New fossils of Mesopithecus from Hasnot, Pakistan.
Here, we report on a new collection of mostly isolated molars of a colobine monkey from near Hasnot on the Potwar Plateau of Pakistan. The specimens are from three late Miocene localities, with ages constrained to between 7.9 and 7.1 Ma. Morphological and metrical comparisons of the new Hasnot molars with those of previously recognized Mesopithecus species and living Asian colobines lead to the conclusion that the Hasnot colobine is most probably Mesopithecus, but not Mesopithecus pentelicus. The most morphologically distinctive aspect of the Hasnot specimens is the lower third molars, which exhibit large and bulbous protoconids set off by deeply incised mesial buccal and median buccal clefts and large, broad distobuccally placed hypoconulids. Colobine specimens previously recovered from the Potwar Plateau have been assigned to Mesopithecus sivalensis, but because these specimens have not yet been fully described, a detailed comparison with the new Hasnot specimens is not yet possible. For these reasons, we assign the new Hasnot colobine fossils to cf. Mesopithecus sp. Mesopithecus was one of the most widespread and successful of late Miocene primates. As a colobine equipped with features of the molar teeth, limbs, and, presumably, gut enabling it to succeed in more highly seasonal woodland environments, Mesopithecus was able to rapidly disperse into and adapt to the conditions in South Asia brought about by profound climatic and concomitant environmental change during the latest Miocene.


Stent-specific fat attenuation index is associated with target vessel revascularization after PCI.
To explore the clinical relevance of stent-specific perivascular fat attenuation index (FAI) in patients with stent implantation. A total of 162 consecutive patients who underwent coronary computed tomography angiography (CCTA) following stent implantation were retrospectively included. The stent-specific FAI at 2 cm adjacent to the stent edge was calculated. The endpoints were defined as target vessel revascularization (TVR) on the stented vessel after CCTA and readmission times due to chest pain after stent implantation. Binary logistic regression analysis for TVR and ordinal regression models were conducted to identify readmission times (0, 1, and ≥ 2) with generalized estimating equations on a per-stent basis. On a per-stent basis, 9 stents (4.5%) experienced TVR after PCI at a median 30 months' follow-up duration. Stent-specific FAI differed significantly among subgroups of patients with stent implantation and different readmission times (p = 0.002); patients with at least one readmission had higher stent-specific FAI than those without readmission (p < 0.001). Bifurcated stents (odds ratio [OR]: 11.192, p = 0.001) and stent-specific FAI (OR: 1.189, p = 0.04) were independently associated with TVR. With no readmission as a reference, stent-specific FAI (OR: 0.984, p = 0.007) was an independent predictor for hospital readmission times ≥ 2 (p = 0.003). Non-invasive stent-specific FAI derived from CCTA was found to be associated with TVR, which was a promising imaging marker for functional assessment in patients who underwent stent implantation. Noninvasive fat attenuation index adjacent to the stents edge derived from CCTA, an imaging marker reflecting the presence of inflammation acting on the neointimal tissue at the sites of coronary stenting, might be relevant clinically with target vessel revascularization. • Non-invasive stent-specific FAI derived from CCTA was associated with TVR (OR: 1.189 [95% CI: 1.007-1.043], p = 0.04) in patients who underwent stent implantation. • Stent-specific FAI significantly differed among a subgroup of patients with chest pain after stent implantation and with different readmission times (p = 0.002); the patients with at least one readmission had higher stent-specific FAI than those without readmission (p < 0.001). • Non-invasive stent-specific FAI derived from CCTA could be used as an imaging maker for the functional assessment of patients following stent implantation.


Inhibition of vasodepressor neurons in the caudal ventrolateral medulla of the rabbit increases both arterial pressure and the release of neuropeptide Y-like immunoreactivity from the spinal cord.
The role of bulbospinal neuropeptide Y (NPY)-containing neurons of the rostral ventrolateral medulla in the rabbit in mediating the increase in blood pressure that occurs during inhibition of cells in the caudal ventrolateral medulla was investigated in urethane-anaesthetized rabbits. In the present experiments bilateral injections of the GABA agonist, muscimol, into the caudal ventrolateral medulla elicited a slowly-developing rise in arterial pressure that was maximal 15 min after the injection. Accompanying this increase in arterial pressure was an increase in the release of NPY-like immunoreactivity (NPY-LI) into the spinal subarachnoid space. This pattern of response is similar to that seen after direct chemical stimulation of the NPY-containing cells of the rostral ventrolateral medulla. Taken together, these findings suggest that tonically active neurons in the caudal ventrolateral medulla exert their effects by inhibiting sympathoexcitatory NPY-containing neurons whose cell bodies are situated in the rostral ventrolateral medulla.


Left ventricular mesenchymal hamartoma, a new hamartoma of the heart.
Primary neoplasms of the heart are rare. Benign entities in adult populations include myxoma, fibroma, lipoma, hamartoma of mature myocytes, and vascular hamartoma. The most common pediatric cardiac neoplasm is the rhabdomyoma. We report a 22-year-old female with a primary left ventricle tumor composed of multiple mature mesenchymal tissues, including mature cardiac myocytes, smooth muscle, fibroblasts, fat, blood vessels including a hemangioma like area, and nerve fibers. The various elements were disorganized, but well differentiated, and showed little mitotic activity, which are features suggestive of a hamartoma. Unlike a cardiac fibroma, which may entrap myocardium at the periphery of the lesion, the present case demonstrated all tissue elements throughout the tumor mass. We suggest that this lesion is sufficiently different from those hamartomas previously described to warrant a new designation, for which we propose the title cardiac mesenchymal hamartoma.


Human mast cell chymase induces the accumulation of neutrophils, eosinophils and other inflammatory cells in vivo.
The roles of chymase in acute allergic responses are not clear, despite the relative abundance of this serine proteinase in the secretory granules of human mast cells. We have isolated chymase to high purity from human skin tissue by heparin-agarose affinity chromatography and Sephacryl S-200 gel filtration procedures, and have investigated the ability of human mast cell chymase to stimulate cell accumulation following injection into laboratory animals. Injection of chymase provoked marked neutrophilia and eosinophilia in the skin of Dunkin Hartley guinea-pigs. Compared with saline injected control animals, there were some 60 fold more neutrophils and 12 fold more eosinophils present at the injection site. Following injection of chymase into the peritoneum of BALB/c mice, there were up to 700 fold more neutrophils. 21 fold more eosinophils, 19 fold more lymphocytes and 7 fold more macrophages recovered than from saline injected controls at 16 h. Doses of chymase as low as 5 ng (1.7 x 10(-13) mole) stimulated an inflammatory infiltrate, and significant neutrophilia was elicited within 3 h. The chymase induced cell accumulation in both the guinea-pig and mouse models was dependent on an intact catalytic site, being reduced by co-injection of proteinase inhibitors or heat inactivation of the enzyme. Co-injection of histamine or heparin significantly reduced the chymase induced neutrophil accumulation, whereas neither histamine nor heparin by themselves had any effect on the accumulation of nucleated cells. No synergistic or antagonist interactions between chymase and tryptase were observed when these two major mast cell proteinases were co-injected into the mouse peritoneum. Our findings suggest that chymase may provide an potent stimulus for inflammatory cell recruitment following mast cell activation.


Noninvasive prenatal diagnosis by cell-free DNA screening for fetomaternal HPA-1a platelet incompatibility.
The development of new noninvasive approaches for the diagnosis of human platelet antigen (HPA)-1 fetomaternal incompatibility has become of great interest. These approaches allow determination of whether the fetus is incompatible or not with the mother and a decision on antenatal therapy to avoid fetal or neonatal alloimmune thrombocytopenia (FNAIT). The objective of this work was to perform rapid, noninvasive prenatal test for HPA-1ab fetal antigen detection after the detection of an HPA-1-homozygous mother by using plasma cell-free DNA (cfDNA). The HPA-1 genotypes of 142 pregnant women and 17 nonpregnant controls were retrospectively determined by high-resolution melting (HRM) polymerase chain reaction (PCR). Coamplification at lower denaturation temperature (COLD) HRM PCR was performed to determine the fetal genotype analyzing cfDNA from all HPA-1bb pregnant women. After the HRM analysis, the following genotypes were identified: HPA-1aa (71.13%), HPA-1bb (2.8%), and HPA-1ab (26.06%). Four HPA-1bb-homozygous pregnant women were carrying an incompatible fetus. Plasma samples from these mothers were analyzed by HRM COLD-PCR. Homozygous HPA-1bb pregnant women carrying an HPA-1ab-heterozygous fetus did not group with either the HPA-1ab or the HPA-1bb controls. Thus, COLD-PCR analysis allows the detection of HPA-1ab-heterozygous fetuses carried by homozygous mothers during first weeks of pregnancy. The fetal genotype from HPA-1bb-homozygous women was detected by a noninvasive prenatal test as soon as 12 weeks of gestation.


Reliability of a modified medication appropriateness index in primary care.
To evaluate the inter-group and intra-group reliability of a modified Medication Appropriateness Index (MAI) for use in primary care. Elderly (>65 years) polypharmacy (> or =5 drugs) patients in Copenhagen County participated in the study. Information concerning their medical history and information regarding each drug taken by them was provided by their own general practitioners. A MAI was scored by two groups of evaluators for every drug. To evaluate inter-group agreement, 211 drugs taken by 30 patients were rated according to the ten criteria making up the MAI. Both evaluator groups provided summaries of comments on the medication of each patient. Intra-group agreement was determined from MAI ratings performed twice at two different times on 86 drugs taken by ten patients. Agreement and chance-adjusted agreement were determined, the latter through kappa statistics. The proportion of positive (ppos) and negative (pneg) agreement was also determined. The overall chance-adjusted inter-group agreement (kappa) was moderate. The agreement was good on the criteria practical directions and drug-disease interaction, moderate on the criteria dosage and duration, fair on the criteria indication, effectiveness, duplication and expense, and poor on the criterion drug-drug interaction. The overall chance-adjusted intra-group agreement was good for all criteria and very good for the criteria indication and practical directions. The MAI is used to quantify appropriate and inappropriate prescribing and changes in prescribing quality in intervention studies. However, caution should be used when comparing results across different settings and evaluators. Our study suggests that the index should only be used in intervention studies if the same group rates the appropriateness pre- and post-intervention.


