level Box-Behnken design with response surface methodology were used to maximize the TOC removal and minimize the H2O2 residual in the effluent of the combined UV-C/H2O2-VUV system for the treatment of an actual slaughterhouse wastewater (SWW) collected from one of the meat processing plants in Ontario, Canada. The irradiation time and the initial concentrations of total organic carbon (TOCo) and hydrogen peroxide (H2O2o) were the three predictors, as independent variables, studied in the design of experiments. The multiple response approach was used to obtain desirability response surfaces at the optimum factor settings. Subsequently, the optimum conditions to achieve the maximum percentage TOC removal of 46.19% and minimum H2O2 residual of 1.05% were TOCo of 213 mg L-1, H2O2o of 450 mg L-1, and irradiation time of 9 min. The attained optimal operating conditions were validated with a complementary test. Consequently, the TOC removal of 45.68% and H2O2 residual of 1.03% were achieved experimentally, confirming the statistical model reliability. Three individual processes, VUV alone, VUV/H2O2, and UV-C/H2O2, were also evaluated to compare their performance for the treatment of the actual SWW using the optimum parameters obtained in combined UV-C/H2O2-VUV processes. Results confirmed that an adequate combination of the UV-C/H2O2-VUV processes is essential for an optimized TOC removal and H2O2 residual. Finally, respirometry analyses were also performed to evaluate the biodegradability of the SWW and the BOD removal efficiency of the combined UV-C/H2O2-VUV processes.


Quality of life and associated characteristics: application of WHOQOL-BREF in the context of Primary Health Care.
This study aimed to identify the characteristics associated to quality of life (QOL) in users of four Basic Health Units (Unidades Básicas de Saúde, UBS) in Belo Horizonte, Minas Gerais. We conducted a cross-sectional study with 930 adult users enrolled in the selected UBS, using a questionnaire containing the WHOQOL-bref instrument and questions about sociodemographic characteristics, lifestyle and health conditions. Following descriptive analysis, we performed simple and multiple linear regression to evaluate the association between the exposure variables and the QOL domains. The highest mean values of QOL were observed in the social relationships domain. The lowest means were observed in the environment domain, with a statistically significant difference between some of the UBS. The worst perceptions of QOL were related to worse health, housing, education and income conditions, as well as problems in social relationships and psychological conditions. Actions are needed to improve QOL in Primary Health Care users through actions promoted by both health professionals and public managers.


Molecular cloning of mast cell growth factor, a hematopoietin that is active in both membrane bound and soluble forms.
We have previously reported the identification of a novel mast cell growth factor (MGF) that was shown to be a ligand for c-kit and is encoded by a gene that maps near the steel locus on mouse chromosome 10. We now report the cloning of cDNAs encoding the MGF protein. The MGF protein encoded by this cDNA can be expressed in a biologically active form as either a membrane bound protein or as a soluble factor. The soluble protein promotes the proliferation of MGF-responsive cell lines and, in the presence of erythropoietin, stimulates the formation of macroscopic [corrected] erythroid and multilineage hematopoietic colonies.


Temperature dependent free energy surface of polymer folding from equilibrium and quench studies.
Langevin dynamics simulation studies have been employed to calculate the temperature dependent free energy surface and folding characteristics of a 500 monomer long linear alkane (polyethylene) chain with a realistic interaction potential. Both equilibrium and temperature quench simulation studies have been carried out. Using the shape anisotropy parameter (S) of the folded molecule as the order parameter, we find a weakly first order phase transition between the high-temperature molten globule and low-temperature rodlike crystalline states separated by a small barrier of the order of k(B)T. Near the melting temperature (580 K), we observe an intriguing intermittent fluctuation with pronounced "1/f noise characteristics" between these two states with large difference in shape and structure. We have also studied the possibilities of different pathways of folding to states much below the melting point. At 300 K starting from the all-trans linear configuration, the chain folds stepwise into a very regular fourfold crystallite with very high shape anisotropy. Whereas, when quenched from a high temperature (900 K) random coil regime, we identify a two step transition from the random coiled state to a molten globulelike state and, further, to a anisotropic rodlike state. The trajectory reveals an interesting coupling between the two order parameters, namely, radius of gyration (R(g)) and the shape anisotropy parameter (S). The rodlike final state of the quench trajectory is characterized by lower shape anisotropy parameter and significantly larger number of gauche defects as compared to the final state obtained through equilibrium simulation starting from all-trans linear chain. The quench study shows indication of a nucleationlike pathway from the molten globule to the rodlike state involving an underlying rugged energy landscape.


