Multifractal analysis of ZnO nanoparticles.
ZnO nanoparticles (NPs) have variety of applications in different fields due to its size, structure, as well as physical and chemical properties. One of its prominent characteristics is its antibacterial behavior. Nonlinear Dynamical Theory (NLD) has a vast scope in the field of material science, especially when subtle correlations are searched for to extract hidden information. Since nano-ZnO materials may be used in inhibiting pathogens, its nonlinear features can be quantified and calibrated with the help of NLD tools. Multi-fractal Analysis (MFA) is an important diagnostic tool of NLD for not only analyzing nonlinear signal or images, but also predicting any spurious events likely to occur in the system under study. Thus, the analysis of the surface texture of the ZnO nano particles formed, using the TEM images and relate it with the variations of the XRD signal using NLD tools, is our first attempt reported here. Further, tools of MFA are used, for the first time, to see if there exists any correlation between the texture of the nano particles formed and the Zone of Inhibition (ZoI) we obtain as an output after allowing certain pathogens inhibit in the presence of the same nano particles. Analysis of TEM images guide us to predict the texture and structure of crystallites of ZnO:Cu samples which are responsible for overall behavior of inhibiting pathogens. In this paper, MFA of ZoI images, TEM images, and signal of four different Cu-doped ZnO nanoparticles are carried out and their outcomes are calibrated for estimating the size and pattern of unknown NPs synthesized under similar physical and chemical condition. Moreover, that MFA can be used reliably to predict spurious or abnormal surface structure or bacterial inhibition is also established.


Utilizing student-led contact tracing initiative to alleviate COVID-19 disease burden in central Pennsylvania.
Contact tracing elicits probable contacts from COVID-19 cases. Our student-led contact tracing initiative promoted isolation of both confirmed and probable cases and quarantine of contacts to reduce disease in Central Pennsylvania. Close contacts of COVID-19 cases were contacted by tracers, advised to quarantine, and monitored for 14 days for symptoms. Symptomatic contacts were classified as probable cases and advised to isolate. Data was collected from March 24, 2020 to May 26, 2020. Poisson regression and linear regression were utilized to examine the relationships between case and number of contacts and proportion of symptomatic contacts. Study sample comprised of 346 confirmed and 157 probable cases. Our results indicate a significant difference in percent of household contacts who became symptomatic between confirmed and probable cases (22% vs. 3%; adjusted P<.01). Similarly, probable cases had significantly fewer non-household contacts compared to confirmed cases (0.87 vs. 0.55; adjusted P<.01). Timely notification of exposure to a COVID-19 positive individual by student contact tracers allowed for probable cases to quarantine early in the disease process. Our data suggests that early quarantine and/or isolation may have directly contributed to probable cases having fewer non-household contacts and a smaller proportion of symptomatic household-contacts compared to confirmed cases.


Alopecia-anosmia-deafness-hypogonadism syndrome revisited: report of a new case.
Johnson et al [1983] reported on a large family with alopecia-anosmia-deafness-hypogonadism syndrome. We report the detailed findings of an unrelated, affected individual and emphasize the presence of hypohidrosis in our case. Our case indicates that this syndrome is not a private syndrome.


The proliferation role of LH on porcine primordial germ cell-like cells (pPGCLCs) through ceRNA network construction.
The transdifferentiation of skin-derived stem cells (SDSCs) into primordial germ cell-like cells (PGCLCs) is one of the major breakthroughs in the field of stem cells research in recent years. This technology provides a new theoretical basis for the treatment of human infertility. However, the transdifferentiation efficiency of SDSCs to PGCLCs is very low, and scientists are still exploring ways to improve this efficiency or promote the proliferation of PGCLCs. This study aims to investigate the molecular mechanism of luteinising hormone (LH) to enhance porcine PGCLCs (pPGCLCs) proliferation. In this study, we dissected the proliferation regulatory network of pPGCLCs by whole transcriptome sequencing, and the results showed that the pituitary-secreted reproductive hormone LH significantly promoted the proliferation of pPGCLCs. We combined whole transcriptome sequencing and related validation experiments to explore the mechanism of LH on the proliferation of pPGCLCs, and found that LH could affect the expression of Hippo signalling pathway-related mRNAs, miRNAs and lncRNAs in pPGCLCs. For the first time, we found that LH promotes pPGCLCs proliferation through the competing endogenous RNA (ceRNA) regulatory networks and Hippo signalling pathway. This finding may help to elucidate the molecular mechanism by which LH promotes pPGCLCs proliferation.


Environmental exposure of road borders to zinc.
The emissions of zinc along roads originating from tyre wear, corrosion of safety fence and other traffic-related sources have been quantified and validated by measured long-term loads in road run-off and airborne solids (drift) for 29 published case studies. The distribution pattern over the road border at various distances from the edge of the paved surface is assessed on the basis of 38 published case studies with measured concentrations in soil. For the impact assessment, the road border is differentiated into a zone that is part of the "technosphere" and the "target zone" beyond that technosphere that can be considered as part of the receiving environment. The "technosphere" of the road includes the central reservation, the hard and the soft shoulder or, if one or both shoulders are not present, the so-called obstacle "free zone" that is defined by road engineers. Pollution within the technosphere may require appropriate management of solid disposal and isolation from groundwater to prevent further distribution of pollutants to the environment. In the target zone along regional roads, the zinc load is about 4 mg/m(2) year and this is of the same order of magnitude as that of atmospheric deposition in areas beyond the influence of roads (background). In the target zone along highways, the zinc load is increased in comparison to the background deposition. The average load of about 38 mg/m(2) year is similar to that in fertilised agricultural land. Because most of the emitted zinc stays in the technosphere, the total amount entering this target zone along highways is limited. From the 140 tons of zinc per year that is released from tyre wear in The Netherlands, 64 tons is emitted in the urban area, 6.5 tons reaches to the target zones of all roads and only 1.1 tons of zinc will enter the target zone along highways. This amount will be further decreased by the application of porous asphalt in the near future. The emission from safety fence corrosion does not enter the target zone. Only in special cases, such as bridges, crossings and squares the release of zinc from these sources may enter the aquatic environment by the discharge of run-off.


Massive bone allografts in large skeletal defects after tumor surgery: a clinical and microradiographic evaluation.
Massive deep-frozen bone allografts were implanted in 13 patients after en bloc tumor resection. Patients were followed up for 14 months to 17 years. Most of the reconstructive procedures included a segmental bone allograft with knee or ankle fusion. Graft infections were the most critical complications in regard to the end results, finally requiring amputation in two cases. There were three stress fractures; two of which were successfully treated without further complication. Graft incorporation was assessed by bone scintimetry in four cases. Isotope uptake by the center of the graft was found to be superior to control bone segments at only 15 years after surgery. Two recovered allograft specimens were available for a microradiographic study. Creeping substitution was a very slow process, initiated at the outer surface of the graft and characterized at 2-3 years after implantation by large, incompletely filled osteons. The present investigation demonstrates that massive bone allografts are very slowly revascularized and are intimately anchored by the host bone. Provided that tumor control is effective and graft infection is avoided, reconstructive surgery with massive bone allografts represents a successful alternative to prosthetic implants in young adult with a long life expectancy.


Mapping spatial and temporal changes in carotid atherosclerosis from three-dimensional ultrasound images.
This study was designed to evaluate changes in carotid atherosclerosis using plaque and wall thickness maps derived from three-dimensional ultrasound (3DUS) images. Five subjects with carotid stenosis were scanned at baseline and 3 mo as part of a placebo-controlled intensive statin treatment study and three subjects with moderate atherosclerosis were scanned at baseline and again within 14 +/- 2 d. 3DUS-derived vessel wall volume (VWV) was measured using manual segmentation to provide segmentation contours that were used to generate scan and rescan carotid atherosclerosis thickness maps and thickness difference maps. There was no significant difference in VWV between scan and rescan for the three subjects scanned twice in 2 wk or the single subject treated with placebo. There was a significant difference between scan and rescan VWV for carotid stenosis subjects treated with atorvastatin (p < 0.001). Carotid atherosclerosis thickness difference maps showed visual qualitative evidence of thickness changes in vessel wall and plaque thickness in the common carotid artery for all statin-treated subjects and no change in a placebo-treated subject and subjects scanned twice in 2 wk. Carotid atherosclerosis thickness difference maps generated from 3DUS images provide evidence of vessel wall and plaque thickness changes for all subjects assessed.


Phytanic acid impairs mitochondrial respiration through protonophoric action.
Refsum disease is a rare, inherited neurodegenerative disorder characterized by accumulation of the dietary branched-chain fatty acid phytanic acid in plasma and tissues caused by a defect in the alphaoxidation pathway. The accumulation of phytanic acid is believed to be the main pathophysiological cause of the disease. However, the exact mechanism(s) by which phytanic acid exerts its toxicity have not been resolved. In this study, the effect of phytanic acid on mitochondrial respiration was investigated. The results show that in digitonin-permeabilized fibroblasts, phytanic acid decreases ATP synthesis, whereas substrate oxidation per se is not affected. Importantly, studies in intact fibroblasts revealed that phytanic acid decreases both the mitochondrial membrane potential and NAD(P)H autofluorescence. Taken together, the results described here show that unesterified phytanic acid exerts its toxic effect mainly through its protonophoric action, at least in human skin fibroblasts.


Anatomic correlations of magnetic resonance images with cadaver cryosections.
The authors present here a correlation of the normal anatomy of the pelvis, as depicted by MRI in multiple planes, with corresponding cadaveric specimens.


Glycated hemoglobin is not an accurate indicator of glycemia in rainbow trout.
Glycation occurs when glucose reacts non-enzymatically with proteins. This reaction depends upon time, ambient glucose concentration, and the molecular conformation of reactive amino acids. Little is known about protein glycation in fishes and the main objective of this study was to measure glycated hemoglobin (GHb) in rainbow trout, a glucose-intolerant species, under normoglycemic and hyperglycemic conditions. We also identified GHb isoforms in vivo and analyzed the structural environment surrounding potential glycation sites. Despite similar glycemia to healthy humans, GHb was an order of magnitude lower in rainbow trout (0.6%) compared with humans (6%) and was not affected by long-term hyperglycemia. Species differences in GHb appear to be related to differences in erythrocyte glucose, and differential expression and glycation of hemoglobin (Hb) isoforms may explain intraspecific differences in rainbow trout GHb. Computer analysis of glucose isomers (ringed-open and α- and β-pyranoses) interacting with the β-chain of rainbow trout HbI and HbIV, and human HbA did not reveal structural or energetic constraints for glucose binding (the initial step of glycation) for rainbow trout Hbs. Overall, there are significant differences between Hb glycation in humans and rainbow trout, and GHb does not appear to be an accurate indicator of glycemia over time in rainbow trout.


