Epigenetic Changes Associated with Early Life Experiences: Saliva, A Biospecimen for DNA Methylation Signatures.
Adverse Childhood Experiences (ACEs), which include traumatic injury, are associated with poor health outcomes in later life, yet the biological mechanisms mediating this association are unknown. Neurocircuitry, immune system and hormone regulation differ from normal in adults reporting ACEs. These systems could be affected by epigenetic changes, including methylation of cytosine (5mC) in genomic DNA, activated by ACEs. Since 5mC levels influence gene expression and can be long-lasting, altered 5mC status at specific sites or throughout the genome is hypothesized to influence mental and physical outcomes after ACE(s). Human and animal studies support this, with animal models allowing experiments for attributing causality. Here we provide a lengthy introduction and background on 5mC and the impact of early life adversity. Next we address the issue of a mixture of cell types in saliva, the most accessible biospecimen for 5mC analysis. Typical human bio-specimens for 5mC analysis include saliva or buccal swabs, whole blood or types of blood cells, tumors and post-mortem brain. In children saliva is the most accessible biospecimen, but contains a mixture of keratinocytes and white blood cells, as do buccal swabs. Even in saliva from the same individual at different time points, cell composition may differ widely. Similar issues affect analysis in blood, where nucleated cells represent a wide array of white blood cell types. Unless variations in ratios of these cells between each sample are included in the analysis, results can be unreliable. Several different biochemical assays are available to test for site-specific methylation levels genome-wide, each producing different information, with high-density arrays being the easiest to use, and bisulfite whole genome sequencing the most comprehensive. We compare results from different assays and use high-throughput computational processing to deconvolve cell composition in saliva samples. Here we present examples demonstrating the critical importance of determining the relative contribution of blood cells versus keratinocytes to the 5mC profile found in saliva. We further describe a strategy to perform a reference-based computational correction for cell composition, and therefore to identify differential methylation patterns due to experience, or for the diagnosis of phenotypes that correlate between traits, such as hormone levels, trauma status and various mental health outcomes. Specific sites that respond to adversity with altered methylation levels in either blood cells, keratinocytes or both can be identified by this rigorous approach, which will then be useful as diagnostic biomarkers and therapeutic targets.


Reconstruction of the Vancomycin-Susceptible Staphylococcus aureus Phenotype From a Vancomycin-Intermediate S. aureus XN108.
The emergence of vancomycin-intermediate Staphylococcus aureus (VISA) has raised healthcare concerns worldwide. VISA is often associated with multiple genetic changes. However, the relative contributions of these changes to VISA phenotypes are incompletely defined. We have characterized VISA XN108 with vancomycin MIC of 12 μg/ml. Genome comparison revealed that WalK(S221P), GraS(T136I), and RpoB(H481N) mutations possibly contributed to the VISA phenotype of XN108. In this study, the above mutations were stepwise cured, and the phenotypes between XN108 and its derivates were compared. We constructed four isogenic mutant strains, XN108-WalK(P221S) (termed as K65), XN108-GraS(I136T) (termed as S65), XN108-RpoB(N481H) (termed as B65), and XN108-WalK(P221S)/GraS(I136T) (termed as KS65), using the allelic replacement experiments with the native alleles derived from a vancomycin-susceptible S. aureus isolate DP65. Antimicrobial susceptibility test revealed K65 and S65 exhibited decreased vancomycin resistance, whereas B65 revealed negligibly differed when compared with the wild-type XN108. Sequentially introducing WalK(P221S) and GraS(I136T) completely converted XN108 into a VSSA phenotype. Transmission electronic microscopy and autolysis determination demonstrated that cell wall thickening and decreasing autolysis were associated with the change of vancomycin resistance levels. Compared with XN108, K65 exhibited 577 differentially expressed genes (DEGs), whereas KS65 presented 555 DEGs. Of those DEGs, 390 were common in K65 and KS65, including those upregulated genes responsible for citrate cycle and bacterial autolysis, and the downregulated genes involved in peptidoglycan biosynthesis and teichoic acid modification. In conclusion, a VSSA phenotype could be completely reconstituted from a VISA strain XN108. WalK(S221P) and GraS(T136I) mutations may work synergistically in conferring vancomycin resistance in XN108.


Molecular pathology and histopathological findings in localized leishmania lymphadenitis.
A rare variant of Leishmaniasis is Localized Leishmania Lymphadenitis which has been occasionally reported from south-eastern parts of Iran. So far, no molecular assay has been performed for diagnosing this variety of Leishmaniasis. Nineteen lymph node paraffin blocks were collected from 1994 to 2007. Parasite load count and histopathological patterns reported on Hematoxylin-Eosin and Giemsa stained slides.DNA extraction was carried out just on the remaining available 7 lymph node paraffin blocks according to QIAamp DNA FFPE kit instructions. A pair of primers and a probe were designed for rRNA ITS region with Allele ID 6.0 software, followed by real time PCR amplification. The most common histopathological pattern was necrotizing granuloma with few Leishman bodies. Parasite load was the highest in submental lymph node (3 ± 1.41 per oil field) which was significantly higher compared to cervical and inguinal nodes (P < 0.05). Absolute load of parasite DNA was detectable in all 7 cases. The positive cases revealed a 201 bpamplicon after electrophoresis of end product which was confirmative for Leishmania tropica. Real time PCR revealed Leishmania tropica as the etiologic agent of Localized Leishmania Lymphadenitis. Although this molecular method is a sensitive diagnostic tool, histopathological findings are still important.


Marine Sediments Illuminate Chlamydiae Diversity and Evolution.
The bacterial phylum Chlamydiae is so far composed of obligate symbionts of eukaryotic hosts. Well known for Chlamydiaceae, pathogens of humans and other animals, Chlamydiae also include so-called environmental lineages that primarily infect microbial eukaryotes. Environmental surveys indicate that Chlamydiae are found in a wider range of environments than anticipated previously. However, the vast majority of this chlamydial diversity has been underexplored, biasing our current understanding of their biology, ecological importance, and evolution. Here, we report that previously undetected and active chlamydial lineages dominate microbial communities in deep anoxic marine sediments taken from the Arctic Mid-Ocean Ridge. Reaching relative abundances of up to 43% of the bacterial community, and a maximum diversity of 163 different species-level taxonomic units, these Chlamydiae represent important community members. Using genome-resolved metagenomics, we reconstructed 24 draft chlamydial genomes, expanding by over a third the known genomic diversity in this phylum. Phylogenomic analyses revealed several novel clades across the phylum, including a previously unknown sister lineage of the Chlamydiaceae, providing new insights into the origin of pathogenicity in this family. We were unable to identify putative eukaryotic hosts for these marine sediment chlamydiae, despite identifying genomic features that may be indicative of host-association. The high abundance and genomic diversity of Chlamydiae in these anoxic marine sediments indicate that some members could play an important, and thus far overlooked, ecological role in such environments and may indicate alternate lifestyle strategies.


Ossifying fibromyxoid tumor with atypical histological features: a case report.
Ossifying fibromyxoid tumor of soft tissues (OFMT) is considered a rare mesenchymal neoplasm. Its main histological features are sheets and ill-defined lobules of rounded bland cells within a fibromyxoid background and a thick collagenous capsule with an incomplete rim of lamellar bone. This lesion occurs mostly in the soft tissues of the lower extremities and limb girdles. In this paper, we describe a mesenchymal tumor removed from the right thigh of a 41 year-old-woman. The neoplasm differed histologically from typical forms of OFMT for areas of moderate cellularity and atypia, nuclear enlargement and small nucleoli. Focally, stromal tongues of osteoid were centrally and irregularly located within the lesion with evident spindling of tumor cells around them. The mitotic activity was low (up to 19 per 50 HPF) and atypical figures were rarely seen. The tumor was positive to S-100 protein, vimentin, CD10, CD56, CD99, ASMA, calponin and collagen IV. Rare elements were positive for cytokeratin AE1/AE3. To the best of our knowledge, this is the first case of atypical OFMT reported to be positive for calponin. The patient is currently alive and well with no evidence of disease at 96 months following surgery. In spite of low-grade histology, OFMT has high local recurrence rate and low metastatic potential, primarily in the lungs, even several years after surgical removal. The recognition of this entity is important. In this report the authors address differential diagnosis and enigmatic histogenesis of this neoplasm.


[Costs and role of ultrasound follow-up of polytrauma patients after initial computed tomography].
To assess the costs and diagnostic gain of abdominal ultrasound follow-up of polytrauma patients initially examined by whole-body computed tomography (CT). A total of 176 patients with suspected multiple trauma (126 men, 50 women; age 43.5 ± 17.4 years) were retrospectively analyzed with regard to supplementary and new findings obtained by ultrasound follow-up compared with the results of exploratory FAST (focused assessment with sonography for trauma) at admission and the findings of whole-body CT. A process model was used to document the staff, materials, and total costs of the ultrasound follow-up examinations. FAST yielded 26 abdominal findings (organ injury and/or free intra-abdominal fluid) in 19 patients, while the abdominal scan of whole-body CT revealed 32 findings in 25 patients. FAST had 81 % sensitivity and 100 % specificity. Follow-up ultrasound examinations revealed new findings in 2 of the 25 patients with abdominal injuries detected with initial CT. In the 151 patients without abdominal injuries in the initial CT scan, ultrasound follow-up did not yield any supplementary or new findings. The total costs of an ultrasound follow-up examination were EUR 28.93. The total costs of all follow-up ultrasound examinations performed in the study population were EUR 5658.23. Follow-up abdominal ultrasound yields only a low overall diagnostic gain in polytrauma patients in whom initial CT fails to detect any abdominal injuries but incurs high personnel expenses for radiological departments.


Effect of topical ozonetherapy on gingival wound healing in pigs: histological and immuno-histochemical analysis.
In this study, the effects of ozonetherapy on secondary wound healing were evaluated histologically and immuno-histochemically. Material and Methods: 8 healthy pigs were used in this study. Six wounds with 10 mm in diameter were created through the punch technique on the palatinal gingiva of each pig. Ozone gas was applied on only 3 wounds (test group) and the remaining 3 were left to natural healing (control group). Biopsy samples were taken from one of the wounds in each group on the third day, from another wound of each group on the seventh day, and from another one on the tenth day. Routine histological analysis and immuno-histochemical staining were performed to investigate transforming growth factor-beta (TGF-β) and (VEGF) expressions. Results: No statistical difference was found between the test and control groups in terms of collagen fibers, epithelial formation and inflammation scores. A VEGF expression found in the test group was statistically higher than control group samples taken on the 3rd and 7th day. There was no statistical difference between the test and control groups in terms of TGF-β expression on any of the sampling days. Conclusion: The topical application of ozone gas could be effective in the early stages of wound healing by increasing the amount of VEGF expression. Clinical Relevance: Topical application of ozone gas may be effective in the early stages of oral wound healing.


