Expression and characterization of recombinant mouse mastocytoma histidine decarboxylase.
The possibility of post-translational processing of mouse mastocytoma histidine decarboxylase (HDC; EC 22.214.171.124) was investigated. The molecular mass of the recombinant HDC expressed in Sf9 cells using HDC cDNA from mouse mastocytoma cells was determined to be 74 kDa by SDS-PAGE. In contrast to the native HDC from mastocytoma cells, the recombinant 74 kDa HDC was essentially inactive and precipitable in Sf9 cells. On the other hand, deletion mutants of the recombinant HDC lacking a C-terminal region equivalent to 10 (64 kDa) or 20 kDa (54 kDa) in size were present as active forms in the soluble fraction of Sf9 cells. To examine the C-terminal deletion of the 74 kDa species yielding the 53 kDa species by means of the immunoblotting analysis, two peptides (corresponding to residues 323-337 and 572-586 of the recombinant 74 kDa HDC peptide) were synthesized, and rabbit antiserum specific for each peptide was prepared. On immunoblotting analysis, anti-peptide 323-337 antiserum recognized both the recombinant 74 kDa and native enzyme subunit peptides, but anti-peptide 572-586 antiserum recognized only the recombinant 74 kDa peptide, i.e., not the native enzyme subunit peptide. Furthermore, HDC activity in the crude extract from Sf9 cells was not precipitable with antipeptide 572-585 antiserum. These results strongly suggest that the 53 kDa subunit peptide of native mastocytoma HDC is derived from the unidentified inactive 74 kDa HDC peptide, probably by post-translational processing of HDC in its C-terminal region.


Structural Brain Volumes of Individuals at Clinical High Risk for Psychosis: A Meta-analysis.
Structural magnetic resonance imaging studies in individuals at clinical high risk (CHR) for psychosis have yielded conflicting results. The aims of this study were to compare intracranial and structural brain volumes and variability of CHR individuals with those of healthy control (HC) subjects and to investigate brain volume differences and variability in CHR subjects with and without transition to psychosis. The PubMed and Embase databases were searched for relevant studies published before June 1, 2020. A total of 34 studies were deemed eligible, which included baseline data of 2111 CHR and 1472 HC participants. In addition, data were included for 401 CHR subjects who subsequently transitioned to psychosis and 1023 nontransitioned CHR participants. Whole-brain and left, right, and bilateral hippocampal volume were significantly smaller in CHR subjects than in HC subjects. Cerebrospinal fluid and lateral ventricle volumes were significantly larger in CHR subjects than in HC subjects. Variability was not significantly different in CHR subjects compared with HC subjects. CHR individuals with and without subsequent transition to psychosis did not show significant differences in any of the volumetric assessments or in variability. This meta-analysis demonstrates reduced whole-brain and hippocampal volumes and increased cerebrospinal fluid and lateral ventricle volumes in CHR individuals. However, no significant differences were observed in any of the volumetric assessments between CHR individuals with and without subsequent transition to psychosis. These findings suggest that although structural brain alterations are present before the onset of the disorder, they may not significantly contribute to the identification of CHR individuals at the highest risk for the development of psychosis.


Second Cancers in Classical Hodgkin Lymphoma and Diffuse Large B-Cell Lymphoma: A Systematic Review by the Fondazione Italiana Linfomi.
The increase of lymphoma patient survival led to a modification of the incidence of long-term sequelae, including second malignancies (SM). Several groups have dealt with the incidence of SM, according to the primary treatment; however, a standardized approach for the early detection and screening of SM in the population of lymphoma survivors should be implemented. A systematic review was conducted by Fondazione Italiana Linfomi (FIL), in order to define the incidence of SM, the impact of modern radiotherapy on SM risk, and the usefulness of tailored follow-up and screening strategies for early diagnosis of SM. Classical Hodgkin lymphoma (cHL) and diffuse large B-cell lymphoma (DLBCL) survivors were investigated. The MEDLINE, Embase, and Cochrane Library databases were checked for relevant reports published up to January 2020. The selection process was reported according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. A total of 27 full-text manuscripts resulted as eligible for the analysis. The incidence of SM in cHL patients treated with ABVD was higher compared to the general population and was even higher in patients treated with intensified regimens. The risk increased over time, as well as after 10-15 years from therapy, and was augmented by radiotherapy exposure. In DLBCL, more intensive regimens (i.e., R-CHOEP or R-MegaCHOEP) vs. R-CHOP were associated with a higher SM incidence. Salvage chemotherapy and autologous stem cell transplants increased the risk of SM in both cHL and DLBCL cohorts. A lower incidence of SM, particularly of breast cancer (BC), was shown in cohorts of cHL survivors treated with reduced radiation volumes and doses (involved fields vs. extended fields), but robust trials are still lacking. Considering the advantage of a structured screening for early detection of SM, all the included studies regarded cHL survivors and screening strategy for early BC detection. Moreover, the authors discuss additional papers, to guide the early diagnosis of lung, colorectal, skin, and thyroid cancer in patients at risk due to family history, drug or RT exposure, or unhealthy lifestyles. These screening strategies all passed through patient awareness. A modern approach to chemotherapy and radiotherapy led to a lower risk of SM, which should be confirmed over time. Early detection of secondary cancers could be achieved through a tailored screening program, according to the individual risk profile.


Variability of predicted propofol concentrations and measured sevoflurane concentrations during general anaesthesia: a single-centre retrospective cohort study.
Variability is high in predicted propofol concentrations during clinical anaesthesia titrated by target-controlled infusion (TCI) to maintain a processed EEG parameter (bispectral index [BIS]) within a specified range. We have shown that the potential for improving the pharmacokinetic model is minimal. The drug titration paradox revealed that titration challenges the classical relationship between drug dose and effect in both individuals and the population. We hypothesised that dynamic factors during surgery beyond the static genetic, epigenetic, and other factors such as age, height, and weight affect the necessary dose. We compared the variability of measured end-tidal sevoflurane concentrations with predicted effect-site propofol concentrations when titrated to a BIS range of 40-60, with the hypothesis that the variability in measured sevoflurane concentrations would not be less than the variability in estimated propofol concentrations. Clinical data from 2280 surgical procedures >1 h in duration were included in the analysis. Anaesthesia with sevoflurane or propofol was based on an institutional protocol. The titration performance for both drugs was assessed by comparing BIS values 30 min after skin incision. The variability of the required concentrations at the same time point was calculated and compared. The achieved 30-min post-incision BIS ranges were not significantly different for sevoflurane or propofol TCI (30 [99% CI: 28-33] and 31 [99% CI: 27-36], respectively). The variability of sevoflurane concentrations was not significantly different from measured predicted propofol concentrations during BIS-guided anaesthesia (normalized concentration range of 0.89 [99% CI: 0.78-0.99] and 0.93 [99% CI 0.87-1.02). Improvements in prediction accuracy of pharmacokinetic models beyond that of those already in clinical use are unlikely to reduce variability in target anaesthetic concentrations across patients in clinical practice.


Dose/response study of aminohydroxypropylidene bisphosphonate in tumor-associated hypercalcemia.
Bisphosphonates (or diphosphonates) constitute a major advance in the treatment of tumor-associated hypercalcemia and also have the potential to prevent or reverse osteolysis in normocalcemic patients. Available information on adequate therapeutic doses and potential toxicity is, however, very fragmentary. This report describes a phase I study of one of the most promising bisphosphonates currently available, aminohydroxypropylidene bisphosphonate (AHPrBP or APD), in tumor-associated hypercalcemia. Only patients remaining hypercalcemic after 48 hours of rehydration were evaluated, and antineoplastic therapy was delayed at least until a normal serum calcium level was reached. AHPrBP was given as two-hour daily infusions for three days, and three different patients were treated at each of the six following dosage levels: 0.01, 0.05, 0.25, 0.75, 1.5, and 3.0 mg/kg per day. The two lowest dosages levels were insufficient to normalize serum and urinary calcium levels, but the efficacy of the four other dosages was very similar. Plasma immunoreactive parathyroid hormone levels increased as a function of calcium levels, whereas urinary hydroxyproline levels did not prove to be a very useful measure of AHPrBP's effects on bone resorption. The drug was generally very well tolerated: only six patients had transient fever and/or decreases in lymphocyte count that were not clearly related to AHPrBP dosage. The only real problem was observed at the highest dosage of 3.0 mg/kg per day in an obese woman in whom high fever and hypotension developed. Efficacy and tolerance in dehydrated patients were verified by treating seven other patients, not previously rehydrated, at 1.0 mg/kg per day for three days. In summary, the therapeutic range of AHPrBP, given for three days as a two-hour infusion daily, lies between 0.25 and 1.5 mg/kg per day. Fasting urinary calcium levels are probably the most reliable and easily measured parameter to monitor AHPrBP's inhibition of bone resorption in normocalcemic patients.


Effect of local sequence inversions on the crystalline antiparallel beta-sheet lamellar structures of periodic polypeptides: implications for chain-folding.
The crystal structure and texture of the monodisperse periodic polypeptide [(AG)3EG(GA)3EG]10 (poly(+/-AG)3EG: A=alanine, G=glycine, E=glutamic acid) were analyzed by X-ray diffraction, Fourier transform infrared spectroscopy, and electron microscopy. Structure determination was aided by comparison with the recently described structure for the related periodic polypeptide [(AG)3EG]36 by Krejchi et al. (Macromolecules 1997;30:5012). Texture-oriented samples of poly(+/-AG)3EG were obtained by crystallization of the polymer from aqueous formic acid solution. The evidence supports an antiparallel (ap) beta-sheet protein structure and the X-ray diffraction signals index on an orthorhombic unit cell with parameters: a=0.950 nm (hydrogen-bond direction), b=1.052 nm (apbeta-sheet stacking direction), c=6.95 nm (chain direction). The absence of the (010) diffraction signal, a prominent signal in the poly(AG)3EG diffraction pattern, implies that the apbeta-sheets are 'apolar', i.e. both surfaces are equally populated with alanyl methyl groups. Selective line broadening of wide-angle diffraction signals with l not equal to 0 gives an estimated crystal size of approximately/= 4 nm in the chain direction. This observation, coupled with the appearance of low-angle particle interference peaks, indicates a crystal thickness considerably less than the chain length and suggests an adjacent-re-entry chain-folded lamellar structure incorporating the apbeta-sheet architecture. The polypeptide folds through gamma-turns, in-phase with the pseudo-octapeptide repeat; the glutamic acid residues occur on the lamellar surfaces. These results and those from the crystalline lamellae of poly(AG)3EG suggest that beta-turns are not compatible with these repetitively stacked apbeta-sheet structures. This implies that intersheet interactions of alanyl methyl groups and glycyl alpha-protons are not sufficiently strong to dictate the folding geometry in these structures.