Mother-child reminiscing at risk: Maternal attachment, elaboration, and child autobiographical memory specificity.
Mother-child reminiscing, the process by which mothers and their children discuss past events and emotional experiences, has been robustly linked with child outcomes, including autobiographical memory. To advance previous work linking elaborative maternal reminiscing with child autobiographical memory specificity, the ability to generate and retrieve specific memories from one's past, it is essential to make distinctions among aspects of elaboration and to consider how maternal risk factors may influence the reminiscing context. The current study evaluated (a) an interaction between emotional and structural elaboration predicting child autobiographical memory specificity and (b) the potential moderating role of maternal adult attachment. Participants consisted of 95 preschool-aged children and their mothers. The sample was predominantly low income and racially diverse. Dyads completed a reminiscing task that was coded for emotional and structural elaboration. Mothers completed the Experiences in Close Relationships questionnaire (ECR-R) to assess attachment-related avoidance and anxiety, and children completed the Autobiographical Memory Test-Preschool Version (AMT-PV) to assess memory specificity. Results indicated that the association between structural reminiscing and child memory specificity was moderated by emotional elements of reminiscing. At high levels of emotional elaboration, mothers with high levels of structural elaboration had children with more specific memory than mothers with low levels of structural elaboration. Moreover, emotional elaboration (a) predicted less specific child memory without high structural support and (b) negatively predicted child specificity at high levels of maternal attachment avoidance and anxiety, a profile associated with fearful avoidance. Future directions and implications are discussed.


Prenatal diagnosis of an infratentorial subdural hemorrhage: case report.
We report a case of a prenatally diagnosed infratentorial subdural hemorrhage. The hematoma located in the posterior cerebral fossa was detected by conventional ultrasound at 24 weeks of gestation. Intrauterine magnetic resonance imaging confirmed the diagnosis. Autopsy of the fetus revealed a well-circumscribed subdural hematoma. The prenatal findings of intracranial bleeding located in the posterior fossa and the prognosis of such cases are discussed.


Chronopharmacokinetic study of a prolonged release form of indomethacin.
The chronopharmacokinetics of indomethacin was studied in patients with rheumatoid diseases after a single oral dose of a new prolonged-release form containing indomethacin 75 mg. The drug was given either at 8, 12 or 20 h and its plasma concentrations, as well as those of its main metabolite, O-desmethyl indomethacin, were followed using a new specific gas chromatographic assay. When given at 20 h plasma indomethacin concentrations did not exhibit a sharp peak and remained much more stable than when the drug was given at 8 or 12 h. In addition, plasma O-desmethyl indomethacin was significantly higher after administration of indomethacin at 20 h than at 8 or 12 h. It is concluded that the pharmacokinetics of the oral prolonged-release form of indomethacin exhibited chronobiological variation. The data are in accordance with clinical studies which suggest that it might be worthwhile to administer this formulation of indomethacin at 20 h.


Influence of pretreatment of cotton yarns prior to biopolishing.
Cellulase is one of the enzymes most commonly used in the textile industry for the biopolishing process. The appropriate choice of pretreatment is a possible route to promoting enzymatic attack in situations in which this is not favored due to the effects of packing. In order to evaluate the influence of pretreatment the yarn was maintained in water for 24h before biopolishing to promote greater spacing between the chains. In the tensile testing the pretreated Combed 13/1 yarn showed a greater percentage reduction in the maximum breaking force following biopolishing, evidencing a stronger enzymatic attack. Also, the Combed 13/1 and OE 14/1 yarns without pretreatment had an approximately 22% reduction in the shrinkage and after pretreatment the Carded 13/1 yarn had the best shrinkage reduction values (18%). These data demonstrate that the introduction of the pretreatment promotes a change in the access of the enzyme to the fiber.


The composite anterolateral thigh flap for knee extensor and skin reconstruction.
The simultaneous reconstruction of a skin defect and lost extensor mechanism of the knee joint is difficult. We present a 31-year-old male who lost the patella and had a 9 × 10 cm skin defect after a total patellectomy for an infected open patellar fracture. A composite anterolateral thigh (ALT) flap including vascularized skin and fascia lata (FL) was elevated. The FL was folded and sutured to the remaining patellar tendon. The skin flap covered the skin defect. The wound healed uneventfully. Thirty months later, the active range of motion of the knee joint was 0°-120° and the extension strength of the knee joint was normal. He could stand on his right leg and walk without assistance. The composite ALT flap is a valuable option in knee reconstruction after a total patellectomy.


A survey of physicians' attitudes toward blood transfusion in patients undergoing cesarean section.
This study was undertaken to evaluate the attitude of anesthesiologists and gynecologists to the use of blood during cesarean section operation and, on the basis of the results, to ascertain the need for improvement of current transfusion guidelines. A scenario-based survey was performed. The response rate was 94% (327/347) among anesthesiologists and 91% (355/391) among gynecologists. The majority of responders selected a hemoglobin threshold ranging from 7.5 to 8.5 g/dL (62%). Threshold hemoglobin concentration differed significantly (P<.001) between anesthesiologists (median, 7.5 g/dL) and gynecologists (median, 8 g/dL). At that threshold, 56% of anesthesiologists compared with 86% of gynecologists administered 2 units of blood (P<.05). When transfusing packed cells, most practitioners would give 2 units regardless of the transfusion threshold. Our findings demonstrate differing approaches to current transfusion protocols. Transfusion consensus recommendations should be improved and unified to enhance red blood cell transfusion practices for relatively young and healthy patients undergoing anesthesia and surgery.


Bioprospecting for novel hydroxyoxylipins in fungi: presence of 3-hydroxy palmitic acid in Saccharomycopsis malanga.
Electron microscopy studies indicated that the major oxylipin 3-hydroxy palmitic acid (16:0) was associated with aggregating vegetative cells and formed a web-like structure around these cells. Cross sections through this structure showed a hydrophilic outer layer and a more hydrophobic inner layer suggesting that the web-like structure is in fact tube-like micelles. This information sheds more light on the role of these hydroxyoxylipins in fungi.


Sub-clinical vascular disease in type 2 diabetic subjects: relationship with chronic complications of diabetes and the presence of cardiovascular disease risk factors.
We evaluated the association between a low ankle-brachial index (ABI), chronic complications of diabetes, and the presence of traditional cardiovascular disease risk factors in subjects with type 2 diabetes but without known cardiovascular disease. We included diabetic subjects (n=923; 52% male; age range 50-85 years) without clinical evidence of coronary, cerebrovascular, or peripheral artery disease (PAD). A history of nephropathy, retinopathy, or neuropathy was collected from the medical records. A 12-lead electrocardiogram and ABI measurements were conducted on all study participants. The mean duration of diabetes was 9.6 years. Prevalence of a low ABI (<0.9) was 26.2%. Multivariate analysis indicated that factors significantly associated with a low ABI were age (OR: 1.06; 95%CI: 1.033-1.084; p<0.001), plasma triglyceride concentration (OR: 1.002; 95%CI: 1.001-1.004; p=0.006), duration of diabetes (OR: 1.029; 95%CI: 1.008-1.051; p=0.007), and smoking habit (OR: 1.755; 95%CI: 1.053-2.925; p=0.03). The presence of nephropathy, neuropathy, retinopathy, left ventricular hypertrophy, left bundle branch block, and atrial fibrillation were all associated with a low ABI, but only renal disease remained significant after adjusting for age, duration of diabetes, and cardiovascular risk factors. A low ABI is highly prevalent in subjects with diabetes and is related to age, duration of diabetes, smoking habit, and hypertriglyceridemia. Although chronic complications are frequently associated with a low ABI, only renal damage is independently associated with peripheral artery disease.


The habituation of higher-order conscious processes: Evidence from mental arithmetic.
A recurring idea in psychology is that one is conscious only of the "outputs" of mental operations, but not of the operations themselves. Often, such "entry into consciousness" occurs involuntarily. To investigate involuntary entry, some experimentalists have used the reflexive imagery task (RIT). The RIT has revealed that, under certain conditions, external stimuli (e.g., line drawings) can elicit involuntary entry of high-level cognitions. In the basic version of the task, participants are presented with visual objects and instructed not to subvocalize (i.e., say in one's head) the names of these objects. Participants cannot suppress these subvocalizations on a majority of the trials. It has been proposed that, if RIT effects resemble a reflex, then perhaps they will habituate as reflexes do. In the "habituation" variant of the RIT, the same stimulus object (e.g., CAT) is presented on ten consecutive trials (ten "instantiations"), in order to induce habituation (i.e., a weakened RIT effect). It remains unknown whether such habituation effects arise for stimulus-elicited processes that depend, not on subvocalization, but on more complex processes, such as mental arithmetic. To illuminate this issue, we conducted a conceptual replication of the "habituation" RIT that involves, on each trial, the participant trying not to add two numbers (e.g., 14 and 2). We assessed whether the habituation effects were stimulus-specific or set-specific. Understanding the boundary conditions of the RIT effect and its habituation illuminates the limits of unconscious processes and the role of conscious processing.


Occurrence and removal of phenolic endocrine disrupting chemicals in the water treatment processes.
This paper evaluated the occurrence and removal efficiency of four selected phenolic endocrine disrupting chemicals (bisphenol A (BPA), octylphenol (OP), nonylphenol (NP) and diethylstilbestrol (DES)) in two drinking waterworks in Jiangsu province which take source water from Taihu Lake. The recombined yeast estrogen screen (YES) and liquid chromatography tandem mass spectrometry (LC-MS/MS) were applied to assess the estrogenicity and detect the estrogens in the samples. The estrogen equivalents (EEQs) ranged from nd (not detected) to 2.96 ng/L, and the estrogenic activities decreased along the processes. Among the 32 samples, DES prevailed in all samples, with concentrations ranging 1.46-12.0 ng/L, BPA, OP and NP were partially detected, with concentrations ranging from nd to 17.73 ng/L, nd to 0.49 ng/L and nd to 3.27 ng/L, respectively. DES was found to be the main contributor to the estrogenicity (99.06%), followed by NP (0.62%), OP (0.23%) and BPA (0.09%). From the observation of treatment efficiency, the advanced treatment processes presented much higher removal ratio in reducing DES, the biodegradation played an important role in removing BPA, ozonation and pre-oxidation showed an effective removal on all the four estrogens; while the conventional ones can also reduce all the four estrogens.


