Effect of thyrotropin-releasing hormone on the locomotor and sensitizing effects of cocaine in rats.
The present study was designed to find out whether single and repeated treatment with thyrotropin-releasing hormone (TRH) changed the cocaine-evoked hyperactivation or sensitization, and whether cross-sensitization occurred between TRH and cocaine. Like cocaine (10 mg/kg), TRH (10 mg/kg) increased the basal activation of rats; however, when given in combination with cocaine (10 mg/kg), TRH (5-10 mg/kg) did not change the locomotor effect of cocaine. On day 10, cocaine challenge of rats treated repeatedly with the psychostimulant (days 1-5) significantly enhanced locomotor hyperactivity compared to the effect of acute cocaine injection in saline-treated (days 1-5) animals. When co-administered with cocaine for 5 days during the development of sensitization, TRH (10 mg/kg) enhanced the effect of the challenge dose of cocaine (10 mg/kg) following a 5-day withdrawal. Given acutely with cocaine on day 10 to cocaine-treated animals, TRH (5-10 mg/kg) did not change the expression of cocaine sensitization. Significant enhancement of the locomotor response to TRH (10 mg/kg) challenge was observed in animals treated repeatedly with TRH. The response to TRH (5-10 mg/kg) was stronger in repeated cocaine-treated rats than in saline-injected ones; similarly, the response to cocaine (10 mg/kg) was more potent in TRH-treated animals compared to saline-injected ones (cross-sensitization). In conclusion, our results indicate that exposure to TRH induces sensitization to its locomotor hyperactivity effect. They also show that TRH enhances the development of cocaine sensitization, but affects neither the expression phase of the phenomenon nor the locomotor hyperactivity induced by a single dose of cocaine. Moreover, cross-sensitization between cocaine and TRH has also been demonstrated. These findings also may provide an insight into the relationship between TRH and cocaine in humans exposed to the psychostimulant.


Images of the month 2: Electrocardiographic QRS alternans caused by gastric volvulus.
QRS electrical alternans is characterised by alternating amplitude of the QRS complexes, and is well-documented in cardiac conditions such as pericardial effusion. We describe a case of QRS alternans in a patient with gastric volvulus.


Nanohydroxyapatite-Protein Interface in Composite Sintered Scaffold Influences Bone Regeneration in Rabbit Ulnar Segmental Defect.
The healing physiology of bone repair and remodeling that occurs after normal fracture is well orchestrated. However, it fails in complex clinical conditions and hence requires augmentation by grafts. In this study, composite nanohydroxyapatite (nHA), poly(hydroxybutyrate) (PHB) and poly(ɛ-caprolactone) (PCL) constituted microspheres sintered three-dimensional scaffold were evaluated in rabbit ulnar segmental defect. A composite scaffold using PHB-PCL-nHA microspheres was developed with protein interface by solvent/non-solvent sintering to provide multiple cues such as biocomposition, cancellous bone equivalent meso-micro multi-scale porosity, and compressive strength. In vitro DNA quantification and alkaline phosphatase (ALP) assays revealed that the protein interfaced composite scaffolds supported osteoblast proliferation and mineralization significantly higher than scaffolds without protein and TCPS (p < 0.05). Scanning electron micrographs of osteoblasts cultured scaffolds demonstrated cell-matrix interaction, cell spreading, colonization and filopodial extension across the porous voids. Cylindrical scaffolds (5 × 10 mm) were implanted following segmental defect (10 mm) in rabbit ulnar bone and compared with untreated control. Radiography (4, 8 and 12 weeks) and µ-computed tomography (12 weeks) analysis showed directional bone tissue formation by bridging defective site in both scaffolds with and without protein interface. Whereas, undesired sclerotic-like tissue formation was observed in control groups from 8 weeks. Histology by hot Stevenel's blue and van Gieson's picrofuchsin staining has confirmed enhanced bone maturation in scaffold groups while presence of osteoids was observed in control after 12 weeks. Thus, the developed composite matrices exhibits osteoinductive, osteoconductive properties and demonstrates its bone regenerative potential owing to its compositional, micro & macro structural and mechanical properties. Graphical abstract.


Attenuation of lung inflammation and fibrosis in CD69-deficient mice after intratracheal bleomycin.
Cluster of differentiation 69 (CD69), an early activation marker antigen on T and B cells, is also expressed on activated macrophages and neutrophils, suggesting that CD69 may play a role in inflammatory diseases. To determine the effect of CD69 deficiency on bleomycin(BLM)-induced lung injury, we evaluated the inflammatory response following intratracheal BLM administration and the subsequent fibrotic changes in wild type (WT) and CD69-deficient (CD69-/-) mice. The mice received a single dose of 3 mg/kg body weight of BLM and were sacrificed at 7 or 14 days post-instillation (dpi). Lung inflammation in the acute phase (7 dpi) was investigated by differential cell counts and cytokine array analyses of bronchoalveolar lavage fluid. In addition, lung fibrotic changes were evaluated at 14 dpi by histopathology and collagen assays. We also used reverse transcription polymerase chain reaction to measure the mRNA expression level of transforming growth factor β1 (TGF-β1) in the lungs of BLM-treated mice. CD69-/- mice exhibited less lung damage than WT mice, as shown by reductions in the following indices: (1) loss of body weight, (2) wet/dry ratio of lung, (3) cytokine levels in BALF, (4) histological evidence of lung injury, (5) lung collagen deposition, and (6) TGF-β1 mRNA expression in the lung. The present study clearly demonstrates that CD69 plays an important role in the progression of lung injury induced by BLM.