Inhibitory effects of pentacyclic triterpenoids from Astilbe rivularis on TGFBIp-induced inflammatory responses in vitro and in vivo.
Transforming growth factor β induced protein (TGFBIp) is an extracellular matrix protein which expression in several cell types is greatly increased by TGF-β. TGFBIp is released by human umbilical vein endothelial cells (HUVECs), and functions as a mediator of experimental sepsis. Pentacyclic triterpenoids bearing a carboxyl group at C-27 position, 3β,6α-dihydroxyolup-20(29)-ene (1), 3β,6β-dihydroxyolean-12-en-27-oic acid (2) and 3β,24-dihydroxyolean-12-en-27-oic acid (3), are representative bioactive molecules in the genus Astilbe that possess cytotoxic, anti-inflammatory and wounds healing activities. Based on the biological effects of C-27 carboxylated pentacyclic triterpenoids, we investigated the anti-inflammatory effects of compounds 1-3 against TGFBIp-mediated vascular inflammatory responses. The anti-inflammatory activities of compounds 1-3 were determined by measuring permeability, leukocytes adhesion and migration, and activation of pro-inflammatory proteins in TGFBIp-activated human HUVECs and mice. We found that compounds 1-3 inhibited TGFBIp-induced barrier disruption, expression of cell adhesion molecules (CAMs) and adhesion/transendothelial migration of neutrophils to human endothelial cells. Each compound also suppressed TGFBIp-induced hyperpermeability and leukocyte migration in vivo. These results suggest that compounds 1-3 possess anti-inflammatory functions by inhibiting hyperpermeability, expression of CAMs, and adhesion and migration of leukocytes, thereby endorsing its usefulness as a therapy for vascular inflammatory diseases.


Theory about interrelationships between macromineral nutrients and growth rate during recovery from undernutrition.
Previous papers of our group have reported that, in the first stages of nutritional recovery, the needs of undernourished infants, in terms of Protein Calories percentage (P%) were higher than normal, and similar to those of other mammals which double their birth weight faster than man. During this period, a high dietary P% produces an accelerated catch-up growth. Therefore, Calcium and Phosphorus balances increase proportionally to weight gain rate (WGR), and Calcium retention per gram of new tissue is dependent on dietary Calcium/Protein ratio. On the other hand, Bernhart demonstrated that there was a direct correlation between the growth rate of the sucklings of several species, including humans, and the percentage of protein and ash in the fluid milk. As a consequence of these facts, we assume that during catch-up growth, in order to attain a normal body composition, dietary level of essential minerals must be related to factors affecting weight gain. These relationships suggest the hypothesis that, during the recovery from undernutrition, in order to meet the needs of the catch-up growth allowed by the Protein/Calories ratio, Calcium and Phosphorus milk concentrations would be in relation to the Protein/Calorie concentration. In this way, Calcium and Phosphorus concentrations might be the limiting factors for attaining a normal body composition. This hypothesis might also be generalized to other minerals in order to prevent them from becoming the limiting factors for attaining a normal body composition.


Alu element insertion in the MLH1 exon 6 coding sequence as a mutation predisposing to Lynch syndrome.
Lynch syndrome (LS) is the most frequent cause of hereditary colorectal cancer. A subset of patients with a history of LS shows no causal germline pathogenic alteration and are identified as having Lynch-like syndrome (LLS). Alu retrotransposons are the most abundant mobile DNA sequences in the human genome and have been associated with numerous human cancers by either disrupting coding regions or altering epigenetic modifications or splicing signals. We report a family first classified as having LLS by Sanger sequencing analysis. Next-generation sequencing (NGS) analysis identified an AluY5a insertion in MLH1 exon 6 that led to exon skipping. This splicing alteration inducing a pathogenic frameshift was found in patients who developed colorectal adenocarcinomas. Retroelement insertion might thus be an important but underestimated mechanism of cancer genetics that could be systematically tested in patients with a phenotype suggesting LS to accurately assess family risk and surveillance approaches.


Role of purines in brain development, from neuronal proliferation to synaptic refinement.
The purinergic system includes P1 and P2 receptors, which are activated by ATP and its metabolites. They are expressed in adult neuronal and glial cells and are crucial in brain function, including neuromodulation and neuronal signaling. As P1 and P2 receptors are expressed throughout embryogenesis and development, purinergic signaling also has an important role in the development of the peripheral and central nervous system. In this review, we present the expression pattern and activity of purinergic receptors and of their signaling pathways during embryonic and postnatal development of the nervous system. In particular, we review the involvement of the purinergic signaling in all the crucial steps of brain development i.e. in neural stem cell proliferation, neuronal differentiation and migration as well as in astrogliogenesis and oligodendrogenesis. Then, we review data showing a crucial role of the ATP and adenosine signaling pathways in the formation of the peripheral neuromuscular junction and of central GABAergic and glutamatergic synapses. Finally, we examine the consequences of deregulation of the purinergic system during development and discuss the therapeutic potential of targeting it at adult stage in diseases with reactivation of the ATP and adenosine pathway. This article is part of the Special Issue on "Purinergic Signaling: 50 years".


Nonsurgical management of osteoarthritis in dogs.
Osteoarthritis (OA), although superficially considered to be deterioration of the joint associated with pain and dysfunction, is actually quite a complex condition. When considering treatment of OA, a multitude of biochemical, physical, and pathologic alterations must be recognized. This article presents a review of the published material regarding various nonsurgical treatments for OA. When there are no data regarding a specific treatment or when a statement is the opinion of the authors, such a deficiency is identified.


Actions of substance P, MIF, TRH and related peptides in the substantia nigra, caudate nucleus and nucleus accumbens.
Neurones in the substantia nigra were found to be sensitive to iontophoretically applied substance P, substance P 1-9 methyl ester and substance P 1-9 amide. Substance P 1-2, 4-9 and 5-9 methyl esters, thyrotropin releasing hormone (TRH), Pyroglutamyl-histidyl-2 methyl prolineamide (methyl TRH), Pyroglutamyl-histidyl-2 methyl prolineamide (methyl TRH), histidyl-proline-diketopiperazine (His-Pro) and MSH releasing inhibiting factor (MIF) were without effect on neurones in this area. Thyrotropin releasing hormone (TRH), methyl TRH, His-Pro and MIF were inactive on neurones in the caudate nucleus and nucleus accumbens. Bilateral injections of substance P and substance P 1-9 methyl ester into the ventral tegmental area (VTA) of conscious rats produced locomotor activity, while similar injections of substance P 4-9 and 5-9 methyl esters did not. The locomotor activity produced by amphetamine was prolonged by TRH, while MIF was devoid of such activity. The data suggest that substance P and substance P 1-9 have similar effects in the substantia nigra, although the mechanism of action is unclear. Thyrotropin releasing hormone and MIF probably do not have acute actions in the brain areas tested.


3-Acetylpyridine lesions and four serotonergic behavioral syndromes in the rat.
We studied the effect of 3-acetylpyridine (3-AP) lesions on the serotonergic-myoclonic syndromes evoked by quipazine (QP), 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), fenfluramine (FF), and p-chloroamphetamine (PCA) in the adult rat. Eleven behaviors were scored from videotapes by an observer blind to drug status. In unlesioned rats, drugs could be differentiated by forelimb and axial myoclonus, pivoting and backing. All drugs significantly suppressed rearing. 3-AP produced a lasting action-enhanced body tremor which differed from axial myoclonus in its vertical direction and rhythmicity. 3-AP lesions modified the effect of drugs on several behaviors, increasing axial (QP, FF, PCA) and forelimb (5-MeO-DMT, FF, PCA) myoclonus and decreasing locomotor score. Prior lesions with 5,7-dihydroxytryptamine did not prevent the effect of 3-AP or any behaviors of the serotonin syndrome, but had a slight effect on the magnitude of forelimb myoclonus, head weaving, and hunching induced by some drugs. Neither lesion abolished or reduced myoclonus. These data suggest that intact 5-HT terminals are not requisite for the tremorogenic and cytotoxic effect of 3-AP. To the extent that chemical lesions with 3-AP are selective for the inferior olive (IO), the role of the IO in myoclonus in several 5-HT rodent myoclonic models appears to be regulatory rather than stimulatory.


Medicaid expansion and risk of eclampsia.
Eclampsia is an indicator of severe maternal morbidity and can be prevented through increased prenatal care access and early prenatal care utilization. The 2014 Medicaid expansion under the Patient Protection and Affordable Care Act allowed states to expand Medicaid coverage to nonelderly adults with incomes up to 138% of the federal poverty level. Its implementation has led to a significant increase in prenatal care access and utilization. This study aimed to assess the association of Medicaid expansion under the Affordable Care Act with eclampsia incidence. This natural experiment study was based on US birth certificate data from January 2010 to December 2018 in 16 states that expanded Medicaid in January 2014 and in 13 states that did not expand Medicaid during the study period. The outcome was eclampsia incidence, the intervention was the implementation of the Medicaid expansion, and the exposure was state expansion status. Using the interrupted time series method, we compared temporal trends in the incidence of eclampsia before and after the intervention in expansion vs non-expansion states with adjustments for patient and hospital county characteristics. Of the 21,570,021 birth certificates analyzed, 11,433,862 (53.0%) were in expansion states and 12,035,159 (55.8%) were in the postintervention period. The diagnosis of eclampsia was recorded in 42,677 birth certificates or 19.8 per 10,000 (95% confidence interval, 19.6-20.0). The incidence of eclampsia was higher for Black people (29.1 per 10,000) than for White (20.7 per 10,000), Hispanic (15.3 per 10,000), and birthing people of other race and ethnicity (15.4 per 10,000). In the expansion states, the incidence of eclampsia increased during the preintervention period and decreased during the postintervention period; in the nonexpansion states, a reverse pattern was observed. A statistically significant difference was observed between expansion and nonexpansion states in temporal trends between the pre- and postintervention periods, with an overall 1.6% decrease (95% confidence interval, 1.3-1.9) in the incidence of eclampsia in expansion states compared with nonexpansion states. The results were consistent in subgroup analyses according to maternal race and ethnicity, education level (less than high school or high school and higher), parity (nulliparous or parous), delivery mode (vaginal or cesarean delivery), and poverty in the residence county (high or low). Implementation of the Affordable Care Act Medicaid expansion was associated with a small statistically significant reduction in the incidence of eclampsia. Its clinical significance and cost-effectiveness remain to be determined.


