Chopping Roughage Length Improved Rumen Development of Weaned Calves as Revealed by Rumen Fermentation and Bacterial Community.
Roughage particle size can influence rumen development, which is also determined by rumen microorganisms and their metabolic end-products. Therefore, the aim of this study was to evaluate the comprehensive effects of roughage length and rumen bacterial community on the rumen development of weaned calves. A total of thirty-six weaned Angus female calves (125 ± 3 d; 161.2 ± 13.0 kg) were randomly assigned to three diets differing in roughage particle size: 4 cm (short length); 24 cm (medium length); and 44 cm (long length). Results showed that chopping roughage increased dry matter intake and organic matter apparent digestibility; altered rumen fermentation indicated by the increased rumen butyrate and valerate concentrations; and increased plasma glucose, cholesterol, and total protein. Chopping roughage affected rumen bacterial community, as indicated by altering the diversity indices; by increasing ruminal bacteria Papillibacter and Eubacterium_hallii_group, which are involved in butyrate production; and by increasing Synergistetes and Mogibacterium, which are involved in bacterial colonization. In conclusion, chopping roughage at 4 cm was shown to improve the rumen bacterial community, alter rumen fermentation, eventually promote the development of rumen.


Does calmodulin mediate stimulus-secretion coupling in the parotid gland? Studies using trifluoperazine.
Calmodulin present in rat parotid homogenates activated cyclic AMP phosphodiesterase activity by 8 to 10 fold. The activation was Ca2+-dependent and reversed by trifluoperazine. Half-maximal inhibition required 12 microM trifluoperazine. Incubation of parotid slices with up to 40 microM trifluoperazine had no effect on the basal rate of amylase and K+ release or on cellular ATP content. Isoproterenol stimulated glucose utilization and substance P stimulated amylase secretion were also unaffected by 40 microM trifluoperazine. 20 or 40 microM Trifluoperazine however inhibited amylase secretion induced by isoproterenol, dibutyryl cyclic AMP, carbamoylcholine or phenylephrine. The possible involvement of calmodulin in regulating enzyme secretion following stimulation of the parotid gland with the various types of agonists is discussed.


Biochemical and molecular characterisation of the bacterial endophytes from native sugarcane varieties of Himalayan region.
Seven endophytic bacterial isolates were finally recovered from native sugarcane varieties at hilly areas namely Berinag, Champawat and Didihat of Uttarakhand state in northern Himalayan region. New isolates and two standard cultures-Azospirillum brasilense and Gluconacetobacter diazotrophicus, were evaluated for their morphological, biochemical and molecular characteristics. Morphologically all were rod shaped, Gram-negative bacteria. Their plant growth promotory properties were also assessed which proved isolates RtBn and StBn as IAA producing. Except isolate StBn, all were phosphate solubilising and except RtBn all produced siderophores. Molecular characterisation of the isolates was performed using amplified 16S r-DNA restriction analysis. Similarity index in unweighted pair group method with arithmetic mean programme clustered the isolates according to their geographical distribution. Native isolates showed insignificant similarity with South American strains used as standards. nifH amplification was observed with all the isolates used in the study which again establish them as potential N-fixers.


Fast ultrasound-assisted treatment of urine samples for chronopotentiometric stripping determination of mercury at gold film electrodes.
This work describes an efficient, fast, and reliable analytical methodology for mercury determination in urine samples using stripping chronopotentiometry at gold film electrodes. The samples were sonicated in the presence of concentrated HC1 and H2O2 for 15 min in order to disrupt the organic ligands and release the mercury. Thirty samples can be treated over the optimized region of the ultrasonic bath. This sample preparation was enough to allow the accurate stripping chronopotentiometric determination of mercury in the treated samples. No background currents and no passivation of the gold film electrode due to the sample matrix were verified. The samples were also analyzed by cold vapour atomic absorption spectrometry (CV-AAS) and good agreement between the results was verified. The analysis of NIST SRM 2670 (Toxic Metals in Freeze-Dried Urine) also validated the proposed electroanalytical method. Finally, this method was applied for mercury evaluation in urine of workers exposed to hospital waste incinerators.


Increased dental comorbidities in patients with psoriasis: a nationwide population-based cohort study in Korea.
Limited data are available regarding the association between psoriasis and common dental conditions. To investigate the risk of potential dental comorbidities in patients with psoriasis. We conducted a nationwide population-based cohort study to analyse the claims data of patients with psoriasis (n = 15 165) and age- and sex-matched controls (n = 75 825). The incidence risk of the following potential dental conditions was analysed: dental caries, pulp and periapical disease, periodontal disease, gingival changes and tooth loss. After adjusting for potential cofactors, the adjusted hazard ratios (aHRs) of dental caries [1.105; 95% confidence interval (CI) 1.078-1.132], pulp and periapical disease (1.07; 95% CI 1.044-1.096) and periodontal disease (1.108; 95% CI 1.088-1.129) were significantly higher than those in the control cohort (P < 0.001). However, among the subset of patients with psoriasis who received systemic antipsoriatic treatment (n = 4275), the aHR risk of all potential dental comorbidities was not significantly higher from that of the control cohort. Patients with psoriasis have an increased risk of dental comorbidities, and systemic antipsoriatic treatment may help mitigate this increased risk.


Radiochemical neutron activation analysis of Fe, Co, Zn, Sb and Se in biomedical and environmental samples.
A radiochemical neutron activation method has been developed for the simultaneous determination of Fe, Co, Zn, Sb and Se levels in cancerous breast tissue, milk samples and fugitive cement dust particulates. Various Standard Reference Materials from NIST, USA (Bovine Liver 1577a, Milk Powder 1549, Coal Fly Ash 1633a and Urban Particulate Matter 1648), IAEA Vienna (Animal Muscle H-4, Milk powder A-11 and Soil-5) and NIES Japan (Pond Sediment) were also analysed for quality control. Samples together with standards were irradiated at a thermal neutron fluence of 10(13) ncm-2s-1 for 2 weeks. After dissolution/fusion together with carriers, the Fe was first separated by extracting with diethyl ether followed by extraction with cupferron in chloroform. From the aqueous phase Co and Zn were extracted using alpha-nitroso-beta-naphthol in chloroform and 2-thenoyltrifluoroacetone in isobutylmethyl ketone, respectively. From another aliquot, Se was first complexed with o-phenylenediamine and extracted in benzene. Later Sb was extracted using KI and 4-(2-pyridylazo)-resorcinol (PAR) in benzene. The method yields reasonably accurate data for monitoring of trace elements in biomedical and environmental specimens.


Red blood cell-mimicking liposomes loading curcumin promote diabetic wound healing.
The excessive inflammatory response is known to be a major challenge for diabetic wound healing, while bacteria secreted toxin, α-hemolysin (Hlα), was recently reported to prolong inflammation and delay diabetic wound healing. In this study, we designed a red blood cell membrane (RBCM)-mimicking liposome containing curcumin (named RC-Lip) for the treatment of diabetic wounds. RC-Lips were successfully fabricated using the thin film dispersion method, and the fusion of RBC membrane with the liposomal membrane was confirmed via surface protein analysis. RC-Lips efficiently adsorbed Hlα, thereby reducing the damage and pro-apoptotic effects of Hlα on keratinocytes. Furthermore, they remarkably facilitated liposome uptake into macrophages with advanced curcumin release and regulation of M2 macrophage polarization. In a diabetic mouse and infected wound model, RC-Lips treatment significantly promoted wound healing and re-epithelialization while downregulating interleukin-1β (IL-1β) and upregulating interleukin-10 (IL-10). In summary, the results showed that the spongiform RC-Lips effectively modulate the inflammatory response after adsorbing Hlα and regulating M2 macrophage polarization, leading to a significant promotion of wound healing in diabetic mice. Hence, this study provides a prospective strategy of efficiently mediating inflammatory response for diabetic wounds.


Do acetylcholine receptor and striated muscle antibodies predict the presence of thymoma in patients with myasthenia gravis?
Acetylcholine receptor (AChR) and striated muscle antibodies (StrAbs) are found frequently in myasthenia gravis (MG) patients with thymoma. In this study we aimed to determine the positive predictive value (PPV) and negative predictive value (NPV) of these antibodies for thymoma in patients with MG. Antibody findings, thymic histology, and onset age were reviewed for 1141 patients with MG. PPV and NPV of these antibodies for thymoma were determined. The PPV of AChR binding antibodies plus StrAbs was highest (50.0%) with onset before the age of 40 years. The PPV of all antibodies was low (<9%) after age 40. Higher StrAb levels did not increase the PPV. The NPV of AChR binding antibodies was high (99.7%) for all ages. Patients without AChR binding antibody are not likely to have a thymoma. StrAbs and AChR binding antibodies are not diagnostic for thymoma, but in early-onset MG their presence should raise the clinical suspicion for thymoma.


Homelessness among patients with schizophrenia in rural China: a 10-year cohort study.
To explore the frequency and risk factors of homelessness among a previously identified cohort of patients with schizophrenia in rural China. A 10-year follow-up investigation among a 1994 cohort (n = 510) of patients with schizophrenia was conducted in Xinjin County, Chengdu, China. Thirty-nine patients (7.8%) experienced homelessness during the follow-up period. The rate of homelessness was 0.9 per 100 person-years during the 10-year follow-up period. Four significant predictors of homelessness remained in the final logistic regression model: living in shabby or unstable house or shelter, positive family history of mental disorders, without income of the patient, and unmarried, divorced, or separated. Risk of homelessness increased substantially with exposure to multiple risk factors. Substantial numbers of homeless patients with schizophrenia are challenges for mental health care and public health. Appropriate community-based services, especially housing services, should be crucial for prevention of homelessness in patients with schizophrenia.


Corrigendum: C1q/TNF-Related Protein 9 Attenuates Atherosclerosis by Inhibiting Hyperglycemia-Induced Endothelial Cell Senescence Through the AMPKα/KLF4 Signaling Pathway.
[This corrects the article DOI: 10.3389/fphar.2021.758792.].


Learning and memory depend on fibroblast growth factor receptor 2 functioning in hippocampus.
Fibroblast growth factor (FGF) signaling controls self-renewal of neural stem cells during embryonic telencephalic development. FGF receptor 2 (FGFR2) has a significant role in the production of cortical neurons during embryogenesis, but its role in the hippocampus during development and in adulthood has not been described. Here we dissociate the role of FGFR2 in the hippocampus during development and during adulthood with the use of embryonic knockout and inducible knockout mice. Embryonic knockout of FGFR2 causes a reduction of hippocampal volume and impairment in adult spatial memory in mice. Spatial reference memory, as assessed by performance on the water maze probe trial, was correlated with reduced hippocampal parvalbumin+ cells, whereas short-term learning was correlated with reduction in immature neurons in the dentate gyrus. Furthermore, short-term learning and newly generated neurons in the dentate gyrus were deficient even when FGFR2 was lacking only in adulthood. Taken together, these findings support a dual role for FGFR2 in hippocampal short-term learning and long-term reference memory, which appear to depend on the abundance of two separate cellular components, parvalbumin interneurons and newly generated granule cells in the hippocampus.