Prospective Audit of Blood Donor Selection Process in a Tertiary Care Hospital of a Developing Country.
The aim of this study was to emphasize the significance of internal audits of the blood donor selection process and documentation in a resource-limited country by assessing compliance with the established protocols, and to identify weak areas in the process. This audit reviewed the donor selection process at the blood bank of Liaquat National Hospital & Medical College, Karachi, over a 6-month period. Seven variables selected as performance indicators were graded as very good (%90-100%), good (80%-89%), satisfactory (70%-79%), or unacceptable (<70%). Blood bank staff was asked for feedback and suggestions. Documentation of donor demographics was not within the acceptable range (documentation rates of 65.14%), donor status records were satisfactory (77.64%), and donor physical exam records were graded as good (86.34%). Five performance indicators were graded as very good (90%-100%). The audit proved productive in identifying major causes of irregularities in documentation and in making valuable suggestions for their rectification.


Socioeconomic aspects of stab and gunshot wounds.
Records of 294 patients with gunshot, stab, or shotgun wounds admitted to Charlotte Memorial Hospital and Medical Center between July 1, 1976 and June 30, 1977 were reviewed. Data were gathered on 24 clinical, social, and economic aspects to discover any patterns in these areas. Eighty-three percent of the patients were male; 71%, black; 70%, unmarried; and 56%, between 16 and 30 years of age. Fifty-five percent came to the hospital between 10 pm and 3 am; 57% on Friday, Saturday, or Sunday; 31% came in June, July, or August. Sixty-four percent were gunshot wounds, 80% of which were by small caliber weapons. Ninety-four percent of all patients survived. The patients "consumed" 3,260 hosptial days, 526 intensive care unit days, 533 units of blood, and 261 operations, totaling 595 hours of operating room time. Hospital charges totaled $668,000, of which 1.1% was paid from private funds and nearly 65% from the taxpayers and other private paying patients.


Drug repurposing using real-world data.
The use of real-world data in drug repurposing has emerged due to well-established advantages of drug repurposing in supplementing de novo drug discovery and incentives in incorporating real-world evidence in regulatory approvals. We conducted a scoping review to characterize repurposing studies using real-world data and discuss their potential challenges and solutions. A total of 250 studies met the inclusion criteria, of which 36 were original studies on hypothesis generation, 101 on hypothesis validation, and seven on safety assessment. Key challenges that should be addressed for future progress in using real-world data for repurposing include isolated data sources with poor clinical granularity, false-positive signals from data mining, the sensitivity of hypothesis validation to bias and confounding, and the lack of clear regulatory guidance.


Production of auto-anti-idiotypic antibody during the normal immune response. XII. An enzyme-linked immunosorbent assay for auto-anti-idiotype antibody.
An enzyme-linked immunosorbent assay (ELISA) to detect anti-idiotype (Id) antibody is described. Using this assay auto-anti-Id was detected in the serum of aged mice immunized with 2,4,6-trinitrophenylated-Ficoll (TNP-F). Hapten eluates from anti-TNP-F immune spleen cells also contained readily detectable auto-anti-Id.


Assessment of the Gene Therapy Immune Response in the Canine Muscular Dystrophy Model.
The immune response is a primary hurdle in the development of gene therapy for neuromuscular diseases. Both innate and adaptive immune responses have been observed in human trials. The canine model is an excellent platform to understand immunological consequences of gene therapy. Over the last several decades, we have conducted gene replacement and gene repair therapies in the canine model of Duchenne muscular dystrophy (DMD) using adeno-associated virus (AAV)-mediated expression of the highly abbreviated micro-dystrophin gene, the larger mini-dystrophin gene, and the Cas9-based CRISPR genome editing machinery. We have evaluated the innate, humoral, and cellular immune responses to the AAV vector and the transgene product. In this chapter, we share our experience in collecting and processing of the dog blood samples for immunological assays, and our protocols for quantitative evaluation of cytokines and chemokines, antibodies, and T-cell responses.