Postoperative perfusion deficits.
The three keys to successful recovery of the critically ill postoperative patient are: (1) in-depth preoperative assessment and risk evaluation; (2) review of intraoperative course and evaluation of risk for perfusion deficit; and (3) diligent postoperative monitoring for early onset of perfusion deficit. Complications arise when metabolic demands exceed the body's ability to supply essential nutrients. The choice of treatment modality is related to the cause of perfusion deficits. Decreased preload and afterload is treated with fluid and vasopressor therapy. Increased preload is best managed by diuretics and venous dilation. Afterload reduction is accomplished with vasodilator therapy and decreases in sympathetic stimulation. Contraction is enhanced with inotropic therapy and management of preload and afterload within normal ranges. Metabolic demands are best managed with tight control of the patient's hemodynamic profile, oxygen consumption, and environmental stimuli. The challenge of managing the critically ill postoperative patient is great, but the rewards of successful recovery are tremendous.


Aniline-induced tryptophan production and identification of indole derivatives from three purple bacteria.
Growth on aniline by three purple non-sulfur bacteria (Rhodospirillum rubrum ATCC 11170, Rhodobacter sphaeroides DSM 158, and Rubrivivax benzoatiliticus JA2) as nitrogen, or carbon source could not be demonstrated. However in its presence, production of indole derivatives was observed with all the strains tested. At least 14 chromatographically (HPLC) distinct peaks were observed at the absorption maxima of 275-280 nm from aniline induced cultures. Five major indoles were identified based on HPLC and LC-MS/MS analysis. While tryptophan was the major common metabolite for all the three aniline induced cultures, production of indole-3-acetic acid was observed with Rvi. benzoatilyticus JA2 alone, while indole-3-aldehyde was identified from Rvi. benzoatilyticus JA2 and Rba. sphaeroides DSM 158. Indole-3-ethanol was identified only from Rsp. rubrum ATCC 1170 and anthranilic acid was identified from Rba. sphaeroides DSM 158.


A synthetic Tn-BSA conjugate vaccine bearing chitotriose as built-in adjuvant.
Chitotriose (CTS), the hydrolysate of chitosan, is readily soluble in water because of the shorter chain lengths of the oligomers and the free amino groups in the d-glucosamine units. In the current study, we report the synthesis of novel conjugate vaccine Tn-BSA-CTS with chitotriose as built-in adjuvant, along with an evaluation of the effect of adjuvant chitotriose (CTS). Immunological evaluations of the resultant conjugate vaccine revealed that Tn-BSA-CTS could provoke the highest titers of IgG antibodies (102,400). The Tn-BSA-CTS conjugate remarkably enhanced both humoral and cellular immunity. The obtained results demonstrate the potential of CTS as a novel vaccine adjuvant in the development of antitumor vaccine and the covalent linkage of tumor vaccine to CTS might be available strategy to increase the efficacy against cancer.


Comparison of health service use trajectories of residential aged care residents reviewed by a hospital avoidance program versus usual care.
To compare health service use trajectories of residential aged care facility (RACF) residents reviewed by the Aged Care Rapid Response Team (ARRT) to RACF residents who received usual care. A retrospective group-based trajectory analysis of RACF residents aged ≥65 years who were reviewed by ARRT during 1 July 2015 to 30 June 2016 was conducted. Health service use trajectories were followed for two years to 30 June 2018 and compared to RACF residents aged ≥65 years who lived in the same Local Health District and received usual care. There were 2,245 ARRT-reviewed resident hospitalisations and 11,892 usual care resident hospital admissions during 2015-16. Trajectory analysis categorised ARRT-reviewed residents into four groups and usual care residents into three groups. Age, comorbid health conditions and dementia were predictors of group membership in both ARRT-reviewed RACF residents and usual care RACF residents. Additionally, gender predicted group membership in ARRT-reviewed RACF residents and fall-related injuries predicted group membership in usual care RACF residents. The identification of health service use trajectories assists in understanding hospital use by older RACF residents and may offer guidance in the design of prevention measures, including hospital avoidance programs.


Normal hepatic insulin receptor autophosphorylation in nonketotic diabetes mellitus.
Insulin receptor autophosphorylation is the earliest recognizable event in insulin action subsequent to insulin binding. To determine if the postbinding hepatic insulin resistance of nonketotic diabetes mellitus could reside in an inability of insulin to stimulate insulin receptor autophosphorylation, we evaluated the ability of insulin to stimulate 32P incorporation into the beta subunit of lectin-purified rat liver plasma membrane insulin receptors. The data indicate that both the absolute plasma membrane insulin receptor autophosphorylation in response to insulin as well as the insulin dose-response relationship for autophosphorylation are normal in diabetic animals when expressed per microgram of protein or per unit of binding activity. The previous data from our laboratory indicates that hepatic insulin resistance in non-ketotic streptozotocin-induced diabetes mellitus is present despite normal to increased insulin binding, is selective, is reversible with insulin treatment and involves an inability of insulin to stimulate the release of the putative mediator of insulin action. We conclude, therefore, that the hepatic insulin resistance of nonketotic diabetes mellitus resides distal to insulin receptor binding and autophosphorylation and is reflected in metabolic events at or near the plasma membrane which may include the generation or release of the putative mediator of insulin action.


[Perioperative myocardial protection in non-cardiac surgery].
Due to ongoing demographic changes more and more older patients with co-existent cardiac diseases undergo non-cardiac surgery. The risk of postoperative complications, notably myocardial ischemia, is raised in these patients. An accurate preparation before surgery including the risk profile and the management of co-medication is of paramount importance. Beta-blockers and statins should be continued perioperatively. The management of platelet aggregations inhibitors requires an interdisciplinary approach. During surgery, tachycardia as well as hypertension and hypotension should be treated consequently. Perioperative myocardial infarction is often asymptomatic and diagnosis can be difficult. Sufficient analgesia is important in postoperative care of patients with co-existing cardiac diseases.


Effects of infusion of branched chain amino-acids enriched TPN solutions on plasma amino-acid profiles in sepsis and trauma patients.
Total parenteral nutrition with branched chain amino-acids enriched solutions has been advocated in patients with sepsis and stress because of favourable effects on nitrogen balance, protein synthesis and immune competence. The rationale for the use of BCAA-enriched solutions is based on their potential to correct the plasma amino-acid imbalances seen in these patients. In a 7-day prospective randomised study we investigated the effects on plasma amino-acid concentrations of a standard amino-acid solution (15.6% BCAA) and a branched chain amino-acid enriched solution (50.2% BCAA) in 101 parenterally fed patients with carefully assessed sepsis and/or stress scores. The infusion of the BCAA-enriched solution led to an imbalance of the essential plasma amino-acids. The branched chain amino-acids valine, leucine and isoleucine increased significantly while the non-BCAA essential amino-acids decreased significantly. In the standard solution the non-BCAA-essential amino-acids increased significantly with a slow and insignificant rise in the levels of the branched chain amino-acids. We conclude that infusion of a BCAA enriched TPN formulation induced amino-acid profile derangements that can be considered ill-suited to the achievement of anti-catabolic effects.


How Efficacious is HRCT Temporal Bone in Determining the Ossicular Erosion in Cases of Safe and Limited Squamous Type CSOM?
HRCT temporal bone is a very valuable radiological investigation. However its still not widely used by otologists for routine surgeries. Ossicular erosion is often encountered unexpectedly in safe cases of CSOM and in limited squamous type of cases. If preoperative diagnosis of ossicular erosion is made then otologist can preoperatively plan ossicular reconstruction techniques leading to improved results. We conducted a study in 60 patients to evaluate the efficacy of HRCT temporal bone in determining ossicular erosion in cases of CSOM. It was a diagnostic observational study where surgical finding of ossicular erosion was taken as a gold standard. Sensitivity specificity; positive predictive value and negative predictive value of HRCT was calculated in detecting malleus; incus and stapes erosion. P value was calculated. Sensitivity and specificity for malleus erosion was 78.5% and 78.1% respectively. Sensitivity and specificity for incus erosion was 73.1% and 57.8% respectively. Sensitivity and specificity for stapes erosion was 52% and 57.1% respectively. P value was less than 0.05. We concluded that HRCT is a good adjunct for determining the ossicular erosion and its use should be encouraged by the otologist.


Several new bacteriophage T4 genes, mapped by sequencing deletion endpoints between genes 56 (dCTPase) and dda (a DNA-dependent ATPase-helicase) modulate transcription.
We have analyzed DNA of wild-type T4 and of 13 independent large viable deletions isolated by Homyk and Weil (Virology 61 (1974) 505-523) and by Little (Virology 53 (1973) 47-59), by sequencing, cloning, and expression studies. The deletions can be explained by illegitimate recombination between short (4- to 15-bp) ectopic repeats. In four deletions, adjacent regions are partially homologous, and in at least one of them, the base adjacent to the overlap was deleted during recombination. The sequence 5'-GGGC, which has not been associated with T4 deletions in other map regions, occurs within three repeats, and near the repeats in four more of the 13 deletions. Five previously named genes, 69, soc, mrh, modA, and dda were mapped relative to the deletion endpoints. Nine additional ORFs were found interspersed between them. One of these shares some similarities with mrh (modulates rpoH; Frazier and Mosig, Gene 88 (1990) 7-14), and another one resembles modA (coding for an ADP-ribosyl-transferase that modifies RNA polymerase alpha subunits, Skórko et al., Eur. J. Biochem. 79 (1977) 55-66) respectively. We found that the host's heat shock sigma factor, sigma32, is phosphorylated, and that Mrh protein modulates this phosphorylation. The ORF dda.9 downstream of mrh has a patchy similarity with conserved C-terminal segments (motifs) of sigma32; therefore, we call it srh. Another ORF, dda.2 located between modA and dda, shares sequence similarity with sigma70, and we call it srd. We consider the possibility that Srh and Srd act as decoys for sigma32, or sigma70, respectively. Expression of several of the ORFs from cloned DNA appears to be toxic to the host bacteria. Mutant clones only could be constructed from gene 69 and from modA. Moreover, dda.2 (srd)-containing bacteria grow extremely slowly, and they form filaments in liquid cultures. Clones carrying mrh and srh show less severe filamentation. Our results highlight the importance of 'non-essential' genes for phage development and evolution.


Sesquiterpenoids and norterpenoids from Vitex negundo.
Chemical investigation on the seeds of Vitex negundo has afforded a new furan-containing sesquiterpenoid, negunfurol (1), a new norlabdane-type diterpenoid, negundoal (2), and two new norursane-type triterpenoids, negundonorins A (3) and B (4), together with two know compounds, 3-formyl-4,5-dimethyl-8-oxo-5H-6,7-dihydronaphtho[2,3-b]furan (5) and 3-epi-corosolic acid (6). Their structures and configurations were elucidated by detailed spectroscopic analyses on the basis of NMR, IR, and MS data. Compound 3 was strongly cytotoxic against ZR-75-30 cell line with IC(50) value of 0.56 ± 0.19 μg/mL, whereas compound 1 was most active against HL-60 cell line with IC(50) value of 0.94 ± 0.26 μg/mL.