Opal-like Multicolor Appearance of Self-Assembled Photonic Array.
Molecular self-assembly of short peptide building blocks leads to the formation of various material architectures that may possess unique physical properties. Recent studies had confirmed the key role of biaromaticity in peptide self-assembly, with the diphenylalanine (FF) structural family as an archetypal model. Another significant direction in the molecular engineering of peptide building blocks is the use of fluorenylmethoxycarbonyl (Fmoc) modification, which promotes the assembly process and may result in nanostructures with distinctive features and macroscopic hydrogel with supramolecular features and nanoscale order. Here, we explored the self-assembly of the protected, noncoded fluorenylmethoxycarbonyl-β,β-diphenyl-Ala-OH (Fmoc-Dip) amino acid. This process results in the formation of elongated needle-like crystals with notable aromatic continuity. By altering the assembly conditions, arrays of spherical particles were formed that exhibit strong light scattering. These arrays display vivid coloration, strongly resembling the appearance of opal gemstones. However, unlike the Rayleigh scattering effect produced by the arrangement of opal, the described optical phenomenon is attributed to Mie scattering. Moreover, by controlling the solution evaporation rate, i.e., the assembly kinetics, we were able to manipulate the resulting coloration. This work demonstrates a bottom-up approach, utilizing self-assembly of a protected amino acid minimal building block, to create arrays of organic, light-scattering colorful surfaces.


Clinical competencies of graduating medical students.
In a survey conducted by the authors, the goals of medical school curricula regarding the clinical competencies of graduating students were explored. Inventories listing 83 clinical skills were sent to 123 U.S. medical schools and to 462 volunteer clinical faculty members at the University of Utah School of Medicine. The responding medical schools singled out 43 clinical skills as definite goals of their curricula, and the practicing physicians identified 49 clinical skills in which graduating medical students should be competent. The study provided an easy mechanism to compare the clinical expectations of practicing physicians and of medical schools regarding medical students.


Structural evidence for substrate-induced synergism and half-sites reactivity in biotin carboxylase.
Bacterial acetyl-CoA carboxylase is a multifunctional biotin-dependent enzyme that consists of three separate proteins: biotin carboxylase (BC), biotin carboxyl carrier protein (BCCP), and carboxyltransferase (CT). Acetyl-CoA carboxylase is a potentially attractive target for novel antibiotics because it catalyzes the first committed step in fatty acid biosynthesis. In the first half-reaction, BC catalyzes the ATP-dependent carboxylation of BCCP. In the second half-reaction, the carboxyl group is transferred from carboxybiotinylated BCCP to acetyl-CoA to produce malonyl-CoA. A series of structures of BC from several bacteria crystallized in the presence of various ATP analogs is described that addresses three major questions concerning the catalytic mechanism. The structure of BC bound to AMPPNP and the two catalytically essential magnesium ions resolves inconsistencies between the kinetics of active-site BC mutants and previously reported BC structures. Another structure of AMPPNP bound to BC shows the polyphosphate chain folded back on itself, and not in the correct (i.e., extended) conformation for catalysis. This provides the first structural evidence for the hypothesis of substrate-induced synergism, which posits that ATP binds nonproductively to BC in the absence of biotin. The BC homodimer has been proposed to exhibit half-sites reactivity where the active sites alternate or "flip-flop" their catalytic cycles. A crystal structure of BC showed the ATP analog AMPPCF(2)P bound to one subunit while the other subunit was unliganded. The liganded subunit was in the closed or catalytic conformation while the unliganded subunit was in the open conformation. This provides the first structural evidence for half-sites reactivity in BC.


A role for APP in Wnt signalling links synapse loss with β-amyloid production.
In Alzheimer's disease (AD), the canonical Wnt inhibitor Dickkopf-1 (Dkk1) is induced by β-amyloid (Aβ) and shifts the balance from canonical towards non-canonical Wnt signalling. Canonical (Wnt-β-catenin) signalling promotes synapse stability, while non-canonical (Wnt-PCP) signalling favours synapse retraction; thus Aβ-driven synapse loss is mediated by Dkk1. Here we show that the Amyloid Precursor Protein (APP) co-activates both arms of Wnt signalling through physical interactions with Wnt co-receptors LRP6 and Vangl2, to bi-directionally modulate synapse stability. Furthermore, activation of non-canonical Wnt signalling enhances Aβ production, while activation of canonical signalling suppresses Aβ production. Together, these findings identify a pathogenic-positive feedback loop in which Aβ induces Dkk1 expression, thereby activating non-canonical Wnt signalling to promote synapse loss and drive further Aβ production. The Swedish familial AD variant of APP (APPSwe) more readily co-activates non-canonical, at the expense of canonical Wnt activity, indicating that its pathogenicity likely involves direct effects on synapses, in addition to increased Aβ production. Finally, we report that pharmacological inhibition of the Aβ-Dkk1-Aβ positive feedback loop with the drug fasudil can restore the balance between Wnt pathways, prevent dendritic spine withdrawal in vitro, and reduce Aβ load in vivo in mice with advanced amyloid pathology. These results clarify a relationship between Aβ accumulation and synapse loss and provide direction for the development of potential disease-modifying treatments.


The effects of perineal management techniques on labor complications.
Many women suffer from perineal trauma during the normal vaginal delivery. Perineal trauma is mainly associated with pain and complications after the childbirth. Perineal management techniques can play a significant role in perineal trauma reduction. This study aimed to compare the effects of perineal management techniques (hands-off technique, Ritgen maneuver and perineal massage using a lubricant during delivery) on the labor complications. This quasi-experimental clinical trial was conducted on 99 primiparous women who referred to Daran Hospital, Isfahan, Iran for normal vaginal delivery in 2009. The subjects were selected using a convenient method and randomly assigned to three groups of Ritgen maneuver, hands-off technique and perineal massage with lubricant. A questionnaire was used to determine the demographic characteristics of the participants and complications after birth. The short form of McGill Pain Questionnaire and the visual analogue scale for pain were also employed. The incidence and degree of perineal tears were evaluated immediately after delivery. Moreover, the incidence and severity of perineal pain were assessed 24 hours and also 6 weeks after delivery. In the Ritgen maneuver group, the frequency of tears, the relative frequency of tear degrees, the severity of perineal pain 24 hours after delivery and the frequency of pain and perineal pain severity 6 weeks after delivery were significantly different from the other two methods. Hands-off technique during parturition of the neonate's head was associated with fewer complications after delivery. It was even better than perineal massage during the parturition.


The TSC1 tumour suppressor hamartin regulates cell adhesion through ERM proteins and the GTPase Rho.
Loss of the tumour-suppressor gene TSC1 is responsible for hamartoma development in tuberous sclerosis complex (TSC), which renders several organs susceptible to benign tumours. Hamartin, the protein encoded by TSC1, contains a coiled-coil domain and is expressed in most adult tissues, although its function is unknown. Here we show that hamartin interacts with the ezrin-radixin-moesin (ERM) family of actin-binding proteins. Inhibition of hamartin function in cells containing focal adhesions results in loss of adhesion to the cell substrate, whereas overexpression of hamartin in cells lacking focal adhesions results in activation of the small GTP-binding protein Rho, assembly of actin stress fibres and formation of focal adhesions. Interaction of endogenous hamartin with ERM-family proteins is required for activation of Rho by serum or by lysophosphatidic acid (LPA). Our data indicate that disruption of adhesion to the cell matrix through loss of hamartin may initiate the development of TSC hamartomas and that a Rho-mediated signalling pathway regulating cell adhesion may constitute a rate-limiting step in tumour formation.


Lipid biosynthesis monitored at the single-cell level in Saccharomyces cerevisiae.
There is increasing interest in bioengineering of lipids for use in functional foods, pharmaceuticals, and biofuels. Saccharomyces cerevisiae is a widely utilized cell factory for biotechnological production, thus a tempting alternative. Herein, we show how its neutral lipid accumulation varies throughout metabolic phases under nutritional conditions relevant for large-scale fermentation. Population-averaged metabolic data were correlated with lipid storage at the single-cell level monitored at submicron resolution by label-free coherent anti-Stokes Raman scattering (CARS) microscopy. While lipid droplet sizes are fairly constant, the number of droplets is a dynamic parameter determined by glucose and ethanol levels. The lowest number of lipid droplets is observed in the transition phase between glucose and ethanol fermentation. It is followed by a buildup during the ethanol phase. The surplus of accumulated lipids is then mobilized at concurrent glucose and ethanol starvation in the subsequent stationary phase. Thus, the highest amount of lipids is found in the ethanol phase, which is about 0.3 fL/cell. Our results indicate that the budding yeast, S. cerevisiae, can be used for the biosynthesis of lipids and demonstrate the strength of CARS microscopy for monitoring the dynamics of lipid metabolism at the single-cell level of importance for optimized lipid production.


Aragonite nanorods in calcium carbonate/polymer hybrids formed through self-organization processes from amorphous calcium carbonate solution.
Nanostructured inorganic/polymer hybrid thin films comprising aragonite nanorods derived from aqueous suspensions of amorphous calcium carbonate (ACC) are prepared. For the formation of calcium carbonate (CaCO₃)/polymer hybrids, spincoated and annealed films of poly(vinyl alcohol) (PVA) that function as polymer matrices are soaked in aqueous colloidal solutions dispersing ACC stabilized by poly(acrylic acid) (PAA). In the initial stage, calcite thin films form on the surface. Subsequently, aragonite crystals start to form inside the PVA matrix that contains PVA crystallites which induce aragonite nucleation. Nanostructured hybrids composed of calcite thin films consisting of nanoparticles and assembled aragonite nanorods are formed in the matrices of PVA.