Pre-pandemic burnout and its changes during the COVID-19 outbreak as predictors of mental health of healthcare workers: A lesson to be learned.
The aim of this study was to identify how previously existing burnout and its changes during the pandemic contributed to PTSD symptoms and psychological distress in a cohort of 388 healthcare workers (HCWs). Each HCW was surveyed in Sep 2019 (before COVID-19) and again in Dec 2020-Jan 2021 (during the pandemic) to assess burnout (MBI); and in the second wave only to assess PTSD (PCL-5-SF), psychological distress (GHQ-12) and resilience (CD-RISC-10). Changes in emotional exhaustion (EE) and depersonalisation (DEP) were stronger in HCWs with lower EE and DEP baseline values. HCWs with higher baseline poor personal accomplishment (PPA) improved more than those with lower baseline values. In multivariable-adjusted models, pre-pandemic EE and its changes were equally associated to both outcomes: standardised-βs of 0.52 and 0.54 for PTSD, respectively; and 0.55 and 0.53 for psychological distress. Changes in DEP were associated with PTSD only (0.10). Changes in PPA had a higher association with psychological distress (0.29) than pre-pandemic PPA (0.13). Resilience was associated with lower psychological distress (-0.25). Preventive actions aimed at reducing EE, e.g., addressing organisational dysfunctions, are needed to mitigate the impact of future crises, whereas improving personal accomplishment levels is a key target to protect HCWs from mental health disorders during a pandemic.


Predictive Design and Analysis of Drug Transport by Multiscale Computational Models Under Uncertainty.
Computational modeling of drug delivery is becoming an indispensable tool for advancing drug development pipeline, particularly in nanomedicine where a rational design strategy is ultimately sought. While numerous in silico models have been developed that can accurately describe nanoparticle interactions with the bioenvironment within prescribed length and time scales, predictive design of these drug carriers, dosages and treatment schemes will require advanced models that can simulate transport processes across multiple length and time scales from genomic to population levels. In order to address this problem, multiscale modeling efforts that integrate existing discrete and continuum modeling strategies have recently emerged. These multiscale approaches provide a promising direction for bottom-up in silico pipelines of drug design for delivery. However, there are remaining challenges in terms of model parametrization and validation in the presence of variability, introduced by multiple levels of heterogeneities in disease state. Parametrization based on physiologically relevant in vitro data from microphysiological systems as well as widespread adoption of uncertainty quantification and sensitivity analysis will help address these challenges.


Fine mapping of a leaf flattening gene Bralcm through BSR-Seq in Chinese cabbage (Brassica rapa L. ssp. pekinensis).
Leaf flattening influences plant photosynthesis, thereby affecting product yield and quality. Here, we obtained a stably inherited leaf crinkled mutant (lcm), derived from the Chinese cabbage doubled haploid (DH) 'FT' line using EMS mutagenesis combined with isolated microspore culture. The crinkled phenotype was controlled by a single recessive nuclear gene, namely Bralcm, which was preliminarily mapped to chromosome A01 by bulked segregant analysis RNA-seq, and further between markers SSRS-1 and IndelD-20 using 1,575 recessive homozygous individuals in F2 population by a map-based cloning method. The target region physical distance was 126.69 kb, containing 23 genes; the marker SSRMG-4 co-segregated with the crinkled trait. Further, we found SSRMG-4 to be located on BraA01g007510.3C, a homolog of AHA2, which encodes H+-ATPase2, an essential enzyme in plant growth and development. Sequence analysis indicated a C to T transition in exon 7 of BraA01g007510.3C, resulting in a Thr (ACT) to Ile (ATT) amino acid change. Genotyping revealed that the leaf crinkled phenotype fully co-segregated with this SNP within the recombinants. qRT-PCR demonstrated that BraA01g007510.3C expression in lcm mutant leaves was dramatically higher than that in wild-type 'FT'. Thus, BraA01g007510.3C is a strong candidate gene for Bralcm, and AHA2 is possibly associated with leaf flattening in Chinese cabbage.


Relation between estimated glomerular filtration rate and composition of coronary arterial atherosclerotic plaques.
It is well known that chronic kidney disease is a risk factor for atherosclerosis. The present study was conducted to identify any relation between the estimated glomerular filtration rate (eGFR) and coronary plaque characteristics using integrated backscatter intravascular ultrasound (IB-IVUS), which can detect coronary plaque composition. We performed IB-IVUS for 201 consecutive patients undergoing percutaneous coronary intervention, and they were divided into 3 groups according to the eGFR values (group 1 [n = 20], ≥90 ml/min/1.73 m(2); group 2 [n = 123], 60 to 90 ml/min/1.73 m(2); and group 3 [n = 58], <60 ml/min/1.73 m(2)). Coronary plaques in nonculprit lesions on 3-dimensional analysis were evaluated using IB-IVUS. The baseline characteristics were similar, except for older age and a greater prevalence of men in group 3. IB-IVUS showed a percentage of lipid volume of 44.7 ± 5.0% in group 1, 53.6 ± 6.2% in group 2, and 63.5 ± 6.2% in group 3 (p <0.01), with a corresponding percentage of fibrous volume of 53.9 ± 4.9%, 45.1 ± 6.0%, and 35.3 ± 6.1%, respectively (p <0.01). The eGFR correlated significantly with both parameters (r = -0.68, p <0.001 and r = 0.68, p <0.001, respectively). In conclusion, lower eGFR levels were associated with greater lipid and lower fibrous contents, contributing to coronary plaque vulnerability.