Pial arteriovenous fistulas: dilemmas in prenatal diagnosis, counseling and postnatal treatment. Report of three cases.
We report three cases of the antenatal appearance of a pial arteriovenous fistula (AVF). In Case 1, the diagnosis of pial AVF was made by ultrasound examination at 32 + 3 weeks of gestation and confirmed by magnetic resonance imaging (MRI) at 34 + 3 weeks of gestation. After birth, the neonate had cardiac insufficiency and an embolization was performed 8 days postpartum which was followed by extended cerebral ischemia and death. In Cases 2 and 3 pial fistulae were diagnosed at birth. In Case 2, the patient was referred following the diagnosis of an aneurysmal malformation of the vein of Galen at 38 weeks of gestation. Owing to immediate delivery following her transfer, no ultrasound examination was performed and the diagnosis of pial AVF was established on the first postnatal day. An embolization was performed and the child is doing well. Case 3 presented with cardiomegaly at 30 weeks of gestation and cerebral ischemic lesions after birth. These cases highlight the difficulties encountered in the prenatal diagnosis of pial AVFs. The diagnosis should be considered in cases of unexplained cardiomegaly and it is also important to make sure that AVFs draining into the vein of Galen are not misdiagnosed as aneurysmal malformations of this vein. The complications of pial AVFs are cardiac failure and cerebral ischemia. Embolization is the treatment of choice; however it is a risky procedure in neonates.


Hydrogen-induced Sulfur Vacancies on the MoS2 Basal Plane Studied by Ambient Pressure XPS and DFT Calculations.
Sulfur vacancy on an MoS2 basal plane plays a crucial role in device performance and catalytic activity; thus, an understanding of the electronic states of sulfur vacancies is still an important issue. We investigate the electronic states on an MoS2 basal plane by ambient-pressure X-ray photoelectron spectroscopy (AP-XPS) and density functional theory calculations while heating the system in hydrogen. The AP-XPS results show a decrease in the intensity ratio of S 2p to Mo 3d, indicating that sulfur vacancies are formed. Furthermore, low-energy components are observed in Mo 3d and S 2p spectra. To understand the changes in the electronic states induced by sulfur vacancy formation at the atomic scale, we calculate the core-level binding energies for the model vacancy surfaces. The calculated shifts for Mo 3d and S 2p with the formation of sulfur vacancy are consistent with the experimentally observed binding energy shifts. Mulliken charge analysis indicates that this is caused by an increase in the electronic density associated with the Mo and S atoms around the sulfur vacancy as compared to the pristine surface. The present investigation provides a guideline for sulfur vacancy engineering.


Preemptive effects of etoricoxib, acetaminophen, nimesulide, and ibuprofen on postoperative pain management after single-implant surgery: A randomized clinical trial.
There is insufficient evidence for pain control in preemptive analgesia (PA) after dental implant surgery, signaling the need for further studies. The objective of this study was to evaluate the efficacy of PA in single dental implant surgeries (SDIS), seeking to identify among the etoricoxib (ETOR), ibuprofen (IBU), nimesulide (NIME), and acetaminophen (ACETA)], which one has the higher efficacy effectiveness in relieving postoperative pain and reducing the use of rescue medication compared to placebo. In this triple-blind, parallel, randomized controlled clinical trial, 135 individuals with a mean age of 57.6 years (±11.7), both genders, were randomly divided into five groups according to the test drug: I-PLACEBO; II-IBU (600 mg); III-NIME (100 mg); IV-ACETA (750 mg); and V-ETOR (90 mg). The occurrence, duration, and intensity of pain were analyzed using the Chi-square, Fisher's exact and ANOVA tests, and the generalized estimating equation models, when appropriate. Test drugs provided a reduction in postoperative pain scores and lower use of rescue medication when compared to placebo. The ETOR group presented significantly lower pain scores, when compared to other active treatments. The IBU group showed the highest mean number of rescue medication used. All test drugs provided a beneficial preemptive effect demonstrated by the reduced postoperative pain and reduced use of rescue medication. The ETOR group presented lower pain scores, and the IBU group showed the highest mean number of rescue medication used among the test groups.


Single-Lens Light-Sheet Fluorescence Microscopy Based on Micro-Mirror Array.
Conventional light sheet fluorescence microscopy (LSFM) utilizes two perpendicularly arranged objective lenses for optical excitation and detection, respectively. Such a configuration often limits the use of high-numerical-aperture (NA) objectives or requires specially designed long-working-distance objectives. Here, a LSFM based on a micro-mirror array (MMA) to enable light sheet imaging with a single objective lens is reported. The planar fluorescent emission excited by the light sheet illumination is collected by the same objective, relayed onto an MMA and detected by a side-view camera. The proposed scheme makes LSFM compatible to single objective imaging system and shows promising candidacy for high spatiotemporal imaging.


Binding of the S(+)- and R(-)-enantiomers of bethanechol to muscarinic receptors in jejunal smooth muscle, nasal mucosa, atrial and ventricular myocardium of the rat.
Both the enantiomers of bethanechol displaced R(-)-[3H]quinuclidinyl benzilate from muscarinic binding sites in homogenates from rat jejunum, nasal mucosa, atrial and ventricular myocardium. Stereoselectivity of receptor binding for S(+)- and R(-)-bethanechol was found in all tissues investigated (Ki S(+) less than Ki R(-)). Different proportions of high and low affinity binding sites for bethanechol enantiomers and S(+)-methacholine in jejunal smooth muscle, atrial and ventricular muscle and the presence of only low affinity binding sites in nasal mucosa point to differences in receptor-effector coupling in these tissues. The relative insensitivity of cardiac tissue for bethanechol compared to methacholine might be related to the much smaller proportion of high affinity binding sites found for S(+)-bethanechol in heart ventricular muscle.


Three-dimensional reconstructions from non-deparaffinized tissue sections.
Three-dimensional (3-D) reconstruction from microscopic images represents a useful tool for the study of biological structures in embryology and developmental biology. However, it is usually necessary to cope with many difficulties connected with the preparation of specimens. In order to minimize mutual displacement of structures in successive sections, the applicability of non-deparaffinized tissue sections for 3-D reconstruction was tested. Chicken embryos were fixed and stained in toto with eosin and then embedded in paraffin. About 30-mum-thick non-deparaffinized serial sections were used for obtaining initial data for 3-D reconstruction of larger stacks of embryonic bodies using either fluorescence or confocal microscope. The same sections served for both collecting optical serial sections of mesonephros as source images for its 3-D reconstruction, and immunohistochemical detection of fibronectin, laminin and vimentin. It was found that sections with retained paraffin preserve the mutual spatial relationships of tissue components as well as provide an excellent differentiation of structure. It makes the process of 3-D reconstruction easier. The localization of the products of immunohistochemical reactions demonstrated the co-localization of fibronectin and laminin in basal laminas and the presence of vimentin in glomeruli and mesenchymal tissue. The use of non-deparaffinized sections represents a less time consuming and more effective alternative to thin histological sections for the purpose of 3-D reconstruction, and enables further application of material.


Surgical repair of partial anomalous pulmonary venous connection shunting from left atrium to innominate vein.
Partial anomalous pulmonary venous connection (PAPVC) causes a left-to-right shunt from the anomalous pulmonary vein (PV) to a systemic vein. We report an uncommon adult case of PAPVC, in which the left upper PV drained into both the innominate vein and the left atrium (LA), demonstrating retrograde shunting from the LA to the innominate vein. The anomaly was surgically repaired.


Aromatase inhibitors in prevention--data from the ATAC (arimidex, tamoxifen alone or in combination) trial and the design of IBIS-II (the second International Breast Cancer Intervention Study).
Current prevention trials have shown that tamoxifen can reduce the incidence of breast cancer by about 30%-40% in high-risk women, but that the risk of thromboembolic disease and endometrial cancer are increased about twofold. An alternative approach for postmenopausal women is to use an aromatase inhibitor to reduce oestrogen to very low levels. Data from the ATAC adjuvant trial indicate that the aromatase inhibitor anastrozole is more effective than tamoxifen in reducing recurrence and preventing new contralateral tumours, and also has a more favourable side-effect profile. This has led us to launch a new prevention trial--IBIS-II--in 6,000 high-risk postmenopausal women comparing anastrozole against placebo. A parallel trial will compare anastrozole against tamoxifen in 4,000 women with locally excised DCIS.


Diagnostic value of K-ras mutation analysis for pancreaticobiliary cytology specimens with indeterminate diagnosis.
Fine-needle aspiration and bile duct brushing cytology have been traditionally used for early detection of pancreaticobiliary malignancy. Quite frequently, the cytological interpretations of these specimens are indeterminate. In this retrospective study, we evaluated the diagnostic value of detecting K-ras (v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog) mutation in pancreaticobiliary cytology specimens that had equivocal cytological diagnoses. A total of 129 cases that had indeterminate cytology diagnoses, K-ras mutational analysis, and histopathological follow-up were retrieved. The cytological interpretations, histopathological diagnoses, and K-ras mutation results were reviewed and analyzed. Overall, the sensitivity and specificity of K-ras mutation for detection of pancreaticobiliary malignancy including adenocarcinoma, intraductal papillary mucinous neoplasm, and mucinous cystic neoplasm were 57% and 94%, respectively. The positive and negative predictive values of K-ras mutation for the presence of pancreaticobiliary malignancy were 94% and 60%, respectively. The results demonstrate that K-ras mutation has a high predictive value for malignancy in patients with indeterminate pancreaticobiliary cytology and should be included as an important adjuvant diagnostic marker. It should be noted that a negative K-ras mutation result does not rule out malignancy, and K-ras mutation can be detected, although infrequently, in morphologically benign conditions.


The ovarian teratomas. A histopathological review of 77 cases.
Seventy-seven cases of ovarian teratomas were studied according to examination modality of surgical specimens and to histologic patterns and frequency of different tissues components. The main histogenetic conjectures were debated also.