Conversion of orally administered 2-n.pentylaminoacetamide into glycinamide and glycine in the rat brain.
Male Sprague Dawley albino rats were treated orally with 2-n.pentylaminoacetamide (10 to 100 mg/kg b.wt). This oral administration provoked a dose-related and time-dependent accumulation of glycinamide in forebrain, cerebellum, and medulla, and to increased levels of glycine in the three brain areas, and of serine in medulla. In kidney, liver and plasma, the accumulation of glycinamide was lower and there was no increase in glycine and serine levels. With a dose of 100 mg/kg b.wt, 28% of the drug were eliminated unchanged and 16% as glycinamide, in urines collected for 24 h. In all tissues examined, 2-n.pentylaminoacetamide and glycinamide levels peaked at 1 h and were nil again after 24 h, the ratio of 2-n.pentylaminoacetamide over glycinamide decreasing more rapidly in brain than in kidney and liver. Contrasting with the effects of 2-n.pentylaminoacetamide, the oral administration of glycinamide (66 mg/b.wt) led, 2 hours later, to similar low rises of glycinamide in plasma and brain. In another control experiment, the intraperitoneal injection of a large dose of glycine (450 mg/kg b.wt) provoked, 30 min later, modest rises of glycine levels in the central nervous system that merely reflected a contamination by plasma glycine.


EBNA antibodies are more useful than complement fixing antibodies in monitoring infectious mononucleosis patients.
Thirty-six patients with infectious mononucleosis (IM) were followed prospectively for both anti-Epstein-Barr virus nuclear antigen (EBNA) and complement-fixing antibodies using the soluble EBV antigen (CF/S). Discrepancies in time between the two reactivities were found, due to the differences in sensitivity of the tests. It is suggested that, in clinical virology laboratories, EBNA and not CF/S tests be used.


ELISA quantitation of IgG subclass antibodies to dietary antigens.
The IgG subclasses of human antibodies against 2 dietary antigens, ovalbumin (OA) and beta-lactoglobulin (BLG), were studied by ELISA using monoclonal anti-human IgG subclass antibodies. Under the assay conditions used, the anti-IgG subclass antibodies were subclass specific. Quantitative estimates of the subclass antibodies were obtained by reference to a 'capture' assay using F(ab')2 anti-light chain antibody as ligand and IgG myelomas as standards. The validity of these estimates was supported by antibody quantitation using the Farr assay. In healthy adults with serum anti-OA or anti-BLG antibodies, anti-OA antibodies were found mainly in the IgG1 (9/11) and IgG4 (6/11) subclasses, whereas 5 sera showed high levels of IgG2 antibodies. In contrast, the IgG subclass distribution of anti-BLG antibodies was predominantly IgG4 (10/10).


Current status and guidelines for the assessment of tumour vascular support with dynamic contrast-enhanced computed tomography.
Dynamic contrast-enhanced computed tomography (DCE-CT) assesses the vascular support of tumours through analysis of temporal changes in attenuation in blood vessels and tissues during a rapid series of images acquired with intravenous administration of iodinated contrast material. Commercial software for DCE-CT analysis allows pixel-by-pixel calculation of a range of validated physiological parameters and depiction as parametric maps. Clinical studies support the use of DCE-CT parameters as surrogates for physiological and molecular processes underlying tumour angiogenesis. DCE-CT has been used to provide biomarkers of drug action in early phase trials for the treatment of a range of cancers. DCE-CT can be appended to current imaging assessments of tumour response with the benefits of wide availability and low cost. This paper sets out guidelines for the use of DCE-CT in assessing tumour vascular support that were developed using a Delphi process. Recommendations encompass CT system requirements and quality assurance, radiation dosimetry, patient preparation, administration of contrast material, CT acquisition parameters, terminology and units, data processing and reporting. DCE-CT has reached technical maturity for use in therapeutic trials in oncology. The development of these consensus guidelines may promote broader application of DCE-CT for the evaluation of tumour vascularity. Key Points • DCE-CT can robustly assess tumour vascular support • DCE-CT has reached technical maturity for use in therapeutic trials in oncology • This paper presents consensus guidelines for using DCE-CT in assessing tumour vascularity.


Turning on the Arp2/3 complex at atomic resolution.
The recently published 2 A X-ray crystal structure of bovine Arp2/3 complex gives us atomic scale insight into Arp2/3-mediated actin nucleation, while cryo-EM work and functional studies begin to fill in exciting mechanistic details.


Liposome-encapsulated DNA-mediated gene transfer and synthesis of human factor IX in mice.
Hemophilia B is an X-chromosome-linked recessive disorder that is caused by a deficiency of biologically active clotting factor IX (FIX). In this work, liposomes (Lip) were used for non-viral, in vivo gene transfer of the human FIX gene into mouse organs. Plasmid DNA, containing the human FIX cDNA under the control of the Moloney murine leukemia virus (MoMLV) long terminal repeat (LTR), was encapsulated in 1-2-microns multilamellar Lip composed of egg phosphatidylcholine (EPC). The percentage of Lip-associated DNA was 47%, and 72% of the Lip DNA was protected from DNase I digestion. The Lip-encapsulated (Len) DNA was injected intravenously into Balb/c mice, and at various times post-injection, various tissues were examined for the presence of the exogenous DNA. Plasmid DNA was detected by Southern blot analysis mainly in the liver and spleen, but small amounts were also detected in the lungs, heart and kidneys. The plasmid DNA was retained in mouse liver cells for at least 7 days post-injection, and remained in an episomal state. The levels of human FIX protein in the mouse plasma were 190-650 pg per ml for 2 to 7 days post-injection. Treatment of mice with chloroquine (Cq) and colchicine (Cc) prior to Lip injection significantly increased the amount of plasmid DNA found in the liver cells, as well as the level of human FIX in the plasma. These results demonstrate the potential use of Len DNA for gene transfer into liver and spleen, and for gene therapy of inherited and acquired disorders.


Combination chemotherapy of carboplatin and gemcitabine against solid tumors: a phase I trial.
Some trials have suggested that the combination of gemcitabine and platinum compounds can have a synergistic effect on several solid tumors, but, at present, the data concerning carboplatin-gemcitabine combinations are not sufficient to allow the planning of phase II trials. The present phase I trial was planned to define the maximum tolerated dose and the dose-limiting toxicity of a carboplatin-gemcitabine combination. Thirty-two patients with advanced, pretreated solid tumors were treated with carboplatin on day 1 and gemcitabine on days 1, 8, and 15 every 28 days. The starting doses of carboplatin and gemcitabine were 3.5 mg/ml per min (area under the curve; AUC), and 600 mg/m2, respectively. The doses of the two agents were alternately increased to 4, 4.5, and 5 mg/ml per min and to 800 and 960 mg/m2, respectively. At each dose level, three patients were initially enrolled. If one of them experienced grade IV hematological toxicity or grade III-IV nonhematological toxicity (with the exception of alopecia), an additional three patients were enrolled at the same dose level. If two or more patients experienced grade IV hematological toxicity or grade III-IV non-hematological toxicity (with the exception of alopecia), the maximum tolerated dose was considered to have been reached, and the dose below this was recommended for further studies. All patients were evaluated weekly for toxicity and after every two courses of chemotherapy for response. Dose-limiting toxicity was hematological, and the maximum tolerated doses were 4.5 mg/ml per min for carboplatin and 800 mg/m2 for gemcitabine. The activity of the carboplatin/gemcitabine combination was encouraging, with a 21.9% response rate (7/32), three complete disease regressions, and a median time to progression of 30 weeks. The gemcitabine doses of day 15 or days 8 and 15 were omitted for hematological toxicity in 57 (50%) and 17 (14.9%) courses of chemotherapy, while no courses of chemotherapy were delayed for grade III-IV hematological or nonhematological toxicity. The maximum tolerated doses suggested by this trial are lower than those in other similar phase I trials, but they are consistent with those reported by most of the trials investigating gemcitabine either in combination with cisplatin or in heavily pretreated patients. Carboplatin 4.5 mg/ml per min on day 1 plus gemcitabine 800 mg/m2 on days 1, 8, and 15 every 28 days may represent a promising schedule for further phase II trials.


Digital transformation of peatland eco-innovations ('Paludiculture'): Enabling a paradigm shift towards the real-time sustainable production of 'green-friendly' products and services.
The world is heading in the wrong direction on carbon emissions where we are not on track to limit global warming to 1.5 °C; Ireland is among the countries where overall emissions have continued to rise. The development of wettable peatland products and services (termed 'Paludiculture') present significant opportunities for enabling a transition away from peat-harvesting (fossil fuels) to developing 'green' eco-innovations. However, this must be balanced with sustainable carbon sequestration and environmental protection. This complex transition from 'brown to green' must be met in real time by enabling digital technologies across the full value chain. This will potentially necessitate creation of new green-business models with the potential to support disruptive innovation. This timely paper describes digital transformation of paludiculture-based eco-innovation that will potentially lead to a paradigm shift towards using smart digital technologies to address efficiency of products and services along with future-proofing for climate change. Digital transform of paludiculture also aligns with the 'Industry 5.0 - a human-centric solution'. However, companies supporting peatland innovation may lack necessary standards, data-sharing or capabilities that can also affect viable business model propositions that can jeopardize economic, political and social sustainability. Digital solutions may reduce costs, increase productivity, improve produce develop, and achieve faster time to market for paludiculture. Digitisation also enables information systems to be open, interoperable, and user-friendly. This constitutes the first study to describe the digital transformation of paludiculture, both vertically and horizontally, in order to inform sustainability that includes process automation via AI, machine learning, IoT-Cloud informed sensors and robotics, virtual and augmented reality, and blockchain for cyber-physical systems. Thus, the aim of this paper is to describe the applicability of digital transformation to actualize the benefits and opportunities of paludiculture activities and enterprises in the Irish midlands with a global orientation.


Mini external fixation for hand fractures and dislocations: The current state of the art.
External fixation devices for the hand provide a versatile approach to various hand injuries. Some fractures and dislocations urge the use of an external minifixation; in other fractures, external minifixation must be seen as an alternative or companion to other methods of hand stabilization. MiniFix is useful to maintain or restore hand function and hand anatomy.