Clinical and echocardiographic differences in three different etiologies of severe mitral stenosis.
In our institute, the causes of mitral stenosis (MS) are generally categorized into three main etiologies-rheumatic MS (RMS), degenerative MS with annular and leaflet calcification, and post-clip MS as a consequence of transcatheter mitral valve repair with clips for treating mitral regurgitation. However, clinical differences among the three etiologies are uncertain. We retrospectively assessed 293 consecutive patients (53 with RMS, 118 with degenerative MS, and 122 with post-clip MS) who had a three-dimensional (3D) transesophageal echocardiography (TEE) derived mitral valve orifice area (MVA) of ≤1.5 cm2 , and a mean transmitral pressure gradient of ≥5 mmHg on transthoracic echocardiography. Although there was no difference in 3D-TEE-derived MVA among the three groups, patients with post-clip MS had a significantly lower mean transmitral pressure gradient compared to those with either of the other two types of MS (10.8 ([7.9-15.2] mmHg vs. 9.6 [7.3-12.5] mmHg vs. 6.9 [6.0-9.2] mmHg; p < .001). Patients with RMS had a higher prevalence of dyspnea. The independent determinants of dyspnea were pressure half time in RMS, 3D-TEE-derived MVA and estimated right atrial pressure in degenerative MS, and left ventricle ejection fraction in post-clip MS. Patients with post-clip MS had the lowest mean transmitral pressure gradient, and patients with RMS had the highest prevalence of dyspnea, despite having a similar 3D-TEE-derived MVA. The determinants of dyspnea were different among the three etiologies of MS.


Cytokeratins in human basal and squamous cell carcinomas: biochemical, immunohistological findings and comparisons with normal epithelia.
The nature of epithelial cell cytokeratins from epidermal basal cell carcinomas (BCC) (8 cases) and squamous cell carcinomas (SCC) (5 cases) was investigated by biochemical and immunological analysis. Cytokeratin proteins were extracted with high salt buffer and triton X 100 and were comparatively analyzed by SDS (sodium dodecyl sulphate) polyacrylamide gel electrophoresis. Both types of tumor showed either an absence or a very low amount (5% of the total protein) of the major protein band (MW 67000) present in normal human epidermis. This correlated well with results of immunolabelling showing that 67000 keratin antisera, only reacted with some dyskeratotic cells in sections of these tumors. Gel electrophoresis showed in BCC and SCC, three distinct groups of predominant polypeptide bands of apparent relative MW: (1) 60-62000 (2) 54-56000 and (3) 49000, representing respectively about 43.0%, 31.0% and 20.4% of the total proteins. Antibodies raised in animals against polypeptide bands C1 (MW 62000), C2 (MW 56000) and C3 (MW 49000) from SCC, strongly labelled (indirect immunofluorescence) all malignant cells present in the 2 kinds of tumors. These antisera showed a preferential reaction with the basal epithelial cells, in sections of human and animal epidermis and mucosa thus, suggesting numerous common antigenic determinants between epithelial cells from diverse origins. On the other hand, strong differences between mucosal and epidermal upper layers were noted with C1, C2, C3 and 67000 antisera. These results are further evidence for the existence of different pathways of keratinization in epidermis and mucosa.


Synthesis of some floctafenine derivatives of expected anti-inflammatory/analgesic activity.
New derivatives related to floctafenine were synthesized and representative examples were screened for their anti-inflammatory and analgesic activities. All compounds tested were found to exhibit anti-inflammatory and analgesic activities and some were more potent than the references, floctafenine and indomethacin, in carragenan-induced rat's paw edema. None of the tested compounds showed an ulcerogenic effect on the p-benzoquinone-induced writhing test in mice.


Increased Sensitivity of Diagnostic Mutation Detection by Re-analysis Incorporating Local Reassembly of Sequence Reads.
Diagnostic genetic testing programmes based on next-generation DNA sequencing have resulted in the accrual of large datasets of targeted raw sequence data. Most diagnostic laboratories process these data through an automated variant-calling pipeline. Validation of the chosen analytical methods typically depends on confirming the detection of known sequence variants. Despite improvements in short-read alignment methods, current pipelines are known to be comparatively poor at detecting large insertion/deletion mutations. We performed clinical validation of a local reassembly tool, ABRA (assembly-based realigner), through retrospective reanalysis of a cohort of more than 2000 hereditary cancer cases. ABRA enabled detection of a 96-bp deletion, 4-bp insertion mutation in PMS2 that had been initially identified using a comparative read-depth approach. We applied an updated pipeline incorporating ABRA to the entire cohort of 2000 cases and identified one previously undetected pathogenic variant, a 23-bp duplication in PTEN. We demonstrate the effect of read length on the ability to detect insertion/deletion variants by comparing HiSeq2500 (2 × 101-bp) and NextSeq500 (2 × 151-bp) sequence data for a range of variants and thereby show that the limitations of shorter read lengths can be mitigated using appropriate informatics tools. This work highlights the need for ongoing development of diagnostic pipelines to maximize test sensitivity. We also draw attention to the large differences in computational infrastructure required to perform day-to-day versus large-scale reprocessing tasks.