The role of ozone-reactive compounds, terpenes, and green leaf volatiles (glvs), in the orientation of Cotesia plutellae.
The emission of inducible volatile organic compounds (VOCs), i.e., inducible terpenes, and green leaf volatiles (GLVs), is a common response of plants to herbivore attack. These VOCs are involved in the orientation of natural enemies, i.e., predators and parasitoids, toward their herbivore prey or hosts (indirect defense of plants). Terpenes and some GLVs are readily oxidized by ozone (O(3)), an important oxidant of the low atmosphere and predicted to increase as a result of anthropogenic activity. It has been recently reported that O(3) degradation of terpenes and GLVs does not affect signaling in two selected tritrophic systems. Natural enemies may have learned to use oxidation products that are more stable in nature to locate their prey. To understand the role of these compounds on the tritrophic system Brassica oleracea-Plutella xylostella-Cotesia plutellae, we assessed the preference of wasps to different combinations of cabbage VOCs (intact vs. herbivore-induced and herbivore-induced vs. herbivore-induced VOCs) in the presence or absence of O(3). We found that C. plutellae preferred P. xylostella-damaged plants at 0 and 120 nl l(-1) O(3) to intact plants at 0 nl l(-1) O(3). However, wasps preferred P. xylostella-damaged plants at 0 nl l(-1) to P. xylostella-damaged plants at 120 nl l(-1) O(3). The results suggest that compounds other than terpenes and GLVs are crucial for the orientation of the wasps, but terpenes and GLVs contribute to the behaviorally active VOC blend of herbivore-damaged cabbages by increasing their attraction to them. The products resulting from oxidation of terpenes and GLVs do not seem to play a role in the host location process as speculated previously.


Teratology of 2,3,7,8-tetrachlorodibenzo-p-dioxin in a complex environmental mixture from the love canal.
The organic phase of a leachate (OPL) from the Love Canal chemical dump site contains more than 100 organic compounds including 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD). The teratogenic potential of OPL was determined in two inbred and one hybrid mouse strain which differ in their sensitivity to aromatic hydrocarbon (Ah) receptor-mediated toxicity. OPL was orally administered in corn oil on Days 6-15 of gestation to C57BL/6J mice (Ahb/Ahb) at doses of 0, 0.1, 0.3, 0.5, and 0.7 g kg-1 day-1 and to DBA/2J (Ahd/Ahd) females, which were mated with either DBA/2J or C57BL/6J males, at 0, 0.5, 1, and 2.0 g kg-1 day-1. In C57BL/6J mice, which express a high-affinity Ah receptor that avidly binds TCDD, the ED50's of OPL for cleft palate and hydronephrosis were 0.44 and 0.11 g OPL kg-1 day-1, respectively. Maternal mortality was 5% at the highest dose. In DBA/2J fetuses, which express a low-affinity receptor, neither treatment-related cleft palate nor hydronephrosis was induced by dose levels that caused 36% maternal mortality. In hybrid D2B6F1 fetuses, the incidence of cleft palate reached only 8% at 2 g OPL kg-1 day-1 but the ED50 for hydronephrosis was 0.76 g OPL kg-1 day-1. TCDD was similarly administered to pregnant C57BL/6J mice at 0, 0.5, 1, 2, and 4 micrograms kg-1 day-1 and to DBA/2J mice at 0, 0.5, 2, 4, and 8 micrograms kg-1 day-1. In C57BL/6J fetuses, the ED50's for cleft palate and hydronephrosis were 4.6 and 0.73 microgram TCDD kg-1 day-1, respectively. In DBA/2J fetuses the ED50's for cleft palate and hydronephrosis were 15.0 and 6.4 micrograms TCDD kg-1 day-1, respectively. Both the OPL and TCDD caused maternal hepatomegaly and thymic atrophy in all strains, but increased only C57BL/6J fetal weights. OPL decreased the number of fetuses per C57BL/6J dam at the two highest doses but there were no other reproductive effects in any of the groups. It was concluded that the OPL is teratogenic and that hydronephrosis is a sensitive measure of TCDD toxicity in a complex organic mixture. Based on the ED50's of OPL- and TCDD-induced cleft palate and hydronephrosis in the C57BL/6J strain, the OPL had TCDD equivalence of 6.6 and 10.5 ppm, respectively. These values compare closely with the chemical analysis of 3 ppm.(ABSTRACT TRUNCATED AT 400 WORDS)


Neuronal Induction of Bone-Fat Imbalance through Osteocyte Neuropeptide Y.
A differentiation switch of bone marrow mesenchymal stem/stromal cells (BMSCs) from osteoblasts to adipocytes contributes to age- and menopause-associated bone loss and marrow adiposity. Here it is found that osteocytes, the most abundant bone cells, promote adipogenesis and inhibit osteogenesis of BMSCs by secreting neuropeptide Y (NPY), whose expression increases with aging and osteoporosis. Deletion of NPY in osteocytes generates a high bone mass phenotype, and attenuates aging- and ovariectomy (OVX)-induced bone-fat imbalance in mice. Osteocyte NPY production is under the control of autonomic nervous system (ANS) and osteocyte NPY deletion blocks the ANS-induced regulation of BMSC fate and bone-fat balance. γ-Oryzanol, a clinically used ANS regulator, significantly increases bone formation and reverses aging- and OVX-induced osteocyte NPY overproduction and marrow adiposity in control mice, but not in mice lacking osteocyte NPY. The study suggests a new mode of neuronal control of bone metabolism through the ANS-induced regulation of osteocyte NPY.


N-(2,3,4-Trifluoro-phen-yl)pyrrolidine-1-carboxamide.
In the title compound, C(11)H(11)F(3)N(2)O, a urea derivative, the best plane through the pyrrole ring makes a dihedral angle of 9.69 (13)° with the benzene ring. The amino H atom is shielded, so that it is not involved in any hydrogen-bonding inter-actions.


Evidence on Vocal Interventions in Adults: A Scoping Review.
To map the evidence on vocal intervention in people over 18 years old. A literature search was conducted using the following electronic databases: Cochrane Library, EMBASE, Latin American and Caribbean Literature on Health Sciences (LILACS), LIVIVO, Pubmed/Medline, Scopus, SpeechBITE, and Web of Science. Gray literature was also used as an information source through searches on Google Scholar, Open Grey, ProQuest Dissertation and Thesis, and the Brazilian digital library of theses and dissertations. Systematic reviews (SR) with a population of individuals over 18 years old were included. The included reviews addressed speech-language pathology interventions in the vocal area with reports of their respective outcome. The methodological quality of the included systematic reviews was analyzed using the AMSTAR II tool. Quantitative analysis was performed by frequency distribution, and qualitative research was analyzed through narrative synthesis. A total of 2,443 references were retrieved, among which 20 studies met the inclusion criteria. The included studies had critically low quality, lacking the use of population, intervention, comparison, and outcome (PICO) components. Among the included SRs, 40% were made in Brazil, 45% were published in the Journal of Voice, and 75% analyzed dysphonic patients. The most frequent intervention was voice therapy (direct therapy associated with indirect therapy approaches). Positive results were observed in most of the outcomes for all studies. Voice therapy was described as inducing positive effects for voice rehabilitation. However, due to the critically low quality of studies, the literature did not enable us to understand the best results for each intervention. Well-designed studies are necessary to clarify the relationship between the intervention goal and how the intervention was evaluated.


Osteonecrosis of the medial tibial plateau after intra-articular corticosteroid injection: A case report.
Intra-articular corticosteroid injection (IACI) is a cost-effective conservative treatment of mild-to-moderate osteoarthritis. Adverse events after this procedure range from life-threatening systemic reactions to self-limiting local reactions. To our knowledge, this is the 1st report of osteonecrosis (ON) in the medial tibial plateau after IACI. An 81-year-old female visited our hospital due to left knee pain of increasing intensity. She presented the sudden onset of severe acute knee pain with long lasting knee pain for several years. The diagnosis was confirmed ON of medial tibial plateau of knee joint by pathologic finding. We conducted a posterior stabilized total-knee arthroplasty with no requirement for bone grafting or additional prosthesis, such as metal augments or stems. At the postoperative 1 year follow-up, the patient was satisfied with the surgery and had no pain during walking and active knee motion. This case especially stress the possibility of ON in medial tibia plateau after IACI. Therefore, clinicians should monitor symptoms after IACI to enable early detection of this complication.


Tensile properties of the supraspinatus tendon.
The tensile properties of the supraspinatus tendon were investigated in 11 shoulders from fresh cadavers. The tendon was divided into three longitudinal strips: anterior, middle, and posterior. Each specimen was mounted on a materials testing machine, with four fluorescent markers placed on both surfaces of the tendon strip. The positions of these markers were recorded during the test by two synchronized video cameras. Load-deformation and strain curves were determined, and the stress-strain curve, strength, and modulus of elasticity were calculated. The posterior strip was thinner in cross section than the others (p = 0.0355). The ultimate load and ultimate stress were significantly greater in the anterior strip (16.5 +/- 7.1 MPa) than in the middle (6.0 +/- 2.6 MPa) and posterior (4.1 +/- 1.3 MPa) strips (p < 0.0001). The modulus of elasticity also was significantly greater in the anterior strip (p < 0.0001), but there was no significant difference between the superficial and deep surfaces. It is concluded that the anterior portion of the supraspinatus tendon is mechanically stronger than the other portions, and it seems to perform the main functional role of the tendon.


A Woman with Systemic Lupus Erythematosus and Odd Valvular Presentation: A Case Report.
BACKGROUND Systemic lupus erythematosus (SLE) is a systemic disease with various cardiac and non-cardiac presentations. We present the case of a young woman with odd presentation of SLE mistakenly identified as a valve abscess that was scheduled for surgery. CASE REPORT This 35-year-old woman presented with rapid progression of aortic stenosis, and the transesophageal echocardiography report showed a misdiagnosed aortic web (congenital) and aortic wall abscess. She was scheduled for surgery as a case of subacute bacterial endocarditis (SBE) and aortic abscess, despite lack of fever. CONCLUSIONS Cardiovascular involvement should be considered in any SLE patient, especially those with high SLE scores, even with negative antiphospholipid antibody. Cardiovascular involvement may be odd and misleading in some cases, which may warrant especial attention and experienced caregivers for clinical reasoning and proper management.


From sleep duration to childhood obesity--what are the pathways?
Sleep duration has been identified as risk factor for obesity already in children. Besides investigating the role of fat mass (FM), this study addressed the question whether endocrine mechanisms act as intermediates in the association between sleep duration and overweight/obesity. Within the framework of the IDEFICS study, the present research was conducted in 609 German resident children aged 2-9 years with information on fasting insulin, C-reactive protein and cortisol levels next to anthropometric measurements and parental questionnaires. Emphasising methodological aspects, an age-specific measure of sleep duration was derived to account for alteration in sleep duration during childhood/period of growth. Multivariate linear regression and quantile regression models confirmed an inverse relationship between sleep duration and measures of overweight/obesity. The estimate for the association of sleep duration and body mass index (BMI) was approximately halved after adjustment for FM, but remained significant. The strength of this association was also markedly attenuated when adjusting for insulin mainly for the upper BMI quantiles (Q80, β = -0.36 vs. β = -0.26; Q95, β = -0.87 vs. β = -0.47). Adjustment for cortisol and CrP did not yield this attenuation. The inverse relationship between sleep duration and BMI is mainly explained by the association between sleep duration and FM. Insulin may explain part of this association, in particular at the upper tail of the BMI distribution.