Evaluation of enterochromaffin cells and melatonin secretion exponents in ulcerative colitis.
To study an assessment of the number of enterochromaffin cells and expression of hydroxyindole-O-methyltransferase in colonic mucosa and urine excretion of 6-sulfatoxymelatonin in patients with ulcerative colitis. The study included 30 healthy subjects (group I-C), 30 patients with ulcerative proctitis [group II-ulcerative proctitis (UP)] and 30 patients with ulcerative colitis [group III-ulcerative colitis (UC)] in acute phases of these diseases. The number of enterochromaffin cells (EC) was estimated in rectal and colonic mucosa. Bioptates were assembled from many different parts of the large intestine. Immunorective cells collected from various parts of the colon were counted according to the Eurovision DAKO (Dako A/S, Copenhagen, Denmark) System in the range of 10 fields in each bioptate at × 200 magnification. The level of mRNA expression of hydroxyindole-O-methyltransferase (HIOMT) in colonic mucosa was estimated with RT-PCR. Urine 6-sulfatoxymelatonin (6-HMS) excretion was determined immunoenzymatically using an IBL (IBL International GmbH, Hamburg, Germany) kit (RE 54031). The number of EC cells in healthy subjects (C) was 132.40 ± 31.26. In patients of group II (UP) and group III (UC) the number of these cells was higher--225.40 ± 37.35 (P < 0.001) and--225.24 ± 40.50 (P < 0.001) respectively. Similar differences were related to HIOMT expression, which was 1.04 ± 0.36 in group C, 1.56 ± 0.56 (P < 0.01) in group UP and 2.00 ± 0.35 (P < 0.001) in group UC. Twenty-four hour 6-HMS urinary excretion was as follows: C--6.32 ± 4.95 μg/24 h, UP - 26.30 ± 7.29 μg/24 h (P < 0.01), UC--2.30 ± 12.56 μg/24 h (P < 0.001). A correlation between number of EC cells and 6-HMS excretion was noted in all groups: r = 0.766 in patients with UP, r = 0.703 with UC and r = 0.8551 in the control group; the correlation between the results is statistically significant. In the acute phases of both UP and UC, proliferation of EC cells and high expression of HIOMT and urine excretion of 6-HMS is noted. These changes may represent a beneficial response in the anti-inflammatory and defense mechanism.


[The influence of pulsed low-intensity laser radiation of the red (635 nm) and infrared (904 nm) spectra on the human mesenchymal stem cells in vitro].
Mesenchymal stem cells (MSC) have for a long time been an object of investigation with a view to elucidating the prospects for their application in clinical medicine and cosmetology. One of the approaches to the non-specific regulation of the activity of these cells at the stage of preliminary in vitro combination is the treatment with low-intensity laser radiation (LILR). The objective of the present study was to evaluate the possibility of using pulsed LILR of the infrared and red spectra for this purpose. We used the 4th passage adhesive MSC cultures based at the umbilical tissue of a donor who gave the informed consent to participate in the study. The source of illumination was a Lazmik-VLOK laser therapeutic apparatus (RU No RZN 2014/1410 dated 06.02.2014) with the matrix laser infrared radiation heads (wavelength 904 nm, light pulse length 108 ns, frequency 1500 Hz). The apparatus was operated either in the multi-frequency Lazmik regime [Moskvin S.V., 2014] with mean power density 0.05 and 0.14 mW/cm2 and the red spectrum (wavelength 635 nm, light pulse length 144 ns, frequency 1500 Hz) or in the multi-frequency Lazmik regime [Moskvin S.V., 2014] with mean power density 0.03 and 0.12. The exposition was 5 min in both regimes. The study has demonstrated that neither the morphological structure nor the viability of mesenchymal stem cells changed under the influence of energy and time parameters used in experiments. The number of cells was shown to slightly increase in comparison with control. The most pronounced effect was documented after illumination with pulse infrared (904 nm) LILR in the multi-frequency Lazmik regime. The maximum effect was observed during a period between days 1 and 3 of cultivation.


COVID-19, flattening the curve, and Benford's law.
For many countries attempting to control the fast-rising number of coronavirus cases and deaths, the race is on to "flatten the curve," since the spread of coronavirus disease 2019 (COVID-19) has taken on pandemic proportions. In the absence of significant control interventions, the curve could be steep, with the number of COVID-19 cases growing exponentially. In fact, this level of proliferation may already be happening, since the number of patients infected in Italy closely follows an exponential trend. Thus, we propose a test. When the numbers are taken from an exponential distribution, it has been demonstrated that they automatically follow Benford's Law (BL). As a result, if the current control interventions are successful and we flatten the curve (i.e., we slow the rate below an exponential growth rate), then the number of infections or deaths will not obey BL. For this reason, BL may be useful for assessing the effects of the current control interventions and may be able to answer the question, "How flat is flat enough?" In this study, we used an epidemic growth model in the presence of interventions to describe the potential for a flattened curve, and then investigated whether the epidemic growth model followed BL for ten selected countries with a relatively high mortality rate. Among these countries, South Korea showed a particularly high degree of control intervention. Although all of the countries have aggressively fought the epidemic, our analysis shows that all countries except for Japan satisfied BL, indicating the growth rates of COVID-19 were close to an exponential trend. Based on the simulation table in this study, BL test shows that the data from Japan is incorrect.


Corynebacterium striatum peritoneal dialysis catheter exit site infection.
Regarded as normal flora of the human skin and mucus membranes, non-diphtheria corynebacteria are frequently dismissed as contaminants or harmless colonizers. Recently, the pathogenic potential of C. striatum has been realized in immunocompromised patients with indwelling medical devices and previous antibiotic exposure. We report here the diagnosis, treatment and clinical outcome of a peritoneal dialysis patient with a C. striatum infection of the catheter exit site. The aim is to present important features to assist in identifying clinically significant infections and provide guidelines for treatment. An immunocompromised patient with previous antimicrobial exposure developed an acute dialysis catheter exit site infection. C. striatum was isolated in pure growth. After initial treatment failure with oral antibiotics and intensified wound care, a satisfactory outcome was ultimately achieved without relapse or loss of the catheter with a 1-month course of vancomycin, 1 g intravenously, administered at 5-day intervals. The virulent capacity of Corynebacterium species should not be underestimated, particularly in high-risk patients. The presence of clinical signs of infection with isolation of the organism in pure culture and the presence of Gram-positive rods on direct Gram stain, especially in association with a leukocyte reaction, supports a cause and effect relationship. Because corynebacteria may be multiresistant, susceptibility testing should be performed on clinically significant isolates. Initial antibiotic selection is influenced by the severity of the infection, however, current experience favors vancomycin in significant infections.


Complete Description of the LaCl3-NaCl Melt Structure and the Concept of a Spacer Salt That Causes Structural Heterogeneity.
Lanthanides are important fission products in molten salt reactors, and understanding their structure and that of their mixtures is relevant to many scientific and technological problems including the recovery and separation of rare earth elements using molten salt electrolysis. The literature on molten salts and specifically on LaCl3 and LaCl3-NaCl mixtures is often fragmented, with different experiments and simulations coinciding in their explanation for certain structural results but contradicting or questioning for others. Given the very practical importance that actinide and lanthanide salts have for energy applications, it is imperative to arrive at a clear unified picture of their local and intermediate-range structure in the neat molten state and when mixed with other salts. This article aims to unequivocally answer a set of specific questions: is it correct to think of long-lived octahedral coordination structures for La3+? What is the nature as a function of temperature of networks and intermediate-range order particularly upon dilution of the trivalent ion salt? Is the so-called scattering first sharp diffraction peak (FSDP) for neat LaCl3 truly indicative of intermediate-range order? If so, why is there a new lower-q peak when mixed with NaCl? Are X-ray scattering and Raman spectroscopy results fully consistent and easily described by simulation results? We will show that answers to these questions require that we abandon the idea of a most prominent coordination state for M3+ ions and instead think of multiple competing coordination states in exchange due to significant thermal energy in the molten state.


Comparative analysis of case screening with varying cough duration and sputum samples for diagnosis of tuberculosis in patients attending the OPD at a tertiary care hospital at Srinagar, India.
Can we minimize cough duration and number of sputum samples in chest symptomatic patients for screening of TB? To evaluate cough of 3 weeks versus 2 weeks duration using two sputum samples versus three samples in chest symptomatic patients attending the OPD. Hospital-based cross-sectional study. Outpatients (2810) with H/O cough of 3 weeks and 2 weeks duration were screened by subjecting them to sputum microscopy for tuberculosis using two sputum samples as well as three samples following standard procedure for sputum collection, staining and acid-fast bacillus (AFB) identification. Those on drugs were not included. Using ≥2 weeks cough, sputum positivity rate was 12%, nearly as high as the sputum positivity among patients with ≥3 weeks cough, i.e. 14%. First sputum smear alone on an average could detect 91.8% cases, while the first two sputum smears could detect on an average 96% cases. The study showed that maximum number of cases was diagnosed by only two sputum smears and added diagnostic value of third specimen was small, i.e. 4%.High sputum positivity rate using ≥2 weeks cough with two sputum samples was seen. The sensitivity analysis of the study showed that using ≥2 weeks cough with two sputum samples gives almost similar values as ≥3 weeks cough with three sputum samples, but this needs further confirmatory results of culture sensitivity. Hence, using ≥2 weeks cough with two sputum samples as the diagnostic criteria for screening of cough patients for TB should be recommended as one way of improving efficient use of scarce resources.