Tobin's q and corporate investment with a pandemic shock.
We analyze the impact of COVID-19 on investment by incorporating a stochastic transmission shock into the standard q theoretical framework. Our model suggests that the adjustment cost amplifies the negative pandemic shock to investment and decreases firm value. In particular, when the infection rate is low, the reduction in investment is higher for firms with low adjustment costs in that they are more sensitive to the infection rate. An optimistic expectation of the arrival rate of a vaccine reduces the probability of executing mitigation policy. Moreover, the uncertainty of the pandemic increases investment and enhances firm value during the pandemic regime.


Morphology of migrating telocytes and their potential role in stem cell differentiation during cartilage development in catfish (Clarias gariepinus).
Telocytes (TCs) are present in a broad range of species and regulate processes including homeostasis, tissue regeneration and immunosurveillance. This novel study describes the morphological features of migrating TCs and their role during cartilage development within the air-breathing organ in Clarias gariepinus, the African sharptooth catfish. Light microscopy (LM), transmission electron microscopy (TEM), and immunohistochemistry (IHC) were used to examine the TCs. TCs had a cell body and telopodes which formed 3D networks in the cartilage canals and extended their telopodes to become the foremost cellular elements penetrating the cartilage matrix. The TCs were also rich in lysosomes that secreted products to the extracellular matrix (ECM). In addition, TCs formed a homocellular synaptic-like structure that had a synaptic cleft, and the presynaptic portion consisted of a slightly expanded terminal of the telopodes which contained intermediate filaments and secretory vesicles. Gap junctions were also identified between TCs, which also connected to mesenchymal stem cells, differentiating chondrogenic cells, macrophages, apoptotic cells, and endothelial cells. In addition to describing the basic morphology of TCs, the current study also investigated migrating TCs. The TC telopodes acquired an irregular contour when migrating rather than exhibiting an extended profile. Migrating TCs additionally had ill-defined cell bodies, condensed chromatin, thickened telopodes, and podoms which were closely attached to the cell body. The TCs also expressed markers for MMP-9, CD117, CD34 and RhoA. In conclusion, TCs may play multiple roles during development and maturation, including promoting angiogenesis, cell migration, and regulating stem cell differentiation. RESEARCH HIGHLIGHTS: Clarias gariepinus telocytes form 3D networks, extend their telopodes and contain lysosomes. Telocytes form a homocellular synaptic-like structure including clefts and a slightly expanded terminal of the telopodes which contains intermediate filaments and secretory vesicles. Gap junctions form between telocytes, which also connect to mesenchymal stem cells, differentiating chondrogenic cells, macrophages, apoptotic cells, and endothelial cells. Migrating telocytes were discovered which had ill-defined cell bodies, condensed chromatin, thickened telopodes exhibiting irregular contours, and podoms which were closely attached to the cell body.


[Estimated production by the official inspection of coal-tar dyes (including dye aluminum lakes) in fiscal year 1998].
There were 284 official inspections of coal-tar and their lakes in fiscal year 1998, and 283 of the lots qualified, one of the 40 samples of Food Yellow No. 5 was rejected. The quality of coal-tar dyes that passed inspection in Japan in fiscal year 1998 reached 150.3 tons. Coal-tar dye production is summarized by manoth in Table 2 and by manufacturer in Table 3. The food coal-tar dye produced in the largest quantity was Food Yellow No. 4, accounting for 44.1% during this period.


Magnetic resonance angiography in a patient with Crohn's disease associated cerebral vasculitis.
Vasculitits of the central nervous system (CNS) is a known complication of chronic inflammatory bowel diseases. We report the case of a female patient with Crohn's disease, developing vasculitis of the CNS with evidence of pathological vessel depiction on magnetic resonance angiography. To our knowledge this is the first case report regarding MRA documentation of vessel changes typical for angiitis in a patient with Crohn-associated vasculitis of the CNS.


Serum cortisol and cortisone levels in newborns with congenital adrenal hyperplasia before the start of therapy.
Sodium loss in infants with salt wasting (SW) congenital adrenal hyperplasia (CAH) does usually not occur within the first week of life. We hypothesized that sufficient mineralocorticoid activity might by temporarily maintained by still appropriate concentrations of cortisol. Plasma samples were obtained from 15 infants with SW-CAH before the onset of sodium loss, 17 patients with simple virilizing (SV)-CAH and 28 healthy infants under 14 days of age. Plasma aldosterone concentrations were significantly lower in SW-CAH infants than in SV-CAH patients and in healthy neonates. Plasma cortisol levels and cortisol/cortisone (F/E) ratios in SW-CAH patients were almost the same as in the SV-CAH and control group. While declining plasma aldosterone levels precede the onset of SW in CAH patients, plasma cortisol concentrations are kept normal in SW-CAH infants, temporarily maintaining sufficient mineralocorticoid activity.