[Cardiac injury in the context of metastatic hepatocellular carcinoma].
Hepatocellular carcinoma with extension or metastasis to the right atrium is an uncommon form of cardiac malignancy. The authors report the case of a 51-year-old patient with hepatocellular carcinoma and thrombi in the portal and mesenteric veins, which histopathology revealed to be metastatic. Echocardiography showed a right atrial mass which in this context has to be considered as a possible cardiac metastasis.


Metastatic solid tumors to the jaw and oral soft tissue: A retrospective clinical analysis of 44 patients from a single institution.
Metastatic solid tumors to the oral cavity are rare, frequently indicative of an end-stage disease process, and associated with poor survival rates. We performed a 20-year retrospective clinical analysis of our institution's cases of solid metastases to the oral cavity, and investigated these patients' clinical outcomes. A retrospective study of patients with metastatic solid tumors to the oral cavity over a 20-year period (October 1996 to September 2015) was conducted at Memorial Sloan Kettering Cancer Center. Patients were selected if they had a histopathologically confirmed diagnosis. Demographic, pathologic, and clinical information were reviewed to identify patient outcomes. A total of 44 patients with metastatic non-melanocytic non-hematopoietic tumor to the oral cavity were identified: 24 males and 20 females (39 adults and 5 children) with a mean age of 54.3 years. In all, 24 cases involved the jaw and 20 cases involved the oral soft tissue. Eight patients (18.2%) had oral cavity metastases as the first indication of an occult malignancy. In adult patients, the common primary sites were the lungs (n = 9, 20%), kidney (n = 7, 16%), breast (n = 5, 11%), and colon (n = 4, 9%); and in pediatric patients the adrenal gland (3/5) was the most common site. Of the adult patients, 33 (84.6%) died of disease. From the time of metastasis diagnosis, patients with jaw metastases had a median and mean survival of 12 months and 27.7 months, respectively. In comparison, patients with oral soft tissue metastases had a median survival time of 5 months, and mean of 8 months. One pediatric patient (20%) died of disease 8 months after metastasis diagnosis. Metastatic solid tumors to the oral cavity can be the first sign of a malignancy. Pediatric patients with oral cavity metastases have a better prognosis compared to adult patients. In this series, adults with oral soft tissue involvement had shorter survival times compared to patients with jaw involvement.


Need for a paradigm shift: the importance of risk factor reduction therapy in treating patients with cardiovascular disease.
Cardiovascular disease remains the number one killer in the United States, despite advances made in diagnosis and therapy. A major shift to expand treatment beyond symptomatic obstructions and infarctions toward comprehensive therapies aimed at treatment of the underlying disease process could decrease the death rate and cost of cardiovascular disease enormously. In the past 5 years, major trials have clearly demonstrated that aggressive intervention with lipid-lowering therapy can dramatically alter the course of disease. Aspirin, smoking cessation, exercise, diet, and other medical and lifestyle interventions can also decrease risk. Successful therapies are not being implemented, however. Making prevention the primary approach to treatment will require increased resource allocation, use of health provider teams, integration of healthcare delivery systems, and expanded emphasis on educating patients about prevention.


Mortality in chronic schizophrenia during decreasing number of psychiatric beds in Finland.
Mortality, especially mortality due to suicides, is higher among patients suffering from schizophrenia than among the general population. Little is known about the factors predicting the mortality of schizophrenia patients. It has also been suggested that mortality among psychiatric patients increases as the number of beds in mental hospitals decreases. These questions were studied in 4338 schizophrenia patients discharged in 1982, 1986, 1990 and 1994 from mental hospitals in Finland. During this period, the number of beds in mental hospitals in Finland decreased from 3.8 to 1.3 per 1000 inhabitants. During the three-year follow-up, 226 patients or 5.2% died. There were no statistically significant differences in mortality between the cohorts. The total mortality was higher in males than in females. Age, physical illness and number of hospital days predicted increased mortality due to natural causes. Mortality due to unnatural causes (suicides and accidents) was predicted by number of prescribed psychosedatives, number of hospitalisations and short duration of illness. Mortality due to unnatural causes was higher in the first year after index discharge from hospital. The reduction in number of beds in mental hospitals does not seem to be associated with increased mortality in chronic schizophrenia. The high mortality of schizophrenia patients indicates the need for careful medical examinations and treatment of physical illnesses, as well as counselling for a healthy lifestyle. Need for psychosedative medication at discharge from hospital and multiple previous hospitalisations may indicate an increased suicide risk and thus requires special attention. In outpatient treatment, it is important to remember that the risk of unnatural death increases during the first years after discharge from hospital.


[Controlled evaluation of a high-resolution three-dimensional magnetic detector system (3D-MAGMA) as a proof of concept - examination of healthy volunteers before and after application of Metoclopramide (MCP)].
Changes in gastric and small bowel motility are a common clinical problem. Currently diagnostic options are limited because each method harbors certain disadvantages. It has been shown that the high-resolution three-dimensional magnetic detector system 3D-MAGMA is capable of reliably measuring gastric and small intestine motor activity. This system allows precise localization of a small magnetic marker and determination of its three-dimensional orientation inside a human body. The aim of the current study was to determine if 3D-MAGMA is reliably able to detect changes in gastric and small bowel motility under controlled conditions. MCP was used as a well known prokinetic agent to shorten the gastric and small bowel passage. 8 healthy volunteers (fasting) underwent motility testing of the stomach and small bowel by 3D-MAGMA with and without administration of MCP (10 mg orally). Among other data the time the capsule needed to pass through the stomach and the duodenum and the time the capsule needed to pass through the first 50 cm of the jejunum were recorded. The retention time of the capsule in the stomach under physiological conditions was 49.1 minutes (median; min. 18 min; max. 88.8 min). The median time the capsule needed to pass through the duodenum was 13.8 minutes (median; min. 1.7 min; max. 24.8 min). The time the capsule needed to pass through the first 50 cm of the jejunum under physiological conditions was 33.0 minutes (median; min. 20.2 min; max. 67.2 min). The retention time of the capsule in the stomach decreased significantly after administration of MCP to 20.9 minutes (median; min. 1.7 min; max. 62.8 min; p = 0.008). The time the capsule needed to pass through the duodenum was also reduced to 7.1 minutes (median; min. 3.1 min; max. 18.3 min; p = 0.055). The time the capsule needed to pass through the first 50 cm of the jejunum was also reduced to 21.7 minutes (median; min. 10.7 min; max. 31.2 min; p = 0.069). 3D-MAGMA is able to accurately detect changes in gastric and small bowel motility. Its clinical use appears conceivable especially in patients with diseases that have impact on gastric and small bowel motility.


Recommendations for the reporting of gastric carcinoma.
It has been evident for decades that pathology reports vary between institutions and even within a single institution. Standardization of reporting is the best way to ensure that information necessary for patient management is included in pathology reports. Two societies, the Association of Directors of Anatomic and Surgical Pathology (ADASP) and the College of American Pathologists (CAP) have published guidelines for the reporting of common cancers. Although not identical, the basic content of the ADASP and CAP guidelines are similar. The American College of Surgery Commission on Cancer (COC) accredits cancer centers in the United States. The ADASP has updated all of its protocols to comply with COC requirements in the form of 37 uniform checklists. The checklists utilize criteria sited in the American Joint Committee on Cancer 2002 staging manual and are formatted for ease of use. They may be used as templates for uniform reporting and are designed be compatible with voice-activated transcription.


Corrigendum: Validation of single nucleotide variant assays for human leukocyte antigen haplotypes HLA-B*15:02 and HLA-A*31:01 across diverse ancestral backgrounds.
[This corrects the article DOI: 10.3389/fphar.2021.713178.].


Characterization of neutral glycosphingolipids from porcine erythrocyte membranes.
1. Six neutral GSL fractions were purified from porcine erythrocyte membranes. 2. They were identified to be LacCer (14% of total neutral GSLs), 2-hydroxy acid-rich and -poor Gb3Cer (3 and 7%, respectively) and Gb4Cer (71%) by means of NMR spectrometry. 3. Monohexosylceramides (5%) were composed of GlcCer and GalCer with near amount. 4. All these GSL classes contained a high concentration (more than 20% of total acids in each class) of 2-hydroxy fatty acids. 5. GalCer and GlcCer contained considerable amounts of C16- and C18-acids, and of C18-phytosphingosine, whereas C24-acids and C18-sphingosine were predominant in the other GSLs. 6. A minor GSL fraction (less than 1% of total neutral GSLs) which migrated more slowly than Gb5Cer on a thin layer plate and composed of several GSL components contained L-fucose.


A scoping review of qualitative geographic information systems in studies addressing health issues.
Qualitative Geographic Information Systems (QGIS) represent an emerging geospatial and qualitative approach to comprehensively understand health issues. This scoping review gathers evidence from 38 articles to illuminate when and how QGIS is used to address health issues. QGIS can contribute to recent health-related studies focusing on determinants of health and health equity at the community rather than individual level, highlight relationships between place and health, and encourage participation from people and communities in health-decision making. If more studies attempt to specify detailed data analysis methods and develop ways to use rich contexts of qualitative data, QGIS can provide greater scope for those working to solve health problems.


Five percent carbon dioxide challenge: valid analogue and marker of panic disorder?
The administration of 5% carbon dioxide (CO2) to patients with panic disorder (PD) induces a behavioral response similar to a naturally occurring panic attack. This article reviews the literature on the nature and incidence of this response. We conclude that the 5% CO2 challenge test is a valid and useful laboratory analogue of naturally occurring panic attacks, and shows promise as a marker to identify a subset of PD patients. Though further research on reliability, validity, and dose-response effects must be conducted, the CO2 challenge test provides important information regarding the phenomenology of panic states.


Using the fast impact of anthropogenic aerosols on regional land temperature to constrain aerosol forcing.
Anthropogenic aerosols have been postulated to have a cooling effect on climate, but its magnitude remains uncertain. Using atmospheric general circulation model simulations, we separate the land temperature response into a fast response to radiative forcings and a slow response to changing oceanic conditions and find that the former accounts for about one fifth of the observed warming of the Northern Hemisphere land during summer and autumn since the 1960s. While small, this fast response can be constrained by observations. Spatially varying aerosol effects can be detected on the regional scale, specifically warming over Europe and cooling over Asia. These results provide empirical evidence for the important role of aerosols in setting regional land temperature trends and point to an emergent constraint that suggests strong global aerosol forcing and high transient climate response.