Immune responses following COVID-19 infection in multiple sclerosis patients using immunomodulatory therapy.
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus type-2 (SARS-CoV-2), has quickly become a global pandemic. Most multiple sclerosis (MS) patients use disease-modifying treatments (DMTs), such as immunomodulators or immunosuppressants. By targeting different types of immune cells, DMTs affect cellular and/or humoral immunity. The potential effects of DMTs on the long-term immune response to COVID-19 is not fully known. Between 16.04.2020 and 15.07.2020, a total of 34 people, 17 of whom were diagnosed with MS according to the 2010 McDonald diagnostic criteria and a control group of 17 individuals who did not have a known systemic disease who were matched according to age, gender, and COVID-19 disease severity, where all received COVID-19 diagnosis with SARS-CoV-2 PCR positivity in nasopharyngeal swab test and immune responses were measured (SARS-CoV-2 IgM and IgG antibody levels COVID 19 ELISA kit), were included in our study. Demographic data of MS patients and the control group, SARS-CoV-2 immune responses, antibody titers and disease year of MS patients, EDSS scores, disease type, and disease duration were determined. All patients were symptomatic for COVID-19. COVID-19 disease severity was divided into three groups as mild, moderate, and severe according to the clinical condition of the patient. Demographic data of MS patients and the control group, SARS-CoV-2 immune responses, antibody titers and disease year of MS patients, EDSS scores, disease type, and disease duration were determined. All patients were symptomatic for COVID-19. COVID-19 disease severity was divided into three groups as mild, moderate, and severe according to the clinical condition of the patient. According to our study results, IgG-type long-term immune responses were lower in MS patients using DMTs than in the healthy population. We hope that our study will provide insight into the COVID-19 vaccine immune responses.


Patterning of the Caenorhabditis elegans head region by the Pax-6 family member vab-3.
The Pax-6 genes are important for eye development in both vertebrates and Drosophila. Mutations in the human PAX6 gene are found in patients with a variety of eye disorders, including aniridia and Peters' anomaly, and mutations in the Drosophila Pax-6 homologue cause the eyeless phenotype. In the nematode Caenorhabditis elegans, vab-3 mutants display many defects in head-region development, including aberrant morphogenesis, transformation of hypodermal (epidermal-like) cell fates to those of posterior homologues, and abnormal specification of neurons. Here we show that vab-3 is a member of the paired-domain-containing Pax-6 gene family and is expressed in head-region cells. This C. elegans Pax-6 locus can also encode proteins lacking the paired domain. Our results suggest that a primordial role of the Pax-6 gene family could have been to pattern part of the head region, and that Pax-6 genes subsequently evolved to be more specifically involved in eye development.


[Parkinson syndrome in parasagittal meningioma (case report)--differential diagnosis for vascular degenerative Parkinson syndrome in the aged].
Reported is a case of parasagittale meningeoma in combination with a bilaterale parkinsonian syndrome. Referred is to the diagnostical problems in the separation of the degenerative-vascular M. Parkinson in the senile age also to the postoperative eminent disappearance of the parkinsonians symptomatic. Essential clinical aspects of extrapyramidal syndrome at intracranial tumors are discussed by means of relevant literature in connection with possible pathophysiological mechanisms of origin.


Optimization of synthesis parameters for mesoporous shell formation on magnetic nanocores and their application as nanocarriers for docetaxel cancer drug.
In this work, Fe3O4@SiO2 nanoparticles were coated with mesoporous silica shell by S-N+I- pathway by using anionic surfactant (S-) and co-structure directing agent (N+). The role of co-structure directing agent (CSDA) is to assist the electrostatic interaction between negatively charged silica layers and the negatively charged surfactant molecules. Prior to the mesoporous shell formation step, magnetic cores were coated with a dense silica layer to prevent iron oxide cores from leaching into the mother system under any acidic circumstances. However, it was found that both dense and mesoporous coating parameters affect the textural properties of the produced mesoporous silica shell (i.e., surface area, pore volume and shell thickness). The synthesized Fe3O4@SiO2@m-SiO2 (MCMSS) nanoparticles have been characterized by low-angle X-ray diffraction, transmission electron microscopy (TEM), and N2 adsorption-desorption analysis, and magnetic properties. The synthesized particles had dense and mesoporous silica shells of 8-37 nm and 26-50 nm, respectively. Furthermore, MCMSS possessed surface area of ca. 259-621 m2·g-1, and pore volume of ca. 0.216-0.443 cc·g-1. MCMSS showed docetaxcel cancer drug storage capacity of 25-33 w/w% and possessed control release from their mesochannels which suggest them as proper nanocarriers for docetaxcel molecules.


Paradigms in Fluorescence Molecular Imaging: Maximizing Measurement of Biological Changes in Disease, Therapeutic Efficacy, and Toxicology/Safety.
Fluorescence molecular imaging (MI) is an important concept in preclinical research that focuses on the visualization of cellular and biological function in a non-invasive fashion to better understand in vivo disease processes and treatment effects. MI differs fundamentally from traditional preclinical imaging strategies in that it generally relies on reporter probes specific for particular targets or pathways that can be used to reveal biological changes in situ, at the site(s) of disease. In contrast, the more established imaging modalities, like magnetic resonance imaging, X-ray, micro X-ray computed tomography, and ultrasound, historically have relied primarily on late-stage anatomical or physiologic changes. The practical application of fluorescence MI, however, has drifted somewhat from the emphasis on quantifying biology, and based on the publication record, it now appears to include any imaging in which a probe or contrast agent is used to non-invasively acquire in vivo endpoint information. Unfortunately, the mere use of a defined biologically specific probe, in the absence of careful study design, does not guarantee that any useful biological information is actually gained, although often useful endpoint results still can be achieved. This review proposes to add subcategories of MI, termed MI biological assessment (or MIBA), that emphasize a focus on obtaining early and clear biological changes associated with disease development, therapeutic efficacy, and drug-induced tissue changes. Proper selection of probes and careful study design are critical for maximizing the non-invasive assessment of in vivo biological changes, and applications of these critical elements are described.


Machine-Learning and Chemicogenomics Approach Defines and Predicts Cross-Talk of Hippo and MAPK Pathways.
Hippo pathway dysregulation occurs in multiple cancers through genetic and nongenetic alterations, resulting in translocation of YAP to the nucleus and activation of the TEAD family of transcription factors. Unlike other oncogenic pathways such as RAS, defining tumors that are Hippo pathway-dependent is far more complex due to the lack of hotspot genetic alterations. Here, we developed a machine-learning framework to identify a robust, cancer type-agnostic gene expression signature to quantitate Hippo pathway activity and cross-talk as well as predict YAP/TEAD dependency across cancers. Further, through chemical genetic interaction screens and multiomics analyses, we discover a direct interaction between MAPK signaling and TEAD stability such that knockdown of YAP combined with MEK inhibition results in robust inhibition of tumor cell growth in Hippo dysregulated tumors. This multifaceted approach underscores how computational models combined with experimental studies can inform precision medicine approaches including predictive diagnostics and combination strategies. SIGNIFICANCE: An integrated chemicogenomics strategy was developed to identify a lineage-independent signature for the Hippo pathway in cancers. Evaluating transcriptional profiles using a machine-learning method led to identification of a relationship between YAP/TAZ dependency and MAPK pathway activity. The results help to nominate potential combination therapies with Hippo pathway inhibition.This article is highlighted in the In This Issue feature, p. 521.


Minimal Clinically Important Differences in 6-Minute Walk Test in Patients With HFrEF and Iron Deficiency.
The 6-minute walk test (6MWT) is widely used to measure exercise capacity; however, the magnitude of change that is clinically meaningful for individuals is not well established in heart failure with reduced ejection fraction (HFrEF). To calculate the minimal clinically important difference (MCID) for change in exercise capacity in the 6MWT in iron-deficient populations with HFrEF. In this pooled secondary analysis of the FAIR-HF and CONFIRM-HF trials, mean changes in the 6MWT from baseline to weeks 12 and 24 were calculated and calibrated against the Patient Global Assessment (PGA) tool (clinical anchor) to derive MCIDs in improvement and deterioration. Of 760 patients included in the 2 trials, 6MWT and PGA data were available for 680 (89%) and 656 (86%) patients at weeks 12 and 24, respectively. The mean 6MWT distance at baseline was 281 ± 103 meters. There was a modest correlation between changes in 6MWT and PGA from baseline to week 12 (r = 0.31; P < 0.0001) and week 24 (r = 0.43; P < 0.0001). Respective estimates (95% confidence intervals) of MCID in 6MWT at weeks 12 and 24 were 14 meters (5;23) and 15 meters (3;27) for a "little improvement" (vs no change), 20 meters (10;30) and 24 meters (12;36) for moderate improvement vs a "little improvement,", -11 meters (-32;9.2) and -31 meters (-53;-8) for a "little deterioration" (vs no change), and -84 meters (-144;-24) and -69 meters (-118;-20) for "moderate deterioration" vs a "little deterioration". The MCID for improvement in exercise capacity in the 6MWT was 14 meters-15 meters in patients with HFrEF and iron deficiency. These MCIDs can aid clinical interpretation of study data.


[Observation of the effectiveness of APFI gel to prevent dental caries].
To observe the effectiveness of APFI Gel applied to pupils to prevent dental caries. 2918 cases of 6 to 13 years old pupils from four urban and countryside primary schools were randomly divided into two groups,the experiment group and the control group. By theirs different school and classes and groups, APFI Gel was used to 2 160 cases of the experimental group to prevent dental caries. The control group consisted of 758 cases. The incidence of dental caries of the two groups were observed in the same time and using the same way. Statistical analysis indicated that the incidence of dental caries in the experimental group decreased by 52.3%,the newly increased DMFT decreased by 60.14% (P<0.01). The incidence of dental caries of the first molar decreased by 52.43%,the newly increased DMFT decreased by 65.52% (P<0.01). It is effective to use APFI Gel to prevent caries.


Neovascularity of a tracheal prosthesis/tissue complex.
Permanent bioincorporation of a microporous tracheal prosthesis will require a stable blood supply to connective tissue supporting an epithelial surface. In experience with over 80 tracheal implants in dogs, we have observed that end-on ingrowth and epithelialization does not occur in the absence of lateral ingrowth, epithelialization is marked by the appearance of a subepithelial network of vessels, and this process must be well advanced by 6 to 8 weeks for long-term stability. These observations were extended by using microangiography to delineate the blood supply of the prosthesis/tissue complex. Six implants of bioelectric polyurethane with 10% gentamicin (3 cm length, 2 cm diameter, 1 to 1.25 mm wall thickness, 60 to 120 mu micropore diameter) were interposed in the dog thoracic trachea and wrapped with an omental pedicle. The aorta was perfused with a barium suspension at elective sacrifice between 10 weeks and 21 months. Radiographs of specimens were correlated with bronchoscopic, gross, and histopathological findings. Neovascularity of the prosthesis/tissue complex can be described in three categories: outer capsule, prosthetic wall, and inner lining. Outer capsule vessels were oriented circumferentially immediately adjacent to the prosthetic wall. They resembled arteries up to 75 mu diameter on microscopy and appeared to develop from the omentum with connections developing to the bronchial circulation. Prosthetic wall vessels up to 75 mu with thin muscular walls were noted to traverse the porous prosthetic wall. The inner lining had a network of subepithelial vessels that connected to the lamina propria vasculature of the native trachea across the anastomoses with vessels up to 120 mu in diameter. We conclude that the omentum provides an immediate blood supply and a base for early connective tissue ingrowth. Epithelialization occurs as early as 3 weeks on the favorable bed, accompanied by vascular connections to the existing lamina propria tracheal vessels. This dual organization of blood supply with connections across the prosthetic wall is probably important to long-term stability of healing.