Characterisation of diamond coatings with different morphologies by Raman spectroscopy using various laser wavelengths.
Since the beginning of low-pressure diamond synthesis, Raman spectroscopy has been widely used to identify and characterise the quality of diamonds. The diamond crystal is characterised by a Raman peak at about 1,332 cm(-1). Other peaks are associated with miscellaneous carbon structures, e.g. graphite and amorphous phases. In recent years, both well-faceted crystalline diamonds and nanocrystalline and ultrananocrystalline diamonds have been investigated. For these fine-grained materials, the diamond peak at 1,332 cm(-1) disappears and the intensities of peaks at other wavelengths increase. To study the influence of the Raman laser wavelength, three lasers were used (472.681 nm, blue; 532.1 nm, green; 632.81 nm, red). For well-faceted diamonds, the Raman spectra with blue and green laser light were similar. A shift of the peak maxima and different intensities were observed. With use of the red laser, a strong luminescence peak and low peak intensities for the various carbon-related peaks occurred. When the diamond morphology changes from well-faceted to fine-grained ballas diamond, the spectra are similar for all three lasers.


Prehospital triage of trauma patients before and after implementation of a regional triage guideline.
Severely injured trauma patients have a considerable mortality rate. One way to reduce the mortality is to ensure optimal triage. The American College of Surgeons Committee on Trauma has since 1986 made guidelines for the triage of trauma patients. These guidelines formed the basis, when the capital region of Denmark implemented a regional trauma triage guideline on February 15th 2016. It is uncertain how the implementation of the regional trauma triage guideline has influenced the triage of trauma patients. The aim of this study was to investigate the changes in admission pattern of trauma patients in the entire region after the implementation of the regional trauma triage guideline. We hypothesized that there would be a reduction in the proportion of trauma patients admitted to the trauma center after the implementation of the regional trauma triage guideline. In this observational cohort study with one-year follow-up, we used a national patient registry in Denmark. We identified trauma patients three years before and three years after the implementation of a new regional trauma triage guideline. The primary outcome was the proportion of trauma patients triaged to the regional trauma center. Secondary outcomes were: 30-day and one-year mortality, overtriage, and undertriage. We found a significant reduction in the proportion of trauma patients triaged to the trauma center from 2115/5951 (35.5%) to 1970/5857 (33.6%), after the implementation of the regional trauma triage guideline, the difference being 1.9% (95% CI: 0.19 to 3.6%); P = 0.03. Further, a significant reduction of overtriage from 15.4% to 9.5% (difference 5.9% with 95% CI of 3.8 to 7.9%) was found. No significant changes in undertriage, 30-day or one-year mortality were found (1.07% vs 0.97%, 4.3% vs 4.5%, and 15.7% vs 16.6% respectively). A significant decrease in the proportion of trauma patients admitted to the trauma center was found after implementation of a new regional trauma triage guideline. A reduction was seen in overtriage, but no changes were found in undertriage and both short-term and long-term mortality remained unchanged.


Trichostrongylus colubriformis rDNA polymorphism associated with arrested development.
Polymerase chain reaction-restriction fragment length polymorphism) was performed on the cistron of rDNA in the two groups of infective larvae Trichostrongylus colubriformis-the population with and without ability to undergo arrested development. General primers designed by Caenorhabditis elegans rDNA were used for the amplification of the rDNA cistron between genes 18S and 28S. Amplified fragments were digested by using a series of restriction endonucleases. Hinc II restriction profiles unique for each T. colubriformis populations were observed, and therefore enzyme Hinc II appears to be useful for the determination of populations with and without the ability to undergo arrested development. Molecular markers of arrested development ability have not been studied on this part of rDNA before.


What's eating the internet? Content and perceived harm of pro-eating disorder websites.
The internet is a popular tool for information dissemination and community building, serving many purposes from social networking to support seeking. However, there may be a downside to using some online support communities. For individuals with eating disorders (EDs), it is possible that certain online communities may reinforce the negative social aspects that encourage these disorders, rather than positive aspects that would facilitate treatment and recovery. Previous research identified several linguistic themes present on pro-eating disorder websites in an attempt to better understand the web-based conversation in the pro-eating disorder movement. We hypothesized that differences in theme presentation may predict changes in perceived harm. The present study sought to understand the perceived harm, and presentation patterns of pro-eating disorder (Pro-ED) website content. We replicated and extended previous research by having laypersons code these websites' content using previously identified linguistic themes and rate perceived harm. Our data replicate and extend the previous research by finding the same associations between co-occurring themes, and investigating associated perceived harm. We found that themes of Sacrifice, Control, Deceit, and Solidarity were associated with the highest perceived harm scores. In addition, we suggest an initial conceptualization of the "Eating Disorder Lifestyle", and its associations with the themes of Isolation, Success, and Solidarity. This research may provide clinicians with information to better understand the potential influence these sites have on eating disorders.