Expression and G-protein coupling of mu-opioid receptors in the spinal cord and dorsal root ganglia of polyarthritic rats.
Although chronic inflammatory pain is known to be associated with hypersensitivity to mu opioid receptor agonists, no evidence for changes in the expression and/or characteristics of central mu opioid receptors has yet been reported in relevant models of this type of pain. In the present study, both immunohistochemical and autoradiographic approaches were used to address this question in polyarthritic rats, on the 4th week after intradermal injection of complete Freund's adjuvant, when inflammatory pain was at its maximum. Immunohistochemical labeling with specific anti-mu opioid receptor antibodies and autoradiographic labeling with [3H]DAMGO showed an upregulation of mu opioid receptors in the dorsal root ganglia but no changes in the density of these receptors in the dorsal horn at the level of L4-L6 segments in polyarthritic compared to age-paired control rats. On the other hand, autoradiographic quantification of the concentration-dependent increase in [35S]GTP-gamma-S binding by the mu-opioid receptor agonist DAMGO did not show any significant differences within the lumbar dorsal horn between polyarthritic and control rats. These data indicate that chronic inflammatory pain caused by polyarthritis was associated with an increased expression of mu-opioid receptors in dorsal root ganglion sensory neurones that did not result in an increased spinal density of these receptors, in spite of their well established axonal transport in the central portion of primary afferent fibres to the dorsal horn. In contrast, axonal transport of mu-opioid receptors in the peripheral portion of these fibres probably accounts for the increased receptor density in inflamed tissues already reported in the literature.


Identification of neomacrophorins isolated from Trichoderma sp. 1212-03 as proteasome inhibitors.
Neomacrophorins I-III (1-3) and X have previously been isolated from Trichoderma sp. 1212-03. Their mode of action against cancer cells and the mechanism of biosynthesis of the characteristic [4.4.3] propellane framework in neomacrophorin X have not been reported. The isolation and characterization of neomacrophorins IV (4), V (5), and VI (6) is reported. Epoxyquinones 1, 4, and 6 potently induced apoptotic cell death in human acute promyelocytic leukemia HL60 cells, while epoxysemiquinols 2, 3, and 5 showed weak activity. This indicates that the epoxyquinone moiety is crucial for apoptosis-inducing activities of neomacrophorins. We also found that neomacrophorins inhibit proteasome in vitro, and 1, 4, and 6 induced significant accumulation of ubiquitinated proteins in HL60 cells. These activities were completely suppressed by a nucleophile, N-acetyl-l-cysteine (NAC). The analysis of reaction mechanisms using LC-MS suggested that C2' and C7' of neomacrophorins could be Michael acceptors in the reaction with NAC methyl ester (NACM). These findings indicated that the electrophilic properties of neomacrophorins are responsible for both their potent biological effects and the biosynthesis of unique [4.4.3] propellane framework in neomacrophorin X.


Bioinactivation FE: A free web application for modelling isothermal and dynamic microbial inactivation.
Mathematical models developed in predictive microbiology are nowadays an essential tool for food scientists and researchers. However, advanced knowledge of scientific programming and mathematical modelling are often required in order to use them, especially in cases of modelling of dynamic and/or non-linear processes. This may be an obstacle for food scientists without such skills. Scientific software can help making these tools more accessible for scientists lacking a deep mathematical or computing background. Recently, the R package bioinactivation was published, including functions (model fitting and predictions) for modelling microbial inactivation under isothermal or dynamic conditions. It was uploaded to the Comprehensive R Archive Network (CRAN), but users need basic R programming knowledge in order to use it. Therefore, it was accompanied by Bioinactivation SE, a user-friendly web application including selected functions in the software for users without a programming background. In this work, a new web application, Bioinactivation FE, is presented. It is an extension of Bioinactivation SE which includes an interface to every function in the bioinactivation package: model fitting of isothermal and non-isothermal experiments, and generation of survivor curves and prediction intervals. Moreover, it includes several improvements in the user interface based on the users' feedback. The capabilities of the software are demonstrated through two case studies using data published in the scientific literature. In the first case study, the response of Escherichia coli to isothermal and non-isothermal treatments is compared, illustrating the presence of an induced thermal resistance. In the second, the effect of nanoemulsified d-limonene on the thermal resistance of Salmonella Senftenberg is quantified.


Temperature and light conditions affect stability of phenolic compounds of stored grape cane extracts.
This study aimed to determine the stability of PCs in grape canes extracts stored at different temperatures and light conditions. The PCs composition was monitored every-two weeks during three months by liquid chromatography coupled to diode array and fluorescence detectors (LC-DAD-FLD). Initially, stilbenes represented 87 % of total PCs. Storage at -20 and 5 °C reduced PCs 8 and 6 %, respectively. When extracts were exposed to 25 and 40 °C, the degradation of (+)-catechin and (-)-epicatechin was faster than under lower temperatures, and light accelerated the degradation kinetics. trans-piceatannol showed particularly sensitive to temperature increase, being mostly degraded after two weeks stored at 40 °C. Conversely, degradation of trans-resveratrol and ε-viniferin was mostly catalyzed by light, since nearly 70 % of them were degraded at 40 °C under light, in comparison with a 23 % reduction of trans-resveratrol and no changes of ε-viniferin at 40 °C in darkness.


Understanding the relationship between asthma and autism spectrum disorder: a population-based family and twin study.
There is some evidence that autism spectrum disorder (ASD) frequently co-occurs with immune-mediated conditions including asthma. We aimed to explore the familial co-aggregation of ASD and asthma using different genetically informed designs. We first examined familial co-aggregation of asthma and ASD in individuals born in Sweden from 1992 to 2007 (n = 1 569 944), including their full- and half-siblings (n = 1 704 388 and 356 544 pairs) and full cousins (n = 3 921 890 pairs), identified using Swedish register data. We then applied quantitative genetic modeling to siblings (n = 620 994 pairs) and twins who participated in the Child and Adolescent Twin Study in Sweden (n = 15 963 pairs) to estimate the contribution of genetic and environmental factors to the co-aggregation. Finally, we estimated genetic correlations between traits using linkage disequilibrium score regression (LDSC). We observed a within-individual association [adjusted odds ratio (OR) 1.33, 95% confidence interval (CI) 1.28-1.37] and familial co-aggregation between asthma and ASD, and the magnitude of the associations decreased as the degree of relatedness decreased (full-siblings: OR 1.44, 95% CI 1.38-1.50, maternal half-siblings: OR 1.28, 95% CI 1.18-1.39, paternal half-siblings: OR 1.05, 95% CI 0.96-1.15, full cousins: OR 1.06, 95% CI 1.03-1.09), suggesting shared familial liability. Quantitative genetic models estimated statistically significant genetic correlations between ASD traits and asthma. Using the LDSC approach, we did not find statistically significant genetic correlations between asthma and ASD (coefficients between -0.09 and 0.12). Using different genetically informed designs, we found some evidence of familial co-aggregation between asthma and ASD, suggesting the weak association between these disorders was influenced by shared genetics.


The Use of Adjuvants for Enhancing Allergen Immunotherapy Efficacy.
One key approach to increase the efficacy and the safety of immunotherapy is the use of adjuvants. However, many of the adjuvants currently in use can cause adverse events, raising concerns regarding their clinical use, and are geared toward productive immune responses but not necessarily tolerogenic responses. Thus, novel adjuvants for immunotherapy are needed and are being developed. Essential is their potential to boost appropriate tolerogenic adaptive immune responses to allergens while limiting side effects. This review provides an overview of adjuvants currently in clinical use or under development and discusses their therapeutic effect in enhancing allergen-induced tolerance.


Topical delivery of low-molecular-weight heparin with surface-charged flexible liposomes.
To increase topical delivery of low-molecular-weight heparin (LMWH), cationic, neutral, and anionic flexible liposomes (cFlexosome, nFlexosome, and aFlexosome) were prepared. The effects of surface charge of Flexosome on physicochemical properties and skin penetration of LMWH were also investigated. Among the different formulations of Flexosome, cFlexosome demonstrated three-times higher entrapment efficiency of LMWH, and better physicochemical stability than nFlexosome and aFlexosome. In vitro skin penetration and in vivo localization into the deeper skin layer of LMWH were significantly greater from cFlexosome compared to other formulations. Changes of skin surface charge after LMWH-cFlexosome application were investigated as a function of time. In the process of skin penetration, the Flexosomes act as drug carrier with the associated LMWH. Overall, macromolecular LMWH could be delivered deeply into the skin by topical application of cFlexosome for the treatment of superficial thrombosis, subcutaneous wounds, bruise, and burns.


Racial differences in long-term social, physical, and psychological health among adolescent and young adult cancer survivors.
The current guidelines for survivorship in adolescents and young adults (AYA) cancer are based on studies conducted in the United States and European AYA survivors. However, previous studies have shown that the health-related quality of life in cancer survivors can vary depending on race, yet the long-term health differences among AYA survivors by race/ethnicity have not been fully explored. Therefore, our aim is to compare the psychosocial and physical health of AYA survivors and their matched controls across different racial and ethnic groups. We conducted a cross-sectional study using US National Health and Nutrition Examination Survey (NHANES) and the Korea NHANES from 2007 to 2018. We included AYA cancer survivors who were diagnosed with any type of cancer aged between 15 and 39 years, and who were adult with aged over 18 years old at survey year. We then stratified the study population by race/ethnicity with Non-Hispanic White (NHW, n = 310), African American (AA, n = 42), Hispanic (n = 81) from NHANES, and Asian (n = 389) from the Korea NHANES. We also selected 5 times age-, sex-, race-, and survey year-matched general population among participants who had never been diagnosed with cancer (N = 4110). Variables were defined using questionnaire data, physical exams, and laboratory tests. Compared to NHW, Hispanics (aOR 1.15, 95% CI 1.00-1.32) had poor or fair general health, lower education (aOR 1.23, 95% CI 1.07-1.40), and lower household income (aOR 1.16, 95% CI 1.01-1.33). AA survivors were more likely to be non-coupled (aOR 1.35, 95% 1.15-1.60) and have hypertension (aOR 1.18, 95% CI 1.03-1.36). Asians were more former/current drinkers (aOR 1.21, 95% CI 1.05-1.40). NHW are more likely to experience psychological limitation. Compared to matched general, NHW and Asian survivors had poor general health and psychological health. This study provides evidence for future studies concerning long-term health after AYA cancer survivorship that may vary according to race.