Radial basis function classifiers to help in the diagnosis of the obstructive sleep apnoea syndrome from nocturnal oximetry.
The aim of this study is to assess the ability of radial basis function (RBF) classifiers as an assistant tool for the diagnosis of the obstructive sleep apnoea syndrome (OSAS). A total of 187 subjects suspected of suffering from OSAS were available for our research. The initial population was divided into training, validation and test sets for deriving and testing our neural classifiers. We used nonlinear features from nocturnal oxygen saturation (SaO(2)) to perform patients' classification. We evaluated three different RBF construction techniques based on the following algorithms: k-means (KM), fuzzy c-means (FCM) and orthogonal least squares (OLS). A diagnostic accuracy of 86.1, 84.7 and 85.5% was provided by the networks developed with KM, FCM and OLS, respectively. The three proposed networks achieved an area under the receiver operating characteristic (ROC) curve over 0.90. Our results showed that a useful non-invasive method could be applied to diagnose OSAS from nonlinear features of SaO(2) with RBF classifiers.


Infections in renal transplant recipients receiving mycophenolate versus azathioprine-based immunosuppression.
Differences in the incidence, etiology, type, and outcome of infections occurring during the first 6 months after transplantation were evaluated in two consecutive cohorts of kidney recipients who received immunosuppressive regimens based on either azathioprine (plus antilymphocyte globulin, cyclosporine A, and prednisone) (ATG-AZA cohort) or mycophenolate-mofetil (plus cyclosporine A and prednisone) (MMF cohort). The overall incidence of infections in the two cohorts was similar (0.99+/-1.06 infections/patient in the MMF cohort and 1.04+/-0.99 in the ATG-AZA cohort, P=0.3), as was the incidence of bacterial and fungal infections. In patients who received mycophenolate, cytomegalovirus disease occurred at a higher incidence (0.3+/-0.54 vs. 0.1+/-0.34 episodes/patient, P=0.005) and affected the upper gastrointestinal tract more frequently (0.21+/-0.48 vs. 0.025+/-0.16 episodes of cytomegalovirus ulcerative esophagitis, gastritis, or duodenitis per patient; P=0.001). A nonsignificant trend toward a higher recipient survival for patients receiving mycophenolate was noted (100% vs. 95%, P=0.07). In multivariate analysis, the following factors were independently associated with a higher risk of cytomegalovirus disease: the serostatus R-/D+ (seronegative recipients who received a kidney from a seropositive donor) (RR=35.7 [95%CI, 7.4-166.7]), treatment with mycophenolate (RR=10.4 [95%CI, 2.7-38.4]), and the development of any episodes of acute rejection (RR=10.1 [95%CI, 2.5-41.6]). These data show that kidney recipients receiving mycophenolate have a higher incidence of cytomegalovirus disease, mainly affecting the upper gastrointestinal tract, compared to those receiving azathioprine-based immunosuppression.


Determinants of Optimal Breastfeeding Practices in Indonesia: Findings From the 2017 Indonesia Demographic Health Survey.
Understanding the factors influencing mothers' decision to breastfeed their infants is essential to formulate effective breastfeeding interventions. This study explored the determinants of optimal breastfeeding indicators in Indonesia. We used the 2017 Indonesia Demographic and Health Survey to analyze factors associated with early initiation of breastfeeding, exclusive breastfeeding (EBF), and continued breastfeeding at 1 year (CBF-1) and 2 years (CBF-2). Multivariate logistic regression models were used to examine bio-demographic, socio-cultural, and behavioral characteristics associated with breastfeeding after considering the survey design effect. The risk of delayed breastfeeding initiation was higher among infants who were born smaller, first-born children, were delivered via cesarean delivery, and did not have immediate skin-to-skin contact (p<0.01). Infant's age, birth pattern, household wealth index, and the mother's occupation and smoking status were predictors of EBF (p<0.05). CBF-1 was less common among first-time mothers and those working in the non-agricultural sector, mothers from wealthier families, and mothers who had cesarean deliveries (p<0.01). Infant's age was negatively associated with CBF-2 (adjusted odds ratio [aOR], 0.85; 95% confidence interval [CI], 0.74 to 0.99). Mothers attending college were less likely to practice CBF-2 than those with no education or primary education (aOR, 0.45; 95% CI, 0.26 to 0.77). The absence of postnatal visits was a risk factor for CBF-1 and CBF-2 (p<0.05). Breastfeeding interventions in Indonesia should pay particular attention to at-risk groups such as women from wealthier families, working outside the agricultural sector, and with a higher education level. Nutrition-sensitive programs (e.g., postnatal care and smoking cessation) should also be encouraged.


Embodying an artificial hand increases blood flow to the investigated limb.
Background: The autonomic nervous system is the main determinant of the blood flow directed towards a body part, and it is tightly connected to the representation of the body in the brain; would the experimental modulation of the sense of ownership of the limb affect its blood perfusion? Methods: In healthy participants, we employed the rubber hand illusion paradigm to modulate limb ownership while we monitored the brachial artery blood flow and resistance of the investigated limb. Results: In all conditions with brush-stroking, we found an initial drop in the blood flow due to tactile stimulation. Subsequently, in the illusion condition where both the rubber and real hand experience synchronous brush-stroking, the blood flow rose significantly faster and reached significantly higher values. Moreover, the increase in blood flow correlated to the embodiment level measured by questionnaires and, negatively, to the change of peripherical vascular resistance. Conclusions: These findings demonstrate that modulating the representation of a body part impacts its blood perfusion.


CNS glia are targets for GDNF and neurturin.
Glial cell line-derived neurotrophic factor (GDNF) and neurturin (NTN) are two closely related growth factors reported to selectively act on distinct neuronal populations in the CNS. Both GDNF and NTN signal through a receptor complex consisting of the signal transducing subunit, Ret, and a ligand-specific binding subunit, termed GDNF family receptor (GFR)alpha-1 and GFRalpha-2, respectively. By using RT-PCR, we observed that mRNAs encoding the subunits of both receptor complexes are widely expressed throughout the developing brain, suggesting the presence of targets for these growth factors other than the ones known today. We provide evidence that these targets include glial cells.


Enzyme specificity: base recognition and hydrolysis of RNA by ribonuclease A.
The substrate specificity of pancreatic ribonuclease A is discussed in light of observations based on accurate X-ray structure analysis of several enzyme-nucleotide complexes. A hypothesis for protein-nucleic acid recognition is presented which proposes that: (a) pyrimidine bases in RNA are recognised by ribonuclease due to the charge complementarity of two groups (the amide nitrogen and the side chain oxygen (OG) of threonine 45) of the protein and relevant atoms in the heterocyclic base (O2 and N3 in pyrimidine nucleotides); (b) interaction of the protein with the ribose moiety of the nucleotides is non-specific; and (c) conformational flexibility in the region of the scissile P-O bond is provided by different locations of the phosphoryl oxygens, rather than by an overall translation of the phosphate moiety.


Chelating peptide-immobilized metal ion affinity chromatography. A new concept in affinity chromatography for recombinant proteins.
We report our experimental results supporting the hypothesis that a specific metal-chelating peptide (CP) on the NH2 terminus of a protein can be used to purify that protein using immobilized metal ion affinity chromatography (IMAC). The potential utility of this approach resides with recombinant proteins since the nucleotide sequence that codes for the protein can be extended to include codons for the chelating peptide and thereby generate the gene for a chimeric CP-protein that can be cloned, expressed, and affinity-purified with immobilized metal ions. The chelating peptide purification handle could then be removed chemically or enzymatically after purification has been achieved to generate a protein with the natural amino acid sequence. The feasibility of using a chelating peptide as a purification handle has been demonstrated using a leuteinizing hormone-releasing hormone (LHRH) analog, 2-10 LHRH, which contains the previously identified chelating peptide, His-Trp, on the NH2 terminus. 2-10 LHRH had a high affinity for a Ni(II) IMAC column due to the NH2-terminal dipeptide sequence His-Trp, forming a coordination complex with Ni(II), whereas the controls, 3-10 LHRH and 4-10 LHRH, lacking the CP sequence, did not bind. Furthermore, 2-10 LHRH could be purified from a mixture of histidine-containing peptides on a Ni(II) IMAC column in one step. His-Trp proinsulin was used as a model of a recombinant CP-protein. The S-sulfonates of His-Trp-proinsulin and proinsulin were isolated from Escherichia coli engineered to overproduce these proteins as trpLE' fusion proteins. His-Trp-proinsulin(SSO3-)6 had a higher affinity for immobilized Ni(II) than proinsulin (SSO3-)6. Both proteins were eluted by decreasing the pH or by introducing a displacing ligand into the buffer. Ni(II) eluted from the column with much higher concentrations of displacing ligand than the proteins.


Human T lymphocyte cAMP-dependent protein kinase: subcellular distributions and activity ranges of type I and type II isozymes.
The role of the type I and type II protein kinase A isozymes in the regulation of human T lymphocyte immune effector functions has not been ascertained. To approach this question, we first characterized the distribution and enzyme activities of the type I and type II protein kinase A (PKA) isozymes in normal, human T lymphocytes. T cells possess both type I and type II isozymes with an activity ratio of 5.0:1 +/- 0.71 (mean +/- SD). The type I isozyme associates predominately with the plasma membrane whereas the type II isozyme localizes primarily to the cytosol. Analyses of isozyme activities demonstrated that T cells from approximately one-third of 16 healthy donors exhibited significantly higher type II isozyme activities (higher type II, type IIH) than the remaining donors (lower type II, type IIL) (mean = 605 +/- 75 pmol.min-1.mg protein-1, P less than 0.001). Scatchard analyses of [3H]cAMP binding in the cytosolic fraction demonstrated similar Kd values (type IIH, 1.1 x 10(-7) M; type IIL, 9.0 x 10(-8) M); however, the Bmax (maximal binding) of the type IIH was 400 fmol/mg protein compared to the Bmax of the type IIL of 126 fmol/mg protein. Scatchard analysis of [3H]cAMP binding to the type I isozyme associated with membrane fragments had a Kd of 5.6 x 10(-8) M and a Bmax of 283 fmol/mg protein. Eadie-Hofstee plots of type IIH and type IIL gave a Km and Vmax of 2.3 mg/ml and 1.5 nmol.mg-1.min-1, and 2.1 mg/ml and 1.6 nmol.mg-1.min-1, respectively. The 3.2-fold higher maximal binding of the type II isozyme in one-third of healthy donors may reflect a greater amount of isozyme protein. The compartmentalization of type I PKA isozyme to the plasma membrane and type II PKA isozyme to the cytosol may serve to localize the isozymes to their respective substrates in T lymphocytes.