Effect of intracordal injection under local anesthesia on vital signs in high-risk patients.
Intracordal injection under local anesthesia is widely performed; however, few studies show hemodynamic changes in the heart rate, blood oxygen saturation, and blood pressure during intracordal injection under local anesthesia. This study examined changes in vital signs (heart rate, blood oxygen saturation, systolic blood pressure, diastolic blood pressure) during intracordal injection under local anesthesia among high-risk patients and investigated whether intracordal injection under local anesthesia could be safely conducted. A retrospective chart review was adopted as the research design. We investigated the changes in vital signs (heart rate, blood oxygen saturation, blood pressure) before and after intracordal injection with basic fibroblast growth factor (bFGF) preparations under local anesthesia in 46 patients who visited our institution and developed unilateral vocal cord paralysis after a thoracic aortic aneurysm, thoracic aortic dissection surgery, thyroid disease, esophageal disease, idiopathic disease, etc. RESULTS: The average operation time for the high-risk group was 3.67 minutes, with the shortest operating time being 2 minutes and the maximum operating time being 13 minutes. The average operation time for the control group was 3.73 minutes, with the shortest operating time being 1 minute and the maximum operating time being 9 minutes. Results before and after intracordal injection with bFGF preparations under local anesthesia for heart rate, blood oxygen saturation, systolic blood pressure, and diastolic blood pressure had P-values of 0.324, 0.394, 0.215, and 0.508, respectively, in the high-risk group, and no significant differences were found. Conversely, heart rate, blood oxygen saturation, systolic blood pressure, and diastolic blood pressure had P-values of 0.057, 0.232, 0.265, and 0.091, respectively, in the control group, and no significant differences were found. Intracordal injection under local anesthesia may be safe, even for patients who require blood pressure management after thoracic aortic disease surgery.


Acute exposure to realistic concentrations of Bisphenol-A trigger health damage in fish: Blood parameters, gene expression, oxidative stress.
Despite much information regarding BPA toxicity in fish and other aquatic organisms, data is still misleading as most studies have utilized concentrations several orders of magnitude higher than those typically found in the environment. As an illustration, eight of the ten studies investigating the impact of BPA on the biochemical and hematological parameters of fish have employed concentrations on the order of mg/L. Therefore, the results may not accurately represent the effects observed in the natural environment. Considering the information above, our study aimed to 1) determine whether or not realistic concentrations of BPA might alter the biochemical and blood parameters of Danio rerio and trigger an inflammatory response in the fish liver, brain, gills, and gut and 2) determine which organ could be more affected after exposure to this chemical. Findings pinpoint that realistic concentrations of BPA prompted a substantial increase in antioxidant and oxidant biomarkers in fish, triggering an oxidative stress response in all organs. Likewise, the expression of different genes related to inflammation and apoptosis response was significantly augmented in all organs. Our Pearson correlation shows gene expression was closely associated with the oxidative stress response. Regarding blood parameters, acute exposure to BPA generated biochemical and hematological parameters increased concentration-dependent. Thus, it can be concluded that BPA, at environmentally relevant concentrations, threatens aquatic species, as it prompts polychromasia and liver dysfunction in fish after acute exposure.


Androgen-induced growth factor and its receptor: demonstration of the androgen-induced autocrine loop in mouse mammary carcinoma cells.
SC-3 cells derived from mouse mammary carcinoma (Shionogi carcinoma 115) exhibit remarkable growth enhancement and cell morphology change in response to androgen stimuli. These events are mediated through an androgen-induced growth factor (AIGF). Amino acid sequence deduced from cDNA reveals that AIGF has 215 amino acids with a signal peptide and scattered regions homologous to fibroblast growth factor (FGF) family proteins. The biological ability of AIGF to stimulate SC-3 cell growth is inhibited by heparin or suramin. More importantly, antisense oligodeoxynucleotide of AIGF can block androgen-induced growth of SC-3 cells. Upon synthesis under the control of androgen, AIGF is immediately secreted into the extracellular space without intracellular accumulation. At the early phase (18-24 h) of androgen stimulation, however, AIGF is mainly associated with the glycosaminoglycan on the cell surface or extracellular matrix. In addition, treatment of SC-3 cells with sulfation blocker (chlorate) or heparitinase results in the abolishment of their ability to respond to androgen or AIGF, indicating that heparan sulfate has important roles for condensing AIGF on or near the cell surface as well as potentiating the biological activity of AIGF. Then, AIGF can bind to the FGF receptor. Northern blot analysis and cDNA cloning indicate that SC-3 cells predominantly express the FGF receptor 1 with some altered amino acid sequences. Transfection of expression vectors of AIGF and this variant form of FGF receptor 1 into FGF receptor-negative myoblast cells (L 6 cells) confirms that a variant form of FGF receptor 1 is a receptor of AIGF. These results clearly demonstrate that an autocrine mechanism is operating in androgen-induced growth of SC-3 cells.