[Treatment of septic olecranon and patellar bursitis by excision and vacuum-assisted closure therapy].
Treatment of septic olecranon and patellar bursitis differs considerably and is currently under discussion. We therefore performed a retrospective study of our patients with septic bursitis in the past 5 years. Between March 2007 and February 2012 we treated 79 patients with septic olecranon (n = 43) and patellar (n = 36) bursitis surgically: 61-males, 18 females, age 51 (range: 11-91) years. Four patients had not been treated before, 25 had suffered recurrences after 1-10 previous procedures, and 9 patients had not improved after conservative therapy. 34 patients presented with traumatic rupture or fistula of their bursae. In all cases we performed a radical bursectomy and vacuum-assisted therapy for 4 to 5 days. In addition, patients received systemic antibiotics. We phoned all patients and were successful in 57 cases (72 %). We questioned these patients for range of movement, limitations at work, pain, sensibility disorder, satisfaction with the result and further surgical procedures. In all cases we took tissue specimens for cultures, in 48 preparations histological examination was performed. Microbiological and histological results are discussed in detail. 40 patients were free of complaints, 15 complained of mild pain, 54 of 57 had unlimited range of motion. Minor discomforts at desk work were reported by 5 of 43 patients, 12 out of 36 patient reported discomfort when performing on their knees. There was no recurrence in the period of investigation. We recommend our treatment concept for septic olecranon and patellar bursitis because patient satisfaction is high and recurrences are reliably avoided. The soft tissue is spared, so that plastic covering procedures are seldom necessary.


Auditory nerve-brain stem evoked potentials in cats during manipulation of the cerebral perfusion pressure.
In order to study the effects of various degrees of cerebral ischemia on the auditory nerve-brain stem evoked potentials (BAEP), the cerebral perfusion pressure (CPP), defined as the difference between mean arterial blood pressure (MAP) and intracranial pressure (ICP), was systemically manipulated in anesthetized, paralyzed and ventilated cats. The CPP was varied by decreasing MAP, either by hemorrhage or by the infusion of a vasodilating drug, and elevating ICP by infusion of mock CSF into the cisterna magna, or by MAP depression and ICP elevation simultaneously. Even though the lower limit of adequate CPP is considered to be 40 mm Hg, the EEG became isoelectric at an average CPP of 24 mm Hg and the BAEP became isoelectric at an average CPP of 7 mm Hg. These extremely low CPP values of 7-24 mm Hg are far below the range of autoregulation of cerebral blood flow (CBF) so that the brain stem auditory pathway is still capable of generating its electrical response (BAEP) at very low CBF. This is paradoxical since these same regions of the brain have been shown to have the highest levels or regional metabolism as shown by their very high local cerebral blood flow and local glucose utilization.


Primary structure and transcriptional regulation of GAP-43, a protein associated with nerve growth.
Nerve regeneration and developmental outgrowth of axons are both correlated with increased synthesis of an axonal membrane protein designated GAP-43. Phosphorylation of an apparently identical protein, present at lower abundance in adult brains, has been correlated with long-term potentiation, a form of synaptic plasticity. We have now isolated a cDNA clone encoding GAP-43 from neonatal rat brain. The amino acid sequence is extremely hydrophilic, with no potential membrane-spanning domains and no sites for N-linked glycosylation, but with a short hydrophobic segment at the protein's amino terminus, consistent with a model in which GAP-43 extends from the cytoplasmic surface of growth cone and synaptic plasma membranes. Among several tissues and cells examined, GAP-43 mRNA is expressed only in neurons. Developmental and regeneration-associated changes in GAP-43 synthesis appear to be mediated largely at the level of transcription of a single gene.


Location of DNA sequences complementary to small nuclear repeat RNA (fr 3-RNA) in relation to DNA sequences coding for albumin and alpha-fetoprotein in rat liver cells.
Rat liver nuclei contain a 29-nucleotides-long RNA (fr 3-RNA) which is transcribed from middle repetitive DNA sequences. By Southern analysis of restriction fragments of rat albumin and alpha-fetoprotein genomic clones, DNA sequences complementary to this RNA were detected on a 4.6 kbp Eco RI fragment located 600 bp downstream from the termination exon of the albumin gene and on a 2 kbp Eco RI-HindIII fragment located 10 kbp downstream from the restriction fragment containing the alpha-fetoprotein site. No sequence complementary to this RNA was found either in the introns of exons of both genes or in the regions extending 7 kbp upstream from the first albumin exon and 10 kbp upstream of the first alpha-fetoprotein exon. We concluded that sequences complementary to fr 3-RNA are present at the 3'-end flanking regions of the rat albumin and alpha-fetoprotein gene complexes.


Influence of argon laser trabeculoplasty on transforming growth factor-beta 2 concentration and bleb scarring following trabeculectomy.
The purpose of this study was to evaluate the influence of previous argon laser trabeculoplasty (ALT) on transforming growth factor-beta 2 (TGF-beta 2) concentration of the aqueous humor and its influence on bleb scarring after trabeculectomy. Fifty-one patients with primary open-angle glaucoma (POAG) and 29 patients with exfoliation (XFS) glaucoma were recruited for this prospective study before undergoing trabeculectomy. Sixty to 200 micro l of aqueous humor were analyzed for total and biologically active TGF-beta 2 concentrations (R and D Systems). TGF-beta 2 levels and a standardized bleb assessment were compared between the ALT- and non-ALT-treated groups. POAG eyes without ALT showed significantly higher total TGF-beta 2 levels (2,317.7+/-1,041.1 pg/ml) than eyes with previous ALT (1,621.6+/-899.6 pg/ml; P=0.026). No significant difference was found for active TGF-beta 2 levels (ALT: 238.1+/-119.0 pg/ml; no ALT: 220.1+/-96.9 pg/ml; P=0.585). In XFS patients ALT did not alter total TGF-beta 2 levels (ALT: 1,524.9+/-624.9 pg/ml, no ALT: 1,220+/-499.1 pg/ml; P=0.20), but active TGF-beta 2 was significantly higher in the ALT-treated (237.0+/-99.7 pg/ml) than in the non-ALT-treated (140.0+/-95.3 pg/ml, P=0.028) group. Bleb grading revealed no statistical difference between the ALT- and non-ALT-treated groups in POAG (P=0.545, Fisher's exact test), whereas XFS patients with ALT were at increased risk for scarring compared to non-ALT-treated patients (P=0.053). ALT appears to increase the risk of scarring in XFS patients because of increased levels of activated TGF-beta 2.


Bleomycin, vincristine, and methotrexate with citrovorum factor rescue in the treatment of advanced squamous cell carcinoma of the cervix.
Fourteen patients with advanced or locally recurrent squamous cell carcinoma of the uterine cervix were treated with bleomycin, vincristine, and moderately high dose methotrexate with citrovorum rescue. Two patients (14%) had a partial response; no patient had a complete response. Two patients were felt to have significant bleomycin associated pulmonary toxicity. This chemotherapy regimen is not felt to be clinically useful in our patient population.


Rapid and quantitative detection of SARS-CoV-2 specific IgG for convalescent serum evaluation.
Convalescent serum with a high abundance of neutralization IgG is a promising therapeutic agent for rescuing COVID-19 patients in the critical stage. Knowing the concentration of SARS-CoV-2 S1-specific IgG is crucial in selecting appropriate convalescent serum donors. Here, we present a portable microfluidic ELISA technology for rapid (15 min), quantitative, and sensitive detection of anti-SARS-CoV-2 S1 IgG in human serum with only 8 μL sample volume. We first identified a humanized monoclonal IgG that has a high binding affinity and a relatively high specificity towards SARS-CoV-2 S1 protein, which can subsequently serve as the calibration standard of anti-SARS-CoV-2 S1 IgG in serological analyses. We then measured the abundance of anti-SARS-CoV-2 S1 IgG in 16 convalescent COVID-19 patients. Due to the availability of the calibration standard and the large dynamic range of our assay, we were able to identify "qualified donors" for convalescent serum therapy with only one fixed dilution factor (200 ×). Finally, we demonstrated that our technology can sensitively detect SARS-CoV-2 antigens (S1 and N proteins) with pg/mL level sensitivities in 40 min. Overall, our technology can greatly facilitate rapid, sensitive, and quantitative analysis of COVID-19 related markers for therapeutic, diagnostic, epidemiologic, and prognostic purposes.


Subtype specific expression and survival prediction of pivotal lncRNAs in muscle invasive bladder cancer.
Comprehensive transcriptome expression analyses of bladder cancer revealed distinct lncRNA clusters with differential molecular and clinical characteristics. In this study, pivotal lncRNAs were assessed for their impact on survival and their differential expression between the molecular bladder cancer subtypes. FFPE samples from chemotherapy-naïve patients with muscle invasive bladder cancer (MIBC) were analyzed on the Nanostring nCounter platform for absolute quantification. An established 36-gene panel was used for molecular subtype classification into basal, luminal and infiltrated MIBC. In a second step, 14 pivotal lncRNAs were assessed for their molecular subtype attribution, and their predictive value in disease-specific survival. In silico validation was performed on a total of 487 MIBC patients (MDA, TGCA and Chungbuk cohort). Several pivotal lncRNAs showed a distinct molecular subtype attribution: e.g. MALAT1 showed a downregulation in the basal subtype (p = 0.009), TUG1 and CBR3AS1 showed an upregulation in the luminal subtype (p ≤ 0.001). High transcript levels of SNHG16, CBR3AS1 and H19 appeared to be predictive for a shorter disease-specific survival. Patients overexpressing putative oncogenes MALAT1 and TUG1 in MIBC tissue presented prolonged survival, suggesting tumor suppressive effects of both lncRNAs. The Nanostring nCounter proved to be a valid platform for the quantification of low-abundance transcripts including lncRNAs.