The raphe neuronal system and serotonergic effects of LSD.
Earlier work from this laboratory had shown that LSD caused significant increases in rat brain serotonin (5-HT). The increase was later localized to a subsynaptosomal fraction consisting largely of synaptic vesicles. However, the source of the increase and the mechanism by which LSD caused the enhanced 5-HT binding or retention had not been elucidated. The present study was undertaken to evaluate the serotonergic effects of LSD following destruction of raphe nuclei with radiofrequency lesions. When LSD was given to animals with large midbrain raphe lesions, it caused significant increases in forebrain of cortical 5-HT up to 48 hr, or 7 days post-lesion, respectively. It was concluded that an intact cell body is not necessary for the expression of the LSD-mediated increases in 5-HT occurring in the nerve-ending. The possible mechanisms by which LSD could act directly at the nerve-ending are discussed.


Migration of T cells from nearby inflammatory foci into antibody bound tissue: a relay of T cell and antibody actions in targeting native autoantigen.
We have reported that binding of antibody to native autoantigen is prerequisite for T cells to target the native antigen in murine autoimmune ovarian disease model (AOD). As a result, ovarian follicles, with target antigen ZP3 (Zona Pellucida 3), are destroyed. In this study, AOD was induced by co-transfer of ZP3-specific CD4(+)T cells and ZP3 antibody. ZP3 CD4(+)T cells, labeled with CFSE, were found to target macrophages in degenerated follicles to form inflammatory foci, which were composed of mainly endogenous CD4(+)T cells (85%). Only endogenous T cells in the foci, with increased CD69(+)expression, further migrated into antibody bound follicles. No F4/80 or MHC II(+)cells were found to co-migrate with the T cells or in follicles. Co-transfer of ZP3 T cell and antibody also induced (1) a transient PMN influx at early stage and (2) a dramatic increase in IL-1 beta expression coincident with the migration in the ovary. These results suggest that ZP3 antibody binding, only in the presence of ZP3 T cells, may cause an inflammatory change in follicles, which attract endogenous T cells from nearby inflammation. Thus, through a relay between T cell and antibody mediated mechanisms, native autoantigen is targeted and destroyed. This mechanism may explain the requirement of antibody in several T cell mediated autoimmune diseases.


Variation in the effect of profitability on prey size selection by the lacertid lizard Psammodromus algirus.
Maximizing the average rate of energy intake (profitability) may not always be the optimal foraging strategy for ectotherms with relatively low energy requirements. To test this hypothesis, we studied the feeding behaviour of captive insectivorous lizards Psammodromus algirus, and we obtained experimental estimates of prey mass, handling time, profitability, and attack distance for several types of prey. Handling time increased linearly with prey mass and differed significantly among prey types when prey size differences were controlled for, and mean profitabilities differed among prey taxa, but profitability was independent of prey size. The attack distance increased with prey length and with the mobility of prey, but it was unrelated to profitability. Thus, lizards did not seem to take account of the rate of energy intake per second as a proximate cue eliciting predatory behavior. This information was combined with pitfall-trap censuses of prey (in late April, mid-June and late July) that allowed us to compare the mass of the prey captured in the environment with that of the arthropods found in the stomachs of sacrificed free-living lizards. In April, when food abundance was low and lizards were reproducing, profitability had a pronounced effect on size selection and lizards selected prey larger than average from all taxa except the least profitable ones. As the active season progressed, and with a higher availability of food, the number of prey per stomach decreased and their mean ize increased. The effect of profitability on size selection decreased (June) and eventually vanished (July-August). This variation is probably related to seasonal changes in the ecology of lizards, e.g. time minimization in the breeding season as a means of saving time for nonforaging activities versus movement minimization by selecting fewer (but larger) prey in the postbreeding season. Thus, the hypothesis that maximizing profitability could be just an optional strategy for a terrestrial ectothermic vertebrate was supported by our data.


Indirect CT venography of the abdominal cavity and lower limbs in patients with the suspicion of pulmonary embolism--indications, technique, diagnostic possibilities.
Multi-slice computed tomography has become the main method to diagnose and evaluate the intensity of acute pulmonary embolism (PE). The most common cause of PE is thrombosis of veins of the lower limbs and pelvis. The paper presents various aspects of the use of combined pulmonary artery arteriography and indirect venography performed using multi-slice tomography in relation to other methods imaging the venous system used so far. The authors presented the techniques of CT examination of venous vessels of the lower limbs, abdominal cavity and pelvis in patients with the suspicion of PE, typical images of lesions, results of studies concerning these issues conducted to date and their own experience based on clinical practice.


Incidence, determinants and consequences of left atrial remodelling after a first anterior myocardial infarction.
Left atrial (LA) volume is an important predictor of mortality and morbidity after myocardial infarction (MI). However, the process of LA remodelling has not been extensively investigated. Our purpose was to analyse the incidence, determinants and consequences of LA remodelling in a cohort of patients with a first anterior MI enrolled in the modern era of MI management. We used data from 246 patients with a first anterior MI who were included in a prospective study on left ventricular (LV) remodelling (REVE-2). Serial echocardiographic studies were performed before discharge and at 3 months and 1 year after MI. LA volume increased from 20.5±5.9 mL/m2 at baseline to 24.6±7.4 mL/m2 at 3 months (P<0.0001 versus baseline) and 25.4±7.6 mL/m2 at 1 year (P<0.0001 versus baseline). Patients with high LA volumes at baseline had higher LV volumes, decreased LV systolic function, increased E/Ea (early transmitral velocity/mitral annular early diastolic velocity ratio) and increased B-type natriuretic peptide concentration. By multivariable analysis, the sole independent predictor of change in LA volume from baseline to 1 year was peak creatine kinase concentration (P<0.0001). Patients with higher LA volumes at baseline were at higher risk of cardiovascular death or rehospitalization for heart failure during follow-up (P=0.015). Despite modern therapeutic management, LA remodelling is common during the first 3 months after anterior MI. Patients with larger infarct size are at greater risk of LA remodelling after discharge.


Procalcitonin: a marker of heart failure.
Serum procalcitonin levels are associated with congestive heart failure, but are not established biomarkers of the disease. We evaluated the predictive value of serum procalcitonin levels for diagnosing heart failure and assessing its severity. This retrospective, case-control study involved 59 subjects (mean age 59.7-10.1 years; 38 males), including 21 outpa- tients and 19 inpatients with heart failure and left ventricular ejection fractions <45%, and 19 healthy controls. Serum procalcitonin levels were measured and compared among the 3 groups. Procalcitonin levels were significantly higher among inpatients (median [interquartile range], 1.45 [0.25-5.801 ng/mL) than among the outpatients (0.35 [0.001.-1.70] ng/mL; P< 0.001) or controls (0.05 [0.02-0.08] ng/mL; P< 0.0011. Using a procalcitonin cut-off level of 0.09 ng/mL, 35 (87.5%) of the 40 inpatients and outpatients were procalcitonin-positive; all control individuals were procalcitonin-negative. Serum procalcitonin levels differentiated between heart failure patients and healthy controls (sensitivity, 88.9% [95% confidence interval, 75.9-96.2%]; specificity, 100% [82.2-100.0%]; positive predictive value, 100% [91.1-100.0%]; negative predictive value, 79.2% [57.8-92.8%]). Pro calcitonin levels were >0.53 ng/mL in 4/21 (19%) outpatients and in 16/19 (84.2%) inpatients. The sensitivity and specificity of serum procalcitonin levels for differentiating between inpatients and outpatients were 84.2% and 81.0%, respectively (positive predictive value 80% [95% confidence interval, 67.6-92.4%] and 85.0% [73.9-96.1%], respectively). Serum procalcitonin levels, showing high sensitivity and specificity for diagnosing and assessing the severity of heart failure in this small study, might be considered ootential heart failure biomarkers.


Calibration of thin-layer chromatography with flame ionization detection for the analysis of natural lipid samples.
Thin-layer chromatography coupled with flame ionization detection has been used to develop a method to quantitate fish lipids. Quantitation of fractionated lipid classes is usually accomplished through calibration with standards. Our work shows that various standards within a class, such as triglycerides or free fatty acids give substantially different responses to the detector. A method has been developed in which a composite sample of salmon lipid is prepared with an internal standard. This technique eliminates the variable detector response observed for compounds within a class and provides more accurate quantitation of oils from which the calibration samples were prepared. The lipid classes quantitated were triglycerides, free fatty acids, phosphatidylethanolamine and phosphatidylcholine.


A community neurologist's personal viewpoint on neurological training.
A study of 200 patients referred to a community neurologist showed that 87.5% of the patients were seen in the office and only 12.5% in hospital. Neurological signs were present in 52% and 28.5% had neurological signs which materially affected the diagnosis. A questionnaire sent to several teaching centers showed that only one center sent students and residents to community neurologists' offices at all and in most centers the resident spent just 10 to 20% of his time seeing out-patients. It was felt that the balance of in-patient/out-patient teaching for students and residents was wrong, and that more emphasis should be placed on the neurological history than on the examination. Proposals are made to involve the community neurologist as well as the academic neurologist in the training of students and residents which would benefit all four groups.


Simulated tricuspid valve echoes in tricuspid atresia.
A case of tricuspid atresia with unusual echocardiographic findings is presented. The echocardiogram was successful in defining great artery interrelationships, ventricular looping, and cavity sizes. An echo pattern resembling the motion of a small tricuspid valve was observed; this was proven to be spurious at catheterization and necropsy. Caution should be exercised in diagnosing the presence of a tricuspid valve on the basis of atypical echoes from the tricuspid valve area.