Heterogeneous electro-Fenton system using Fe-MOF as catalyst and electrocatalyst for degradation of pharmaceuticals.
In recent years, heterogeneous electro-Fenton processes have gained considerable attention as an alternative to homogeneous processes. In this context, the aim of this study is the use of a commercial iron metal-organic framework (Fe-MOF), Basolite® F-300, as a base material for the design of a heterogeneous electro-Fenton treatment system for the removal of antipyrine. Initially, the catalyst was applied as powder in aqueous solution and three key parameters of the electro-Fenton process (pH, Fe-MOF concentration and current density) were evaluated and optimized by a Central Composite Design Face Centred (CCD-FC) using antipyrine removal and energy consumption as response functions. Near complete antipyrine removal (94%) was achieved under optimal conditions: pH 3, Fe-MOF 157.78 mg/L and current density 6.67 mA/cm2, obtaining an energy consumption of 0.29 W·h per mg of antipyrine removed. Later, two electrocatalysts (Fe-MOF functionalized cathodes), prepared by different Fe-MOF immobilisation approaches (composite of carbon black/polytetrafluoroethylene or by electrospinning on Ni foam), were synthesized. Their characterisation showed notable Fe-MOF incorporation into the material and favourable properties as electrocatalysts. Both Fe-MOF functionalized cathodes were evaluated in the removal of antipyrine at different pH (acidic and natural) and current density (27.78 and 55.56 mA/cm2), achieving in the best conditions removal levels around 80% in 1 h without any operational problems. In addition, several intermediates generated during the treatment were identified and their toxicity estimated. According to the obtained results, the degradation compounds have less toxicity than the parent compounds, confirming the effectiveness of the treatment.


Two slow stages in refolding of bovine carbonic anhydrase B are due to proline isomerization.
Kinetics of refolding of bovine carbonic anhydrase B have been studied by the "double-jump" technique (i.e. the dependence of protein refolding on delay time in the unfolded state after fast unfolding). It is shown that two stages (the slow with a relaxation time of t1/2 approximately equal to 120 s and the superslow with t1/2 approximately equal to 600 s) observed during refolding of bovine carbonic anhydrase B are due to trans-cis isomerization of proline residues. The dependences of rate constants of these processes on temperature and on the final denaturant concentration were measured. Activation energies of both processes are the same, Ea = 18(+/- 2) kcal/mol. The rate constants of protein refolding do not depend on the final concentration of urea under native conditions. In addition, the rate of isomerization of essential proline residues in the "molten globule" intermediate state of bovine carbonic anhydrase was measured and found to be equal to that for unstructural polypeptides. The effect of several proline residues on carbonic anhydrase refolding is discussed.


Age-dependent changes in fat- and water-soluble vitamins-National Health and Nutrition Examination Surveys study.
Aging is an independent risk factor for the development of various diseases associated, among others, with detrimental blood levels of fat- and water-soluble vitamins. Thus, the objective of this study is to investigate age-related changes in blood levels of vitamin A, B12, C, D, and E. Subject serum vitamin levels were obtained from the combined National Health and Nutrition Examination Surveys (NHANES). NHANESIII and NHANES 1999-2000, 2001-2002, 2003-2004, and 2005-2006. The raw data set was stratified into five age groups G1- G5: 20 ≤ G1 < 30, 30 ≤ G2 < 40, 40 ≤ G3 < 50, 50 ≤ G4 < 60, and 60 ≤ G5 < 70 years of age. Age stratified data was cleaned using the modified Horn algorithm. The reference range for the vitamin level of a specific age group was defined as data between the first and third quartile of the subject defined by normal blood pressure and normal bone density. Age-dependent changes in serum/plasma vitamin levels were assessed using the bootstrap technique with 10,000 repeats and Bonferroni adjustment. There was a continuous increase in vitamin A, B12, D, and E levels in the blood. However, the vitamin C concentration remained virtually constant in all age groups. There was a lack of cross-correlations between lipid and water-soluble vitamin levels and blood pressure and bone health. The following reference levels for vitamin A, B12, C, D, and E in subjects older than 20 years of age were established: vitamin A: 1.32-2.8 mmol/L, vitamin B12: 257.94-498.33 pmol/L, vitamin C: 38.18-79.2 mmol/L, vitamin D: 76.33-199.36 nmol/L and vitamin E: 3.65-41.12 μmol/L.


Growth stage-based modulation in physiological and biochemical attributes of two genetically diverse wheat (Triticum aestivum L.) cultivars grown in salinized hydroponic culture.
Hydroponic experiment was conducted to appraise variation in the salt tolerance potential of two wheat cultivars (salt tolerant, S-24, and moderately salt sensitive, MH-97) at different growth stages. These two wheat cultivars are not genetically related as evident from randomized polymorphic DNA analysis (random amplified polymorphic DNA (RAPD)) which revealed 28% genetic diversity. Salinity stress caused a marked reduction in grain yield of both wheat cultivars. However, cv. S-24 was superior to cv. MH-97 in maintaining grain yield under saline stress. Furthermore, salinity caused a significant variation in different physiological attributes measured at different growth stages. Salt stress caused considerable reduction in different water relation attributes of wheat plants. A significant reduction in leaf water, osmotic, and turgor potentials was recorded in both wheat cultivars at different growth stages. Maximal reduction in leaf water potential was recorded at the reproductive stage in both wheat cultivars. In contrast, maximal turgor potential was observed at the boot stage. Salt-induced adverse effects of salinity on different water relation attributes were more prominent in cv. MH-97 as compared to those in cv. S-24. Salt stress caused a substantial decrease in glycine betaine and alpha tocopherols. These biochemical attributes exhibited significant salt-induced variation at different growth stages in both wheat cultivars. For example, maximal accumulation of glycine betaine was evident at the early growth stages (vegetative and boot). However, cv. S-24 showed higher accumulation of this organic osmolyte, and this could be the reason for maintenance of higher turgor than that of cv. MH-97 under stress conditions. Salt stress significantly increased the endogenous levels of toxic ions (Na(+) and Cl(-)) and decreased essential cations (K(+) and Ca(2+)) in both wheat cultivars at different growth stages. Furthermore, K(+)/Na(+) and Ca(2+)/Na(+) ratios decreased markedly due to salt stress in both wheat cultivars at different growth stages, and this salt-induced reduction was more prominent in cv. MH-97. Moreover, higher K(+)/Na(+) and Ca(2+)/Na(+) ratios were recorded at early growth stages in both wheat cultivars. It can be inferred from the results that wheat plants are more prone to adverse effects of salinity stress at early growth stages than that at the reproductive stage.


Children are more exploratory and learn more than adults in an approach-avoid task.
Intuitively, children appear to be more exploratory than adults, and this exploration seems to help children learn,. However, there have been few clear tests of these ideas. We test whether exploration and learning change across development using a task that presents a "learning trap." In this task, exploitation-maximizing immediate reward and avoiding costs-may lead the learner to draw incorrect conclusions, while exploration may lead to better learning but be more costly. In Studies 1, 2, and 3 we find that preschoolers and early school-aged children explore more than adults and learn the true structure of the environment better. Study 3 demonstrates that children explore more than adults even though they, like adults, predict that exploration will be costly, and it shows that exploration and learning are correlated. Study 4 shows that children's and adults' learning depends on the evidence they generate during exploration: children exposed to adult-like evidence learn like adults, and adults exposed to child-like evidence learn like children. Together, these studies support the idea that children may be more exploratory than adults, and this increased exploration influences learning.


Colorectal Cancer Screening With Repeated Fecal Immunochemical Test Versus Sigmoidoscopy: Baseline Results From a Randomized Trial.
The comparative effectiveness of sigmoidoscopy and fecal immunochemical testing (FIT) for colorectal cancer (CRC) screening is unknown. Individuals aged 50-74 years living in Southeast Norway were randomly invited between 2012 and 2019 to either once-only flexible sigmoidoscopy or FIT screening every second year. Colonoscopy was recommended after sigmoidoscopy if any polyp of ≥10 mm, ≥3 adenomas, any advanced adenomas, or CRC was found or, subsequent to, FIT >15 μg hemoglobin/g feces. Data for this report were obtained after complete recruitment in both groups and included 2 full FIT rounds and part of the third round. Outcome measures were participation, neoplasia detection, and adverse events. Age-standardized detection rates and age-adjusted odds ratios (ORs) were calculated. We included 139,291 individuals: 69,195 randomized to sigmoidoscopy and 70,096 to FIT. The participation rate was 52% for sigmoidoscopy, 58% in the first FIT round, and 68% for 3 cumulative FIT rounds. Compared to sigmoidoscopy, the detection rate for CRC was similar in the first FIT round (0.25% vs 0.27%; OR, 0.92; 95% confidence interval [CI], 0.75-1.13) but higher after 3 FIT rounds (0.49% vs 0.27%; OR, 1.87; 95% CI, 1.54-2.27). Advanced adenoma detection rate was lower in the first FIT round compared to sigmoidoscopy at 1.4% vs 2.4% (OR, 0.57; 95% CI, 0.53-0.62) but higher after 3 cumulative FIT rounds at 2.7% vs 2.4% (OR, 1.14; 95% CI, 1.05-1.23). There were 33 (0.05%) serious adverse events in the sigmoidoscopy group compared to 47 (0.07%) in the FIT group (P = .13). Participation was higher and more CRC and advanced adenomas were detected with repeated FIT compared to sigmoidoscopy. The risk of perforation and bleeding was comparable. Clinicaltrials.gov, Number: NCT01538550.


Review: Host-pathogen dynamics of seagrass diseases under future global change.
Human-induced global change is expected to amplify the disease risk for marine biota. However, the role of disease in the rapid global decline of seagrass is largely unknown. Global change may enhance seagrass susceptibility to disease through enhanced physiological stress, while simultaneously promoting pathogen development. This review outlines the characteristics of disease-forming organisms and potential impacts of global change on three groups of known seagrass pathogens: labyrinthulids, oomycetes and Phytomyxea. We propose that hypersalinity, climate warming and eutrophication pose the greatest risk for increasing frequency of disease outbreaks in seagrasses by increasing seagrass stress and lowering seagrass resilience. In some instances, global change may also promote pathogen development. However, there is currently a paucity of information on these seagrass pathosystems. We emphasise the need to expand current research to better understand the seagrass-pathogen relationships, serving to inform predicative modelling and management of seagrass disease under future global change scenarios.


Indirect measurements of field-scale hydraulic conductivity of waste from two landfill sites.
Management and prediction of the movement and distribution of fluids in large landfills is important for various reasons. Bioreactor landfill technology shows promise, but in arid or semi-arid regions, the natural content of landfilled waste may be low, thus requiring addition of significant volumes of water. In more humid locations, landfills can become saturated, flooding gas collection systems and causing sideslope leachate seeps or other undesirable occurrences. This paper compares results from two different approaches to monitoring water in waste. At the Brock West Landfill in eastern Canada, positive pore pressures were measured at various depths in saturated waste. The downward seepage flux through the waste is known, thus the vertical saturated hydraulic conductivity of the waste at this landfill was determined to be 3 × 10(-7)cm/s. By comparison, the Spadina Landfill in western Canada is predominantly unsaturated. The infiltration of moisture into the waste was measured using moisture sensors installed in boreholes which determined arrival time for moisture fronts resulting from major precipitation events as well as longer-term change in moisture content resulting from unsaturated drainage during winter when frozen ground prevented infiltration. The unsaturated hydraulic conductivity calculated from these data ranged from approximately 10(-6)cm/s for the slow winter drainage in the absence of significant recharge to 10(-2)cm/s or higher for shallow waste subject to high infiltration through apparent preferential pathways. These two very different approaches to field-scale measurements of vertical hydraulic conductivity provide insight into the nature of fluid movement in saturated and unsaturated waste masses. It is suggested that the principles of unsaturated seepage apply reasonably well for landfilled waste and that the hydraulic behavior of waste is profoundly influenced by the nature and size of voids and by the degree of saturation prevailing in the landfill.