Comparative aspects of milk proteins.
The current status of knowledge of the major proteins of milks of various species is evaluated. Most of the non-bovine milk proteins are homologous with the recognized families of those of Bos taurus, alpha S1-caseins, alpha S2-caseins, beta-caseins, kappa-caseins, beta-lactoglobulins, and alpha-lactalbumins, each family representing a separate genetic locus specific to the mammary gland. No prominent milk protein not homologous to one of these families has yet been discovered in milk of any species. Genetic polymorphism resulting from substitutions in the polypeptide chains and various degrees of post-translational phosphorylation, glycosylation, and proteolysis have been identified in milk proteins of several species. Total protein production ranges among species from about 0.5 to 10 g/d per kg0.75 maternal weight. Proportions of the several proteins vary greatly among species, but few accurate analytical data are available except for total casein and total whey protein contents.


Impact of Perioperative Oral Steroid Use on Low-frequency Hearing Preservation After Cochlear Implantation.
To investigate the efficacy of a perioperative oral steroid taper on low-frequency hearing preservation after cochlear implantation. Retrospective case series. Tertiary referral center. Consecutive cochlear implant recipients between January 2012 and December 2014 who were candidates for a hearing preservation approach based on preoperative pure tone thresholds were identified. A subgroup of patients received a 2-week oral corticosteroid taper beginning 3 days before surgery. All patients were implanted using standard length electrodes. The preservation of low-frequency pure tone thresholds on the first postoperative audiogram was assessed. Secondary outcome measures included the respective impacts of age, diabetes, and electrode array type on hearing preservation, the durability of hearing preservation over time, and the development of medical complications related to steroid use. Twenty-seven ears met inclusion criterion, and the mean age at implantation was 49.8 years (median 62 yr, range 2-81 yr). Twenty patients (74.1%, mean age 48.7 yr) received an oral corticosteroid taper, whereas 7 (25.9%, mean age 53.1 yr) did not. The rate (p < 0.01) and degree (p < 0.01) of hearing preservation as measured at implant activation was greater for patients who received an oral steroid taper than those who did not. There were no medical complications related to steroid use. A 2-week oral prednisone taper beginning before surgery may positively affect the incidence and degree of low-frequency hearing preservation after cochlear implantation.


In vitro bacterial penetration of coronally unsealed endodontically treated teeth.
Forty-five root canals were cleaned, shaped, and then obturated with gutta-percha and root canal sealer, using a lateral condensation technique. The coronal portions of the root filling materials were placed in contact with Staphylococcus epidermidis and Proteus vulgaris. The number of days required for these bacteria to penetrate the entire root canals was determined. Over 50% of the root canals were completely contaminated after 19-day exposure to S. epidermidis. Fifty percent of the root canals were also totally contaminated when the coronal surfaces of their fillings were exposed to P. vulgaris for 42 days.


An unusual virus from the parasitic wasp Cotesia melanoscela.
Certain strains of the braconid parasitoid Cotesia melanoscela carry two different viruses within their ovaries, one of which (here designated CmV2) is apparently not a polydnavirus. Virus replication occurs in the ovarian calyx and in some other tissues of both male and female parasitoids; as yet, no replication has been observed in the testis, however. In addition, CmV2 is one of only two parasitoid viruses known to replicate in host insect larvae, and we not show that this virus is also capable of replicating in vitro; the virus is nevertheless nonpathogenic for gypsy moth larvae. The virus is not transmissible per os, either to host animals or to larvae of parasitoid strains lacking it. CmV2 is stably maintained within strains carrying it apparently by a vertical transmission mode involving the maternal line; transmission via the male germ line could not be demonstrated. While purification of the virus was not achieved, preliminary work allows us to suggest the genome consists of a single double-stranded DNA molecule of approximately 125 kb.


It Takes a Village: A Narrative Review of Anesthesiology Mentorship.
Mentorships play a critical role in the development of physician careers and should be tailored within a structured, evidence-based mentoring program to ensure mutual benefit and avoidance of pitfalls. We offer a narrative review of the current literature and commentary on mentoring at the medical student, GME trainee, and early career faculty levels within anesthesiology, and propose a framework on which an effective mentoring program can be implemented.


Predicting the impact of school-based treatment for urinary schistosomiasis given by the Ghana Partnership for Child Development.
Mathematical models can be used to predict the impact of interventions to control infectious diseases. In this paper, an epidemiological model is used to predict the impact of chemotherapy of school-age children infected with Schistosoma haematobium, in a programme conducted by the Ghana Partnership for Child Development in the Volta Region, Ghana. Existing data were used to validate the predictions of the model, demonstrating convincingly the ability of the model to make correct predictions. Predictions of trends in mean egg count, infection prevalence and prevalence of heavy infection (> 50 eggs/10 mL urine) were then made for the period 1997-1999, and will be compared to the data collected in the programme in the future.


Cold-induced hemolysis in a hypertonic milieu.
Suspension of human erythrocytes at 37 degrees C in an environment made hypertonic by increasing concentrations of sodium chloride and sucrose was followed by hemolysis when the temperature was lowered to 0 degrees C. Two distinct stages were involved in this hemolytic phenomenon, the first being incubation with hypertonic solute at some temperature above 20 degrees C with an increasing effect up to 45 degrees C, and the second stage consisting of lowering the temperature below 15 degrees C with increasing hemolysis down to 0 degrees C. The rate of cooling was not an important factor, but the presence of ions reduced the extent of cold-induced hemolysis in hypertonic sucrose. No significant release of membrane phospholipid and cholesterol accompanied this hemolysis. The solubilization of membrane protein components was investigated, with some differences appearing on sodium dodecyl sulfate polyacrylamide gel electrophoresis between hypertonic and isotonic supernatants. Spectrin could not be identified in solubilized form. Correlation of the temperatures of note in these studies with results from the literature on other biological effects of temperature-induced phase transitions in membrane lipids strongly points to the conclusion that such transitions are involved in the mechanism of cold-induced hypertonic hemolysis. It is postulated that the hypertonic milieu has resulted in membrane-protein alteration damage which prevents normal adaption to the new physical state of the membrane lipids during cooling.


Feasibility and basic acoustic characteristics of intelligent long-term bowel sound analysis in term neonates.
Bowel dysfunction continues to be a serious issue in neonates. Traditional auscultation of bowel sounds as a diagnostic tool in neonatal gastrointestinal problems is limited by skill and inability to document and reassess. Consequently, in order to objectively and noninvasively examine the viability of continuous assessment of bowel sounds, we utilized an acoustic recording and analysis system to capture bowel sounds and extract acoustic features in term neonates. From May 1, 2020 to September 30, 2020, 82 neonates who were hospitalized because of hyperbilirubinemia were included. For 20 h, a convolutional neural network-based acoustic recorder that offers real-time, wireless, continuous auscultation was employed to track the bowel sounds of these neonates. (1) Usable data on five acoustic parameters of bowel sound was recorded for 68 neonates, and the median values were as follows: The rate was 25.80 times/min [interquartile range (IQR): 15.63-36.20]; the duration was 8.00 s/min (IQR: 4.2-13.20); the amplitude was 0.46 (IQR: 0.27-0.68); the frequency was 944.05 Hz (IQR: 848.78-1,034.90); and the interval time was 2.12 s (IQR: 1.3-3.5). (2) In comparison to the parameters of the bowel sounds recorded from the right lower abdomen in 68 infants, the acoustic parameters of the 10 out of 68 infants from chest controls and blank controls were considerably different. (3) The 50%-75% breast milk intake group had the highest rate, the longest duration, and the highest amplitude of bowel sounds, while the >75% breast milk intake group had the highest frequency of bowel sounds. (4) Compared with neonates without hyperbilirubinemia, there was no significant difference in the five parameters of bowel sounds in hyperbilirubinemia infants; nor was there a significant effect of phototherapy and non-phototherapy status on the parameters of bowel sounds during bowel sound monitoring in hyperbilirubinemia patients. (5) A mild transient skin rash appeared on the skin of three infants. No other adverse events occurred. The acoustic recording and analysis system appears useful for monitoring bowel sounds using a continuous, invasive, and real-time approach. Neonatal bowel sounds are affected by various feeding types rather than hyperbilirubinemia and phototherapy. Potential influencing factors and the significance of their application in neonatal intestinal-related disorders require further research.


Stimulation of food intake and growth of chickens by cyproheptadine: lack of interaction with the effects of pinealectomy and melatonin.
Cyproheptadine stimulates food intake and growth in some species of mammal; its effects are reported here in chickens. Growing cockerels of an egg-laying strain were given 0.32 mg/d by mouth, which resulted in significant increases in weight gain and food intake, including feeding during the night. Increasing daily doses of up to 1.6 mg/kg body weight stimulated intake in a dose-related manner, while 1.92 mg/kg had the same effect as 0.96 mg/kg. Neither pinealectomy, which is known to stimulate food intake, nor treatment with melatonin, which depresses intake, interacted with the effects of cyproheptadine on food intake, showing that its effect is not mediated by the pineal gland.


Treatment with modified intravesical oxybutynin chloride for neurogenic bladder in children.
We have previously reported that intravesical oxybutynin chloride with hydroxypropylcellulose (modified intravesical oxybutynin) is an effective therapeutic agent for patients with detrusor overactivity. In this study, we report on the efficacy, safety and side effects of modified intravesical oxybutynin administration in children with neurogenic bladder. Modified intravesical oxybutynin (1.25mg/5 mL, twice a day) was administered to four children (three males and one female) with neurogenic bladder (detrusor overactivity and/or low compliance bladder), who were previously unresponsive to or experienced intolerable side effects from oral medications. A cystometrogram was obtained before, 1 week after, and 1 year after the first intravesical instillation of modified oxybutynin. We also carefully observed anticholinergic side effects, occurrence of urinary tract infection and degree of incontinence during this treatment. After 1 week, both cystometric bladder capacity and compliance were improved in all patients, and detrusor overactivity was undetectable in three of four patients. At 1 year, there was further improvement in bladder compliance in three patients, and detrusor overactivity was not observed in two patients. Significant improvement in the degree of incontinence was achieved. No systemic anticholinergic side effects were observed in any of the patients. One patient with vesicoureteral reflux discontinued the therapy after 2 months due to upper urinary tract infections. Modified intravesical oxybutynin is an effective and relatively safe therapeutic option for children with neurogenic bladders.


Does Alzheimer's disease stem in the gastrointestinal system?
Over the last decades, our knowledge of the key pathogenic mechanisms of Alzheimer's disease (AD) has dramatically improved. Regarding the limitation of current therapeutic strategies for the treatment of multifactorial diseases, such as AD, to be translated into the clinic, there is a growing trend in research to identify risk factors associated with the onset and progression of AD. Here, we review the current literature with a focus on the relationship between gastrointestinal (GI)/liver diseases during the lifespan and the incidence of AD, and discuss the possible mechanisms underlying the link between the diseases. We also aim to review studies evaluating the possible link between the chronic use of the most common GI medications and the future risk of AD development.