What Are the Predictors of Altered Central Pain Modulation in Chronic Musculoskeletal Pain Populations? A Systematic Review.
Altered central pain modulation is the predominant pain mechanism in a proportion of chronic musculoskeletal pain disorders and is associated with poor outcomes. Although existing studies predict poor outcomes such as persistent pain and disability, to date there is little consensus on what factors specifically predict altered central pain modulation. To review the existing literature on the predictive factors specifically for altered central pain modulation in musculoskeletal pain populations. This is a systematic review in accordance with supplemented PRISMA guidelines. A systematic search was performed by 2 mutually blinded reviewers. Relevant articles were screened by title and abstract from Medline, Embase, PubMed, CINAHL, and Web of Science electronic databases. Alternative sources were also sought to locate missed potential articles. Eligibility included studies published in English, adults aged 18 to 65, musculoskeletal pain, baseline measurements taken at the pre-morbid or acute stage, > 3-month follow-up time after pain onset, and primary outcome measures specific to altered central pain modulation. Studies were excluded where there were concurrent diseases or they were non-predictive studies. Risk of bias was assessed using the quality in prognostic studies (QUIPS) tool. Study design, demographics, musculoskeletal region, inclusion/exclusion criteria, measurement timelines, predictor and primary outcome measures, and results were extracted. Data were synthesized qualitatively and strength of evidence was scored using the grading of recommendations, assessment, development, and evaluations (GRADE) scoring system. Nine eligible articles were located, in various musculoskeletal populations (whiplash, n = 2; widespread pain, n = 5; temporomandibular disorder, n = 2). Moderate evidence was found for 2 predictive factors of altered central pain modulation: 1) high sensory sensitivity (using genetic testing or quantitative sensory tests), and 2) psychological factors (somatization and poor self-expectation of recovery), at a pre-morbid or acute stage baseline. At the times of the article publications, the current definitions and clinical guidelines for identifying altered central pain modulation were not yet available. Careful interpretation of the information provided using current knowledge and published guidelines was necessary to extract information specific to altered central pain modulation in some of the studies, avoiding unwarranted assumptions. Premorbid and acute stage high sensory sensitivity and/or somatization are the strongest predictors of altered central pain modulation in chronic musculoskeletal pain to date. This is the first systematic review specifically targeting altered central pain modulation as the primary outcome in musculoskeletal pain populations. Early identification of people at risk of developing chronic pain with altered central pain modulation may guide clinicians in appropriate management, diminishing the burden of persistent pain on patients and heath care providers alike. Systematic Review Registration no.: PROSPERO 2015:CRD42015032394.Key words: Predictive factors, pre-morbid and acute stage baselines, altered central pain modulation, chronic musculoskeletal pain, sensory processing, somatization.


Thin-Wall GaN/InAlN Multiple Quantum Well Tubes.
Thin-wall tubes composed of nitride semiconductors (III-N compounds) based on GaN/InAlN multiple quantum wells (MQWs) are fabricated by metal-organic vapor-phase epitaxy in a simple and full III-N approach. The synthesis of such MQW-tubes is based on the growth of N-polar c-axis vertical GaN wires surrounded by a core-shell MQW heterostructure followed by in situ selective etching using controlled H2/NH3 annealing at 1010 °C to remove the inner GaN wire part. After this process, well-defined MQW-based tubes having nonpolar m-plane orientation exhibit UV light near 330 nm up to room temperature, consistent with the emission of GaN/InAlN MQWs. Partially etched tubes reveal a quantum-dotlike signature originating from nanosized GaN residuals present inside the tubes. The possibility to fabricate in a simple way thin-wall III-N tubes composed of an embedded MQW-based active region offering controllable optical emission properties constitutes an important step forward to develop new nitride devices such as emitters, detectors or sensors based on tubelike nanostructures.


Genetic variation is associated with differences in facilitative and competitive interactions in the Rhizobium leguminosarum species complex.
Competitive and facilitative interactions influence bacterial community composition, diversity and functioning. However, the role of genetic diversity for determining interactions between coexisting strains of the same, or closely related, species remains poorly understood. Here, we investigated the type (facilitative/inhibitory) and potential underlying mechanisms of pairwise interactions between 24 genetically diverse bacterial strains belonging to three genospecies (gsA,C,E) of the Rhizobium leguminosarum species complex. Interactions were determined indirectly, based on secreted compounds in cell-free supernatants, and directly, as growth inhibition in cocultures. We found supernatants mediated both facilitative and inhibitory interactions that varied greatly between strains and genospecies. Overall, gsE strains indirectly suppressed growth of gsA strains, while their own growth was facilitated by other genospecies' supernatants. Similar genospecies-level patterns were observed in direct competition, where gsA showed the highest susceptibility and gsE the highest inhibition capacity. At the genetic level, increased gsA susceptibility was associated with a non-random distribution of quorum sensing and secondary metabolite genes across genospecies. Together, our results suggest that genetic variation is associated with facilitative and competitive interactions, which could be important ecological mechanisms explaining R. leguminosarum diversity.


Prevalence of HIV, hepatitis B virus, and hepatitis C virus among incarcerated people in Iran: a systematic review and meta-analysis.
Incarcerated people are at higher risk for HIV, Hepatitis B Virus (HBV), and Hepatitis C Virus (HCV) infections. This review systematically summarized the evidence on the prevalence of these infections among incarcerated people in Iran. A systematic review and meta-analysis. We searched Embase, PubMed, Web of Science, Scopus, PsychInfo, Iranian databases, including IranMedex, Magiran, Scientific Information Database (SID), and IranDoc. A grey literature review was conducted to find unpublished reports from the Ministry of Health and experts throughout the country. Included studies reported data on the prevalence of HIV, HBV, or HCV infections. A random-effects meta-analysis was performed to estimate the pooled prevalence. A meta-regression analysis was also conducted. Of 1461 screened records, 23 records were eligible (total participants = 199,855). The pooled prevalence of HIV (17 studies), HBV (6 studies), and HCV (10 studies) was 2.77% (95% CI: 1.96, 3.70), 2.89% (95% CI: 2.28, 3.56), and 21.57% (95% CI: 13.62, 30.76), respectively. Meta-regression analyses showed that HIV (P-value = 0.05) and HCV (P-value = 0.02) were reduced over time using survey year as the interested variable in the model. Also, lifetime history of drug injection had a significant association with the HIV infection (P-value = 0.03). The findings suggest that the prevalences of these infections are relatively considerable among Iranian incarcerated people. These findings support developing interventions to reduce the risk of the acquisition and circulation of these infections among incarcerated people, and continued harm reduction programs among most at-risk incarcerated people, as well as HCV treatment.


NAFLD in the Elderly.
Non-alcoholic fatty liver disease (NAFLD) is an increasingly prevalent disease globally. Current estimates are that 24% of the adult population, thus, one billion individuals worldwide, are affected. Interestingly, the prevalence of fatty liver seems to peak between 40─50 years of age in males and 60─69 years in females, often slightly decreasing in older (>70 years) cohorts. Furthermore, several risk factors for NAFLD development, such as hypertension, diabetes, hyperlipidemia, and obesity are higher in older adults. The diagnosis and management strategies in older adults are sometimes challenging, and certain age-specific factors have to be taken into account by healthcare professionals. In this review, we provide an overview of considerations relevant to the management and diagnosis of NAFLD in older adults (age >65 years) and discuss the types of pharmacological interventions available for the management of non-alcoholic steatohepatitis (NASH) in the aging population.


Effect of orally administered neomycin on uterine growth in young mice and rats.
Neomycin has been widely used as a gut antibiotic in preconditioning animals for the experimental evaluation of biomaterials and biomedical devices. As a chance observation during a routine conditioning process, it was noticed that orally administered neomycin retarded uterine growth in growing mice and rats. Body weights and the weights of liver and spleen were uneffected, although there was a marginal increase in the kidneys' weight. This finding is consistent with the theory that a change induced in intestinal flora activity mediated a uterotrophic influence of dietary fiber.


Hypothalamic gene expression in ω-3 PUFA-deficient male rats before, and following, development of hypertension.
Dietary deficiency of ω-3 fatty acids (ω-3 DEF) produces hypertension in later life. This study examined the effect of ω-3 DEF on blood pressure and hypothalamic gene expression in young rats, before the development of hypertension, and in older rats following the onset of hypertension. Animals were fed experimental diets that were deficient in ω-3 fatty acids, sufficient in short-chain ω-3 fatty acids or sufficient in short- and long-chain ω-3 fatty acids, from the prenatal period until 10 or 36 weeks-of-age. There was no difference in blood pressure between groups at 10 weeks-of-age; however, at 36 weeks-of-age ω-3 DEF animals were hypertensive in relation to sufficient groups. At 10 weeks, expression of angiotensin-II(1A) receptors and dopamine D(3) receptors were significantly increased in the hypothalamic tissue of ω-3 DEF animals. In contrast, at 36 weeks, α(2a) and β(1) adrenergic receptor expression was significantly reduced in the ω-3 DEF group. Brain docosahexaenoic acid was significantly lower in ω-3 DEF group compared with sufficient groups. This study demonstrates that dietary ω-3 DEF causes changes both in the expression of key genes involved in central blood pressure regulation and in blood pressure. The data may indicate that hypertension resulting from ω-3 DEF is mediated by the central adrenergic system.


Consumption of flavonoid-rich fruits, flavonoids from fruits and stroke risk: a prospective cohort study.
We sought to examine the prospective associations of specific fruit consumption, in particular flavonoid-rich fruit (FRF) consumption, with the risk of stroke and subtypes of stroke in a Japanese population. A study followed a total of 39 843 men and 47 334 women aged 44-76 years, and free of CVD, diabetes and cancer at baseline since 1995 and 1998 to the end of 2009 and 2012, respectively. Data on total and specific FRF consumption for each participant were obtained using a self-administrated FFQ. The hazard ratios (HR) of stroke in relation to total and specific FRF consumption were estimated through Cox proportional hazards regression models. During a median follow-up of 13·1 years, 4091 incident stroke cases (2557 cerebral infarctions and 1516 haemorrhagic strokes) were documented. After adjustment for age, BMI, study area, lifestyles, dietary factors and other risk factors, it was found that total FRF consumption was associated with a significantly lower risk of stroke in women (HR = 0·70; 95 % CI 0·58, 0·84), while the association in men was not significant (HR = 0·93; 95 % CI 0·79, 1·09). As for specific FRF, consumptions of citrus fruits, strawberries and grapes were found associated with a lower stroke risk in women. Higher consumptions of FRF, in particular citrus fruits, strawberries and grapes, were associated with a lower risk of developing stroke in Japanese women.


Fluorescence of radiation-induced collagen aggregates.
Tropocollagen shows higher ultraviolet fluorescence (emission max, about 305 nm) and lower blue fluorescence (emission max. about 420 nm) than the dimers and tetramers isolated from irradiated collagen. This indicates dityrosine structures in the radiation-induced collagen aggregates.