Neurovisual profile in children affected by Angelman syndrome.
Angelman syndrome (AS) is a rare neurogenetic disorder caused by altered expression of the maternal copy of the UBE3A gene. Together with motor, cognitive, and speech impairment, ophthalmological findings including strabismus, and ocular fundus hypopigmentation characterize the clinical phenotype. The aim of this study was to detail the neurovisual profile of children affected by AS and to explore any possible genotype-phenotype correlations. Thirty-seven children (23 females, mean age 102.8 ± 54.4 months, age range 22 to 251 months) with molecular confirmed diagnosis of AS were enrolled in the study. All underwent a comprehensive video-recorded neurovisual evaluation including the assessment of ophthalmological aspects, oculomotor functions, and basic visual abilities. All children had visual impairments mainly characterized by refractive errors, ocular fundus changes, strabismus, discontinuous/jerky smooth pursuit and altered saccadic movements, and/or reduced visual acuity. Comparing the neurovisual profiles between the deletion and non-deletion genetic subgroups, we found a significant statistical correlation between genotype and ocular fundus hypopigmentation (p = 0.03), discontinuous smooth pursuit (p < 0.05), and contrast sensitivity abnormalities (p < 0.01) being more frequent in the deletion subgroup. Subjects affected by AS present a wide spectrum of neurovisual impairments that lead to a clinical profile consistent with cerebral visual impairment (CVI). Moreover, subjects with a chromosome deletion show a more severe visual phenotype with respect to ocular fundus changes, smooth pursuit movements, and contrast sensitivity. Early detection of these impaired visual functions may help promote the introduction of neurovisual habilitative programs which can improve children's visual, neuromotor, and cognitive outcomes.


Assessment of ornithine decarboxylase activity in rectal mucosa as a marker for colorectal adenomas and carcinomas.
We have investigated the role of ornithine decarboxylase activity in rectal mucosa as a marker for colorectal neoplasia. Biopsies of normal rectal mucosa were taken from 18 patients with adenomas greater than 1 cm diameter, 11 with carcinomas and 16 controls. The mean ornithine decarboxylase activity in normal rectal mucosa of adenoma patients, 6.52 nmol CO2 released h-1 (mg cell protein)-1, was significantly lower than that in controls, 16.8, P = 0.006. The difference in rectal ornithine decarboxylase activities between cancer patients, 3.58, and controls was also significant, P = 0.001. These preliminary results suggest that ornithine decarboxylase may be a useful marker in screening for colorectal neoplasia.


The phosphoenolpyruvate: sugar phosphotransferase system of Streptococcus salivarius. Identification of a IIIman protein.
A double-spontaneous mutant resistant to the growth inhibitory effect of alpha-methylglucoside and 2-deoxyglucose was isolated from Streptococcus salivarius. This mutant strain, called alpha S3L11, did not grow on mannose and grew poorly on 5 mM fructose and 5 mM glucose. Isolated membranes of strain alpha S3L11 were unable to catalyse the phosphoenolpyruvate-dependent phosphorylation of mannose in the presence of purified enzyme I and HPr. Addition of dialysed membrane-free cellular extract of the wild-type strain to the reaction medium restored the activity. The factor that restored the phosphoenolpyruvate-mannose phosphotransferase activity to membranes of strain alpha S3L11 was called IIIman. This factor was partially purified from the wild-type strain by DEAE-cellulose chromatography, DEAE-TSK chromatography, and molecular seiving on a column of Ultrogel AcA 34. This partially purified preparation also enhanced the phosphoenolpyruvate-dependent phosphorylation of glucose, fructose, and 2-deoxyglucose in strain alpha S3L11.


Sphingomyelinase activities in cultured skin fibroblasts from patients with Niemann-Pick Disease.
Sphingomyelinase activity in cultured skin fibroblasts from a fetus affected with infantile-type Niemann-Pick disease was 0.5% of control activity; the activities in cells from two patients with adult-type disease (Cases 2 and 3) were 5.0% and 59.0%. Sphingomyelinase activiy was separated into three peaks (I-III) by isoelectric focusing. The isoelectric points were 4.5, 4.9, and 5.2 for peaks I, II, and III, respectively. The three peaks in the Case 2 cells were drastically reduced; only a very small peak could be distinguished (pI of 4.7). On the other hand, three peaks were observed in the Case 3 cells. Peak I had a pI of 4.4, peak II a pI of 4.7, and peak III a pI of 5.2. Peak I was found at near normal level, but both peaks II and III were markedly reduced. Sphingomyelinase in the peak I fraction obtained from isoelectric focusing in Case 3 cells was found to have the same Km value as that in control cells.


Clinical epidemiological insights into urinary incontinence.
Urinary incontinence (UI) is very common and heterogeneous among women with limited knowledge of progression or prognosis. Evidence based on clinical epidemiology can help to better understand the natural history of UI. We examine the challenges of UI definition and its subtypes, its impact on quality of life and health-seeking behavior. We review the proposed pathophysiology of UI subtypes and known risk factors as they relate to our current knowledge of the disease state. Finally, we emphasize the role of epidemiology in the process of acquiring new insight, improving knowledge, and translating this information into clinical practice. Stress UI is most common overall, but mixed UI is most prevalent in older women. The three UI subtypes have some common risk factors, and others that are unique, but there remains a significant gap in our understanding of how they develop. Although the pathophysiology of stress UI is somewhat understood, urgency UI remains mostly idiopathic, whereas mixed UI is the least studied and most complex subtype. Moreover, there exists limited information on the progression of symptoms over time, and disproportionate UI health-seeking behavior. We identify areas of exploration (e.g., epigenetics, urinary microbiome), and offer new insights into a better understanding of the relationship among the UI subtypes and to develop an integrated construct of UI natural history. Future epidemiological strategies using longitudinal study designs could play a pivotal role in better elucidating the controversies in UI natural history and the pathophysiology of its subtypes leading to improved clinical care.


Optical Coherence Tomography Biomarkers of Inflammation in Diabetic Macular Edema Treated by Fluocinolone Acetonide Intravitreal Drug-Delivery System Implant.
The fluocinolone acetonide (FAc) intravitreal drug-delivery system implant is a recent, second-line, intravitreal drug for the management of diabetic macular edema (DME). FAc acts against DME with a major anti-inflammatory effect. Despite the already proved efficacy, a number of patients still show persistent DME and require anti-VEGF retreatment. The main aim of the present study was to assess the relationship between quantitative biomarkers of inflammation and both DME recovery and the need for additional anti-VEGF in eyes treated by FAc implant. The study was designed as prospective and interventional with 1 year of follow-up. We analyzed structural optical coherence tomography (OCT) quantitative biomarkers of inflammation, namely choroidal hyperreflective foci (HF) and the choroidal vascularity index (CVI), and we assessed the relationship with other clinically relevant biomarkers and the outcome achieved after 1 year. Moreover, we stratified DME eyes in good and poor responders to FAc implant to highlight clinically relevant differences. Our study included 50 eyes (50 patients) treated by FAc implant. We found significant best-corrected visual acuity (BCVA) and central macular thickness (CMT) improvements after 1 year. Good responders started with worse visual acuity and higher CMT than poor responders, but gained letters significantly at the end of the follow-up, whereas poor responders showed stable BCVA values. Good responders were characterized by significantly higher choroidal HF and lower CVI than poor responders. Poor responders required significantly higher additional anti-VEGF treatments. Quantitative structural OCT biomarkers of inflammation allowed distinguishing different inflammatory profiles of DME. The inflammatory component helped to categorize DME eyes in good and poor responders to FAc implant.


Salivary gland anlage tumor: Evaluation and management of a rare pediatric condition.
Neonates and infants are obligatory nasal breathers. Nasal obstruction can therefore be life-threatening and prompt recognition of its cause is critical. Salivary gland anlage tumor (SGAT) is a rare, benign condition that can present with nasal obstruction and respiratory distress within the first weeks of life. Our objective was to outline the clinical presentation, evaluation, and management of SGAT and provide a review of existing literature. A retrospective chart review was performed at a tertiary children's hospital. A comprehensive literature search for SGAT was conducted using Medline, Embase, PubMed, and EBSCO. We present a case from our institution to describe the clinical approach to SGAT. Forty-one cases of previously reported SGAT, plus our new patient, were included. Patients presented with respiratory distress (30/42, 71.4%), feeding difficulty (14/42, 33.3%) and/or upper airway obstruction (13/42, 31.0%). The majority of tumors were in the nasopharynx (25/42, 59.5%). Surgical excision (36/42, 85.7%) was most commonly performed. Surgical approaches have evolved to include transoral, transpalatal, transnasal endoscopic or a combination of the above. Our patient had a suspected residual/recurrent tumor, later found to be negative on pathology. To date, there have been no reported recurrences. SGAT is a rare pediatric condition that is often excluded from the differential diagnosis of nasal obstruction. Clinical evaluation includes flexible nasopharyngoscopy and neuroimaging. Management involves surgical resection, except in cases of spontaneous expulsion. Tissue pathology is required for definitive diagnosis. Tissue biopsy should be performed on follow-up if there is a suspicion for recurrence.


[Percutaneous tumor ablation].
Percutaneous tumor ablation has faced a major growth in recent years with progressive expansion of clinical indications and subsequent adoption by national and international guidelines. Such techniques have become popular due to their minimally invasive profile and precise image-guided targeting resulting into a significant decrease of the procedure-related morbidity. Traditionally, malignant, and to lesser extent benign tumors, have been treated with these new techniques in several different organs including liver, kidney, lung and bone. More recently, other anatomic districts/organs including thyroid, breast, uterus and soft tissues have also been treated. Nevertheless, in order to optimize clinical results, precise knowledge of physical principles underlying these new techniques is of paramount importance, since technical adjustments may be provided according to specific tissue features (e.g. vascularization, density, etc.) and clinical indications of the procedure. Therefore, the goal of this review article is to present all the available ablation techniques with particular regard to their underlying physical principles and most common clinical indications.