Helicobacter pylori recombinant UreG protein: cloning, expression, and assessment of its seroreactivity.
Helicobacter pylori is a human pathogen and during the process of infection, antigens from the bacterium elicit strong host humoral immune responses. In our previous report, native H. pylori UreG protein showed good reactivity with sera from H. pylori patients. This study was aimed at producing the recombinant form of the protein (rUreG) and determining its seroreactivities. The coding sequence of H. pylori UreG was cloned and the recombinant protein expressed and purified by affinity chromatography using nickel nitrilotriacetic acid (Ni-NTA) resin. The antigenicity of rUreG to detect H. pylori specific antibodies was determined by western blot, using HRP-conjugated anti-human IgG and IgA antibodies as probes. A total of 70 sera, comprising 30 positive and 40 control serum samples, were used. The positive sera were from culture-positive H. pylori-infected patients with duodenal ulcers, gastric ulcers, or gastritis. The control sera comprised three types of samples without detectable H. pylori antibodies, i.e. healthy individuals (with no history of gastric disorders) (n = 10); patients who attended an endoscopy clinic (because of gastrointestinal complaints) but were H. pylori culture negative (n = 20); and people with other diseases (n = 10). Additionally, hyperimmune mice serum against rUreG was raised and tested with the native and recombinant UreG protein. The ureG gene fragment was successfully cloned and expressed in both soluble and insoluble forms. Western blots on rUreG protein showed 70% (21/30) and 60% (18/30) reactivity with patients' sera when probed with HRP-conjugated anti-human IgG and IgA antibodies, respectively; and the combination of the IgG and IgA western blots showed reactivity of 83.3% (25/30). By comparison, 97.5% and 92.5% of the control sera showed no reactivity when probed with HRP-conjugated anti-human IgG and IgA antibodies, respectively. Both the H. pylori lysate antigen and rUreG protein displayed a distinctive band at the expected molecular weight when probed with the hyperimmune mice serum. The rUreG protein was successfully cloned and expressed and showed good reactivity with H. pylori culture-positive patients' sera and no reactivity with most control sera. Thus, the diagnostic potential of this recombinant protein merits further investigation.


Genomic analysis of ST88 community-acquired methicillin resistant Staphylococcus aureus in Ghana.
The emergence and evolution of community-acquired methicillin resistant Staphylococcus aureus (CA-MRSA) strains in Africa is poorly understood. However, one particular MRSA lineage called ST88, appears to be rapidly establishing itself as an "African" CA-MRSA clone. In this study, we employed whole genome sequencing to provide more information on the genetic background of ST88 CA-MRSA isolates from Ghana and to describe in detail ST88 CA-MRSA isolates in comparison with other MRSA lineages worldwide. We first established a complete ST88 reference genome (AUS0325) using PacBio SMRT sequencing. We then used comparative genomics to assess relatedness among 17 ST88 CA-MRSA isolates recovered from patients attending Buruli ulcer treatment centres in Ghana, three non-African ST88s and 15 other MRSA lineages. We show that Ghanaian ST88 forms a discrete MRSA lineage (harbouring SCCmec-IV [2B]). Gene content analysis identified five distinct genomic regions enriched among ST88 isolates compared with the other S. aureus lineages. The Ghanaian ST88 isolates had only 658 core genome SNPs and there was no correlation between phylogeny and geography, suggesting the recent spread of this clone. The lineage was also resistant to multiple classes of antibiotics including β-lactams, tetracycline and chloramphenicol. This study reveals that S. aureus ST88-IV is a recently emerging and rapidly spreading CA-MRSA clone in Ghana. The study highlights the capacity of small snapshot genomic studies to provide actionable public health information in resource limited settings. To our knowledge this is the first genomic assessment of the ST88 CA-MRSA clone.


[Determination of the composition of renal calculi by x-ray spectrometry].
X-ray spectrophotometry shows undoubtful advantages versus conventional chemical methods employed in the analysis of kidney stones. In fact, it is possible to detect little crystals that are very important in the genesis and treatment of urinary calculosis.