Binding sites for pituitary adenylate cyclase activating polypeptide (PACAP): comparison with vasoactive intestinal polypeptide (VIP) binding site localization in rat brain sections.
Pituitary adenylate cyclase activating polypeptide (PACAP) is structurally similar to vasoactive intestinal polypeptide (VIP). We investigated the characteristics and topographical distribution of [125I]PACAP binding sites compared with those of [125I]VIP binding sites in the rat brain. Radiolabeled PACAP and VIP showed highly specific binding to sections at the level of the dorsal hippocampus. The specific binding of [125I]PACAP was 10 times higher than that of [125I]VIP in hippocampal sections. [125I]PACAP binding was scarcely displaced by unlabeled VIP, while [125I]VIP binding was effectively displaced by unlabeled PACAP. Therefore, PACAP binding sites may reflect both PACAP specific binding sites and VIP/PACAP binding sites. However, the amount of VIP/PACAP binding sites was negligibly low. Autoradiography revealed that [125I]PACAP binding sites were dense in the piriform cortex, diagonal band, accumbens nucleus, anterior part of the striatum, hippocampal formation, habenular nucleus, lateral hypothalamic area, superior colliculus and dorsal raphe nucleus. Moderate to high labeling was observed in the medial septal nucleus, olfactory tubercle, caudal part of the striatum, most parts of the thalamus, supraoptic and periventricular hypothalamic nuclei, central gray, substantia nigra pars compacta, locus coeruleus, pontine reticular nucleus and cerebellum. Distribution pattern was remarkably different from that of [125I]VIP binding sites in the hippocampal formation, lateral hypothalamic area, substantia nigra pars compacta, pontine reticular nucleus and cerebellum. The present results suggest that PACAP may have a physiological role in the regulation of the central nervous system.


Evaluating bone health in women with oestrogen receptor positive breast cancer (ERBC) starting aromatase inhibitors.
There is an increase in fractures in women with oestrogen receptor positive breast cancer (ERBC) particularly those taking aromatase inhibitors (AIs). How to identify women at osteoporosis risk, assess bone health and who to treat, are questions not adequately answered by previous studies. We present an audit of osteoporosis risk factors, bone mineral density (BMD) measurement and other data relevant to bone health (falls and laboratory tests) in 85 women with ERBC starting AIs. Only 9/85 (11%) women overall and only 2/13 with previous peripheral fragility fractures had osteoporosis. Of note, secondary hyperparathyroidism was present in 40% of women <60 years; 67% of women 60-69 years and 75% of women >70 years. Reliance on BMD alone to guide decisions for osteoporosis prevention treatment in those taking AIs would lead to few women being treated. Osteoporosis risk in women taking AIs is likely influenced by factors other than those encompassed by BMD alone.


Efficacy validation of synthesized retinol derivatives In vitro: stability, toxicity, and activity.
Retinol (vitamin A) is used as an antiwrinkle agent in the cosmetics industry. However, its photo-instability makes it unsuitable for use in general cosmetic formulations. To improve the photo-stability of retinol, three derivatives (3, 4, and 5) were synthesized and their biological activities were analyzed. 1H NMR and HPLC analysis indicated that derivatives 3 and 5 were much more stable than retinol under our sunlight exposure conditions. When human adult fibroblasts were treated, the IC(50) of derivative 3 was 96 microM, which is similar to that of retinol, as determined by the MTT assay. Derivatives 4 and 5 were 2.5 and 8 times more toxic than retinol, respectively. At 1 microM treatment, like retinol, derivatives 3 and 4 were specifically active for RARalpha out of six retinoid receptors (RAR/RXRalpha, beta, gamma). Dose-dependent analysis confirmed that derivative 4 was as active as retinol and the other two derivatives were less active for RARalpha. The effect of our derivatives on the expression of collagenase, an indicator of wrinkle formation, was measured using the transient co-expression of c-Jun and RT-PCR in HaCaT cells. Collagenase promoter activity, which is increased by c-Jun expression, was reduced 42% by retinol treatment. The other derivatives inhibited collagenase promoter activity similarly. These results were further confirmed by RT-PCR analysis of the collagenase gene. Taken together, our results suggest that retinol derivative 3 is a promising antiwrinkle agent based on its higher photo-stability, lower RARalpha activity (possibly indicating reduced side effects), and similar effect on collagenase expression.


Subspecies variation in Greek strains of Chlamydophila abortus.
The Greek chlamydial strains FAS, FAG, VPG and LLG, isolated from aborted sheep or goat foetuses, had been previously characterized as divergent on the basis of mouse cross-protection experiments, with LLG and its homologous POS significantly different from the rest in inclusion morphology, polypeptide profiles and reactivity with monoclonal antibodies. To determine the genetic basis of their divergence the 16S-23S ribosomal intergenic spacer was analysed by RFLP analysis of PCR 16SF2/23R amplicons. Using the restriction enzymes BfaI, SfcI, HpaI, BclI, DdeI and AclI, the strains were classified as Chlamydophila abortus. However, digestion with RsaI made it possible to differentiate strains FAS, FAG and VPG from strains LLG and POS, generating DNA fragments of 530/55 and 585bp, respectively. By subsequent sequence analysis of the 23S domain I rRNA gene only strain FAS was identical to reference strain A22 of C. abortus. Strains FAG and VPG presented an identical nucleotide deviation at position 593 of signature sequences. Strains LLG and POS presented three identical nucleotide deviations at positions 156, 186 and 307. Variation within the domain I signature sequences for the examined abortion strains was < or =0.69%. In conclusion, substantial genetic and biological diversity among strains of C. abortus was demonstrated, suggesting that subspecies variation status for certain strains may be applicable. Our findings suggest that differentiation may be possible at a subspecies level by RFLP analysis.


MR and ultrasound of the hands and wrists in rheumatoid arthritis. Part II. Added clinical value.
Advanced imaging has become just as vital for diagnosing, staging, and monitoring disease in rheumatoid arthritis (RA) patients as it is for cancer patients. Part 1 of this review discussed synovitis, tenosynovitis, erosions, and osteitis-key imaging findings that occur in patients with RA. Part 2 will now show how these features, in combination with clinical and serologic data, can assist clinical decision-making at various stages of a patient's disease course. Specifically, assessing current disease activity and prognosticating future aggressiveness inform treatment decisions at initial presentation, during medical treatment, and at clinical remission. In addition to summarizing the current literature on advanced imaging in RA, clinical examples from different stages throughout the disease course will illustrate practical approaches for applying these research results. Last, this review will describe potential future roles of imaging in RA patients.


A risk-adjustment model for patients presenting to hospitals with out-of-hospital cardiac arrest and ST-elevation myocardial infarction.
Patients with ST-elevation myocardial infarction (STEMI) complicated by an out-of-hospital-cardiac-arrest (OHCA) may vary widely in their probability of dying. Large variation in mortality may have implications for current national efforts to benchmark operator and hospital mortality rates for coronary angiography. We aimed to build a risk-adjustment model of in-hospital mortality among OHCA survivors with concurrent STEMI. Within the Cardiac Arrest Registry to Enhance Survival (CARES), we included adults with OHCA and STEMI who underwent emergent angiography within 2 hours of hospital arrival between January 2013 and December 2019. Using multivariable logistic regression to adjust for patient and cardiac arrest factors, we developed a risk-adjustment model for in-hospital mortality and examined variation in patients' predicted mortality. Of 2,999 patients (mean age 61.2 ± 12.0, 23.1% female, 64.6% white), 996 (33.2%) died during their hospitalization. The final risk-adjustment model included higher age (OR per 10-year increase, 1.50 [95% CI: 1.39-1.63]), unwitnessed OHCA (OR, 2.51 [1.99-3.16]), initial non-shockable rhythm [OR, 5.66 [4.52-7.13]), lack of sustained pulse for > 20 minutes (OR, 2.52 [1.88-3.36]), and longer resuscitation time (increased with each 10-minute interval) (c-statistic = 0.804 with excellent calibration). There was large variability in predicted mortality: median, 25.2%, inter-quartile-range: 14.0% to 47.8%, 10th-90th percentile: 8.2 % to 74.1%. In a large national registry, we identified 5 key predictors for mortality in patients with STEMI and OHCA and found wide variability in mortality risk. Our findings suggest that current national benchmarking efforts for coronary angiography, which simply adjusts for the presence of OHCA, may not adequately capture patient case-mix severity.


Design, synthesis, and biological evaluation of 1,6-naphthyridine-2-one derivatives as novel FGFR4 inhibitors for the treatment of colorectal cancer.
Aberrant FGFR4 signaling has been implicated in the development of several cancers, making FGFR4 a promising target for cancer therapy. Several FGFR4-selective inhibitors have been developed, yet none of them have been approved. Herein, we report a novel series of 1,6-naphthyridine-2-one derivatives as potent and selective inhibitors targeting FGFR4 kinase. Preliminary structure-activity relationship analysis was conducted. The screening cascades revealed that 19g was the preferred compound among the prepared series. 19g demonstrated excellent kinase selectivity and substantial cytotoxic effect against all tested colorectal cancer cell lines. 19g induced significant tumor inhibition in a HCT116 xenograft mouse model without any apparent toxicity. Notably, 19g exhibited excellent potency in disrupting the phosphorylation of FGFR4 and downstream signaling proteins mediated by FGF18 and FGF19. Compound 19g might be a potential antitumor drug candidate for the treatment of colorectal cancer.


Effect of vanadium on bone metabolism in weanling rats: zinc prevents the toxic effect of vanadium.
The effect of vanadium on bone metabolism was investigated in the femoral diaphysis of weanling rats. Vanadium pentoxide (1.0-20.0 mumol V/100 g b.wt.) was administered orally for 3 days. The doses of 15.0 and 20.0 mumol V/100 g caused a significant increase in serum calcium concentration. Bone alkaline phosphatase activity was increased significantly by the doses of 1.0-20.0 mumol V/100 g, while bone acid phosphatase activity was not altered significantly. Bone DNA content was increased significantly by the dose of 1.0-10.0 mumol V/100 g. Bone calcium content was not altered significantly by administration of vanadium. The increase in serum calcium concentration caused by administration of vanadium (20.0 mumol/100 g) was prevented completely by simultaneous injection of zinc sulfate (15.3 mumol Zn/100 g) for 3 days, although zinc alone did not have any effect. Administration of zinc (15.3 mumol/100 g) produced an appreciable increase in bone alkaline phosphatase activity, DNA content, and calcium content. These increases were not enhanced significantly by simultaneous injection of vanadium (2.0 and 20.0 mumol V/100 g). The present study indicates that a comparatively low dose of vanadium may play a nutritional role in bone formation of weanling rats, and that zinc can prevent the relevation of the toxic effect of vanadium with higher doses.


Induction of vascular smooth muscle cell growth by selective activation of the thrombin receptor. Effect of heparin.
The synthetic peptide, SFLLRNPNDKYEPF, has been recently described as a peptide mimicking the new amino-terminus created by cleavage of the thrombin receptor, therefore acting as an agonist of the thrombin receptor. This peptide was a potent mitogen for rabbit arterial smooth muscle cells (SMC) and exhibited the same activity as that of native alpha-thrombin. Both compounds stimulated the proliferation of growth-arrested SMCs with half-maximum mitogenic responses at 1 nM. NAPAP, a synthetic inhibitor of the enzymatic activity of thrombin, specifically inhibited thrombin-induced SMC growth (IC50 = 0.35 +/- 0.04 microM) but was without effect on the mitogenic effect of the agonist peptide. These results therefore demonstrate that the mitogenic effect of alpha-thrombin for SMCs is intimately linked to its esterolytic activity. Heparin, which inhibited fetal calf serum-induced SMC growth, was without effect on thrombin-induced SMC growth but strongly reduced the mitogenic effect of the agonist peptide (IC50 = 32 +/- 5 micrograms/ml). This effect was not related to the anti-coagulant activity of heparin but was highly dependent on molecular mass and on the global charge of the molecule and was also observed for other sulphated polysaccharides such as pentosan polysulphate.