Harnessing interdisciplinary education in biochemistry and molecular biology: A report on the IUBMB/PSBMB 2019 "harnessing interdisciplinary education in biochemistry and molecular biology" conference.
The "Harnessing Interdisciplinary Education in Biochemistry and Molecular Biology" education conference was held on November 13-15, 2019 in Manila, Philippines. The conference was sponsored by the International Union of Biochemistry and Molecular (IUBMB). With over 400 attendees from 22 countries themes discussed by the speakers and enthusiastic participants ranged from teaching biochemistry and molecular biology at all levels and to students in a range of disciplines.


Chromosomal rearrangements by an IS2 insertion in phage Mu-1.
We have isolated and characterized a mutant of temperate phage Mu-1 carrying an IS2 insertion in the middle of its beta region. This mutant gives rise spontaneously to secondary mutants which have deletions of different sizes adjacent to IS2. One particular derivative however, was found to have acquired an additional insertion sequence adjacent to IS2. This derivative gave rise to tertiary mutants carrying a deletion next to the tandem insertion. The tandem insertion was located at the same place in the Mu beta region as another 2.6 kb insertion independently isolated by Chow et al. (1977) and was found to be homologous to that insertion. The properties of this particular secondary mutant show that Mu phage particles lacking their S end are defective for growth and lysogenisation.


Montelukast inhibition of resting and GM-CSF-stimulated eosinophil adhesion to VCAM-1 under flow conditions appears independent of cysLT(1)R antagonism.
Montelukast (MLK) is a cysteinyl leukotriene receptor-1 (cysLT(1)R) antagonist with inhibitory effects on eosinophils, key proinflammatory cells in asthma. We assessed the effect of MLK on resting and GM-CSF-stimulated eosinophil adhesion to recombinant human (rh)VCAM-1 at different flow rates using our novel microflow system. At 1 or 2 dyn cm(-2), shear-stress unstimulated eosinophils tethered immediately to rhVCAM-1, "rolled" along part of the channel until they tethered, or rolled without tethering. At flow rates greater than 2 dyn cm(-2), adherent eosinophils began to be displaced from rhVCAM-1. MLK (10 nM and 100 nM) gave partial ( approximately 40%) but significant (P<0.05) inhibition of unstimulated eosinophil adhesion to rhVCAM-1 at 1 or 2 dyn cm(-2) shear stress. Once adhered, unstimulated eosinophils did not exhibit morphological changes, and GM-CSF-stimulated eosinophil adhesion under flow was characterized by greater cell flattening with significant (P<0.05) inhibition of adherent cell numbers by 100 nM MLK observed. This effect appeared specific for MLK, as the analog (E)-3-[[[3-[2-(7-chloro-2-quinolinyl)ethenyl]phenyl]-[[3-dimethylamino)-3-oxopropyl]thio]methyl]thio]-propanoic acid, sodium salt, had no significant effect on eosinophil adhesion to VCAM-1. The possibility that LTC(4), released from unstimulated or GM-CSF-treated eosinophils, contributed to their adhesion to VCAM-1 was excluded as the LT biosynthesis inhibitor 3-[1-(p-Chlorobenzyl)-5-(isopropyl)-3-t-butylthioindol-2-yl]-2,2-dimethylpropanoic acid had no inhibitory effect, and exogenously added LTC(4) did not enhance eosinophil adhesion. In contrast, LTD(4) enhanced eosinophil adhesion to VCAM-1, an effect blocked by MLK (10 and 100 nM). These findings demonstrate that MLK-mediated inhibition of unstimulated and GM-CSF-stimulated eosinophil adhesion to VCAM-1 under shear-stress conditions appears independent of cysLT(1)R antagonism.


Conservative management of Retzius space hematoma following spontaneous vaginal delivery in a woman with an unscarred uterus: A case report.
A retroperitoneal hematoma in obstetrics is very rare following spontaneous vaginal delivery. It requires a high index of suspicion, especially in a hemodynamically unstable patient with no active bleeding or external trauma postpartum, as early intervention is needed to prevent maternal morbidity and mortality. Conservative management may be an appropriate strategy in managing large hematomas even though surgical evacuation is classically recommended. We report the case of a 39-year-old woman, para three, with a hematoma of the Retzius space after spontaneous uncomplicated vaginal delivery. The patient had sudden abdominal pain associated with urinary retention, two hours after delivery. She had a palpable mass at the anterior upper part of the vaginal wall, near the fornices, but no abnormality was detected at the labia majora, labia minora and lower part of the vagina. A transabdominal ultrasound scan revealed a mixed-echogenicity mass between the bladder and lower part of the uterus measuring 110 × 90 × 60 mm. The patient's hemoglobin level dropped from 12 g/dL to 10 g/dL. Given the patient's clinically stable state, she was managed conservatively with antibiotics, analgesics and one unit of packed red blood cells, and was discharged home day 5 postpartum. This case supports the conservative management of even large Retzius space hematomas for hemodynamically stable patients. A high index of suspicion and thorough evaluation are required when encountering a complaint of urinary retention and abdominal pain postpartum.


Sexual dysfunction in women: what can urologists contribute?
Urologists have led the basic science and clinical research of organic-based issues in male sexual dysfunction. Concerning scientific, evidence-based, biologic-focused information, the field of sexual dysfunction in women is relatively new compared with sexual dysfunction in men. Basic science, epidemiology, physiology, pathophysiology, diagnosis, and treatment data on women's sexual health issues are now more regularly published than ever before, with the urologic community once again leading the way. This article reviews some pioneering, resourceful, creative, and novel contributions that urologists have made to enhance the understanding of sexual dysfunction in women. As is obvious in infertility treatment, sexual medicine health care requires biologic and psychologic attention to both members of the couple. The goal of all sexual medicine health care providers is to provide the best health care delivery to women and men with sexual health concerns.


Recombinant zoster vaccine coverage in the United States: An analysis of claims-based data.
Recombinant zoster vaccine (RZV) is recommended for individuals ≥ 50 years of age for protection against herpes zoster (HZ). This study quantifies RZV coverage and assesses predictors for RZV vaccination using a U.S. claims database. Univariate linear regression provided annual prevalence of RZV vaccination and multivariable logistic regression provided ORs and 95% CIs for associations between predictors and RZV vaccination. A total of 4,124,315 individuals (19,080,914 person-years) were included in this study. Since receiving FDA approval for the prevention of HZ, RZV coverage (of at least one dose) has reached approximately 17% within the eligible U.S. population by January 2021, although significant disparities between demographic groups were noted. Our findings suggest that HZ vaccine coverage may be reduced below goal in the U.S. and highlights the importance of continuing to monitor RZV vaccination. Additionally, as our study found disparities in vaccine coverage, attention towards marginalized and medically underserved populations is needed.


X-Ray Structure and In Vitro Anti-Tumoural Activity of the Dimeric Bis[(2-Phenyl-1,2-Dicarba-Closo-Dodecaborane-1-Carboxylato)-Di-n-Butyltin] Oxide.
X-ray diffraction studies reveal the structure of {[(2-C(6)H(5)-1,2-C(2)B(10)H(10)-1-COO)Bu(2)Sn](2)O}(2), 1, to conform to the common motif found for {[(R'COO)R(2)Sn](2)O}(2) compounds. The dimer features a central Bu(2)Sn(2)O(2) unit (two-fold symmetry) with the two Bu(2)Sn groups being linked via bridging oxygen atoms, each of which also carries an exocyclic Bu(2)Sn moiety. The two pairs of exo- and endo-cyclic tin atoms are each linked via an almost symmetrically bridging carboxylate ligand and the two remaining ligands coordinate an exocyclic tin atom only, in the monodentate mode. The in vitro anti-tumour activity of 1, determined against a variety of cell lines, is compared with those of the corresponding 2-methylcarboranylacetate, derivative 2, and with clinically used compounds.


Superior colliculus connections with the extraocular motor nuclei in the cat.
Direct and indirect projections from the cat superior colliculus to the extraocular motor nuclei were studied using the orthograde autoradiographic tracing method, the retrograde horseradish peroxidase technique, and Golgi methods. The results show that the superior colliculus projects to the central gray matter directly overlying the oculomotor complex. This projection arises almost entirely from the rostral third of the colliculus, and it terminates most heavily over the rostral half of the oculomotor complex. Dendrites of oculomotor cells extend into this tectal termination zone, making direct tecto-oculomotor contacts possible. Central gray cells within this termination zone project bilaterally to the abducens nuclei. It is proposed that the superior colliculus projection to the supraoculomotor central gray matter and the projection from the central gray matter to the abducens nuclei play a role in convergent eye movements. The superior colliculus projects lightly to a cell group directly ventrolateral to the trochlear nucleus. The superior colliculus sends a small direct projection to the contralateral abducens nucleus and a substantial projection to wide regions of the reticular formation that have been shown previously to project, in turn, to the abducens nucleus. Colliculus cells projecting to the abducens nucleus and adjacent reticular formation are located only in the caudal three-fourths of the colliculus, where they become increasingly concentrated at successively more caudal levels. It is proposed that the graded density of the cells of origin of this projection is the basic structural mechanism by which the colliculus generates horizontal foveating saccades of different amplitudes. Laminar analysis of the origin of all the superior colliculus projections to the extraocular motor regions described here revealed that they arise mostly from the stratum griseum intermedium.


Significance of biparietal diameter differences between twins.
Twins of dissimilar size have increased risks both at delivery and in the neonatal period. When dissimilar growth is severe, it should be reflected in birthweight and biparietal diameter (BPD) growth. Sonograms were done on 74 of 106 sets of twins delivered from July 1, 1973, to June 30, 1977. Excluding prematurity and birth trauma, the difference in BPD between twins with normal outcomes in the last scan prior to delivery was 1.32 +/- 0.20 mm (mean +/- SE) and the difference in birthweight was 250.3 +/- 31.4 g (mean +/- SE). In 7 sets of twins with poor outcomes (intrauterine fetal demise or severe intrauterine growth retardation) without central nervous system anomalies the difference in BPD between twins in the last scan, while both fetuses were alive, was 6.86 +/- 1.06 mm (mean +/- SE) and the difference in birthweight was 604.3 +/- 217.2 g (mean +/- SE). Both the BPDs and birthweights are significantly different at the P less than 0.01 level. Large differences in BPD between twins may possibly indicate compromise of one twin.