Virtual Visit Trends in Nursing Homes During the COVID-19 Pandemic.
Background: Physical distancing and visiting restrictions during the COVID-19 pandemic particullarly posed significant challenges in providing timely medical care in nursing homes. Virtual visits were pivotal in providing both scheduled and urgent patient care in addition to in-person care when possible. These virtual visits could have been used to provide urgent medical care than the regular scheduled visits. We hypothesize that regular non-COVID-19-related virtual visits in the evaluated nursing home facilities were lower than COVID-19-related virtual visits during this period. The objective was to compare the frequency of COVID-19-related virtual visits with non-COVID-19-related virtual visits performed in three suburban nursing homes in Michigan from December 2020 through February 2022. Methods: Retrospective chart review of 283 patients, comprising 563 virtual visits. The most frequent ICD-10 diagnostic codes used by providers for primary encounters were analyzed for three participating facilities Results: Only 13.8% (78/563) of all virtual visits during the study period were for COVID-19 as a primary encounter. In total 86.1% (485/563) of visits were non-COVID-19 related, which comprised most frequently M6281 muscle weakness (45), E119 diabetes type with complications (20), NI86 end-stage renal disease (11), N390 urinary tract infection (10), G309 Alzheimer's disease (10), and I4891 unspecified atrial fibrillation (10). Conclusion: We found that the primary ICD-10 diagnosis codes for virtual COVID-19-related visits were significantly lower than non-COVID-19-related virtual visits in our study population. This trend could be associated with multiple system-based factors. Further studies to examine factors responsible for these findings are warranted.


Changes in DNA content during in vitro transformation of mouse salivary gland epithelium.
DNA content was measured in single cells in situ during the in vitro development of neoplastic transformation in epithelial cells from mouse salivary glands. The earliest change in DNA content was found in stage III of the transformation process (a preneoplastic stage). In foci of these cells, the percentage of tetraploid (4C) cells was 30--60% compared with the starting tissue and early primary cultures, which were diploid. The stage III foci eventually gave rise to subtetraploid tumorigenic cell lines. The studies suggested that during in vitro development of neoplastic transformation in salivary gland epithelium, tetraploids were generated that then underwent a period of chromosome instability and loss. Evidence was also presented that a similar mechanism may be operating in transformation of salivary gland epithelium in vivo. A possible mechanism for transformation on the basis of chromosome imbalance was discussed.


Self-reported oral hygiene habits, health knowledge, and sources of oral health information in a group of Japanese junior high school students.
The purpose of the present study was to analyze self-reported oral hygiene habits, sources of oral health information, and oral health knowledge in a group of Japanese junior high school students and to determine whether there is a need for improvement in the school's present oral health instruction. A sample of 110 students aged 12-14 in Chiba City were surveyed by means of a questionnaire composed of 24 multiple choice questions. The questions focused on: (1) experience of school-based oral health education, (2) sources of oral health information, (3) knowledge about dental caries, periodontal disease, and the preventive action of fluoride, (4) oral hygiene habits, and (5) dietary behavior. Results showed that more than two-thirds of the students had participated in some kind of school-based oral health education program. Most students (76%) claimed that toothbrushing was the main event attended and 63% claimed that toothbrushing was the main subject they had been taught. The school nurse was identified by 48% of the students as their main source of oral health information in school-based oral health education. When asked to identify their main source of oral health information, most of the students identified "school". Half of the students (48%) identified dental plaque as the main cause of dental caries but only 31%, as the main cause of periodontal disease. Few students (11%) were able to identify the preventive action of fluoride; 58% answered "I don't know"). These results suggest that a meaningful target for the oral health education of children should be the improvement of the school's oral health instruction.


Fluoromethylsulfinyl radicals: spectroscopic characterization and photoisomerization via intramolecular hydrogen shift.
Two new sulfinyl radicals, CHF2SO˙ and CH2FSO˙, have been generated in the gas phase through homolytic cleavage of the weak S-S bonds in disulfane oxides CHF2S(O)SCF3 and CH2FS(O)SCF3 by high-vacuum flash pyrolysis (HVFP) at ca. 500 °C. The IR spectroscopy characterization of the two fluoromethylsulfinyl radicals in solid N2 (10 K), Ar (10 K), and Ne (3 K) matrices reveals the presence of two conformers for CHF2SO˙ (gauche and cis) and one conformer for CH2FSO˙ (gauche). Upon 266 nm laser irradiation, these radicals undergo both isomerization and decomposition in the matrices. In addition to the dominant formation of the elusive oxathiyl radicals CHF2OS˙ (gauche and cis) and CH2FOS˙ (gauche) via 1,2-alkyl migration, two higher-energy carbon-centered radicals ˙CF2SOH and ˙CHFSOH bearing similar molecular structures to hydroperoxyalkyl radicals (˙QOOH) form via intramolecular 1,3-hydrogen shift in the two sulfinyl radicals. Additionally, the involvement of 1,3-hydrogen shift in CHF2OS˙ and CH2FOS˙ is also indicated by the observation of the fragmentation species. The identification of these radicals by matrix-isolation IR and UV-vis spectroscopy is aided by the quantum chemical calculations at the B3LYP/6-311++G(3df,3pd) level of theory. The stability of the isomers of the two sulfinyl radicals CHF2SO˙ and CH2FSO˙ has been discussed according to the experimental observations and also based on the CCSD(T)-F12a/aug-cc-pVTZ//B3LYP/6-311++G(3df,3pd) calculated energy profiles.