Photochemical treatment of plasma with amotosalen and long-wavelength ultraviolet light inactivates pathogens while retaining coagulation function.
The INTERCEPT Blood System, a photochemical treatment (PCT) process, has been developed to inactivate pathogens in platelet concentrates. These studies evaluated the efficacy of PCT to inactivate pathogens in plasma and the effect of PCT on plasma function. Jumbo (600 mL) plasma units were inoculated with high titers of test pathogens and treated with 150 micromol per L amotosalen and 3 J per cm(2) long-wavelength ultraviolet light. The viability of each pathogen before and after treatment was measured with biological assays. Plasma function was evaluated through measurement of coagulation factors and antithrombotic protein activities. The levels of inactivation expressed as log-reduction were as follows: cell-free human immunodeficiency virus-1 (HIV-1), greater than 6.8; cell-associated HIV-1, greater than 6.4; human T-lymphotropic virus-I (HTLV-I), 4.5; HTLV-II, greater than 5.7; hepatitis B virus (HBV) and hepatitis C virus, greater than 4.5; duck HBV, 4.4 to 4.5; bovine viral diarrhea virus, 6.0; severe acute respiratory syndrome coronavirus, 5.5; West Nile virus, 6.8; bluetongue virus, 5.1; human adenovirus 5, 6.8; Klebsiella pneumoniae, greater than 7.4; Staphylococcus epidermidis and Yersinia enterocolitica, greater than 7.3; Treponema pallidum, greater than 5.9; Borrelia burgdorferi, greater than 10.6; Plasmodium falciparum, 6.9; Trypanosoma cruzi, greater than 5.0; and Babesia microti, greater than 5.3. Retention of coagulation factor activity after PCT was expressed as the proportion of pretreatment (baseline) activity. Retention was 72 to 73 percent of baseline fibrinogen and Factor (F)VIII activity and 78 to 98 percent for FII, FV, FVII, F IX, FX, FXI, FXIII, protein C, protein S, antithrombin, and alpha2-antiplasmin. PCT of plasma inactivated high levels of a wide range of pathogens while maintaining adequate coagulation function. PCT has the potential to reduce the risk of transfusion-transmitted diseases in patients requiring plasma transfusion support.


Inhibition of vascular smooth muscle tone by the H+, K+-ATPase inhibitor SCH 28080.
Vascular smooth muscle is thought to possess an H+-K+ ATPase that contributes to the regulation of intracellular K+ concentration and pH. We have examined the effect of the H+, K+-ATPase inhibitor SCH 28080 on vascular smooth muscle tone in guinea-pig and human isolated arteries, and on 86Rb+ uptake in cultured guinea-pig aortic smooth muscle cells. SCH 28080 (0.1-300 microM) produced relaxation of isolated guinea-pig aorta, guinea-pig pulmonary artery and human pulmonary artery. Relaxation occurred in tissues pre-contracted with phenylephrine, histamine or the thromboxane mimetic U44069. Relaxation. was reversible, and was not affected by tetrodotoxin, indomethacin, nordihydroguiaretic acid (NDGA), 1-aminobenzotriazole (1-ABT), N(G)-nitro-L-arginine methyl ester (L-NAME), removal of the endothelium or removal of extracellular K+. SCH 28080 had no effect on 86Rb+ uptake in cultured guinea-pig aortic smooth muscle cells. In conclusion, SCH 28080 relaxes vascular smooth muscle at concentrations known to inhibit the H+-K+ ATPase. The persistence of relaxation in a K+-free medium and the failure of SCH 28080 to inhibit 86Rb+ uptake suggest that relaxation may be unrelated to H+, K+-ATPase inhibition, and indicate that this agent may not be considered as a selective H+, K+-ATPase inhibitor in vascular preparations.


Coffee and tea consumption, dietary fat intake and serum cholesterol concentration of Finnish men and women.
The association between the consumption of coffee and tea and serum cholesterol concentration was studied in a population sample of 653 men and 695 women from east and south-west Finland. Cholesterol and high density lipoprotein (HDL) cholesterol were determined from fresh serum samples. Smoking and the intake of coffee, tea and alcohol were assessed by a questionnaire, and nutrient intake was determined from 3-day food records. Serum cholesterol and non-HDL cholesterol showed a positive and linear association with coffee consumption in men. In women, no such significant linear association was evident, although the highest mean serum cholesterol levels were found in subjects consuming seven to nine cups of coffee daily. Both in men and in women coffee consumption was positively associated with smoking and the intake of saturated and monounsaturated fatty acids and cholesterol. Serum cholesterol values, adjusted for age, body mass index, smoking, dietary cholesterol, fatty acids, alcohol and physical activity, showed a significant linear association with coffee consumption in men but not in women. Although coffee consumption and high intake of saturated fatty acids and cholesterol were related both in men and in women, adjustment for dietary and other confounding factors did not remove the association between coffee consumption and serum cholesterol concentration in men.


Potentiation of ethyl para-nitrophenyl phenyl-phosphonothioate (EPN)-induced inhibition of liver microsomal carboxylesterase by NAD in vitro in rats.
The higher inhibition of liver microsomal carboxylesterase (CEase) by EPN, as compared to that of acetylcholinesterase (AchE) may be, at least in part, explained by the present findings that NAD potentiated the anti-CEase, but not anti-AchE, action of EPN. This phenomenon was referred to as "NAD-effect" in this paper. NAD-effect was not due to the increased formation of oxygen analog of EPN (EPN=O) by NAD addition through liver microsomal cytochrome P-450 catalyzed monoxygenase, because the amounts of EPN=O formed during incubation in the presence and absence of NAD were not significantly changed as shown by gaschromatography-mass spectrometric estimations. In addition, HAD-effect could be observed in the experiments even under carbon monoxide atmosphere. Such NAD-effect was observed only when NAD, EPN and an unidentified component bound to liver microsomal membrane were co-existent in the incubation mixture.


The Comparison of Ottawa Ankle Rules and Shetty test performances in foot-ankle trauma patients visited to the emergency department.
The Ottawa Ankle Rules (OARs) and Shetty test (ST), are assessment guidelines intended to minimize radiographs in patients with ankle trauma. The aim of this study is to determine and compare the effectiveness of OARs and ST in patients admitted to the emergency department (ED) with foot and ankle trauma. This prospective cohort study was carried out in the ED of a tertiary care teaching hospital. OARs and ST were practiced by different doctors to patients, who were admitted with foot and ankle trauma. X-ray images were analyzed by a radiologist. Accuracy measures were covered such as sensitivity, specificity, positive predictive value, negative predictive value. The study was completed a total of 207 patients, after achieving the inclusion and exclusion criteria. The mean age of the patients was 33.1±16.3, and 96 (46.4%) were female. For OARs, it was determined that as sensitivity 97.22%, specificity 48.89%, positive predictive value 50.36%, negative predictive value 97.06%, positive likelihood ratio 1.9 and negative likelihood ratio 0.06. If the OARs had been used, there would have been a 32.8% reduction in the ankle X-ray system. For the ST, it was determined that as sensitivity 51.39%, specificity 85.93%, positive predictive value 66.07%, negative predictive value 76.82%, positive likelihood ratio 3.65 and negative likelihood ratio 0.57. The OARs can be used as a screening tool, due to causing the high sensitivity in foot and ankle traumas. The ST was found to be inefficient in this study. In addition, the significant reduction in the number of X-rays with the use of OARs is another major result of the study.


Global monkeypox case hospitalisation rates: A rapid systematic review and meta-analysis.
Estimates of the case hospitalization rate and case fatality rate when hospital care is available for monkeypox (MPX) infections have not been well defined. This rapid systematic review and meta-analysis aimed to estimate the case hospitalisation rate and case fatality rate where hospital care is available. We systematically searched PubMed, Embase, the Lancet Preprints, and MedRxiv for studies published between Jan 1, 1950 and Aug 2, 2022. We included documents which contained both the number of cases and associated hospitalisations of MPX infections. From eligible studies we extracted the country, the year of the study, the study design type, the clade of MPX, the participant characteristics, transmission type, any treatments used, number of cases (including suspected, probable, or laboratory confirmed diagnosis), number of hospitalizations, hospitalized patient outcomes, and case definition. Case hospitalization rate (CHR) was defined as the proportion of cases that were admitted to hospital care while case fatality rate (CFR) was defined as the proportion of cases that died. CHR and CFR were analysed in a fully Bayesian meta-analytic framework using random effects models, including sub-group analysis with heterogeneity assessed using I2. Of the 259 unique documents identified, 19 studies were eligible for inclusion. Included studies represented 7553 reported cases among which there were 555 hospitalizations. Of the 7540 cases for which outcomes were available, there were 15 recorded deaths. The median age of cases was 35 years (interquartile range 28-38, n = 2010) and primarily male (7339/7489, 98%) in studies where age or sex were available. Combined CHR was estimated to be 14.1% (95% credible interval, 7.5-25.0, I2 97.4%), with a high degree of heterogeneity. Further analysis by outbreak period indicates CHRs of 49.8% (28.2-74.0, I2 81.4%), 21.7% (7.2-52.1, I2 57.7%), and 5.8% (3.2-9.4, I2 92.4%) during the pre-2017, 2017-2021, and 2022 outbreaks, respectively, again with high levels of heterogeneity. CFR was estimated to be 0.03% (0.0-0.44, I2 99.9%), with evidence of large heterogeneity between the studies. There is limited data for MPX hospitalization rates in countries where MPX has been traditionally non-endemic until the current outbreak. Due to substantial heterogeneity, caution is needed when interpreting these findings. Health care organizations should be cognizant of the potential increase in healthcare utilization. Rapid identification of infection and use of appropriate therapies such as antivirals play a role reducing the CHR and associated CFR. None.