Hypertension, vascular cognitive disorders and neuroprotection.
The role of the antihypertensive therapy in preventing vascular cognitive disorders in elderly persons without a history of stroke is a matter of debate. This review focuses on cognitive disorders in elderly hypertensive patients. Relevant papers were identified by searches in PubMed from 1946 until February 2007 using the keywords 'cerebral blood flow autoregulation', 'vascular cognitive disorders', 'neuroimaging in hypertension', 'antihypertensive treatment' and 'neuroprotection in cerebral ischemia'. Excessive blood pressure lowering in patients with long-standing hypertension may increase the risk of cerebral hypoperfusion, white matter lesions and consequent cognitive decline. White matter lesions have been found in the majority of patients with long-standing hypertension. They correlate with vascular cognitive disorders, particularly impairments of attention and executive function, while memory is relatively preserved. Cerebral small vessel disease in elderly patients should be taken into account when antihypertensive treatment is considered. Renin-angiotensin blockade, some calcium channel blockers and statins are thought to possess neuroprotective action. For prevention of cerebral hypoperfusion in elderly hypertensives blood pressure lowering should be cautiously controlled. The increased risk of white matter lesions is an indication for early neuroprotection. The combination of renin-angiotensin blockade or calcium channel blockers with statins may become a promising preventive strategy against cognitive decline in elderly hypertensives. Cerebral white matter protection is a future challenge.


MRI findings in cerebral fat embolism.
The purpose of this retrospective study was to demonstrate the MRI features of cerebral manifestations in patients with fat embolism syndromes in comparison with cerebral CT (CCT). Magnetic resonance imaging was performed according to standard protocols revealing multiple small non-confluent hyperintense intracerebral lesions larger than 2 mm on proton-density and T2-weighted images to various extents in three of four patients with clinically suspected cerebral fat embolism. Cerebral CT was negative in all patients. Our findings confirm that MRI can detect cerebral fat embolism with a higher sensitivity than CCT. Thus, MRI should be the first choice for imaging of cerebral fat embolism.


Endovascular recanalization of the superior mesenteric artery in the context of mesenteric bypass graft infection.
Mesenteric prosthetic graft infection is a rare and challenging clinical scenario. A patient is described who developed recurrent abdominal pain after occlusion of an iliomesenteric prosthetic bypass. Endovascular recanalization of the native superior mesenteric artery, which had been occluded for more than 10 years, was accomplished using axillofemoral through-wire access and a steerable guiding catheter. The infected prosthetic was then explanted and his graft-enteric fistula repaired. Technical and strategic considerations are discussed.


Tumour cell budding and spread through air spaces in squamous cell carcinoma of the lung - Determination and validation of optimal prognostic cut-offs.
Prognostic stratification of patients with squamous cell carcinomas of the lung (SCC-L) is challenging. Therefore, we investigated several histomorphological parameters (tumour cell budding (TCB), spread through air spaces (STAS), tumour-stroma-ratio, immune cell infiltration) which could potentially serve as prognostic parameters in SCC-L. We aimed to systematically determine optimal cut-off-values and assess the prognostic capability of these patterns. We furthermore assessed interobserver variability (IOV) for prognostically significant patterns TCB and STAS. The Cancer Genome Atlas (TCGA) study cohort consisted of 335 patients with SCC-L. Histomorphological parameters analysed comprised TCB, minimal cell nest size (MCNS), STAS, stroma content and immune cell infiltration. The most significant cut-off-values were determined and univariate and multivariate survival outcomes were estimated. The identified cut-off-points were validated in an independent SCC-L cohort (n = 346 patients). Two experienced pathologists probed IOV in the validation cohort. In the TCGA study cohort, TCB, STAS and immune cell infiltration were identified as significant prognostic parameters. TCB-high tumours, a high number of STAS foci, extensive STAS for distance of STAS in alveoli and a low immune cell infiltration remained as independent prognostic factors in multivariate Cox proportional hazard analyses for overall survival (OS). The significance of TCB, number of STAS foci and distance of STAS in alveoli for OS could be validated in the validation cohort. IOV reached a Kappa ≥ 0.89 for prognostic parameters. We determined optimal cut-offs and identified TCB and STAS (number of STAS foci, distance of STAS in alveoli) as independent and uncorrelated prognostic factors for patients with SCC-L. The significance was validated in a large independent cohort. IOV was almost perfect for prognostic parameters. We propose the application of TCB- and STAS-based grading in SCC-L as prognostic morphological classifiers.


Dopamine in the Turkey retina-an impact of environmental light, circadian clock, and melatonin.
Substantial evidence suggests that dopamine and melatonin are mutually inhibitory factors that act in the retina as chemical analogs of day and night. Here, we show an impact of environmental light, biological clock, and melatonin on retinal levels of dopamine and its major metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) in the turkey. In turkeys held under different light (L) to dark (D) cycles (16L:8D, 12L:12D, 8L:16D), retinal levels of dopamine and DOPAC fluctuated with daily rhythms. High levels of dopamine and DOPAC were observed during light hours and low during dark hours. Under the three photoperiodic regimes, rhythms of dopamine and DOPAC were out of phase with daily oscillation in retinal melatonin content. In constant darkness, dopamine and DOPAC levels oscillated in circadian rhythms. Light deprivation resulted, however, in a significant decline in amplitudes of both rhythms. Injections of melatonin (0.1-1 mumol/eye) during daytime significantly reduced retinal levels of DOPAC. This suppressive effect of melatonin was more pronounced in the dark-adapted than light-exposed turkeys. Quinpirole (a D(2)/D(4)-dopamine receptor agonist; 0.1-10 nmol/eye) injected to dark-adapted turkeys significantly decreased retinal melatonin. Our results indicate that in the turkey retina: (1) environmental light is the major factor regulating dopamine synthesis and metabolism; (2) dopaminergic neurones are controlled, in part, by intrinsic circadian clock; and (3) dopamine and melatonin are components of the mutually inhibitory loop.


Extended written pre-operative information about possible complications at cardiac surgery--do the patients want to know?
It is important that patients for whom cardiac surgery is planned are supplied with structured oral and written information regarding their disease and its treatment, so that they can understand and discuss the coming operation and the risk of complications. The aim was to describe patients' experiences of information regarding possible complications related to cardiac surgery, both before and after the operation. A comparison was made between patients who received detailed written information (intervention group) regarding possible complications and patients who received conventional information (control group). One hundred eighty-two patients were included in the intervention group and 156 in the control group. Questionnaires were distributed and experiences, anxiety and depression (the Hospital Anxiety and Depression Scale, HADS), and avoidance or intrusion distress (the Impact of Event Scale, IES) were measured before and 8 weeks after the surgery. Seventy-two percent of the intervention group and 69% of the control group wanted information about both common and rare complications. Patients in the intervention group were significantly more satisfied with all aspects of the information compared to the control group both pre- and post-operatively. There were no significant differences between the groups for either the HADS or the IES. Most, but not all, patients in the present study were positive to the extended written detailed information about risk of complications in connection with cardiac surgery. Detailed information can be a useful base for fruitful conversations between the health care personnel and the patients. The patients and their next of kin are informed, and better prepared if complications occur.


Genetic analysis based on 15 autosomal short tandem repeats (STRs) in the Chaouia population, western center Morocco, and genetic relationships with worldwide populations.
The complex demographic history of human populations in North Africa has resulted in a high degree of genetic heterogeneity across the region. However, little is known about the pattern of these genetic variations in its current populations. The present study provides new data on the genetic background of Chaouia, an Arabic-speaking North African population in the western center of Morocco. A random sample of 150 unrelated healthy individuals from Chaouia was assessed using the AmpFLSTR Identifiler kit. The most polymorphic markers were D21S11 and D18S51, with 23 and 22 alleles, respectively. After Bonferroni's correction, two loci (TH01 and D18S51) deviated from Hardy-Weinberg equilibrium. The phylogeny analysis separated North African populations into northeastern and northwestern groups. The Chaouia population was clustered with northwestern Africans. It was the closest to the Berbers of Azrou. The Chaouia shared close genetic affinities with populations from North Africa, the Middle East, and Europe, particularly Iberians, and to a lesser extent with sub-Saharan populations. The pattern of genetic admixture varied across North African populations without a clear correlation between their geographic (northeastern or northwestern) or linguistic identities (Arab or Berber), however, genetic heterogeneity among Berbers was observed. These findings suggest that the diversity observed in North African populations extends geographical and linguistic boundaries. It is further linked to each population's unique and complex demographic history. Human North African population genetics seems to present an intriguing landscape for future studies in the region and its surrounding populations to trace the origins of the genetic heterogeneity observed in these populations.


Evaluating aroma quality of black tea by an olfactory visualization system: Selection of feature sensor using particle swarm optimization.
Aroma is an important index to evaluate the quality and grade of black tea. This work innovatively proposed the sensory evaluation of black tea aroma quality based on an olfactory visual sensor system. Firstly, the olfactory visualization system, which can visually represent the aroma quality of black tea, was assembled using a lab-made color sensitive sensor array including eleven porphyrins and one pH indicator for data acquisition and color components extraction. Then, the color components from different color sensitive spots were optimized using the particle swarm optimization (PSO) algorithm. Finally, the back propagation neural network (BPNN) model was developed using the optimized characteristic color components for the sensory evaluation of black tea aroma quality. Results demonstrated that the BPNN models, which were developed using three color components from FTPPFeCl (component G), MTPPTE (component B) and BTB (component B), can get better results based on comprehensive consideration of the generalization performance of the model and the fabrication cost of the sensor. In the validation set, the average of correlation coefficient (RP) value was 0.8843 and the variance was 0.0362. The average of root mean square error of prediction (RMSEP) was 0.3811 and the variance was 0.0525. The overall results sufficiently reveal that the optimized sensor array has promising applications for the sensory evaluation of black tea products in the process of practical production.