Nursing responsibilities and social justice: an analysis in support of disciplinary goals.
Social justice is asserted as a responsibility of the nursing profession. However, a reliable conception of social justice that can undergird practice, research, education, and policy endeavors has proved elusive. We discuss this as a problem for the profession and propose Powers and Faden's model of social justice as useful for nursing purposes because of its focus on exploring and rectifying underlying causes of injustice as they lie within the fabric of society. Their model asserts 6 essential dimensions of well-being as universal human needs. These dimensions are interrelated and nonhierarchical. A serious deficiency in any one affects other dimensions and interferes with the ability to experience "a minimally decent life." The model is applied to the problem of child abuse and the effects of its aftermath on well-being as an example of its potential for structuring nursing knowledge development, practice, and policy initiatives.


Promoter RNA sequencing (PRSeq) for the massive and quantitative promoter analysis in vitro.
Analysis of promoter strength and specificity is important for understanding and engineering gene regulation. Here, we report an in vitro promoter analysis method that can achieve both massiveness and quantitativeness. In this approach, a pool of single-stranded DNA with a partially randomized promoter sequence to be analyzed is chemically synthesized. Through enzymatic reactions, the randomized sequence will be copied to the downstream region, resulting in a template DNA pool that carries its own promoter information on its transcribed region. After in vitro transcription of the DNA pool with an RNA polymerase of interest, the sequences of the resulting transcripts will be analyzed. Since the promoter strength linearly correlates to the copy number of transcript, the strength of each promoter sequence can be evaluated. A model experiment of T7 promoter variants demonstrated the quantitativeness of the method, and the method was applied for the analysis of the promoter of cyanophage Syn5 RNA polymerase. This method provides a powerful approach for analyzing the complexity of promoter specificity and discrimination for highly abundant and often redundant alternative sigma factors such as the extracellular function (ECF) sigma factors.


Effect of dopamine content in rat brain striatum on anesthetic requirement: an in vivo microdialysis study.
This study investigated the changes in anesthetic requirement caused by administration of two different concentrations (0.1 microM and 1. 0 microM/h) of dopamine into the rat striatum. During the measurement of minimum alveolar concentration (MAC), each dopamine solution was continuously injected directly into rat striatum by microdialysis technique. During perfusion of the lower dose, MAC did not change. During the higher dose of dopamine, MAC decreased by approximately 30%.


Sono-intercalation of CdS nanoparticles into the layers of titanate facilitates the sunlight degradation of Congo red.
In this paper, the degradation of Congo red (CR) as a dye was investigated by a new synthetic photocatalyst. The synthesis was done through the intercalation of CdS in the layers of titanate (K2Ti4O9) by the assistance of ultrasound. The photocatalyst was prepared via ion-exchange reaction and sulfuration processes in the presence of ultrasonic irradiation. The samples were characterized by the field emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), ultraviolet-visible spectra (UV-Vis), and Fourier transform infrared spectroscopy (FTIR). The deposition of CdS nanoparticles on the surface and between the spaces of titanate layers led to the shift of absorption edge of titanate to the visible light region. The photocatalytic degradation mechanism of CR has been evaluated through the addition of some scavengers to the solution. In addition, the stability and reusability of the catalyst were examined in this work too.


Structure and properties of Ti-7.5Mo-xFe alloys.
The present work is a study of a series of Ti-7.5Mo-xFe alloys, with the focus on the effect of iron addition on the structure and mechanical properties of the alloys. Experimental results indicate that alpha" phase-dominated binary Ti-7.5Mo alloy exhibited a fine, acicular martensitic structure. When 1 wt% or more iron was added, the entire alloy became equi-axed beta phase structure with a grain size decreasing with increasing iron content. A thermal omega phase was formed in the alloys containing iron of roughly between 0.5 and 3 wt%. The largest quantity of omega phase and highest microhardness were found in Ti-7.5Mo-1Fe alloy. The binary Ti 7.5Mo alloy had a lower microhardness, bending strength and modulus than all iron-containing alloys. The largest bending strength was found in Ti-7.5Mo-2Fe alloy. The present alloys with iron contents of about 2-5 wt% seem to have a great potential for use as an implant material.


Presence of microtubule-associated protein 2 in chromaffin cells.
We have examined bovine adrenal chromaffin cells in culture for the presence of the microtubule-associated protein 2. Chromaffin cells could be identified in culture on the basis of their staining with antibodies directed against secretory granule proteins. Using immunoperoxidase staining microtubule-associated protein 2 immunoreactivity was demonstrated to be present in chromaffin cells but not fibroblasts in culture. Microtubule-associated protein 2 immunoreactivity was present in the cell body, processes and varicosities of the chromaffin cells. Microtubule-associated protein 2 polypeptides were shown to be present in an adrenal medullary homogenate but not chromaffin granule membranes by immunoblotting. The results indicate that the neuronal cytoskeletal polypeptide microtubule-associated protein 2 is present in adrenal chromaffin cells. The presence of microtubule-associated protein 2 in both neurons and chromaffin cells may be related to their common embryonic origin.


A systematic review and meta-analysis of low back pain and its associated factors among school teachers in Africa.
Low back pain (LBP) is a key social, economic, and public health problem in the world. The impact of LBP is given less priority and is empirically unrepresented in low- and middle-income countries as a result of the focus on more pressing and life-threatening health issues, including infectious diseases. In Africa, the prevalence of LBP is irregular and increasing among schoolteachers on account of teaching activities performed under suboptimal working conditions. Therefore, the objective of this review was to estimate the pooled prevalence and associated factors of LBP among school teachers in Africa. This systematic review and meta-analysis was designed based on the PRISMA guidelines. A comprehensive systematic literature search focused on LBP in African school teachers was conducted using the PubMed/MEDLINE, CINAHL, and CABI databases, regardless of publication timelines, from October 20 to December 3, 2022. In addition, gray literature was searched using Google Scholar and Google Search. Data were extracted in Microsoft Excel by using the JBI data extraction checklist. The overall effect of LBP was estimated using a random effect model via DerSimonian-Laird weights. The pooled prevalence and odds ratio of associated factors with 95% CI were computed using STATA 14/SE software. The I2 test and Egger's regression test were used to assess heterogeneity and publication bias, respectively. A total of 585 articles were retrieved, and 11 eligible studies involving a total of 5,805 school teachers were included in this systematic review and meta-analysis. The overall estimated pooled prevalence of LBP in African school teachers was found to be 59.0% (95% CI: 52.0%-65.0%). Being female [POR: 1.53; 95% CI (1.19, 1.98)], being older [POR: 1.58; 95% CI (1.04, 2.40)], being physically inactive [POR: 1.92; 95% CI (1.04, 3.52)], having sleep problems [POR: 2.03; 95% CI (1.19, 3.44)] and having a history of injury [POR: 1.92; 95% CI (1.67, 2.21)] were factors significantly associated with LBP. The pooled prevalence of LBP was high among school teachers in Africa compared to developed nations. Sex (female), older age, physical inactivity, sleep problems, and a history of previous injury were predictors of LBP. It is suggested that policymakers and administrators ought to gain awareness of LBP and its risk factors to put existing LBP preventive and control measures into action. Prophylactic management and therapeutic strategies for people with LBP should also be endorsed.


Aesthetics and power considerations in multiple testing--a contradiction?
In this paper we discuss aesthetical concepts and requirements for reasonable multiple test procedures. Aesthetical considerations lead to logical decision patterns which are conceivable and, if possible, simple to use and to communicate. Such considerations are sometimes contradictory to the ubiquitous requirement of maximizing power for a multiple test procedure. We illustrate the necessary trade-offs with several examples. We start by considering important logical properties and then discuss three different concepts of monotonicity. Afterwards we have a closer look at the recently proposed "fallback procedure" and show that it has some less appealing properties. Finally, we investigate the distribution of the numbers of significant results with respect to both expectation and variance.


Are zinc levels in seminal plasma associated with seminal leukocytes and other determinants of semen quality?
To evaluate a potential association of zinc levels with seminal leukocytes, the outcome of semen cultures; and semen quality and sperm fertilizing capacity. Prospective study. Outpatient infertility clinic of a university hospital. Two hundred fifty-six randomly chosen asymptomatic males from subfertile couples. None. Determination of zinc in seminal plasma by flame atomic absorption spectroscopy. In aliquots of the same ejaculates the following tests were performed: immunocytochemical round cell differentiation to determine leukocyte counts and ratios, microbial screening, and comprehensive evaluation of semen quality (sperm analysis, biochemical parameters, antisperm antibody testing, and in vitro examination of sperm ability to penetrate cervical mucus). The patients underwent medical history, clinical examination, and postcoital testing. Subsequent fertility was determined (controlled for female infertility factors). The concentration of zinc in seminal plasma did not correlate in a statistically significant way with leukocytes in semen, nor was it associated with bacterial colonization. There was no statistically significant relationship of zinc in seminal plasma or serum with semen quality parameters nor with local antisperm antibody testing of the IgG or IgA class. Zinc levels did not influence sperm capacity to penetrate cervical mucus in vitro or in vivo, and did not affect subsequent fertility. The zinc level in seminal fluid and serum is not associated with silent male genital tract infection (indicated by seminal leukocytes); nor is it related to semen cultures in asymptomatic individuals. The lack of association with other semen quality parameters indicates that the routine determination of zinc levels during infertility investigation is not recommended.


The long-term urological response of neonates with myelodysplasia treated proactively with intermittent catheterization and anticholinergic therapy.
Urinary tract management in children with myelodysplasia is controversial. Some advocate observation alone, while others believe that the prophylactic institution of intermittent catheterization and anticholinergic therapy may help to prevent deterioration. A nonrandomized prospective study was instituted to compare the urological outcomes of a cohort of children who were at risk for urological deterioration on the basis of bladder-sphincter dyssynergia and/or high filling or voiding pressures. Those at risk were observed until deterioration occurred, or were placed on prophylactic intermittent catheterization with or without anticholinergic medication. Of 44 children at risk 35 followed by observation alone had urinary tract deterioration, whereas only 3 of 20 at risk treated with prophylactic intermittent catheterization had deterioration with time. Proactive bladder treatment significantly reduced the incidence of upper urinary tract deterioration and need for surgical intervention.