Reproducibility and persistence of abnormal transmitral flow velocity patterns detected by pulsed Doppler ultrasound.
This prospective study examines the reproducibility and persistence of abnormal transmitral flow detected using pulsed Doppler ultrasound on 2 separate occasions between 2 days and 6 weeks apart. The 22 patients included were accepted consecutively from those having an abnormal diastolic flow pattern at initial examination. Abnormal flow velocity patterns were defined as those exhibiting reversal of the ratio of the passive filling velocity (E) and active atrial transport velocity (A). There was no significant difference between the separately recorded values for the ratio of the peak E and A velocities or of the ratio of the planimetered areas beneath each of the velocity waves, with positive correlations for both sets of values (r = 0.68, r = 0.67). Significant positive correlation also existed between the mean rates of acceleration to each of the E and A velocity peaks of the transmitral waveform recorded on separate occasions (r = 0.68, r = 0.95). Interobserver variation for the analysis of hard-copy pulsed Doppler recordings between two trained observers was less than 5% and intraobserver error for recording analysis was less than 2% for both observers. Abnormal transmitral flow velocity patterns persist unchanged in the absence of therapeutic intervention and the acceptably small observer error in the recording and analysis of such flow patterns allows consistent and clinically reliable data to be obtained.


Pia arachnoid contains substance P originating from trigeminal neurons.
Immunoreactive substance P is present in measurable amounts in pia arachnoid from rat, cat, dog and calf. Levels of substance P in this tissue are comparable to those found in peripheral structures receiving innervation from dorsal root or trigeminal ganglia. Separation and measurement of bovine pia-arachnoid extract by reverse phase high performance liquid chromatography and radioimmunoassay reveals a single peak of activity with a retention time identical to that of substance P. Unilateral lesions of the trigeminal ganglia decrease substance P levels within cat pia arachnoid and accompanying blood vessels ipsilaterally by greater than 50%. These data indicate that most of the substance P surrounding pial blood vessels resides within afferent nerve fibres from trigeminal ganglion cells.


Initial 24-h perfusion index of ICU admission is associated with acute kidney injury in perioperative critically ill patients: A retrospective cohort analysis.
The relationship between perfusion index (PI) and organ dysfunction in patients in the intensive care unit (ICU) is not clear. This study aimed to explore the relationship between PI and renal function in the perioperative critical care setting and evaluate the predictive efficiency of PI on patients with acute kidney injury (AKI) in the ICU. This retrospective analysis involved 12,979 patients who had undergone an operation and were admitted to the ICU in Peking Union Medical College Hospital from January 2014 to December 2019. The distribution of average PI in the first 24 h after ICU admission and its correlation with AKI was calculated by Cox regression. Receiver operating characteristic (ROC) curves were generated to compare the ability of PI, mean arterial pressure (MAP), creatinine, blood urea nitrogen (BUN), and central venous pressure (CVP) to discriminate AKI in the first 48 h in all perioperative critically ill patients. Average PI in the first 24 h served as an independent protective factor of AKI (Odds ratio [OR]=0.786, 95% confidence interval [CI]: 0.704-0.873, P <0.0001). With a decrease in PI by one unit, the incidence of AKI increased 1.74 times. Among the variables explored for the prediction of AKI (PI, MAP, creatine, BUN, and CVP), PI yielded the highest area under the ROC curve, with a sensitivity of 64.34% and specificity of 70.14%. A cut-off value of PI ≤2.12 could be used to predict AKI according to the Youden index. Moreover, patients in the low PI group (PI ≤2.12) exhibited a marked creatine elevation at 24-48 h with a slower decrease compared with those in the high PI group (PI >2.12). As a local blood flow indicator, the initial 24-h average PI for perioperative critically ill patients can predict AKI during their first 120 h in the ICU.


Clinical comparison of hetastarch and albumin in postoperative cardiac patients.
Hetastarch, 6% hydroxyethyl starch solution, is an artificial colloid proposed for use as a volume expander. There is concern that hetastarch, like dextran, may adversely affect coagulation. To compare the effects of hetastarch with 5% albumin in postoperative patients, 60 consecutive patients who underwent coronary artery bypass were prospectively randomized into two study groups. Both groups were comparable in all respects preoperatively. Group 1 (27 patients) received a mean of 1,241 ml of 5% albumin and Group 2 (33 patients) a mean of 1,210 ml of hetastarch as volume replacement within the first 24 postoperative hours. Indices of postoperative hepatic, renal, and pulmonary function did not differ significantly between the groups immediately postoperatively, at 24 hours postoperatively, or at 7 days postoperatively. Hematocrits, platelet counts, prothrombin times, partial thromboplastin times, and serum fibrinogen levels were comparable between the two groups at all times. The mean volume of chest tube drainage did not differ between the groups (Group 1, 495 +/- 216 ml; Group 2, 637 +/- 402 ml; not significant), and no patient required reexploration for bleeding. Eighteen percent of Group 1 and 15% of Group 2 patients received banded blood during their hospitalization and required similar amounts (Group 1, 0.37 unit per patient; Group 2, 0.36 unit per patient; not significant). The use of hetastarch as a postoperative volume expander after myocardial revascularization is safe and effective, and results in substantial financial savings.


Diffusion tensor imaging in unclear intramedullary tumor-suspected lesions allows separating tumors from inflammation.
Prospective diagnostic study. Primary imaging-based diagnosis of spinal cord tumor-suspected lesions is often challenging. The identification of the definite entity is crucial for dedicated treatment and therefore reduction of morbidity. The aim of this trial was to investigate specific quantitative signal patterns to differentiate unclear intramedullary tumor-suspected lesions based on diffusion tensor imaging (DTI). Medical Center - University of Freiburg, Germany. Forty patients with an unclear tumor-suspected lesion of the spinal cord prospectively underwent DTI. Primary diagnosis was determined by histological or clinical work-up or remained indeterminate with follow-up. DTI metrics (FA/ADC) were evaluated at the central lesion area, lesion margin, edema, and normal spinal cord and compared between different diagnostic groups (ependymomas, other spinal cord tumors, inflammations). Mean DTI metrics for all spinal cord tumors (n = 18) showed significantly reduced FA and increased ADC values compared to inflammatory lesions (n = 8) at the lesion margin (p < 0.001, p = 0.001) and reduced FA at the central lesion area (p < 0.001). There were no significant differences comparing the neoplastic subgroups of ependymomas (n = 10) and other spinal cord tumors (n = 8), but remaining differences for both compared to the inflammation subgroup. We found significant higher ADC (p = 0.040) and a trend to decreased FA (p = 0.081) for ependymomas compared to inflammations at the edema. Even if distinct differentiation of ependymomas from other spinal cord neoplasms was not possible based on quantitative DTI metrics, FA and ADC were feasible to separate inflammatory lesions. This may avoid unnecessary surgery in patients with unclear intramedullary tumor-suspected lesions.


Defining "laparoscopy" through review of technical details in JSLS.
The term "laparoscopy" has lost some precision in its definition due to the proliferation in techniques of access to the abdominal cavity. Currently, procedures performed with radical differences in port size, placement, and even need for an extraction incision may be characterized as "laparoscopic." However, the general public and many insurers divide procedures in the simplified categories of laparoscopic or open. Our aim was to characterize the typical laparoscopic operation through review of the technical details of a year's worth of articles in JSLS. We assembled and analyzed a database of all articles in JSLS from 2008-2009 (4 issues starting with Volume 12, #4). For comparison, we also reviewed articles from 1 decade ago (Volume 2). All procedural details were compiled, including means of access, number and size of ports, incision length, and conversion rates. In the most recent year, there were 81 articles for analysis, compared to 39 in the earlier year. Few articles listed all technical details, as only 58% of reports described mode of access and 56% described the number of ports used. Access was nearly evenly divided between Hasson and Veress techniques. The average number of ports in both study periods was 4, although there was a trend toward smaller port sizes in the current year. Among those studies specifying incision length, the average was 6.1cm in both groups. The technical operative details are lacking in many reports. Based on review of published studies, most procedures are done with 4 ports, 3 of which are ≥10mm in size. Until there is greater clarity in technical description, the precise definition of laparoscopy will remain elusive.


Structural requirements of bile acid transporters: C-3 and C-7 modifications of steroidal hydroxyl groups.
The apical sodium dependent bile acid transporter (ASBT) and sodium-taurocholate cotransporting polypeptide (NTCP) are potential prodrug targets, but the structural requirements for these transporters are incompletely defined. The objective of this study was to evaluate the effect of C-3 and C-7 substitution on bile acid interaction with these bile acid transporters. Nineteen bile acid analogs were tested against ASBT and NTCP for binding, as well as translocation. Results indicated that ASBT and NTCP accommodated a wide range of substituents for binding, but all major C-7 modifications resulted in analogs that did not demonstrate active uptake by either ASBT or NTCP. A C-3 modification that was not tolerated at C-7 still afforded translocation via ASBT and NTCP, confirming the relative unacceptability of C-7 modification. Both ASBT and NTCP demonstrated a generally similar binding potency. Results suggest that drug conjugation to the C-3 hydroxyl group, rather than C-7, has potential to lead to a successful prodrug targeting ASBT and NTCP.


Effects of Stretching Exercise on Heart Rate Variability During Pregnancy.
Little evidence exists for effects of low-intensity exercises such as stretching on cardiovascular health in pregnant women. Our aim was to evaluate the effect of a 20-minute stretching exercise on heart rate variability (HRV), blood pressure (BP), and heart rate (HR) in healthy pregnant women. In 15 pregnant women with a mean (SD) age of 29.47 (4.07) years and mean (SD) gestational weeks of 26.53 (8.35), HRV, and BP were measured before and after the 20-minute stretching exercise. Compared with before the stretching exercise, standard deviation of the normal-to-normal intervals, total variability of heart rate, increased by 7.40 milliseconds (t = -2.31, P = .04) and root mean square of successive differences, a surrogate measure of parasympathetic outflow, also increased by 11.68 milliseconds (Z = -2.04, P = .04) after the stretching exercise. Diastolic BP and HR decreased by 2.13 mm Hg (t = 1.93, P = .07) and 3.31 bpm (t = 2.17, P = .05), respectively, but they did not reach statistical significance. These preliminary data suggest that 20 minutes of stretching exercise may promote cardiovascular health by attenuating the loss of parasympathetic tone associated with pregnancy.


Cellular responses in crustaceans under white spot syndrome virus infection.
Innate immunity plays the most important system responsible for protecting crustaceans against invading pathogens. White spot syndrome virus (WSSV) is considered a serious pathogen in crustaceans with high cumulative mortality and morbidity in infected animals. Understanding the mechanism of the response of hosts to WSSV infection is necessary, which is useful for effective prevention in controlling infection. In this review, we summarize the participation of signaling pathways (toll, immune deficiency, JAK/STAT, endocytosis, mitogen-activated protein kinase, PI3K/Akt/mTOR, cGAS-STING, Wingless/Integrated signal transduction, and prophenoloxidase (proPO) cascade) and the activity of cells (apoptosis, autophagy, as well as, reactive oxygen species and antioxidant enzymes) in the cellular-mediated immune response of crustaceans during WSSV infection. The information presented in this current review is important for a better understanding of the mechanism of the response of hosts to pathogens. Additionally, this provides a piece of basic knowledge for discovering approaches to strengthen the immune system and resistance of cultured animals against viral infections.