Characterization of a partial cDNA clone detected by imidazoline receptor-selective antisera.
A cDNA clone has been isolated from a human hippocampal cDNA expression library by relying on the selectivity of two antisera that are specific for imidazoline binding proteins. A 1789 bp cDNA clone was sequenced and shown to contain a single open-reading frame that predicts a 66 kDa polypeptide, but it is truncated based on its lack of a stop codon and poly-A+ tail. Two regions of homology exist for the predicted amino acid sequence in common with chromogranin-A and B proteins, a zinc finger protein, and the ryanodine receptor. Northern blot analyses of poly-A+ mRNA from 36 human tissues indicated two differentially expressed transcripts of 6.0 and 9.5 kb. The 6.0 kb mRNA form was enriched in brain and endocrine tissues as compared to other tissues, but not in strict concordance with I1-imidazoline binding sites. The highest overall amounts of the combined transcripts were found in pituitary. In situ hybridization histochemistry revealed an enrichment of the message in neuronal cell bodies of the rat hippocampus and cerebellar cortex. This clone has some of the properties expected of an imidazoline receptor.


Identification and immunological characterization of lipid metabolism-related molecular clusters in nonalcoholic fatty liver disease.
Nonalcoholic fatty liver disease (NAFLD) is now the major contributor to chronic liver disease. Disorders of lipid metabolism are a major element in the emergence of NAFLD. This research intended to explore lipid metabolism-related clusters in NAFLD and establish a prediction biomarker. The expression mode of lipid metabolism-related genes (LMRGs) and immune characteristics in NAFLD were examined. The "ConsensusClusterPlus" package was utilized to investigate the lipid metabolism-related subgroup. The WGCNA was utilized to determine hub genes and perform functional enrichment analysis. After that, a model was constructed by machine learning techniques. To validate the predictive effectiveness, receiver operating characteristic curves, nomograms, decision curve analysis (DCA), and test sets were used. Lastly, gene set variation analysis (GSVA) was utilized to investigate the biological role of biomarkers in NAFLD. Dysregulated LMRGs and immunological responses were identified between NAFLD and normal samples. Two LMRG-related clusters were identified in NAFLD. Immune infiltration analysis revealed that C2 had much more immune infiltration. GSVA also showed that these two subtypes have distinctly different biological features. Thirty cluster-specific genes were identified by two WGCNAs. Functional enrichment analysis indicated that cluster-specific genes are primarily engaged in adipogenesis, signalling by interleukins, and the JAK-STAT signalling pathway. Comparing several models, the random forest model exhibited good discrimination performance. Importantly, the final five-gene random forest model showed excellent predictive power in two test sets. In addition, the nomogram and DCA confirmed the precision of the model for NAFLD prediction. GSVA revealed that model genes were down-regulated in several immune and inflammatory-related routes. This suggests that these genes may inhibit the progression of NAFLD by inhibiting these pathways. This research thoroughly emphasized the complex relationship between LMRGs and NAFLD and established a five-gene biomarker to evaluate the risk of the lipid metabolism phenotype and the pathologic results of NAFLD.


Confronting two biomolecular techniques to detect NRF2 gene polymorphism biomarkers.
Gene polymorphism biomarkers identify individual susceptibility to environmental and occupational hazards. The conventional approach considers polymerase chain reaction (PCR) followed by restriction fragment length polymorphism analysis (RFLP), a reliable but expensive and time-consuming two-step procedure. Therefore we evaluated the simpler method confronting two-pair primers (CTPP)-PCR for its robustness and applicability to epidemiologic studies. We compared CTPP-PCR and PCR-RFLP techniques to detect two NRF2 polymorphisms in a set of biological samples. CTPP-PCR produced contradictory results and required the orthogonal technique for confirming the data. In contrast to PCR-RFLP, CTPP-PCR of NRF2 polymorphisms resulted in ambiguous genotyping which strongly jeopardized heterozygosis classification. The necessity of long optimization and control procedures nullified the potential advantages of CTPP-PCR in terms of costs and time.


Comparative cost-effectiveness of robot-assisted and standard laparoscopic prostatectomy as alternatives to open radical prostatectomy for treatment of men with localised prostate cancer: a health technology assessment from the perspective of the UK National Health Service.
Robot-assisted laparoscopic prostatectomy is increasingly used compared with a standard laparoscopic technique, but it remains uncertain whether potential benefits offset higher costs. To determine the cost-effectiveness of robotic prostatectomy. We conducted a care pathway description and model-based cost-utility analysis. We studied men with localised prostate cancer able to undergo either robotic or laparoscopic prostatectomy for cure. We used data from a meta-analysis, other published literature, and costs from the UK National Health Service and commercial sources. Care received by men for 10 yr following radical prostatectomy was modelled. Clinical events, their effect on quality of life, and associated costs were synthesised assuming 200 procedures were performed annually. Over 10 yr, robotic prostatectomy was on average (95% confidence interval [CI]) £1412 (€1595) (£1304 [€1473] to £1516 [€1713]) more costly than laparoscopic prostatectomy but more effective with mean (95% CI) gain in quality-adjusted life-years (QALYs) of 0.08 (0.01-0.15). The incremental cost-effectiveness ratio (ICER) was £18 329 (€20 708) with an 80% probability that robotic prostatectomy was cost effective at a threshold of £30 000 (€33 894)/QALY. The ICER was sensitive to the throughput of cases and the relative positive margin rate favouring robotic prostatectomy. Higher costs of robotic prostatectomy may be offset by modest health gain resulting from lower risk of early harms and positive margin, provided >150 cases are performed each year. Considerable uncertainty persists in the absence of directly comparative randomised data.


Perspectives on consciousness in patients with disorders of consciousness from brain injury: group concept mapping study across clinic, research, and families.
An effective healthcare system depends on clinic, research, and patient/relatives interactions. Such interactions may at their core be challenged by misalignments of concepts and the practices that constitute them. The concept of consciousness and what is experienced and understood as signs of consciousness in patients with severe acquired brain injury is one of these potential areas of misalignment. Different perspectives and experiences of consciousness are challenging the delivery of care and the high-stake decision-making process on the potential withdrawal of treatment. The enhanced uncertainties call for reflections on how key stakeholders perceive and identify consciousness in current clinical encounters and practice. The study empirically explores the actual experiences and conceptions of consciousness concerning patients with disorders of consciousness (DoC) from the perspectives of researchers, health professionals, and relatives of patients, to understand the challenges of the diversity of understandings of consciousness. Engaging the stakeholders by employing Group Concept Mapping methodology, the study developed a situated conceptual map, which reflects nuances and the importance of perspectives on and signs of consciousness. Twenty-seven participants contributed to the generation of ideas, 14 took part in the structuring of statements and 10 took part in the validation meeting to interpret the cluster rating map. A total of 85 unique statements were identified and organized into six clusters: (1) Presence, (2) Intentional Activity, (3) Experience of self, (4) Participation in Social Interaction, (5) (Repeated) Response, and (6) Unspecific Reaction. The conceptual mapping demonstrates an extensive overlap in perspectives on consciousness among participants, prioritizing signs that are observable at the bedside. The study provides a first step toward a future framework for the difficult process of decision-making concerning a segment of patients with DoC. The study highlights the importance of repeatable signs of consciousness observed at the bedside and the patient's ability to participate in social interactions, while also considering the importance of non-clinically observable signs of consciousness.


Vocal cord paralysis associated with pleuroparenchymal fibroelastosis: A case report and literature review.
Here, we report a case of idiopathic pleuroparenchymal fibroelastosis (PPFE) that progressed to pulmonary aspergilloma, aspiration pneumonia, and left vocal cord paralysis (VCP). To date, five cases of PPFE with VCP have been reported, including the present case. Aspiration pneumonia occurred in three cases, leading to death in two cases. Four cases had left-sided paralysis, in two of which, the paralysis occurred on side opposite to the predominant side (right side) of PPFE. Structural mechanisms underlying the recurrent laryngeal nerve could be involved. This report may further highlight the existence of hoarseness and dysphagia in PPFE.


Visualisation of cerebrospinal fluid flow patterns in albino Xenopus larvae in vivo.
It has long been known that cerebrospinal fluid (CSF), its composition and flow, play an important part in normal brain development, and ependymal cell ciliary beating as a possible driver of CSF flow has previously been studied in mammalian fetuses in vitro. Lower vertebrate animals are potential models for analysis of CSF flow during development because they are oviparous. Albino Xenopus laevis larvae are nearly transparent and have a straight, translucent brain that facilitates the observation of fluid flow within the ventricles. The aim of these experiments was to study CSF flow and circulation in vivo in the developing brain of living embryos, larvae and tadpoles of Xenopus laevis using a microinjection technique. The development of Xenopus larval brain ventricles and the patterns of CSF flow were visualised after injection of quantum dot nanocrystals and polystyrene beads (3.1 or 5.8 μm in diameter) into the fourth cerebral ventricle at embryonic/larval stages 30-53. The fluorescent nanocrystals showed the normal development of the cerebral ventricles from embryonic/larval stages 38 to 53. The polystyrene beads injected into stage 47-49 larvae revealed three CSF flow patterns, left-handed, right-handed and non-biased, in movement of the beads into the third ventricle from the cerebral aqueduct (aqueduct of Sylvius). In the lateral ventricles, anterior to the third ventricle, CSF flow moved anteriorly along the outer wall of the ventricle to the inner wall and then posteriorly, creating a semicircle. In the cerebral aqueduct, connecting the third and fourth cerebral ventricles, CSF flow moved rostrally in the dorsal region and caudally in the ventral region. Also in the fourth ventricle, clear dorso-ventral differences in fluid flow pattern were observed. This is the first visualisation of the orchestrated CSF flow pattern in developing vertebrates using a live animal imaging approach. CSF flow in Xenopus albino larvae showed a largely consistent pattern, with the exception of individual differences in left-right asymmetrical flow in the third ventricle.


Materials-based receptors: design principle and applications.
This review focuses on recent developments and growth potential in colorimetric and/or fluorimetric chemosensors based on rationally designed materials and suitable for use in highly selective and sensitive naked-eye detection of environmental and biological analytes.