Mechanical, Material and Morphological Adaptations of Healthy Lower Limb Tendons to Mechanical Loading: A Systematic Review and Meta-Analysis.
Exposure to increased mechanical loading during physical training can lead to increased tendon stiffness. However, the loading regimen that maximises tendon adaptation and the extent to which adaptation is driven by changes in tendon material properties or tendon geometry is not fully understood. To determine (1) the effect of mechanical loading on tendon stiffness, modulus and cross-sectional area (CSA); (2) whether adaptations in stiffness are driven primarily by changes in CSA or modulus; (3) the effect of training type and associated loading parameters (relative intensity; localised strain, load duration, load volume and contraction mode) on stiffness, modulus or CSA; and (4) whether the magnitude of adaptation in tendon properties differs between age groups. Five databases (PubMed, Scopus, CINAHL, SPORTDiscus, EMBASE) were searched for studies detailing load-induced adaptations in tendon morphological, material or mechanical properties. Standardised mean differences (SMDs) with 95% confidence intervals (CIs) were calculated and data were pooled using a random effects model to estimate variance. Meta regression was used to examine the moderating effects of changes in tendon CSA and modulus on tendon stiffness. Sixty-one articles met the inclusion criteria. The total number of participants in the included studies was 763. The Achilles tendon (33 studies) and the patella tendon (24 studies) were the most commonly studied regions. Resistance training was the main type of intervention (49 studies). Mechanical loading produced moderate increases in stiffness (standardised mean difference (SMD) 0.74; 95% confidence interval (CI) 0.62-0.86), large increases in modulus (SMD 0.82; 95% CI 0.58-1.07), and small increases in CSA (SMD 0.22; 95% CI 0.12-0.33). Meta-regression revealed that the main moderator of increased stiffness was modulus. Resistance training interventions induced greater increases in modulus than other training types (SMD 0.90; 95% CI 0.65-1.15) and higher strain resistance training protocols induced greater increases in modulus (SMD 0.82; 95% CI 0.44-1.20; p = 0.009) and stiffness (SMD 1.04; 95% CI 0.65-1.43; p = 0.007) than low-strain protocols. The magnitude of stiffness and modulus differences were greater in adult participants. Mechanical loading leads to positive adaptation in lower limb tendon stiffness, modulus and CSA. Studies to date indicate that the main mechanism of increased tendon stiffness due to physical training is increased tendon modulus, and that resistance training performed at high compared to low localised tendon strains is associated with the greatest positive tendon adaptation. PROSPERO registration no.: CRD42019141299.


Advances and challenges toward developing kidney organoids for clinical applications.
Kidney organoids have enabled modeling of human development and disease. While methods of generating the nephron lineage are well established, new protocols to induce another lineage, the ureteric bud/collecting duct, have been reported in the past 5 years. Many reports have described modeling of various hereditary kidney diseases, with polycystic kidney disease serving as the archetypal disease, by using patient-derived or genome-edited kidney organoids. The generation of more organotypic kidneys is also becoming feasible. In this review, I also discuss the significant challenges for more sophisticated disease modeling and for realizing the ambitious goal of generating transplantable synthetic kidneys.


Spectroelectrochemical study of water oxidation on nickel and iron oxyhydroxide electrocatalysts.
Ni/Fe oxyhydroxides are the best performing Earth-abundant electrocatalysts for water oxidation. However, the origin of their remarkable performance is not well understood. Herein, we employ spectroelectrochemical techniques to analyse the kinetics of water oxidation on a series of Ni/Fe oxyhydroxide films: FeOOH, FeOOHNiOOH, and Ni(Fe)OOH (5% Fe). The concentrations and reaction rates of the oxidised states accumulated during catalysis are determined. Ni(Fe)OOH is found to exhibit the fastest reaction kinetics but accumulates fewer states, resulting in a similar performance to FeOOHNiOOH. The later catalytic onset in FeOOH is attributed to an anodic shift in the accumulation of oxidised states. Rate law analyses reveal that the rate limiting step for each catalyst involves the accumulation of four oxidised states, Ni-centred for Ni(Fe)OOH but Fe-centred for FeOOH and FeOOHNiOOH. We conclude by highlighting the importance of equilibria between these accumulated species and reactive intermediates in determining the activity of these materials.


Manufacturing technology of banana-assorted breads: The fermentative characteristics affected by different banana cultivars.
Taiwan produces large quantities of bananas in the southern area. Recently, due to the export quantity has been greatly reduced, in order to efficiently maintain the banana agriculture and economy, the development of alternate uses of bananas has become urgently in need. Bananas contain a fair amount of nutrients with low glycemic index. Currently, as the bread consumption is increasing, we tried to manufacture banana-assorted breads. The desiccated powders of Musa sapientum var TC2-425 Linn [(genomically, called as Musa (AAA) (MA)] and Musa basjoo "Nam Wa" (MB) were separately incorporated at 15%, 20%, and 25% (denoted as MA15-MA25 and MB15-MB25). Results indicated that MA exhibited higher contents of moisture, ash, crude protein, and lutein, while with lower crude fat, crude fibers, carbohydrate, sodium, total soluble sugars, and pectin. The contents of taste compounds (name, samples in decreasing order) were as follows: 5'-CMP (MB25, MB20); 5'-GMP (MA25, MA20); 5'-AMP (MB25, MA15); 5'-XMP (MA25, MA20); 5'-IMP (MA25, MB20, MB25); and 5'-UMP (MA20, MA25, MB20). Hedonic scoring (HS) indicated MA15, MA20, MB15, and MB20 were more acceptable. Textural profile analysis (TPA; for 0-6 days, only 0-4 days are shown) revealed that "flavor," "mouthfeel," "hardness," "gumminess," and "chewiness" were the determinant key roles. Conclusively, due to different chemical constituent of banana, different recipes must be considered. The bread acceptability is affected by the fermentative profile which in turn is governed by the contents of soluble sugars, pectin, taste compounds, and the overall activity of yeast cells.


Sexual Health and Drug Use Prevention for Black Girls (The Dreamer Girls Project): Protocol for an Intervention Development.
Substance use among adolescent girls is associated with numerous risk characteristics, including engaging in sexual risk behaviors, which can lead to HIV and sexually transmitted infection (STI) diagnoses. This is an important phenomenon to target as there is a significant race-gendered paradox that occurs when Black girls use and misuse drugs. When misuse occurs among this group, they are more likely to face harsher consequences and worse health outcomes than boys and other ethnic-minority girls. Therefore, there is a need to understand the risk and protective factors of drug use and sexual risk behaviors among Black girls and develop a robust intervention that can cater for this group. We propose the development of a strengths-based prevention education intervention for Black girls between the ages of 13 and 18 years to promote protective factors. A sequential, mixed methods study will be conducted, and we will use the first 3 steps of the ADAPT-ITT (assessment, decision, adaptation, production, topical experts, integration, training, testing) framework to begin the development of the intervention. Three aims will be described in this protocol. First, aim 1 is to explore sociocultural risk and protective factors among Black girls between the ages 13 and 18 years in drug use and HIV/STI prevention using focus group methodology and surveys. We will conduct at least 10 focus groups to include up to 75 Black girls or until we reach saturation. Our target sample size for the quantitative portion of the study will be 200 participants. Aim 2 will focus on deciding upon an intervention based on findings from aim 1 and forming a youth advisory board to guide intervention development. Aim 3 will be to conduct a pretest of the intervention with the youth advisory board to determine if the intervention is feasible and will be accepted by Black girls. The study is part of a 2-year research pilot study award from the National Institutes of Mental Health. Data collection for this study began in October 2021. For aim 1, data collection is 95% complete. We expect to complete all data collection for aim 1 on or before May 30, 2023. Study activities for aim 2 are occurring simultaneously as data are being collected and analyzed and will be completed in the summer of 2023. Study activities for aim 3 will begin in the fall of 2023. This study will be one of the few interventions that address both sexual health and drug use together and cater to Black girls. We anticipate that the intervention will be beneficial for Black girls across the nation to work on building culturally appropriate prevention education and building peer social supports, resulting in reduction or delayed substance use and improved sexual health. ClinicalTrials.gov NCT05014074; https://clinicaltrials.gov/ct2/show/NCT05014074. DERR1-10.2196/45007.


Phosphonates and their degradation by microorganisms.
Phosphonates are a class of organophosphorus compounds characterized by a chemically stable carbon-to-phosphorus (C-P) bond. Wide occurrence of phosphonates among xenobiotics polluting the environment has aroused interest in pathways and mechanisms of their biodegradation. Only procaryotic microorganisms and the lower eucaryotes are capable of phosphonate biodegradation via several pathways. Destruction of the non-activated C-P bond by the C-P lyase pathway is of fundamental importance, and understanding of the process is a basic problem of biochemistry and physiology of microorganisms. This review offers analysis of available data on phosphonate-degrading microorganisms, degradation pathways, and genetic and physiological regulation of this process.


Ketamine for palliative sedation in the emergency department.
Palliative sedation to treat severely distressing symptoms in those with a poor prognosis is well-accepted. We discuss palliative sedation in the Emergency Department and the use of ketamine. We present the case of a patient with angioedema of the tongue and severe respiratory distress. The patient's nursing home was unable to control her symptoms and she was transferred to the Emergency Department. The patient received fentanyl 50 μg i.v. and ketamine 50 mg i.v. every 5 min until adequate palliative sedation was achieved. Ketamine can be considered for Emergency Department palliative sedation in selected patients. Identifying and caring for unmet palliative care needs is an important skill for Emergency Medicine.


Predicting dry matter intake in beef cattle.
Technology that facilitates estimations of individual animal dry matter intake (DMI) rates in group-housed settings will improve production and management efficiencies. Estimating DMI in pasture settings or facilities where feed intake cannot be monitored may benefit from predictive algorithms that use other variables as proxies. This study examined the relationships between DMI, animal performance, and environmental variables. Here we determined whether a machine learning approach can predict DMI from measured water intake variables, age, sex, full body weight, and average daily gain (ADG). Two hundred and five animals were studied in a drylot setting (152 bulls for 88 d and 53 steers for 50 d). Collected data included daily DMI, water intake, daily predicted full body weights, and ADG using In-Pen-Weighing Positions and Feed Intake Nodes. After exclusion of 26 bulls of low-frequency breeds and one severe (>3 standard deviations) outlier, the final number of animals used for modeling was 178 (125 bulls, 53 steers). Climate data were recorded at 30-min intervals throughout the study period. Random Forest Regression (RFR) and Repeated Measures Random Forest (RMRF) were used as machine learning approaches to develop a predictive algorithm. Repeated Measures ANOVA (RMANOVA) was used as the traditional approach. Using the RMRF method, an algorithm was constructed that predicts an animal's DMI within 0.75 kg. Evaluation and refining of algorithms used to predict DMI in drylot by adding more representative data will allow for future extrapolation to controlled small plot grazing and, ultimately, more extensive group field settings.


Health surveillance of workers exposed to tetrachloroethylene in dry-cleaning shops.
Behavioral, renal, hepatic and pulmonary tests were applied to 22 subjects exposed to tetrachloroethylene in 6 dry-cleaning shops. The results were compared with those obtained in 33 subjects non-occupationally exposed to organic solvents. The intensity of exposure was monitored by personal environmental monitoring and by urine analysis for trichloroacetic acid and expired air and venous blood analysis for tetrachloroethylene. The time-weighted average exposure to tetrachloroethylene amounted to 21 ppm (range 9 to 38 ppm). The correlation between the concentration of tetrachloroethylene in ambient air sampled with the charcoal tube method and with a passive dosimeter indicates that the latter can correctly estimate the time-weighted average exposure to the solvent. In view of the long biological half-life of tetrachloroethylene, the internal dose may be better estimated by measuring its concentration in blood 16 h after the end of exposure (i.e. before resuming work the next morning). The present study suggests that if the blood concentration of tetrachloroethylene does not exceed 1 mg/l, 16 h after the end of exposure, the time-weighted average exposure is likely to have been below 50 ppm. Exposure to such level for 6 years on the average does not seem to exert any adverse effect on the central nervous system, the liver and the kidney.