Acute animal and human poisonings from cyanotoxin exposure - A review of the literature.
Cyanobacterial blooms are a potential health hazard due to the ability of some species to produce toxins that are harmful to other living organisms. This review provides a comprehensive summary of anecdotal and case reports on acute poisonings in animals and humans attributable to cyanotoxin exposure in fresh- and brackish-waters. Approximately two-thirds of reported poisonings have occurred in Europe and the United States. Dogs and livestock account for the majority of reported cases involving animal exposure to cyanotoxins, while recreational activities are responsible for approximately half of reported incidents involving human exposure. Due to data limitations it is difficult to estimate the total number of animals and humans affected by cyanotoxins, however, some general observations regarding frequency and numbers affected are made. The review demonstrates that cyanotoxins have, and will likely to continue to have, potentially serious consequences for public health and animal welfare worldwide.


[Surgical and conservative therapy of scaphoid pseudarthrosis].
Should an asymptomatic scaphoid pseudarthrosis be eliminated by surgery? Two patient populations were followed up in order to be able to answer this central question. The first group comprised 49 unoperated patients and the second group 55 patients in whom Matti Russe reconstructive surgery had led to healing of the bone and in whom the operation had been carried out at least three years previously. The period of observation was up to 25 years. The study yielded the following findings: 1. The spontaneous course automatically terminates in radiocarpal arthrosis. It begins after five to ten years in the radiocarpal joint and also affects the intracarpal joint after a further ten years. Besides an increasing shortening of the scaphoid bone, an exacerbating carpus collapse can also be observed. 2. Neither the position of the fracture, left- or righthandedness nor the patient's occupation affect the course. Only necrosis of the proximal fragment favors the development of arthrosis. 3. The operated patients have much better results both clinically and radiologically. The development of arthrosis is slowed down (but not stopped) by the operation. 4. A DISI deformity left behind after the operation does not affect the development of arthrosis. 5. The earlier the operation is carried out, the more favorable the course. 6. We attribute the relatively high rate of arthrosis in Matti-Russi reconstructive operation (69%) to an excessively long immobilization. For this reason, we prefer internal fixation with a Herbert screw.


[MRI-based 3-D analysis of the glenohumeral translation in patients with shoulder instability].
Until now, pathological translation of the glenohumeral joint could not be assessed three-dimensionally and in functionally important arm positions in the living. The objektive of this study was therefore to develop an MR-based technique for determining the three-dimensional glenohumeral translation in functionally relevant positions in vivo. In an open MR scanner both shoulder joints of 5 volunteers with an unilateral traumatic instability were examined in different positions of abduction and rotation. After semiautomatic segmentation, 3D reconstruction of the bony structures of the shoulder girdle was performed and the center of mass of the glenoid cavity was determined and used as reference point. In a virtual reality, the midpoint of the humeral head was assessed and its position relative to the center of mass of the glenoid cavity was calculated. At 30 degrees of abduction, in both shoulders, the humeral head was positioned inferior and posterior relative to the glenoid cavity (healthy: 0.42 +/- 1.1 inf., 0.75 +/- 1.0 mm post.; unstable: 1.31 +/- 0.87 mm inf., 0.51 +/- 1.28 mm post.) The maximal translation (to anterior and inferior) was observed both on the healthy side (mean 1.0 mm, max. 1.8 mm) and in the unstable shoulders (mean 2.5 mm, max. 4.6 mm) with the arm in 90 degrees of abduction and external rotation, thus being 1.7 to 2.5 times higher in the pathological shoulders. With this technique the glenohumeral translation can be quantified three-dimensionally in functionally important positions and without projectional artefacts. In the future, this method can be applied to patients with different entities of shoulder instability.


Gendered perceptions of osteoporosis: implications for youth prevention programs.
The presentation of osteoporosis as a woman's disease in prevention information influences how osteoporosis is perceived and how prevention information is internalized and applied. Using the Health Belief Model as a framework, gendered perceptions of osteoporosis were investigated in Canadian young adults to inform the design of prevention programs. A combination of the Osteoporosis Health Belief Scale (OHBS) and semi-structured interviews were used to explore participants' perceptions of osteoporosis severity, susceptibility, and motivation to engage in prevention activities. Sixty multiethnic men and women aged 17-30 years living in Hamilton, Ontario, Canada participated in the study. While the findings from the OHBS indicated that both genders scored high for self-efficacy, the results from the qualitative interviews showed ambivalent attitudes toward prevention behaviors, indicating a disconnect between quantitative and qualitative findings. Perceptions related to severity and susceptibility revealed that while osteoporosis was generally viewed as a woman's disease, perceived individual risk of disease was a negotiation between larger gender constructs of osteoporosis and a variety of risk factors. This study indicates that osteoporosis prevention programs should consider actively acknowledging gendered and youth-based conceptions of osteoporosis in order to increase prevention behaviors in the whole population to reduce future disease.


Effect of medication adherence on disease activity among Japanese patients with rheumatoid arthritis.
For the optimum efficacy of disease-modifying anti-rheumatic drugs (DMARDs), patients need to be adherent to their medication regimen. To clarify the effects of medication adherence on disease activity in Japanese patients with rheumatoid arthritis (RA), we conducted a cohort study in patients with various stages of RA. Patients were enrolled from the Kyoto University RA Management Alliance cohort, and followed up prospectively for 12 months. In this study, a total of 475 patients were analyzed and divided into 9 groups according to their medication adherence and the RA disease duration. The primary outcomes were based on the rate of a disease flare. The secondary outcomes were the changes in disease activity score using 28 joints (DAS28-ESR), simplified disease activity index (SDAI) and physical disability by health assessment questionnaire-disability index (HAQ). The changes in DAS28-ESR, HAQ, and the risk of disease flare in the highly adherent patients were significantly lower than those of the less adherent patients among the groups with RA ≤ 4.6 years but not those among the other groups. Taken together, this study identified a significant association between medication adherence and the disease flare during early-stage RA or short disease duration. These results emphasize the need to pay more attention to medication adherence in preventing the disease progression of RA.


Impact of modality choice on rates of hospitalization in patients eligible for both peritoneal dialysis and hemodialysis.
Hospitalization rates are a relevant consideration when choosing or recommending a dialysis modality. Previous comparisons of peritoneal dialysis (PD) and hemodialysis (HD) have not been restricted to individuals who were eligible for both therapies. ♢ We conducted a multicenter prospective cohort study of people 18 years of age and older who were eligible for both PD and HD, and who started outpatient dialysis between 2007 and 2010 in four Canadian dialysis programs. Zero-inflated negative binomial models, adjusted for baseline patient characteristics, were used to examine the association between modality choice and rates of hospitalization. ♢ The study enrolled 314 patients. A trend in the HD group toward higher rates of hospitalization, observed in the primary analysis, became significant when modality was treated as a time-varying exposure or when the population was restricted to elective outpatient starts in patients with at least 4 months of pre-dialysis care. Cardiovascular disease, infectious complications, and elective surgery were the most common reasons for hospital admission; only 23% of hospital stays were directly related to complications of dialysis or kidney disease. ♢ Efforts to promote PD utilization are unlikely to result in increased rates of hospitalization, and efforts to reduce hospital admissions should focus on potentially avoidable causes of cardiovascular disease and infectious complications.


The Importance of Spatiotemporal Information in Biological Motion Perception: White Noise Presented with a Step-like Motion Activates the Biological Motion Area.
Humans can easily recognize the motion of living creatures using only a handful of point-lights that describe the motion of the main joints (biological motion perception). This special ability to perceive the motion of animate objects signifies the importance of the spatiotemporal information in perceiving biological motion. The posterior STS (pSTS) and posterior middle temporal gyrus (pMTG) region have been established by many functional neuroimaging studies as a locus for biological motion perception. Because listening to a walking human also activates the pSTS/pMTG region, the region has been proposed to be supramodal in nature. In this study, we investigated whether the spatiotemporal information from simple auditory stimuli is sufficient to activate this biological motion area. We compared spatially moving white noise, having a running-like tempo that was consistent with biological motion, with stationary white noise. The moving-minus-stationary contrast showed significant differences in activation of the pSTS/pMTG region. Our results suggest that the spatiotemporal information of the auditory stimuli is sufficient to activate the biological motion area.


Management of diabetic retinopathy.
Sub-Saharan Africa faces an epidemic of diabetes. Visual loss from diabetic retinopathy (DR) is both preventable and treatable. This article reviews the epidemiology and clinical features of DR and current evidence-based interventions in three areas: primary prevention of retinopathy by optimum medical management, early detection of pre-symptomatic disease and management of established retinopathy to prevent or mitigate visual loss. There are significant challenges to DR care in resource poor environments. Appropriate provision of effective interventions by health services can reduce social and economic costs associated with patient care.


Daytime Activity Is Associated With Discharge to Home in Older Adults Recovering From Critical Illness.
Hospitalized older adults recovering from critical illness after transition of care out of an intensive care unit (ICU) are often inactive, which may affect discharge disposition and hospital length of stay (LOS). The current study explored relationships between early post-ICU activity, discharge disposition, and LOS. Actigraphy measured post-ICU daytime and nighttime activity (mean activity counts/min). Prospective chart review provided discharge disposition and LOS (days). Independent samples t tests compared post-ICU daytime activity by discharge disposition. Multivariate regression examined associations between post-ICU activity and LOS. Post-ICU daytime activity was greater among those discharged home (54.42 [SD = 29.3 counts/min]) than those discharged to a facility (33.26 [SD = 24.26 counts/min]): t(26) = 2.054, p = 0.050). Lower post-ICU daytime activity was associated with longer LOS (β = -0.322, p = 0.041). Future research should investigate whether post-ICU daytime inactivity during hospitalization is a modifiable risk factor for worse outcomes among older adults discharged from the ICU. [Journal of Gerontological Nursing, 47(2), 13-19.].


Diagnosing liver metastases: a Bayesian analysis.
Clinicians frequently perform tests to determine whether patients have liver metastases. Optimal use of a laboratory test requires that the clinician know the test's operating characteristics (its sensitivity and specificity) and have an estimate of the pretest probability that disease is present. We have surveyed studies that examined the value of four biochemical and three imaging tests in establishing a diagnosis of hepatic metastases in patients who underwent an invasive procedure to establish the presence or absence of disease. We have pooled the data from these studies to arrive at values for the sensitivity and specificity of each of these tests, and calculated the predictive values for these tests over a wide range of pretest probabilities of disease. Several examples illustrate how this information may be used clinically. We provide a framework for the optimal interpretation of these commonly ordered tests and indicate the data needed for their complete analysis.