Preschool hearing screening: pass/refer rates for children enrolled in a head start program in eastern North Carolina.
This 4-year project investigated the pass/refer rates of preschool children in a hearing screening program. Three- and 4-year-old children who attended Head Start centers in rural, traditionally medically underserved, eastern North Carolina participated (n = 1,462). Screening procedures and pass/refer criteria were based on the Guidelines for Audiologic Screening (American Speech-Language-Hearing Association [ASHA], Panel on Audiologic Assessment, 1997). Only 54% (n = 787) of children passed the initial screening (i.e., passed all three of the screening components, which included pure-tone audiometry, tympanometry, and otoscopy), and an additional 22% (n = 323) passed the rescreening, for an overall pass rate of 76%. The initial pass rate was 90%, 71%, and 71% for otoscopy, tympanometry, and pure-tone audiometry, respectively. After the initial screening, 675 children were referred (i.e., 83%, 2%, and 15% for audiologic rescreening, medical evaluation, or both, respectively). About 71% (n = 478) received the recommended evaluation. Follow-up assessment compliance after the rescreening was poor. Slightly more than 10% of children were evaluated. The hearing status of 267 (i.e., 18.3%) children was never determined. Six (i.e., 0.5%) of the 1,195 children who completed the audiologic screening and/or received diagnostic audiologic assessment were confirmed to have hearing loss. Methodological factors that may have contributed to this high refer rate include the use of all screening techniques (pure tones, tympanometry, and otoscopy), procedural considerations in testing protocol and pass/refer criteria, and the demographic characteristics of the children screened.


Association of Hearing Impairment with Incident Depressive Symptoms: A Community-Based Prospective Study.
The aim was to investigate the potential association between hearing impairment and incident depressive symptoms. Using a prospective community-based cohort study in France (the Paris Prospective Study III), participants aged 50-75 years were recruited between 2008 and 2012 and thereafter followed up every 2 years up to 2018. Hearing impairment, measured at study recruitment by audiometry testing, was defined as a pure tone average >25 decibels in the better ear. Incident depressive symptoms, measured using the validated 13-item Questionnaire of Depression 2nd version, was assessed during follow-up. Multivariate generalized estimating equations were used to compute odds ratio (OR) and 95% confidence intervals (CI). Among 7591 participants free of depressive symptoms at baseline (mean age 59.8 years, 63% of men), 14.3% had hearing impairment. Over 6 years of follow-up, 479 subjects (6.3%) had incident depressive symptoms. The OR for incident depressive symptoms was 1.36 for subjects with baseline hearing impairment (95% CI, 1.06-1.73). A pooled analysis of 4 published prospective studies yielded a multivariable relative risk of baseline hearing impairment for incident depressive symptoms of 1.29 (95% CI, 1.09-1.53). In this community-based prospective cohort study of participants aged 50 to 75 years, baseline hearing impairment was associated with a 36% increased odds of incident depressive symptoms.


Expression of Hsp70 reveals significant differences between fin regeneration and inflammation in Paramisgurnus dabryanus.
Hsp70 is the most strongly induced in response to various cellular stresses and a good candidate for investigating its role in tissue injury. We firstly cloned full-length cDNA of hsp70 from Paramisgurnus dabryanus (PdHsp70) by RACE method (GenBank: KP402408.1). Then regeneration and inflammation of fin were established by amputation and scratch respectively. Quantitative RT-PCR detected the PdHsp70 began to increase rapidly its expression at 1 days post amputation (dpa) and reached the peak at 2 dpa during fin regeneration. Its expression was also up-regulated at 2 days post scratch (dps) of inflammation but still significant weaker in comparison with it in regenerated fin at 2 dpa. Next, immunohistochemistry analysis of PdHsp70 showed that PdHsp70 located mainly in the deeper epidermis of regenerated fin and was stronger than its expression in the scratched inflammatory fin which was involved in whole epidermal. SDS-PAGE and Western blotting confirmed that the PdHsp70 protein expressed efficiently in Escherichia coli BL21. These findings have implied that PdHsp70 are implicated in different regulation of regeneration and inflammation in response to injury stimulation. During the regeneration, it is involved in the formation of wound epidermis by mediating cellular protection whereas it can modulate inflammatory by activating the innate immune response.