High-resolution susceptibility-weighted imaging at 3 T with a 32-channel head coil: technique and clinical applications.
The purpose of this article is to illustrate the utility of susceptibility-weighted imaging (SWI) as an adjunct to routine MRI of the brain in neurologic disorders. SWI is a 3D spoiled gradient-echo sequence that combines phase and magnitude information to provide a high sensitivity for the detection of blood degradation products, calcifications, and iron deposits.


How to put hypnosis into a placebo pill?
Many case studies and several controlled clinical trials have indicated the effectiveness of hypnotherapy for some medical conditions. However, because of methodological inadequacies hypnotherapy is still criticized for not having strong scientific evidence to support its claims. While randomized placebo-controlled clinical trial is generally accepted as the gold standard study design, creating a credible placebo control for hypnotherapy is a major challenge. This paper recommends "neutral hypnosis" as a credible placebo control for hypnotherapy trials.


Accelerated partial-breast irradiation versus whole-breast irradiation for early-stage breast cancer patients undergoing breast conservation, 2003-2010: a report from the national cancer data base.
Previous studies have demonstrated an increase in the utilization of accelerated partial-breast irradiation via brachytherapy (APBI-b), but larger, more contemporary studies examining overall APBI use are lacking. A total of 575,438 nonneoadjuvant American Joint Committee on Cancer stage 0 to II breast conservation patients were selected from the National Cancer Data Base from 2003 to 2010 who underwent either whole-breast irradiation or APBI. Overall, 59,396 patients (10.3 %) underwent APBI. The use of APBI for the entire cohort increased from 3.4 % in 2003 to 12.8 % (p < 0.001) in 2008 and then decreased to 12.4 % in 2010. Three-dimensional conformal radiation increased from 0.8 to 2.2 %, intensity-modulated radiotherapy increased from 0.7 to 1.3 %, and brachytherapy (APBI-b) increased from 2.0 to 8.9 %. The most significant factors associated with APBI use were patient age and facility location. Patients 80-89 years old were 3.8 times more likely to undergo APBI compared to patients 30-39 years old (odds ratio [OR] 3.77, 95 % confidence interval [CI] 3.45-4.10, p < 0.001). Patients living in the West census region were 2.0 times more likely to undergo APBI compared to patients living in the Northeast (OR 2.0, 95 % CI 1.93-2.15, p < 0.001). Using the American Society of Radiation Oncology (ASTRO) guidelines, among patients with noninvasive cancer who received APBI, 95.6 % were categorized as "cautionary" and 4.4 % as "unsuitable." Of the invasive patients, 43.8 % were categorized as "suitable," 47.0 % as "cautionary," and 9.2 % as "unsuitable." The utilization of APBI has stabilized at approximately 12 % starting in 2008. The majority of APBI is delivered using APBI-b, with patient age being the most significant factor associated with APBI use.


MOVI-daFIT! Intervention: Rationale and design of a cluster randomized controlled trial testing the effects on improving adiposity, cognition, and subclinical atherosclerosis by increasing cardiorespiratory fitness in children.
High-intensity interval training (HIIT) programs have demonstrated positive effects on cardiorespiratory fitness and cardiometabolic parameters, but their impact on other health parameters (such as body mass and fat) and cognition remains unclear. This paper presents the rationale and methods of a HIIT after-school physical activity (PA) intervention (MOVI-daFIT!) on reducing fat mass and cardiovascular risk, and improving physical fitness, executive function, and academic achievement among children aged 9 to 11 years old. A cluster randomized controlled trial (RCT), including 10 schools from Cuenca province, Spain, was designed. Schools were randomly assigned to the MOVI-daFIT! intervention and to the control group. Children were evaluated at the beginning (September 2017) and at the end (June 2018) of the school year. Children in the intervention group were involved in 60-minute after-school sessions 4 days per week developed in the school setting. Each session consisted of 15 minutes of set-up and warm-up games, 28 minutes of games using the HIIT protocol, and 10 minutes of cool down. In addition, children in the intervention and control groups received 2 regular 50-minute physical education sessions per week, as it is compulsory by law in Spanish schools. This study will determine the effect of an after-school physical activity intervention (MOVI-daFIT!), designed as a HIIT program, on reducing fat mass and cardiovascular risk, and improving fitness and cognition, including executive function and academic achievement.


Dietary glycerol monolaurate protects Cherax quadricarinatus against white spot syndrome virus infection.
Glycerol monolaurate (GML), one of the medium-chain fatty acid esters, is often used as an emulsifier or preservative. Its biological functions include antibacterial and antiviral activities. In this study, we examined the effects of dietary GML on the resistance of the red claw crayfish to WSSV infection. Crayfish fed with 4 g/kg GML showed higher survival rate and lower WSSV copy numbers than the control after WSSV infection. A RT-qPCR analysis showed that GML supplementation enhanced the expression of immune-related genes, especially JAK and caspase. Our data indicate that GML affects the immune parameters of crayfish, including the total hemocyte counts and phenoloxidase, acid phosphatase, superoxide dismutase, lysozyme, and peroxidase activities. After treatment with GML, the apoptosis of hemocytes increased significantly in both WSSV-infected and uninfected crayfish. In summary, GML reduced the mortality of WSSV-infected crayfish, perhaps by modulating the innate immunity of the crayfish. Our study shows that GML can be used to induce the innate immunity and enhance the immune protection of the red claw crayfish against WSSV infection, either therapeutically or as a preventive measure.


Variations in plasma growth hormone concentrations in laying hens.
1. Variations in plasma concentrations of growth hormone (GH) and luteinising hormone (LH) were measured by radioimmunoassay in blood samples taken during the ovulatory cycle of the domestic hen. 2. A peak in LH concentrationas observed 4 h prior to ovulation. 3. Plasma GH concentrations were quite variable but a significant increase was observed between 2 h before and 2 h after ovulation and the concentration remained elevated for about 4 h thereafter.


Structure-specific metabolism of flavonol molecules by Bacillus subtilis var. natto BCRC 80517.
Flavonols (3-hydroxy flavones) have been studied for their beneficial bioactivities for human health. Recently, we reported that a flavonoid phosphate synthetase (BsFPS) from Bacillus subtilis BCRC 80517 can transform several flavonoids into their phosphate conjugates, which become more water-soluble and thus increase the oral bioavailability. However, the in vivo metabolism of different flavonols has yet to be determined. Here, we investigated biotransformation of three flavonols (quercetin, kaempferol and fisetin) by B. subtilis BCRC 80517. C-ring cleavage products of quercetin and kaempferol, i.e., 2-protocatechuoyl-phloroglucinol carboxylic acid (2-PCPGCA), were produced, whereas two phosphate derivatives of fisetin (fisetin 4'-O-phosphate and fisetin 3'-O-phosphate) were generated by cultivation with B. subtilis BCRC 80517. Our results indicated that there are structure-specific metabolic pathways in B. subtilis toward different flavonols, where the 5-hydroxy group determines metabolic priority. Our findings provide new insights for developing bioproduction platform to produce flavonol phosphate derivatives for nutraceutical applications.


Vitamin D Supplementation Influences Ultramarathon-Induced Changes in Serum Amino Acid Levels, Tryptophan/Branched-Chain Amino Acid Ratio, and Arginine/Asymmetric Dimethylarginine Ratio.
Exercise affects serum levels of amino acids and their metabolites, with important metabolic consequences. Since vitamin D impacts skeletal muscle protein degradation, we hypothesised that it would also impact exercise-induced changes in serum amino acid levels and the serum levels of arginine metabolites, influencing the body's ability to synthesise NO. Accordingly, we analysed the effect of a single high-dose vitamin D supplementation on the serum levels of various amino acids in ultramarathon runners. Thirty-five male amateur runners were assigned to the supplemented group, administered 150,000 IU vitamin D in vegetable oil 24 h before the run (n = 16), or the control (placebo) group (n = 19). Blood was sampled 24 h before, immediately after, and 24 h after the run. Changes in the serum levels of some amino acids were distinct in the two groups. The asymmetric dimethyl arginine levels were significantly decreased immediately after the run and increased 24 h later and were not affected by the supplementation. The symmetric dimethyl arginine levels were increased after the run in both groups but were lower in the supplemented group than in the placebo group 24 h after the run. The dimethylamine levels increased significantly in the supplemented group as compared to the placebo group. In conclusion, vitamin D impacts exercise-induced changes in serum amino acids and methylated arginine metabolites.


Coating of magnetic nanoparticles affects their interactions with model cell membranes.
The use of functionalized iron oxide nanoparticles of various chemical properties and architectures offers a new promising direction in theranostic applications. The increasing applications of nanoparticles in medicine require that these engineered nanomaterials will contact human cells without damaging essential tissues. Thus, efficient delivery must be achieved, while minimizing cytotoxicity during passage through cell membranes to reach intracellular target compartments. Differential Scanning Calorimetry (DSC), molecular modeling, and atomistic Molecular Dynamics (MD) simulations were performed for two magnetite nanoparticles coated with polyvinyl alcohol (PVA) and polyarabic acid (ARA) in order to assess their interactions with model DPPC membranes. DSC experiments showed that both nanoparticles interact strongly with DPPC lipid head groups, albeit to a different degree, which was further confirmed and quantified by MD simulations. The two systems were simulated, and dynamical and structural properties were monitored. A bimodal diffusion was observed for both nanoparticles, representing the diffusion in the water phase and in the proximity of the lipid bilayer. Nanoparticles did not enter the bilayer, but caused ordering of the head groups and reduced the area per lipid compared to the pure bilayer, with MAG-PVA interacting more strongly and being closer to the lipid bilayer. Results of DSC experiments and MD simulations were in excellent agreement. Our findings demonstrate that the external coating is a key factor that affects nanoparticle-membrane interactions. Magnetite nanoparticles coated with PVA and ARA did not destabilize the model membrane and can be considered promising platforms for biomedical applications. Understanding the physico-chemical interactions of different nanoparticle coatings in contact with model cell membranes is the first step for assessing toxic response and could lead to predictive models for estimating toxicity. DSC in combination with MD simulations is an effective strategy to assess physico-chemical interactions of coated nanoparticles with lipid bilayers.