Linear-dendritic block copolymer for drug and gene delivery.
Dendrimers as a new class of polymeric materials have a highly ordered branched structure, exact molecular weight, multivalency and available internal cavities, which make them extensively used in biology and drug-delivery. Concurrent with the development of dendrimers, much more attention is drawn to a novel block copolymer which combines linear chains with dendritic macromolecules, the linear-dendritic block copolymer (LDBC). Because of the different solubility of the contrasting regions, the amphiphilic LDBCs could self-assemble to form aggregates with special core-shell structures which exhibit excellent properties different from traditional micelles, such as lower critical micelle concentration, prolonged circulation in the bloodstream, better biocompatibility, and lower toxicity. The present review briefly describes the type of LDBC, the self-assembly behavior in solution, and the application in delivery system including the application as drug carriers and gene vectors. The interactions between block copolymers and drugs are also summarized to better understand the release mechanism of drugs from the linear-dendritic block copolymers.


Inhibition of cyclooxygenase-independent platelet aggregation by low vitamin E concentration.
Platelet aggregation induced by threshold concentrations of agonists such as collagen, PAF or epinephrine was inhibited in vitro by 100 microM aspirin but was restored by stimulating platelets with high concentrations of collagen, PAF or by a combination of epinephrine and PAF. Incubating aspirin-treated platelets with 50-100 microM vitamin E or vitamin E acetate inhibited platelet aggregation by high concentrations of collagen and PAF and by the combination of epinephrine and PAF; platelet thromboxane A2 formation was less than 10% in samples incubated with 100 microM aspirin. Apyrase, added to aspirin-treated platelet, did not influence platelet aggregation induced by epinephrine and PAF. The present study suggests that concentrations of vitamin E as low as 50-100 microM inhibit cyclooxygenase-independent platelet aggregation when combined with an inhibitor of the arachidonate pathway.


An early appraisal of the methods of tissue expansion and the transverse rectus abdominis musculocutaneous flap in reconstruction of the breast following mastectomy.
In a 2-year prospective study, the results of two methods of breast reconstruction were compared. The tissue expansion and implant method was found to offer an acceptable reconstruction, but it was associated with a high rate of complications and revisions. The transverse rectus abdominis musculocutaneous flap reconstruction provided a more satisfactory reconstruction, with fewer major complications as well as a higher degree of patient satisfaction and less patient dissatisfaction. The present study does not address the long-term results of either procedure.


TRP channel antagonists as potential antitussives.
Cough is a troublesome symptom associated with many respiratory diseases. In some instances cough can become prolonged and excessive, and chronic cough of various aetiologies is a common presentation to specialist respiratory clinics. However, current treatment options are limited. Despite its importance, our understanding of the mechanisms that provoke cough is poor. Recent investigation has focused on the interaction between G-protein-coupled receptors and ion channels expressed on airway sensory nerves that are responsible for driving the cough reflex. In particular, the Transient Receptor Potential class of ion channels appears to play a major role as a regulator of the afferent arm of the cough reflex and could be involved in the heightened cough response observed in disease states. Current research investigating the pathogenesis of cough supports the development of TRP channel inhibitors as novel and selective treatment modalities.


Development and content validation of a surgical safety checklist for operating theatres that use robotic technology.
To identify and assess potential hazards in robot-assisted urological surgery. To develop a comprehensive checklist to be used in operating theatres with robotic technology. Healthcare Failure Mode and Effects Analysis (HFMEA), a risk assessment tool, was used in a urology operating theatre with innovative robotic technology in a UK teaching hospital between June and December 2011. A 15-member multidisciplinary team identified 'failure modes' through process mapping and flow diagrams. Potential hazards were rated according to severity and frequency and scored using a 'hazard score matrix'. All hazards scoring ≥8 were considered for 'decision tree' analysis, which produced a list of hazards to be included in a surgical safety checklist. Process mapping highlighted three main phases: the anaesthesia phase, the operating phase and the postoperative handover to recovery phase. A total of 51 failure modes were identified, 61% of which had a hazard score ≥8. A total of 22 hazards were finalised via decision tree analysis and were included in the checklist. The focus was on hazards specific to robotic urological procedures such as patient positioning (hazard score 12), port placement (hazard score 9) and robot docking/de-docking (hazard score 12). HFMEA identified hazards in an operating theatre with innovative robotic technologies which has led to the development of a surgical safety checklist. Further work will involve validation and implementation of the checklist.


Clinical reporting of radiographs by radiographers: Policy and practice guidance for regional imaging networks.
Radiographer reporting is an essential component of imaging across the United Kingdom. Since the previous policy and practice guidance in 2004 the role and contribution of reporting radiographers has changed significantly. The move to imaging networks further reinforces the need for consistency in scope of practice and clinical governance for radiographer reporting. This guidance provides a consistent, evidence-based template for planning a reporting service, resourcing, clinical governance, preceptorship, volume and frequency of reporting, a peer learning framework and expected standards. Developed for North Central and East London, this framework and standards will help reduce unwarranted variation. Consistency in practice could help maximise the contribution of radiographer reporting.


Bioactivities of water-soluble polysaccharides from Jisongrong mushroom: anti-breast carcinoma cell and antioxidant potential.
Polysaccharides were extracted from Jisongrong mushroom. Jisongrong polysaccharides was a water-soluble compound. Its molecular weight was about 7.4×10(4) Da. HPLC analysis showed that this polysaccharides was composed of mannose, ribose, rhamnose, glucose, xylose, galactose and arabinose in the molar contents of 3.3, 17.3, 6.0, 12.4, 98.4 and 2.1 μM, respectively. In the range of 2800-3500 cm(-1), peaks at 2958 and 3407 cm(-1) belonging to -C-H of -CH2 groups, were observed in polysaccharides. When Jisongrong polysaccharides were orally administrated to rats for 2 months, level of lipid peroxidation products and activities of antioxidant enzymes in the blood were significantly decreased and enhanced compared to control rats. Moreover, Jisongrong polysaccharides still markedly inhibited cancer cells proliferation. These results suggested that Jisongrong polysaccharides possess a strong antioxidant and antitumour activities.


Enzymatic hydrolysis of fractionated products from oils thermally oxidized in the laboratory.
Enzymatic hydrolysis of the acylglycerol products obtained from thermally oxidized vegetable oils was studied. Corn, sunflower and soybean oils were heated in the laboratory at 180 C for 50, 70 and 100 hr with aeration and directly fractionated by silicic acid column chromatography. By successive elution with 20%, then 60% isopropyl ether in n-hexane, and diethyl ether, the thermally oxidized oils were separated into three fractions: the nonpolar fraction (monomeric compounds), slightly polar fraction (dimeric compounds), and polar fraction comprising oligomeric compounds. Enzymatic hydrolysis with pancreatic lipase showed that the monomers were hydrolyzed as rapidly as the corresponding unheated oils, the dimers much more slowly, and the oligomeric compounds barely at all. Overall, the hydrolysis of the dimers was less than 23% of that for the monomers, with small differences among the oils. Longer heating periods resulted in greater reductions in hydrolysis of the dimeric compounds. These results suggest that the degree of enzymatic hydrolysis of the fractionated acylglycerol compounds is related to differences in the thermal oxidative deterioration, and amounts of polar compounds in the products.


Association between cholesterol and 2,3-diphosphoglycerate in genetically selected hooded rat lines.
We have developed two strains of hooded rats with differing erythrocyte oxygen affinities by selection on red cell 2,3-diphosphoglycerate levels. Genetic studies have shown that these strains differ at one DPG-level-determining locus. This article reports the results of a study which involved measurement of plasma cholesterol levels in rats from the strains and the F2 progeny of strain intercrosses. Low-DPG strain rats, with high oxygen affinity, had significantly higher mean cholesterol levels than High-DPG rats. Animals from the extremes of the F2 distribution of DPG levels showed similar, significantly different mean cholesterol levels, indicating that the negative association between DPG and cholesterol levels in strain rats was not due to inadvertent fixation of unrelated genes during selection on DPG. The possibility is discussed that high oxygen affinity, brought about by low DPG levels, may be causative in increasing cholesterol levels.


Synthesis and antineoplastic activity of ethylene glycol phenyl aminoethyl ether derivatives as FOXM1 inhibitors.
FOXM1 signalling pathways are highly expressed in multiple human cancers. Based on the crystal structure of the FOXM1 DNA binding domain, our preliminary research found ethylene glycol (4-benzyloxyphenyl) cyclopentylaminoethyl ether XST20, which could inhibit ovarian cancer cell proliferation and showed a medium affinity for the truncated protein FOXM1. This study intended to develop a FOXM1 inhibitor with stronger affinity and higher efficiency to be utilized as a molecular tool and drug candidate. We evaluated the optimization direction through molecular docking and systematically modified the structure of XST20. A novel class of ethylene glycol phenyl aminoethyl ether derivatives were synthesized, their anticancer activity and mechanism were evaluated, and the structure-activity relationship was summarized. Compound S2 showed a stronger affinity for FOXM1 and improved its activity with a broad-spectrum anticancer effect. S2 displayed selective antiproliferative activity against cancer cells with high expression levels of FOXM1 proteins. S2 should be a good chemobiological tool and a potential leading compound for future studies of anticancer drugs targeting FOXM1.


Therapeutic Potential of Combinative shRNA-Encoded Lentivirus-Mediated Gene Silencing to Accelerate Somatosensory Recovery After Spinal Cord Trauma.
Neuropathic pain following spinal cord injury (SCI) remains a difficult problem that affects more than 80% of SCI patients. Growing evidence indicates that neuroinflammatory responses play a key role in neuropathic pain after SCI. Short hairpin RNA (shRNA) interference is an efficient tool for the knockdown of disease-related specific gene expression after SCI, yet insufficient data is available to establish guidelines. In this study, we have constructed the transient receptor potential ankyrin 1 (TRPA1) shRNA encoded-lentiviral vector (LV-shTRPA1) and P38 MAPK shRNA encoded-lentiviral vector (LV-shP38) to investigate the silencing effects of shRNAs and their ability to reprogram the neuroinflammatory responses, thereby enhancing somatosensory recovery after SCI. Our in vitro data employing HEK293-FT and activated macrophages demonstrated that delivered LV-shRNAs showed high transduction efficacy with no cytotoxicity. Furthermore, a combination of LV-shP38 and LV-shTRPA1 was found to be most effective at suppressing target genes, cutting the expression of pro-inflammatory and pro-nociceptive factors in the dorsal horn of the spinal cord and dorsal root ganglia, thus contributing to the alleviation of neuronal hypersensitivities after SCI. Overall, our data demonstrated that the combination LV-shP38/shTRPA1 produced a synergistic effect for immunomodulation and reduced neuropathic pain with a favorable risk-to-benefit ratio. Collectively, our LV-mediated shRNA delivery will provide an efficient tool for gene silencing therapeutic approaches to treat various incurable disorders.