Risk assessment of pesticide exposure on health of Pakistani tobacco farmers.
Tobacco is an important cash crop of Pakistan. Pesticides are commonly used to increase the crop yield, but their health impact has not been studied yet. The objectives of the study were to determine the frequency of pesticide poisoning and to explore the knowledge, attitudes and practices (KAP) towards safety measures among the tobacco farmers in Swabi, Pakistan. One hundred and five tobacco farmers involved in pesticide application were randomly selected from two villages of district Swabi. A structured questionnaire was used for clinical and KAP information. Plasma cholinesterase (PChE) levels were measured by Ellman's method by using GD Italy kits. All tobacco farmers were males with a mean (SD) age of 26 (9) years. The majority of the farmers reported multiple symptoms headache, dizziness, vomiting, shortness of breath, muscle weakness and skin rash correlate with the clinically significant depression of PChE levels. Out of 105 pesticide applicators, 58 (55%) had post-exposure reduction in PChE levels <20% from baseline, 35 (33%) had mild poisoning (20-40% reduction) and 12 (11%) had moderate poisoning (>40% reduction). Most of the farmers did not use any personal protective equipment during pesticide handling. Only a few used shoes (31%), masks (14%) and gloves (9%) during pesticide spray. In conclusion, the tobacco farmers had mild to moderate pesticide poisoning, which was correlated with depression in PChE levels. Moreover, most farmers had little knowledge about the safety measures, casual attitude and unsatisfactory safety practices with regard to the use of basic protective equipments during pesticide applications on the tobacco crop.


Genome-wide identification of ZmHMAs and association of natural variation in ZmHMA2 and ZmHMA3 with leaf cadmium accumulation in maize.
P1B-type ATPases, known as heavy metal ATPases (HMAs), play an important role in the control of cadmium (Cd) accumulation in plants. In this study, a total of 12 ZmHMA genes were identified in the maize genome and particularly classified into six clusters based on their phylogenetic relationship and motif compositions. Furthermore, the expression patterns of different ZmHMA genes varied with developmental stages, and were tissue specific under normal conditions. ZmHMA2 and ZmHMA3 genes exhibited significant up-regulation under Cd treatment. Eventually, the association analysis between 103 inbred lines and alleles in ZmHMA2 and ZmHMA3 revealed that one insertion-deletion (InDel) in the intron from ZmHMA2 was associated with leaf Cd concentration under low Cd condition at the seedling stage. Twenty polymorphisms in ZmHMA3 were significantly associated with leaf Cd concentration under various Cd levels at seedling and maturing stages. Five single nucleotide polymorphisms (SNPs) and two InDels of these significantly associated polymorphic loci from ZmHMA3 caused the amino acid substitutions and insertion or deletion events. Importantly, the proteins encoded by ZmHMA2 and ZmHMA3 genes were located in the plasma membrane. This comprehensive analysis will provide an important theoretical basis for future functional verification of ZmHMA genes to unravel the mechanisms of Cd accumulation in leaves of maize. Additionally, the favorable alleles in ZmHMA3 will lay a foundation for the marker-assisted selection of low Cd accumulation in maize.


Complementary and alternative medicine use for treatment and prevention of late-life mood and cognitive disorders.
Late-life mood disorders and cognitive aging are the most common reasons for using complementary and alternative therapies. The amount of rigorous scientific data to support the efficacy of complementary therapies in the treatment of depression or cognitive impairment is extremely limited. The areas with the most evidence for beneficial effects are exercise, herbal therapy (Hypericum perforatum), the use of fish oil, and, to a lesser extent, acupuncture and relaxation therapies. There is a need for further research involving randomized, controlled trials to investigate the efficacy of complementary and alternative therapies in the treatment of depression and cognitive impairment in late-life. This research may lead to the development of effective treatment and preventive approaches for these serious conditions.


Perspectives on Analytical Treatment Interruptions in People Living with HIV and Their Health Care Providers in the Landscape of HIV Cure-Focused Studies.
Analytical treatment interruptions (ATIs) aim to assess effects of HIV cure-focused interventions, but poses potential risks. Understanding of ATI acceptability among people living with HIV (PLHIV) and their HIV health care providers (HHP) is limited. Two international online surveys for PLHIV and HHP assessed understanding and acceptability of monitoring strategies during ATI. Survey items included the following: frequency of CD4, viral load (VL) and clinical assessment, CD4 and VL threshold to restart antiretroviral therapy (ART), acceptability of detectable viremia during ATI, and potential risks of ATI. Responses were collected from July 2017 to January 2018, and a descriptive analysis was performed. Responses to questions asked in both surveys were compared by χ2 test. Four hundred forty-two completed the PLHIV survey: 22% identified as female, 39% older than 50 years of age, and 64% identified as gay/homosexual/lesbian. Ninety-five percent were on ART, of which 83% reported an undetectable VL. The preferred frequency of CD4, VL, and clinical monitoring during ATI was monthly. Thirty-five percent of respondents preferred VL to remain undetectable during ATI and would not accept any sustained period of viremia, compared to 18% of 144 HHP (p < .01). Having previously interrupted ART predicted preference for VL to remain undetectable during ATI (odds ratio 0.6, p = .05). Both clinicians and PLHIV were concerned about HIV transmission during ATI. Our work demonstrates that PLHIV expectations of ATI in cure-focused clinical trials do not align with current practices, with PLHIV less accepting of viremia during ATI and preferring less frequent monitoring. Clear education messages and careful consent processes need to be developed in relationship to ATIs in HIV cure research.


Maintaining Outcomes of Internet-Delivered Cognitive-Behavioral Therapy for Depression: A Network Analysis of Follow-Up Effects.
Background: Depression is a highly prevalent mental disorder, but only a fraction of those affected receive evidence-based treatments. Recently, Internet-based interventions were introduced as an efficacious and cost-effective approach. However, even though depression is a heterogenous construct, effects of treatments have mostly been determined using aggregated symptom scores. This carries the risk of concealing important effects and working mechanisms of those treatments. Methods: In this study, we analyze outcome and long-term follow-up data from the EVIDENT study, a large (N = 1,013) randomized-controlled trial comparing an Internet intervention for depression (Deprexis) with care as usual. We use Network Intervention Analysis to examine the symptom-specific effects of the intervention. Using data from intermediary and long-term assessments that have been conducted over 36 months, we intend to reveal how the treatment effects unfold sequentially and are maintained. Results: Item-level analysis showed that scale-level effects can be explained by small item-level effects on most depressive symptoms at all points of assessment. Higher scores on these items at baseline predicted overall symptom reduction throughout the whole assessment period. Network intervention analysis offered insights into potential working mechanisms: while deprexis directly affected certain symptoms of depression (e.g., worthlessness and fatigue) and certain aspects of the quality of life (e.g., overall impairment through emotional problems), other domains were affected indirectly (e.g., depressed mood and concentration as well as activity level). The configuration of direct and indirect effects replicates previous findings from another study examining the same intervention. Conclusions: Internet interventions for depression are not only effective in the short term, but also exert long-term effects. Their effects are likely to affect only a small subset of problems. Patients reporting these problems are likely to benefit more from the intervention. Future studies on online interventions should examine symptom-specific effects as they potentially reveal the potential of treatment tailoring. Clinical Trial Registration: ClinicalTrials.gov, Identifier: NCT02178631.


Azo dyes and human health: A review.
Synthetic azo dyes are widely used in industries. Gerhardt Domagk discovered that the antimicrobial effect of red azo dye Prontosil was caused by the reductively cleaved (azo reduction) product sulfanilamide. The significance of azo reduction is thus revealed. Azo reduction can be accomplished by human intestinal microflora, skin microflora, environmental microorganisms, to a lesser extent by human liver azoreductase, and by nonbiological means. Some azo dyes can be carcinogenic without being cleaved into aromatic amines. However, the carcinogenicity of many azo dyes is due to their cleaved product such as benzidine. Benzidine induces various human and animal tumors. Another azo dye component, p-phenylenediamine, is a contact allergen. Many azo dyes and their reductively cleaved products as well as chemically related aromatic amines are reported to affect human health, causing allergies and other human maladies.


Pre-Transplant Prediction of Acute Graft-versus-Host Disease Using the Gut Microbiome.
Gut microbiota is thought to influence host responses to allogeneic hematopoietic stem cell transplantation (aHSCT). Recent evidence points to this post-transplant for acute graft-versus-host disease (aGvHD). We asked whether any such association might be found pre-transplant and conducted a metagenome-wide association study (MWAS) to explore. Microbial abundance profiles were estimated using ensembles of Kaiju, Kraken2, and DeepMicrobes calls followed by dimensionality reduction. The area under the curve (AUC) was used to evaluate classification of the samples (aGvHD vs. none) using an elastic net to test the relevance of metagenomic data. Clinical data included the underlying disease (leukemia vs. other hematological malignancies), recipient age, and sex. Among 172 aHSCT patients of whom 42 developed aGVHD post transplantation, a total of 181 pre-transplant tool samples were analyzed. The top performing model predicting risk of aGVHD included a reduced species profile (AUC = 0.672). Beta diversity (37% in Jaccard's Nestedness by mean fold change, p < 0.05) was lower in those developing aGvHD. Ten bacterial species including Prevotella and Eggerthella genera were consistently found to associate with aGvHD in indicator species analysis, as well as relief and impurity-based algorithms. The findings support the hypothesis on potential associations between gut microbiota and aGvHD based on a data-driven approach to MWAS. This highlights the need and relevance of routine stool collection for the discovery of novel biomarkers.