Detection of the ovulatory-luteinizing hormone surge with an enzyme-linked immunospecific human urinary luteinizing hormone assay: applicability to nonhuman primates.
Heterologous antibodies have frequently been used to develop assays in other species. Human urinary LH kits, widely available for predicting the LH surge, offer a unique opportunity to determine the timing of ovulation and mating in nonhuman primates. We tested three commercially available ovulation predictor kits for utility in two macaque species. Midfollicular, midcycle, and castrate urines and their corresponding serum samples were assessed for LH activity using established RIAs as well as urinary ovulation kits. Macaque LH did not sufficiently cross-react with the human urinary anti-LH antibodies in any of the predictor test kits. Although these kits offer excellent results in predicting ovulation by measurement of urinary LH in humans, they appear not to be applicable for urinary LH detection in rhesus nor cynomolgus macaques.


Editorial Introduction: Effects of Gun Violence on Communities and Recent Theoretical Developments.
The Journal of Primary Prevention is dedicating this special issue to the topic of gun violence and the detrimental effects it has on communities. The papers represent original research articles providing scientific evidence on the unintended consequences of gun violence and exposure to such violence in neighborhoods and communities. These papers also take seriously the role of theory in our understanding of gun violence. Funding for gun violence research is experiencing a resurgence, and these papers substantively contribute to that narrative.


Non-uniformly sampled Maximum Quantum spectroscopy.
Maximum-Quantum (MaxQ) NMR is an approach that exploits the simple lineshape (a singlet) of the highest possible coherence quantum order for a given spin system to help resolving the interpretation of the spectrum of complex mixtures. In this setup, resolution in the indirect, multiple-quantum, dimension is crucial, and it may be linked to a long duration of the signal acquired along this axis. We explored if this boundary on the length of the indirect dimension could not necessarily translate into extended experimental times by applying Non-Uniform Sampling (NUS) schemes in conjunction with Recursive Multi-Dimensional Decomposition (R-MDD) data processing. The actual value of the MaxQ order depends on the size of the spin system, so that for a mixture several MQ correlation spectra must be recorded to detect all possible molecular fragments. As the sparseness of the MQ datasets vary dramatically in going from higher (sparser) to lower (denser) coherence orders, the optimal compressing conditions and the fidelity of NUS/R-MDD scheme may vary along the series of MQ spectra. The NUS-MaxQ approach is demonstrated on the aromatic region of the 1H spectrum of a mixture of 10 simple aromatic molecules.


The size of the pancreas in diabetes mellitus.
To determine whether there was an association between the size of the pancreas and the type of diabetes, ultrasonography of the pancreas was performed on 57 diabetic patients: 14 with Type 1 (insulin-dependent) diabetes, 10 insulin-treated and 33 tablet-treated patients with Type 2 (non-insulin-dependent) diabetes, and 19 non-diabetic subjects. The pancreas of patients with Type 1 diabetes was markedly smaller (p < 0.0001) than the pancreas in non-diabetic subjects. The pancreas of patients with Type 2 diabetes was more moderate in size: larger (p < 0.001) than that of Type 1 diabetic patients but smaller (p < 0.5) than the pancreas of the control group. Pancreatic size of patients with Type 2 diabetes was also related to basal insulin secretion with insulin-deficient patients (low or undetectable C-peptide) having smaller (p < 0.05) pancreases than those with normal insulin secretion. There was no difference in the size of the pancreas in the different treatment groups of Type 2 diabetic patients. Pancreatic size did not correlate with age, body mass index or the duration of diabetes. We conclude that the pancreas is a smaller organ in patients with diabetes mellitus and that the decrement in size is maximal in insulin-dependent/insulin-deficient subjects. Ultrasonography, therefore, can potentially serve to discriminate between the different types of diabetes.


[Feasibility study of intra-utero surgical repair of fetal lamb].
To evaluate the feasibility of intra-utero fetal lamb surgical repair. Six twin lambs underwent surgery intra-utero at 112 days of gestation (term 140 approximately 160 days). After maternal laparotomy and Hysterotomy, fetal lamb's toe was excised or its cleft lip was repaired in one of twin. At 30 to 32 days post operation, five lambs were spontamcously delivered and the other was cesarean delivery to full term gestation. Fetal wounds healed without inflammation and scar formation. The methods of fetal lamb intro utero surgical repair is feasible.


Endonasal dacryocystorhinostomy in children: Our experience.
Epiphora affects approximately 20% neonates, but most resolve spontaneously. Dacryocystorhinostomy (DCR) is indicated only when conservative management fails. To observe clinical presentation, treatment modalities and effectiveness of endoscopic DCR in paediatric population. It is a prospective study of 21 children done at our tertiary care hospital from 2011 to 2016. All were initially subjected to a trial of conservative management. Those that responded and didn't require surgery were excluded. The age group ranged from 40 days to 11.5 years. 19 underwent unilateral & 2 underwent bilateral endoscopic DCR. After a 6 month follow-up, 20 children were benefitted by surgery, 2 had an incomplete resolution and 1 required revision surgery. The overall success rate was 95.23% and failed cases were mainly due to post-traumatic distortion of the anatomy. No major complications were noted. Endoscopic DCR is safe and effective in children presenting with persistent epiphora.


Perceived behavioral problems of school aged children in rural Nepal: a qualitative study.
Studies on child behavioral problems from low and middle income countries are scarce, even more so in Nepal. This paper explores parents', family members' and teachers' perceptions of child behavioral problems, strategies used and recommendations to deal with this problem. In this study, 72 free list interviews and 30 Key Informant Interviews (KII) were conducted with community members of Chitwan district in Nepal. The result suggest that addictive behavior, not paying attention to studies, getting angry over small issues, fighting back, disobedience, and stealing were the most commonly identified behavioral related problems of children, with these problems seen as interrelated and interdependent. Results indicate that community members view the family, community and school environments as being the causes of child behavioral problems, with serious impacts upon children's personal growth, family harmony and social cohesion. The strategies reported by parents and teachers to manage child behavioral problems were talking, listening, consoling, advising and physical punishment (used as a last resort). As perceived by children and other community dwellers, children in rural Nepalese communities have several behavioral related problems. The findings suggest that multi-level community-based interventions targeting peers, parents, teachers and community leaders could be a feasible approach to address the identified problems.


Nurse managers' perception of night-shift napping: A cross-sectional survey.
Night-shift work often results in sleep deprivation, and this in turn results in fatigue that jeopardizes both nurse and patient safety. Napping is considered a viable deterrent to fatigue, yet hospital administration has been slow to adopt napping. To identify nurse managers' knowledge and approval of napping practices for nurses on night shifts. Nurse managers at nine Jordanian hospitals (n = 129) were surveyed using an Arabic version of a questionnaire previously used in a Canadian study. Descriptive statistics were used to describe results, and a one-way ANOVA was used to determine if relationships existed among nurse manager's approval of napping and nurse demographic characteristics. The majority of nurse managers (61%) knew nurses were napping during breaks. However, the managers reported there was no written policy for napping. A majority thought there were more benefits to napping than drawbacks. Some 55% of nurse managers recognized fatigue as a cause of errors or incidents regarding patient safety, and 40% perceived fatigue to be a factor in staff injuries. This study supports an urgent need for shared responsibility among nursing administration, and bedside nurses to develop evidence-based programs to counteract the effects of nurse fatigue.


[Health Service Utilization by Homeless Persons: Analysis of the Role of Enabling Factors, Pain and Gender using the Gelberg-Andersen Model].
The aim of the study was to find factors that influence health service utilization by homeless people. In a field study, a sample of 51 homeless men and 47 homeless women in the German county of Baden-Württemberg participated in face-to-face-interviews with a questionnaire designed for this study. Analyses were performed using multiple logistic regression models. Variables were organized using the Gelberg-Andersen Behavioral Model for Vulnerable Populations. Satisfied subsistence needs (OR 1.33, 95%-CI [1.03-1.72] regarding utilization of vaccinations), a stable source of primary care (OR 12.2 [1.81-82] regarding utilization of early detection examinations; quasi-complete separation regarding use of GP services) social networks (OR 2.9 [1.13-7.5] regarding utilisation of early detection examinations; OR 0.63 [0.41-0.98] regarding emergency department visits) and technological ressources (OR 2.2 [1.13-4.4] regarding use of GP services) had a positive influence on the pattern of health service utilization. Pain was correlated with more emergency department visits (OR 1.72 [1.22-2.4]) and hospitalizations (OR 1.66 [1.19-2.3]). The results showed differences between homeless men and women. The factors of influence found in this study should be addressed in the care of homeless persons. Integration of social care into the regular health care system is necessary for early detection and treatment of complex social and medical needs of vulnerable populations. This requires interprofessional approaches in medical education and training focussing on the situation of vulnerable populations and on social determinants of health.


Degeneration of cochlear neurons after amikacin intoxication in the rat.
Intoxication with high doses of the aminoglycoside antibiotic amikacin in a supranormal sensitive period in the rat induces complete destruction of the inner and outer hair cells in the organ of Corti in all turns, whereas the supporting cells remain partially preserved in the upper turns. With increasing survival time, the number of ganglion cells in the spiral ganglion decreases progressively, reaching a minimum of about 10% surviving cells after 12 months. Both type I and type II neurons are subject to retrograde degeneration, although type-II cells degenerate more slowly than type-I cells. The presence or absence of supporting cells in the organ of Corti does not seem to influence neuronal degeneration. This retrograde degeneration is similar in all animals so far studied but its time course is different from different species. Retrograde degeneration after destruction of Corti's organ is a long-lasting process and is never completed at once. This must be taken into consideration in the treatment of total deafness with electric stimulation of surviving neurons.


Involvement of tyrosyl residue(s) in binding of endothelin and sarafotoxin to their receptors in rat brain and heart.
The possible involvement of tyrosyl residue(s) in the binding of endothelins and sarafotoxins to their receptors was examined by the use of tetranitromethane. Incubation of rat cerebellar, hypothalamic, caudate putamen and atrial membranes with the reagent (100 microM, pH 8.1, 20 min) was accompanied by a decrease in their capacity to bind endothelins and sarafotoxin. Experiments employing nitration at different pH values (6.0 vs. 8.1) and studies on the effect of dithiothreitol on the nitrated preparations indicated that the modified residue(s) is most probably a tyrosyl and not a cysteinyl residue, and that there is no oligomerization of the receptors. These data are discussed in relation to the structural data recently obtained by cloning and expression of the endothelin/sarafotoxin receptors.