A community pharmacy-led intervention for opioid medication misuse: A small-scale randomized clinical trial.
Stemming the opioid epidemic requires testing novel interventions. Toward this goal, feasibility and acceptability of a Brief Motivational Intervention-Medication Therapy Management (BMI-MTM) intervention was examined along with its impact on medication misuse and concomitant health conditions. We conducted a two-group randomized trial in 2 community pharmacies. We screened patients for prescription opioid misuse at point-of-service using the Prescription Opioid Misuse Index. Participants were assigned to standard medication counseling (SMC) or SMC + BMI-MTM (referred to as BMI-MTM herein). BMI-MTM consists of a pharmacist-led medication counseling/brief motivational session and 8-weekly patient navigation sessions. Assessments were at baseline, 2-, and 3-months. Primary outcomes included feasibility, acceptability, and mitigation of opioid medication misuse. Secondary outcomes included pain and depression. Outcomes were analyzed with descriptive and multivariable statistics (intent-to-treat [ITT] and adjusted for number of sessions completed [NUMSESS]). Thirty-two participants provided informed consent (74.4% consent rate; SMC n = 17, BMI-MTM n = 15; 3-month assessment retention ≥93%). Feasibility was demonstrated by all BMI-MTM recipients completing the pharmacist session and an average of 7 navigation sessions. BMI-MTM recipients indicated ≥4.2 (5 maximum) level of satisfaction with the pharmacist-led session, and 92.4% were satisfied with navigation sessions. Compared to SMC at 3-months, BMI-MTM recipients reported greater improvements in misuse (ITT: Adjusted Odds Ratio [AOR] = 0.13; 95% CI = 0.05, 0.35, p < 0.001. AOR = 0.05; 95% CI = 0.01, 0.25; p < 0.001), pain (ITT: В = 8.8, 95% CI=-0.95, 18.5, p = 0.08; NUMSESS: В = 14.0, 95% CI = 3.28, 24.8, p = 0.01), and depression (ITT: B= -0.44; 95% CI=-0.65, -0.22; p < 0.001. B= -0.64; 95% CI=-0.82, -0.46; p < 0.001). BMI-MTM is a feasible misuse intervention associated with superior satisfaction and outcomes than SMC. Future research should test BMI-MTM in a large-scale, fully-powered trial.


Electric- Field-Modified In Situ Precise Deposition of Electrospun Medical Glue Fibers on the Liver for Rapid Hemostasis.
Precise deposition of nanofibers is still an important issue in the applications of electrospinning (e-spinning), especially in rapid hemostasis of organs such as the liver, lung, and kidney. In this study, we propose an electric field-modified e-spinning technique with a metal cone attached to the spinning nozzle to realize controllable precise deposition of fibers. The deposition range of the e-spun fibers is tunable by changing the size of the metal cone, and the mechanism is attributed the focused electric field verified by theoretical simulations. This electric field-modified e-spinning method was further used to in situ precisely deposit medical glue N-octyl-2-cyanoacrylate (NOCA) fibers onto the resection site of rat liver to realize rapid hemostasis within 10 s. Postoperative pathological results indicate that less inflammatory response and tissue adhesion are observed in this electric field-modified e-spinning group compared with that of traditional airflow-assisted group. This technique combined with our designed handheld e-spinning device could be used in emergency medical treatment, clinics, field survival, and home care for its portability and precise deposition characteristics.


Quantitative analysis of immunocompetent cells in human normal oral and uterine cervical mucosa, oral papillomas and leukoplakias.
Using monoclonal antibodies reacting with T-cell subpopulations, Langerhans cells and macrophages, the number and distribution of cells of the immune system in normal oral and cervical mucosa was determined and statistically compared with that in oral papillomas and oral leukoplakias. Increased numbers of labelled cells were found in oral leukoplakias and particularly in oral papillomas. In the epithelium of all specimens, Langerhans cells and T-lymphocytes of the suppressor/cytotoxic phenotype as well as of the helper phenotype were seen. Suppressor/cytotoxic and helper T-lymphocytes were in equal numbers in the epithelium of oral papillomas, but were about 2:1 in all other lesions. In normal oral epithelium, macrophages were rare but were in greater numbers in leukoplakias and papillomas. In the connective tissue of all lesions, more labelled cells were present than in epithelium with T-lymphocytes predominant. Although Langerhans cells were rare in connective tissue, many were seen in oral papillomas.


Enhanced production of xylose from corncob hydrolysis with oxalic acid as catalyst.
The acid-catalyzed treatment was a conventional process for xylose production from corncob. To increase the release of xylose and to reduce the by-products formation and water usage, the oxalic acid was used as catalyst to hydrolyze the corncob and the hydrolytic conditions were investigated. The highest xylose yield of 32.7 g L-1, representing 96.1% of total theoretical xylose yield, was obtained using 1.2% oxalic acid after hydrolysis for 120 min at 130 °C, which was more than 10% higher than that of sulfuric acid-catalyzed hydrolysis. Mixed acids-catalyzed hydrolysis performed a synergistic effect for xylose production and 31.7 g L-1 of xylose was reached after reacting for 90 min with oxalic acid and sulfuric acid at a ratio of 1:4 (w/w). A kinetic model was developed to elucidate the competitive reaction between xylose formation and its degradation in the hydrolysis process, and the experimental data obtained in this study were perfectly in agreement with that of predicted from the model. Furthermore, the final xylose yield of 85% was achieved after purification and crystallization. It was demonstrated that xylose production from the corncob hydrolysis with oxalic acid as the catalyst was an effective alternative to the traditional sulfuric acid-based hydrolysis.


The role of dendritic cells in allergic diseases.
Allergic diseases are important diseases that affect many patients worldwide. Over the past few decades, the incidence of allergic diseases has increased significantly due to social development and increased environmental degradation, which has placed a huge economic burden on public health and even led to an increase in mortality. Substantial progress has been made in the understanding of the mechanisms of allergic diseases, and past studies have shown that the occurrence and development of allergic diseases are closely related to changes in the state of the immune system. With the study and in-depth understanding of innate immune lymphocytes, researchers have gradually discovered that dendritic cells (DC) play an important role in many allergic diseases. DC are the body's main antigen-presenting cells, which ingest, process, and hand allergens, and then secrete chemokines such as chemokine ligands 17(CCL17), CCL22, and upregulate their own surface co-stimulating molecules. Then DC present the antigen peptide to the initial T cells and further differentiate them into helper T cells 2(Th2). As an important part of humoral immunity, Th2 participates in the regulation of type 2 immune response through the secretion of cytokines such as interleukin 4(IL-4), IL-5, and IL-13 and plays a leading role. However, our current research on DC is limited and its status in allergic diseases is unclear.Among them, allergic rhinitis, allergic asthma, atopic dermatitis, and food allergy are DC-mediated Th2 immune-related factor disorder-related allergic diseases, and some progress has been made in recent years in the study of the pathogenesis of these diseases. This paper outlines the common phenotypes and activation pathways of DC in different allergic diseases as well as potential research directions to improve the understanding of its immunomodulatory role in different allergic diseases and ultimately find new ways to treat these diseases.


Prophylactic cranial irradiation in advanced breast cancer: a case for caution.
Prophylactic cranial irradiation (PCI) has a well-recognized role in the treatment of leukemia and small-cell lung cancer. Clinical utility has yet to be determined for breast cancer, where an emerging group at high risk of brain metastasis has fuelled consideration of PCI. In reviewing our experience with PCI as part of a complex protocol for advanced breast cancer, we present descriptive data on late central nervous system outcomes in those receiving PCI. After high-dose anthracycline-based induction chemotherapy, Stage IIIB/IV breast cancer responders underwent tandem autologous marrow transplantation. Those in continued remission were referred for PCI. Whole-brain radiotherapy was delivered by usual means, at 36 Gy in 20 fractions. Twenty-four women, with median age 45 (28-61), were enrolled between 1995 and 1998. Disease was largely metastatic (79%), and 75% were previously exposed to chemotherapy or hormonotherapy. Ten patients received PCI, at a median of 13.4 (11.8-16.5) months from study entry. Six patients developed brain metastases, 2 despite PCI. Striking functional decline was documented in 3 patients (at 9 months, 4 years, and 5 years post-PCI), including one previously high-functioning woman requiring full care for posttreatment dementia. We present a series of advanced breast cancer patients treated prophylactically with whole-brain radiotherapy following an aggressive chemotherapy regimen. Although the therapeutic benefit of PCI is not ascertainable here, we describe brain metastases occurring despite PCI and serious long-term neurobehavioral sequelae in PCI-treated patients. Any further investigation of PCI in high-risk breast cancer will need to be approached with caution.


Metal catalyst-free selective acetosyringone synthesis from rice straw lignin.
In recent decades, due to abundance (second most abundant natural polymer after cellulose) and sustainability, lignin has attracted much interest from different researchers to use as a raw material for producing various value-added materials such as polymer and fuel. In addition to that, the aromatic structure of lignin makes it a suitable candidate for producing platform chemicals with aromatic rings. As a result, lignin depolymerization has become an interesting process to derive different phenolic monomers like vanillin, acetosyringone, and guaiacol. Among them, due to the bioactive characteristics and efficiency of acetosyringone in plant regulatory systems, the production of acetosyringone from lignin has been presented in this work. A green and cost-effective method was developed for the selective formation of acetosyringone via depolymerization of isolated rice straw lignin (RSL) by using metal catalyst-free conditions in the biphasic medium and described. The RSL was characterized with various spectroscopic techniques such as FT-IR, solid-state 13C NMR, XPS, and TGA. The selectivity of synthesized acetosyringone during depolymerization of RSL was checked from GC-MS analysis. The molecular structure and purity of acetosyringone isolated from preparative thin layer chromatography (TLC) were confirmed with the help of 1H NMR and HRMS, respectively.


Use of reflected green light for specific identification of islets in vitro after collagenase isolation.
A simple technique is described that permits specific identification in vitro of isolated islets as contrasted with samll lymph nodes.


Atherosclerotic carotid artery disease in patients with retinal ischemic syndromes.
The extracranial carotid systems of 105 patients with retinal ischemia were examined using B-mode ultrasonography with integrated pulsed Doppler. Sixty-four patients had amaurosis fugax (AF), 17 central retinal artery occlusions (CRAO), and 21 branch retinal artery occlusions (BRAO). The prevalence of carotid stenosis (greater than or equal to 60%) ipsilateral to the symptomatic eye was low (16%). Eighty-six percent of AF patients had either no plaque causing less than a 60% stenosis. A significant proportion of subjects with normal duplex scans had alternative explanations for their retinal ischemia (eg, migraine, cardiac embolus). Patients with Hollenhorst plaques were more likely to have stenotic or ulcerated plaque (p = 0.04). The degree of carotid stenosis correlated significantly with the number of vascular risk factors identified in individual patients (p = 0.02). The presence of risk factors was more common in CRAO and BRAO patients compared with the AF group. Combined ultrasound-Doppler investigations of the carotid bifurcation are valuable noninvasive tools for the screening of patients with retinal ischemia.


Creatine kinase isoenzyme (CK-BB) in combination to prostatic acid phosphatase measured by RIA in the diagnosis of prostatic cancer.
Creatine kinase isoenzyme (CK-BB) measured by mass was used to determine its value in the early diagnosis of prostatic cancer. Sera of patients with prostatic carcinoma of various stages (treated and untreated) were compared to normal male sera and sera of patients with benign hyperplasia of the prostate (BPH) with respect to CK-BB. The sera were simultaneously tested for PAP content. The sensitivity of the CK-BB-RIA was 1.63 +/- 0.08 microgram/1 and reproducibility in the higher and lower concentration range 7.6% and 10.5%, respectively. CK-BB alone or in combination with PAP is no marker for early detection of prostatic cancer. In individual cases changes occurred similar to those found with a malignant growth of the prostate.