ASP2397 Is a Novel Natural Compound That Exhibits Rapid and Potent Fungicidal Activity against Aspergillus Species through a Specific Transporter.
Current therapies against invasive pulmonary aspergillosis (IPA) have a limited cure rate. Given that a delay in treatment initiation may be fatal, a new drug with rapid-onset and potent fungicidal activity is needed. The novel cyclic hexapeptide ASP2397 (currently known as VL-2397) exhibited antifungal activity against Aspergillus fumigatus (including azole-sensitive and azole-resistant isolates), A. terreus, and A. flavus at an MIC range of 1 to 4 μg/ml in human serum. Time-kill curve experiments showed that ASP2397 reduced germinated conidia of A. fumigatus by more than 1 log10 CFU within 6 h. In addition, ASP2397 inhibited hyphal elongation from germinated conidia of A. fumigatus, A. terreus, and A. flavus more rapidly than voriconazole. Under conditions of delayed treatment initiation in an IPA mouse model, ASP2397 had efficacy superior to that of posaconazole, with 100% survival and over 1 log10 CFU/g reduction in lung fungal burden. Histopathological investigation of lungs also showed that ASP2397 markedly suppressed disease progression. To clarify its mechanism of action, we generated a UV-induced mutant of A. fumigatus with low susceptibility to ASP2397. The mutant had a point mutation in the siderophore transporter gene sit1, which is absent in mammalian cells. These findings suggest that ASP2397 may improve clinical treatment options for IPA.


N-terminal region of CusB is sufficient for metal binding and metal transfer with the metallochaperone CusF.
Gram-negative bacteria, such as Escherichia coli, utilize efflux resistance systems in order to expel toxins from their cells. Heavy-metal resistance is mediated by resistance nodulation cell division (RND)-based efflux pumps composed of a tripartite complex that includes an RND-transporter, an outer-membrane factor (OMF), and a membrane fusion protein (MFP) that spans the periplasmic space. MFPs are necessary for complex assembly and have been hypothesized to play an active role in substrate efflux. Crystal structures of MFPs are available, however incomplete, as large portions of the apparently disordered N- and C-termini are unresolved. Such is the case for CusB, the MFP of the E. coli Cu(I)/Ag(I) efflux pump CusCFBA. In this work, we have investigated the structure and function of the N-terminal region of CusB, which includes the metal-binding site and is missing from previously determined crystal structures. Results from mass spectrometry and X-ray absorption spectroscopy show that the isolated N-terminal 61 residues (CusB-NT) bind metal in a 1:1 stoichiometry with a coordination site composed of M21, M36, and M38, consistent with full-length CusB. NMR spectra show that CusB-NT is mostly disordered in the apo state; however, some slight structure is adopted upon metal binding. Much of the intact protein's function is maintained in this fragment as CusB-NT binds metal in vivo and in vitro, and metal is transferred between the metallochaperone CusF and CusB-NT in vitro. Functional analysis in vivo shows that full-length CusB is necessary in an intact polypeptide for full metal resistance, though CusB-NT alone can contribute partial metal resistance. These findings reinforce the theory that the role of CusB is not only to bind metal but also to play an active role in efflux.


Systemic vascular effects of cyclosporin A treatment in normotensive rats.
The immunosuppressive drug cyclosporin A (CsA) frequently induces hypertension, but the mechanism(s) is unknown. Thus, we examined the mechanism(s) by which CsA increases arterial blood pressure (MAP) in the normotensive rat. Three different treatment modalities were used. First, chronic CsA treatment (20 mg/kg/day, s.c., for 1 week) significantly increased MAP from 109.6 +/- 2.3 mm Hg to 125.8 +/- 2.9 mm Hg (P less than .05). Second, subacute i.v. infusion of CsA (20 mg/kg daily for 3 days) increased MAP to even higher values (140.5 +/- 2.3 mm Hg), which correlated significantly with the highest circulating values of the drug. The pressor effect after i.v. infusion appears to be unrelated to endogenous release of catecholamines, because phentolamine, which abolishes the response to exogenous norepinephrine, failed to prevent the CsA-induced pressor response. Third, i.v. bolus injections of CsA (10-20 mg/kg) evoked immediate, dose-dependent and short-lasting increases in MAP (+15-25 mm Hg) in both anesthetized and conscious rats. Ganglionic blockade did not prevent this effect, rather, a 2- to 3-fold increase in amplitude (+40-60 mm Hg) and duration (+30-45 min) of the CsA-induced pressor response was observed in anesthetized rats. Heart rate was not increased significantly by either acute or chronic administration of CsA. Our results suggest that both CsA-induced pressor responses and hypertension are due to a peripheral action unrelated to sympathetic outflow. Furthermore, CsA's hypertensive effect is accompanied by severe morphological changes in the vascular endothelium and smooth muscle cells. In addition, CsA-treated rats showed significantly attenuated vasodilatory responses to prostacyclin and sodium nitroprusside, and increased pressor responses to norepinephrine. Thus, a direct vascular action of CsA is likely to contribute to the alterations on systemic vascular responsiveness, as well as to the hypertensive effect of the drug.


Spirituality and the physician executive.
The "s" word can now be spoken without flinching in health care organizations. Spirituality is becoming a common topic in management conferences around the world. Many U.S. corporations are recognizing the role of spirituality in creating a new humanistic capitalism that manages beyond the bottom line. Spirituality refers to a broad set of principles that transcend all religions. It is the relationship between yourself and something larger, such as the good of your patient or the welfare of the community. Spirituality means being in right relationship to all that is and understanding the mutual interdependence of all living beings. Physician executives should be primary proponents of spirituality in their organizations by: Modeling the power of spirituality in their own lives; integrating spiritual methodologies into clinical practice; fostering an integrative approach to patient care; encouraging the organization to tithe its profits for unmet community health needs; supporting collaborative efforts to improve the health of the community; and creating healing environments.


Comparative effects of home- and group-based exercise on balance confidence and balance ability in older adults: cluster randomized trial.
Exercise can modify fall risk factors such as balance and mobility impairments. However, can exercise improve balance confidence? In one strength-training study, researchers reported that a change in balance confidence was not uniformly associated with changes in objective measures of fall risk or physical performance. In fact, some participants' balance confidence decreased while their physical abilities increased and vice versa. The aim of this study was to compare changes in balance confidence and balance ability resulting from three exercise interventions (home-based resistance and balance training (RBT), group-based RBT and group-based walking), and the concomitant relationships between change in balance confidence and change in ability. It was hypothesized that participants in the group-based RBT program would improve their balance confidence and performance more than those in the home-based or walking programs. In a cluster-randomized design, nine retirement villages were assigned to one of the three exercise groups. One hundred and sixty-seven independent-living residents (aged 65-96 years) participated. Each group exercised twice weekly for 20 weeks. Objective balance ability was measured using timed tandem and one-leg stands (static balance), and the 8-foot (2.5 m) up-and-go test (dynamic balance/agility). Balance confidence was assessed using the self-report Activities-specific Balance Confidence (ABC) Scale. Participants in the group-based RBT program improved their static balance scores more than those in the home-based program; however, improvements in balance confidence were greater among participants in the home-based program (all p < 0.05). Discordance between static balance and balance confidence change scores was evident for up to 20% of participants. Change in ABC score was weakly correlated with a change in the up-and-go test score. Exercise training can improve balance confidence and balance ability in retirement village residents. However, as has been shown previously, this study found that exercise interventions may improve balance ability without associated increases in balance confidence and vice versa. Whether the ABC score and balance ability can be enhanced by providing a tailored intervention to improve balance confidence in combination with a RBT program requires further study.


Blood pressure in adolescence and early adulthood related to obesity and birth size.
Obesity is an established risk factor for higher systolic (SBP) and diastolic (DBP) blood pressure in adolescence and early adulthood, but birth size may also have a role. We analyzed the effects of adolescent and adult obesity and birth size on BP in the young adult. In a prospective longitudinal study, anthropometric measurements were obtained at birth on 67 boys and 67 girls born in Boston. Their body mass indices (BMI) and BP were recorded 17 years and 30 years later. For women, adolescent and early adult obesity appeared to be the stronger determinants of higher BP, although smaller head and chest circumferences at birth may also be related. We found some evidence of birth (ponderal index [PI] and head circumference) anthropometric influences on age 17 BP levels in boys. By age 30, body mass variables were the dominant predictors of male BP levels. Female BMI at age 17 was positively correlated with birth adiposity (PI), but BMI at 30 was related only to age 17 BMI. Similarly, male BMI at 17 years was higher for those who weighed more at birth, but BMI at 30 years was again related only to age 17 BMI. We conclude that adult weight and weight gain are the major determinants of adult BP.


[Orbital decompression in non-thyroid-associated diseases].
Hypoxia triggers hypoxia-inducible factor (HIF). Not only hypoxia triggers downstream HIF target genes for transcription, as intermittent hyperoxia also possesses similar capabilities, suggesting that fluctuations in oxygen availability may be equally important for inducing HIF transcription. This review describes some of the mechanisms, whereby intermittent hyperbaric hyperoxia may explain some of the observations during hyperbaric oxygen therapy such as enhanced wound healing, angiogenesis and tissue healing, and concludes that oxidative stress enhances certain antibiotics in infection control.


CD5-positive B-cell malignancies frequently express cross-reactive idiotypes associated with IgM autoantibodies.
Using monoclonal antibodies (MAb) specific for cross-reactive idiotypes (CRIs) associated with human monoclonal IgM autoantibodies, we examined 57 biopsy specimens that previously had been noted to have immunohistologic features of CD5-positive B-cell small lymphocytic (SL) non-Hodgkin's lymphoma (NHL). Twenty-five lymphoma specimens were noted to be from patients with chronic lymphocytic leukemia (CLL). Eight of thirty-four (24%) immunoglobulin (Ig) kappa light-chain expressing lymphomas reacted with 17.109, a MAb specific for a major CRI encoded by a conserved Ig kappa variable region gene (Vk gene) of the VkIIIb sub-subgroup. All 17.109-reactive tissues and two 17.109-negative specimens were recognized by another MAb specific for VkIIIb framework determinant(s). Seven of all fifty-six (13%) Ig-expressing tumors bound G6, a MAb specific for an autoantibody heavy-chain-associated CRI that is encoded by a conserved antibody heavy chain variable region gene(s) (VHgene) of the VH1 subgroup. All seven G6-positive lymphomas and two G6-negative tumors reacted with Cc1, another MAb specific for a rheumatoid factor heavy-chain-associated CRI. A third autoantibody-heavy-chain-associated CRI, termed Lc1, was expressed by seven (13%) other lymphomas. Finally, a fourth MAb specific for RF heavy-chain-associated CRI, named B6, detected two additional tumors. The expression frequencies of autoantibody-associated CRIs among SL NHL patients without peripheral lymphocytosis did not differ from those noted among patients with CLL but were significantly higher than those observed among patients with NHL of follicular center-cell origin. These data imply that the malignant B cells of patients with either CD5-positive B-cell SL NHL or CLL express a restricted set of Ig V genes that have not substantially diversified from the germline DNA.