Nonextraction treatment of Class II, Division 1 malocclusions.
Nonextraction treatment of three different types of Class II, Division 1 malocclusions that focused on solving the imbalances of the dentofacial configuration have been presented. Diagnostic features encountered were anterior alveolar hyperplasia that required simultaneous maxillary incisor intrusion and retraction, severe mandibular crowding requiring functional alveolar arch development, and maxillary prognathism requiring distal movement of the maxilla and incisor retraction. Since many factors contribute to the makeup of various types of Class II, Division 1 malocclusions, orthodontic mechanics should address the specific needs of each patient.


Purification of the mRNAs encoding the subunits of larval serum proteins 1 and 2 of Drosophila melanogaster.
The messenger RNAs for the four subunits of larval serum proteins (LSPs) 1 and 2 were purified from third instar fat body total RNA by fractionating oligo(dT)-selected RNAs on the basis of size. Translations of RNA fractions in vitro showed that the LSP mRNAs were free of other fat body messenger activities, but they could not be completely resolved from each other. The molecular weights of the LSP mRNAs, estimated from their electrophoretic mobilities in 50% formamide/1.4% agarose gels, ranged from 1.0 X 10(6) to 1.35 X 10(6). These estimates are at least 20% larger than the size of RNA necessary to encode each LSP polypeptide.


Two Blood Monocytic Biomarkers (CCL15 and p21) Combined with the Mini-Mental State Examination Discriminate Alzheimer's Disease Patients from Healthy Subjects.
Alzheimer's disease (AD) is a progressive neurodegenerative disorder. In AD, monocytes migrate across the blood-brain barrier and differentiate into microglia, are linked to inflammatory responses and display age-dependent decreases in telomere lengths. Six monocyte-specific chemokines and the (telomere-associated) tumor suppressor proteins p53 and p21 were determined by multiplex immunoassay in plasma and monocyte extracts of patients with AD or mild cognitive impairment, and levels were compared between patients and controls (without cognitive impairment). CCL15 (macrophage inflammatory protein-1δ), CXCL9 (monokine-induced by interferon-γ) and p21 levels were decreased in monocytes of AD patients compared with controls. The combination of monocytic CCL15 and p21 together with the Mini-Mental State Examination enables to differentiate AD patients from controls with high specificity and sensitivity.


Cholesterol 25-hydroxylase suppresses SARS-CoV-2 replication by blocking membrane fusion.
Cholesterol 25-hydroxylase (CH25H) is an interferon (IFN)-stimulated gene that shows broad antiviral activities against a wide range of enveloped viruses. Here, using an IFN-stimulated gene screen against vesicular stomatitis virus (VSV)-SARS-CoV and VSV-SARS-CoV-2 chimeric viruses, we identified CH25H and its enzymatic product 25-hydroxycholesterol (25HC) as potent inhibitors of SARS-CoV-2 replication. Internalized 25HC accumulates in the late endosomes and potentially restricts SARS-CoV-2 spike protein catalyzed membrane fusion via blockade of cholesterol export. Our results highlight one of the possible antiviral mechanisms of 25HC and provide the molecular basis for its therapeutic development.


The New Zealand white rabbit animal model of acute radiation syndrome: hematopoietic and coagulation-based parameters by radiation dose following supportive care.
Animal models that accurately reflect human responses to radiation injury are needed for advanced mechanistic investigation and development of effective therapeutics. The rabbit is an established animal model accepted by the FDA for studies of cardiovascular disease, lipid metabolism, the development of anticoagulants, testing of bone implants, and the development of treatments for infectious diseases such as HIV. The purpose of this study was to investigate the New Zealand White (NZW) Rabbit model as a model of acute radiation exposure because of its established similarity to human vascular, immune, and coagulation responses. Two sequential studies were performed in a total of 81 male NZW rabbits, 16-20 weeks of age. All animals underwent clinical observations and peripheral blood analyses following a single dose of 0, 6, 7, 8, 8.5, 9, or 10 Gy of total body irradiation via a 6 MV Linear accelerator photon source on day 0. Animals were treated with timed release fentanyl patch (days 0-30), subcutaneous hydration (day 1, Study 2 only), and oral sulfamethoxazole/trimethoprim 30 mg/kg once daily (days 3-30) and were followed for 30 days or to time of mortality. Study 1 revealed the estimated LD30, -50, -70, and -90 with 95% confidence intervals (CI) at 30 days to be 6.7 (CI: 5.9-7.4), 7.3 (CI: 6.7-7.8), 7.9 (CI: 7.3-8.4), and 8.8 (CI: 7.9-9.7) Gy, respectively. In study 2, a survey of blood coagulation and biochemical parameters were performed over time and necropsy. Complete blood counts taken from animals exposed to 7, 8, or 10 Gy, demonstrated dose-dependent depletion of lymphocytes, neutrophils, and platelets. Platelet counts recovered to baseline levels in survivors by day 30, whereas lymphocyte and neutrophil counts did not. Decedent animals demonstrated grade 3 or 4 neutropenia and lymphopenia at time of death; 64% of the decedents experienced a 30% or greater drop in hematocrit. Decedent animals demonstrated more than 100% increases from serum baseline levels of blood urea nitrogen, creatinine, aspartate aminotransferase, and triglyceride levels at the time of death whereas survivors on average demonstrated modest or no elevation. This NZW rabbit model demonstrates dose-dependent depletion of hematopoietic parameters. The LD50/30 of 7.8 Gy (95% CI: 6.6-8.4) with supportive care appears to be close to the ranges reported for rhesus macaques (5.25-7.44 Gy) and humans (6-8 Gy) with supportive care. These findings support the utility of the NZW rabbit model for further mechanistic investigation of acute radiation exposure and medical countermeasure testing.


Bronchocutaneous fistula after chest-tube placement: A rare complication of tube thoracostomy.
Bronchocutaneous fistula is a pathologic communication between the bronchus, pleural space, and subcutaneous tissue. It can occur as a complication of positive pressure ventilation and pneumonectomy. Diagnosis is made by imaging studies. Treatment options are endoscopic repair, parietal pleurectomy, and pleurodesis. Our patient is a 53-year-old woman who had a difficult chest-tube placement for complicated parapneumonic effusion. Computed tomography scan revealed a fistulous tract from the bronchus to the skin at the site of the original chest tube, and chest x-ray film revealed a subcutaneous fistulous air tract in the lateral chest. It is usually an acquired condition; congenital bronchocutaneous fistula is rare. We report a case of bronchocutaneous fistula after chest-tube placement.


Tissue reactions around a hydroxyapatite-coated hip prosthesis. Case report of a retrieved specimen.
Bone reactions were studied around a titanium, hydroxyapatite (HA)-coated Osteonics (Allendale, NJ) bipolar hip prosthesis, which was revised for severe midthigh pain 4 years after implantation. Inspection of the retrieved prosthesis using a dissecting microscope revealed scarce remnants of a coating-like material on the surface of the prosthesis; however, histology of this layer and histology of the bony side of the bone--HA interface failed to reveal any remnants of an HA coating. The interface was covered predominantly by trabecular bone, which closely followed the contour of the prosthesis, and was partly woven nonmineralized bone. At locations where mineralized bone faced the prosthesis, many small dark titanium wear particles were found. Similar particles were found in macrophages in the intertrabecular medullary space. Polyethylene wear particles were specifically located in macrophages in a soft tissue interface at more distal levels along the stem of the prosthesis. Although the observations presented in this case cannot be generalized, it clearly shows that the HA coating layer had completely disappeared after 4 years. More detailed retrieval studies and longer clinical follow-up studies are needed before a final evaluation of the behavior of HA coatings and long-term fixation of HA-coated prostheses can be made.


Fundamentals and applications of needle trap devices: a critical review.
The needle trap device (NTD) is an extraction trap that contains a sorbent inside a small needle, through which fluid can be actively drawn into and out of by a gas-tight syringe or pump, or analytes can be introduced passively to the trap by diffusion. The needle trap (NT) is a potentially solventless sampling technique/sample preparation and introduction device. Both fluid-borne analytes and particles can be trapped inside the needle and then adsorbed analytes are desorbed in an inlet of analytical instrument and introduced for identification and quantification. The fluid may be either gaseous or liquid. The objectives of this critical review are to summarize the theory of the sampling process for both active and passive time-average extraction modes in addition to outlining the evolution of the technology and main applications.


Evaluation of different extraction procedures for determination of organic Mercury species in petroleum by high performance liquid chromatography coupled with cold vapor atomic fluorescence spectrometry.
An extraction procedure for extracting organic mercury species including methylmercury (MeHg) and ethylmercury (EtHg) from petroleum samples was developed. Three extraction methods (shaking, ultrasonic and microwave assisted extraction) using different extraction solvents (TMAH, KOH/CH3OH, HCl and acidic CuSO4/KBr) were investigated by comparing the extraction efficiency of the organic mercury species. Microwave assisted extraction at 60 W for 5 min using TMAH (tetramethylammonium hydroxide, 25%, m/v) provided the most satisfactory extraction efficiency for MeHg and EtHg in petroleum at 86.7% ± 3.4% and 70.6% ± 5.9%, respectively. Speciation analysis of mercury was done by on-line coupling of high performance liquid chromatography with cold vapor generation atomic fluorescence spectrometry (HPLC-CV-AFS). The proposed method was successfully applied to analyze several crude oil and light oil samples. The concentrations of MeHg ranged from under detection limit to 0.515 ng g(-1), whereas EtHg was not detected in the samples. This method can be a very useful tool in evaluating the risk of mercury emissions from petroleum.


Serum complexes of insulin-like growth factor-1 modulate skeletal integrity and carbohydrate metabolism.
Serum insulin-like growth factor (IGF) -1 is secreted mainly by the liver and circulates bound to IGF-binding proteins (IGFBPs), either as binary complexes or ternary complexes with IGFBP-3 or IGFBP-5 and an acid-labile subunit (ALS). The purpose of this study was to genetically dissect the role of IGF-1 circulatory complexes in somatic growth, skeletal integrity, and metabolism. Phenotypic comparisons of controls and four mouse lines with genetic IGF-1 deficits-liver-specific IGF-1 deficiency (LID), ALS knockout (ALSKO), IGFBP-3 (BP3) knockout, and a triply deficient LID/ALSKO/BP3 line-produced several novel findings. 1) All deficient strains had decreased serum IGF-1 levels, but this neither predicted growth potential or skeletal integrity nor defined growth hormone secretion or metabolic abnormalities. 2) IGF-1 deficiency affected development of both cortical and trabecular bone differently, effects apparently dependent on the presence of different circulating IGF-1 complexes. 3) IGFBP-3 deficiency resulted in increased linear growth. In summary, each IGF-1 complex constituent appears to play a distinct role in determining skeletal phenotype, with different effects on cortical and trabecular bone compartments.