Metastatic Colon Cancer - An Effective Treatment Protocol of Integrative Therapies Including Electromagnetic Field Frequencies: A Case Report.
Colorectal cancer is the third most common cancer worldwide, with 25% of patients being diagnosed with metastatic disease, mostly in the liver, resulting in poor survival. Standard treatment of stage-IV colorectal cancer consists of primary tumour resection followed by chemotherapy. Here, we report on the treatment effectiveness using integrative therapies in a 52-year-old male with metastatic colon cancer and liver lesions to achieve stable partial remission with an overall high level of wellbeing. After surgical removal of the primary tumour, the 8-month integrative treatment regime consisted of standard anti-angiogenesis treatment, as well as multiple non-standard but evidence-based therapies, including high-dose intravenous nutrients and herbal therapies, oral intake of repurposed medication and nutritional supplements, and a 4-month targeted electromagnetic field/Rife frequency therapy. The integrative therapies used in this case study were highly tolerable and effective in the treatment of metastatic colon cancer with liver lesions, achieving substantial tumour response and stable partial remission with a high level of wellbeing.


A systematic review of brain frontal lobe parcellation techniques in magnetic resonance imaging.
Manual volumetric measurement of the brain's frontal lobe and its subregions from magnetic resonance images (MRIs) is an established method for researching neural correlates of clinical disorders or cognitive functions. However, there is no consensus between methods used to identify relevant boundaries of a given region of interest (ROI) on MRIs, and those used may bear little relation to each other or the underlying structural, functional and connective architecture. This presents challenges for the analysis and synthesis of such results. We therefore performed a systematic literature review to highlight variations in the anatomical boundaries used to measure frontal regions, contextualised by up-to-date evidence from histology, hodology and neuropsychology. We searched EMBASE and MEDLINE for studies in English reporting three-dimensional boundaries for manually delineating the brain's frontal lobe or sub-regional ROIs from MRIs. Exclusion criteria were: exclusive use of co-ordinate grid systems; insufficient detail to allow method replication; publication in grey literature only. Papers were assessed on quality criteria relating to bias, reproducibility and protocol rationale. There was a large degree of variability in the three-dimensional boundaries of all regions used by the 208 eligible papers. Half of the reports did not justify their rationale for boundary selection, and each paper met on average only three quarters of quality criteria. For the frontal lobe and each subregion (frontal pole, anterior cingulate, dorsolateral, inferior-lateral, and orbitofrontal) we identified reproducible methods for a biologically plausible target ROI. It is hoped that this synthesis will guide the design of future volumetric studies of cerebral structure.


Reproductive coercion, intimate partner violence, and pregnancy risk among adolescent women with a history of foster care involvement.
The current study is the first to explore the prevalence of reproductive coercion among adolescent women currently or previously involved in the U.S. foster care system. Reproductive coercion (RC), a form of intimate partner violence (IPV) involving exertion of power over a partner by controlling their reproductive health and decision making, is a significant public health concern. Existing research on RC has primarily been conducted in either healthcare settings or on college campuses. Foster youth are disproportionately impacted by both adolescent pregnancy and interpersonal violence. RC may contribute to this elevated risk. We conducted a cross-sectional survey in 2015 and 2016 of adolescent women (n=136), ages 16-24 years old, seeking services from youth-serving agencies affiliated with a child welfare system in Pennsylvania, United States. Participants completed measures assessing RC, experiences of physical and sexual violence, sexual behaviors, and pregnancy. We used multivariable logistic regression to assess associations between RC and study outcomes. The sample was predominantly African American (67.4%) and largely identified as something other than heterosexual (46.6%). Nearly one-third of the sample (30.1%) reported a history of RC, with the most common being male partners telling them not to use birth control. High rates of IPV (62.1%), lifetime pregnancy (43.4%), and unwanted pregnancy (30.9%) were also reported. RC was associated with significantly higher odds of IPV (Adjusted Odds Ratio (AOR) = 4.22, 95% Confidence Interval (CI): 1.60, 11.13), multi-perpetrator rape (AOR 3.56, 95% CI: 1.04, 12.24), pregnancy (AOR = 5.39, 95% CI: 2.14, 13.60), and unintended pregnancy (AOR 5.39, 95% CI: 2.04, 14.25). Young women reporting RC also had elevated odds for using alcohol or drugs before sex (AOR = 4.34, 95% CI: 1.72, 10.97) and having sex with a male partner 5 years or more older (AOR = 7.32, 95% CI: 2.84, 18.87). No significant differences emerged between RC and sociodemographic characteristics. These data suggest women involved in the U.S. foster care system, particularly women of color and/or LGBTQ+ identified who comprised the majority of participants in the current study, may be at an increased risk for experiencing RC and other forms of IPV associated with adolescent pregnancy. In addition to efforts to prevent IPV and sexual violence, assessment for RC, healthy relationships education, and access to sexual and reproductive health care may mitigate these risks and improve outcomes for these young women.


Opioid-modulating peptides: mechanisms of action.
Opioids are involved in the physiological control of numerous functions of the central nervous system, particularly nociception. It appears that some endogenous neuropeptides, called anti-opioids, participate in an homeostatic system tending to reduce the effects of opioids. Neuropeptide FF (NPFF) and cholecystokinin (CCK) possess these properties and, paradoxically, the opioid peptides nociceptin and dynorphin display some anti-opioid activity. All these peptides exhibit complex properties as they are able to both counteract and potentiate opioid activity, acting rather as modulators of opioid functions. The purpose of this review is to highlight that two different mechanisms are clearly involved in the control of opioid functions by opioid-modulating peptides: a circuitry-induced mechanism for nociceptin and dynorphin, and a cellular anti-opioid mechanism for NPFF and CCK. The knowledge of these mechanisms has potential therapeutic interest in the control of opioid functions, notably for alleviating pain and/or for the treatment of opioid abuse.


The influence of STEM definitions for research on women's college attainment.
Prior research has inconsistently operationalized Science, Technology, Engineering, and Math (STEM) fields, presenting an interpretation challenge. A content analysis of 51 quantitative, gender-focused, higher education-oriented, STEM-related studies in the ERIC database published between January 2010 and July 2018 revealed that only 13 articles used an existing STEM definition. In 15, STEM was not explicitly defined, and others defined STEM independently. This wide range of definitions may lead to confusion or misrepresentation of findings for interventions and practices to support women in STEM. To illustrate the issue and prompt recommendations for future research, this study uses data from the United States National Center for Education Statistics' Education Longitudinal Study (ELS:2002/12) to investigate the connection between STEM definition and the outcome of college degree completion, comparing results by gender for five ways of operationalizing STEM fields. We found the size, direction, and significance of the gender gap depended on STEM operationalization. When STEM was defined as high paradigm fields, the odds of women attaining a non-STEM degree were higher than otherwise. When social science fields were included in STEM, there was no statistically significant difference by gender. When looking specifically at fields considered related to science and engineering, the direction of the relationship was reversed. While our findings follow expectations about social science fields and gender, it is noteworthy that results regarding STEM degree completion by gender for science and engineering-related fields were opposite those of high paradigm STEM fields. This result highlights that the definition of STEM matters, and inconsistent operationalization in the literature presents an interpretation challenge. We argue the field should strive to find common categorizations of STEM that retain the legitimate variation in how STEM can and should be defined, while providing a basis for consistent comparison. We recommend researchers and practitioners developing research-based practices: 1) interpret research findings understanding potential inconsistency from different STEM operationalizations, 2) explicitly describe STEM operational definitions to enable comparing findings, 3) routinely analyze sensitivity to alternate STEM definitions, and 4) find common STEM categorizations that retain legitimate variation while providing a basis for consistent comparison.


Racial Disparities in Cardiovascular Health Among the Acute Coronary Syndrome Population.
The relative distribution of proportions of cardiovascular health (CVH) categories within racial groups has been examined. However, little scientific evidence exists on the gap trend in racial/ethnic disparities in mean CVH score among non-Hispanic (NH) Whites and Blacks. This study examined the trend(s) in the gap(s) in predicted CVH scores between NH Whites and Blacks over 10 years. In a cross-sectional analytical study, 10 years of Medical Expenditure Panel Survey data from 2008 to 2018 were pooled, utilizing multivariate Poisson's regression of CVH metrics on race, while controlling for relevant covariates. The interactions of acute coronary syndrome (ACS) with CVH metrics, and other key variables such as trends and grouped Charlson Comorbidity Index allowed for variations in the effect of these variables on the subgroups. The mean gap in CVH scores was on average 0.15 [95% confidence interval (CI) 0.137 to 0.170], with Blacks consistently having reduced odds of having ideal CVH until 2014. The overall impact of having an ACS decreased acquired CVH scores by 24.1% [95% CI -0.275 to 0.207], and was equal for both racial subgroups (P < 0.05). The Affordable Care Act (ACA)-trend was positive, increasing the likelihood of improved CVH in the sample (P < 0.05), deflecting a downward trend in acquired CVH scores for both races, as the gap narrowed into more recent years. The CVH gap was stabilized by the ACA, but never really converged, suggesting that efforts to reduce existing disparities between Blacks and NH Whites in the United States would require government policies to look beyond mere "access" and/or "affordability" to health care.


Anti-Depressant Properties of Crocin Molecules in Saffron.
Saffron is a valued herb, obtained from the stigmas of the C. sativus Linn (Iridaceae), with therapeutic effects. It has been described in pharmacopoeias to be variously acting, including as an anti-depressant, anti-carcinogen, and stimulant agent. The therapeutic effects of saffron are harbored in its bioactive molecules, notably crocins, the subject of this paper. Crocins have been demonstrated to act as a monoamine oxidase type A and B inhibitor. Furthermore, saffron petal extracts have experimentally been shown to impact contractile response in electrical field stimulation. Other research suggests that saffron also inhibits the reuptake of monoamines, exhibits N-methyl-d-aspartate antagonism, and improves brain-derived neurotrophic factor signaling. A host of experimental studies found saffron/crocin to be similarly effective as fluoxetine and imipramine in the treatment of depression disorders. Saffron and crocins propose a natural solution to combat depressive disorders. However, some hurdles, such as stability and delivery, need to be overcome.