Concentration responses to organochlorines in Phragmites australis.
Phragmites australis shows potential for the phytoremediation of chlorinated chemicals. Also there has been some attempt to determine the phytotoxic effects of organochlorines (OC). This study reports for lindane (HCH), monochlorobenzene (MCB), 1,4-dichlorobenzene (DCB) and 1,2,4-trichlorobenzene (TCB), a no-observed-effect-concentration (NOEC(7d)) that was 1000-300,000 times higher than environmental concentrations. Nevertheless, the combined OC mixture (NOEC(7d) level of each congener) induced a synergistic toxic effect, causing a severe drop (70%) in chlorophyll concentration. The mixture 0.2 mg L(-1) MCB+0.2 mg L(-1) DCB+2.5 mg L(-1) TCB+0.175 mg L(-1) HCH, that was 15 times more concentrated than environmental OC mixture, did not cause phytotoxicity during 21 days. Antioxidant enzymes were affected immediately after the start of exposure (3 days), but the plants showed no signs of stress thereafter. These data suggest that environmental OC mixtures do not pose a significant risk to P. australis.


Ciprofloxacin in management of urinary tract infection.
Ciprofloxacin is a new quinolone derivative which is particularly well adapted for the treatment of bacterial urinary tract infection. Virtually all uropathogens are susceptible, and the development of resistance is uncommon. Its pharmacokinetic characteristics reveal that effective concentrations of the drug are easily achieved with twice a day oral therapy in the blood, urine, kidneys, and prostate--even in advanced renal failure. The drug is well tolerated, even with prolonged courses of therapy. It will be particularly useful in the treatment of antibiotic-resistant, complicated, and/or prostatic infection.


Novel CHOP activator LGH00168 induces necroptosis in A549 human lung cancer cells via ROS-mediated ER stress and NF-κB inhibition.
C/EBP homologous protein (CHOP) is a transcription factor that is activated at multiple levels during ER stress and plays an important role in ER stress-induced apoptosis. In this study we identified a novel CHOP activator, and further investigated its potential to be a therapeutic agent for human lung cancer. HEK293-CHOP-luc reporter cells were used in high-throughput screening (HTS) to identify CHOP activators. The cytotoxicity against cancer cells in vitro was measured with MTT assay. The anticancer effects were further examined in A549 human non-small cell lung cancer xenograft mice. The mechanisms underlying CHOP activation were analyzed using luciferase assays, and the anticancer mechanisms were elucidated in A549 cells. From chemical libraries of 50 000 compounds, LGH00168 was identified as a CHOP activator, which showed cytotoxic activities against a panel of 9 cancer cell lines with an average IC50 value of 3.26 μmol/L. Moreover, administration of LGH00168 significantly suppressed tumor growth in A549 xenograft bearing mice. LGH00168 activated CHOP promoter via AARE1 and AP1 elements, increased DR5 expression, decreased Bcl-2 expression, and inhibited the NF-κB pathway. Treatment of A549 cells with LGH00168 (10 μmol/L) did not induce apoptosis, but lead to RIP1-dependent necroptosis, accompanied by cell swelling, plasma membrane rupture, lysosomal membrane permeabilization, MMP collapse and caspase 8 inhibition. Furthermore, LGH00168 (10 and 20 μmol/L) dose-dependently induced mito-ROS production in A549 cells, which was reversed by the ROS scavenger N-acetyl-L-cysteine (NAC, 10 mmol/L). Moreover, NAC significantly diminished LGH00168-induced CHOP activation, NF-κB inhibition and necroptosis in A549 cells. LGH00168 is a CHOP activator that inhibits A549 cell growth in vitro and lung tumor growth in vivo.


Regulation of inflammation by VEGF/BDNF signaling in mouse retinal Müller glial cells exposed to high glucose.
The inflammatory changes seem to play an important role in the development of diabetic retinopathy (DR). Anti-VEGF therapy has been testified to inhibit inflammation in animal models of diabetes, but the detailed mechanisms during this process are not yet clear. Müller glial cells (MGCs) in the mammalian retina are deeply involved in DR, while the BDNF overexpression reduces inflammation in diabetic mice. In this research, we aimed to explore the relationship between VEGF and BDNF in mouse retinal MGCs during inflammation of diabetes. We examined the expression of glutamine-synthetase (GS), glial fibrillary acidic protein (GFAP), vascular-endothelial growth factor (VEGF), interleukin-1beta (IL-1β), and tumor necrosis factor-alpha (TNF-α) at different time points after mouse retinal MGCs exposed to high glucose (25 mM). We also explored changes in the expression of brain-derived neurotrophic factor (BDNF), nuclear factor kappa B (NF-κB), IL-1β, and TNF-α in MGCs after treatments with anti-VEGF, VEGF siRNA, BDNF siRNA, BDNF recombination protein, and NF-κB inhibitor. In mouse retinal MGCs exposed to high glucose, BDNF was increased after treatments with anti-VEGF or VEGF siRNA. BDNF was decreased in MGCs from VEGF overexpressed mice. Moreover, the expressions of NF-κB, IL-1β, and TNF-α changed with BDNF: NF-κB, IL-1β, and TNF-α were increased after treatments with BDNF siRNA; NF-κB, IL-1β, and TNF-α were decreased after treatments with BDNF recombination protein. VEGF may regulate cytokines (IL-1β and TNF-α) by BDNF/NF-κB signaling pathway. The regulation of the VEGF/BDNF/NF-κB signaling pathway may be a significant therapeutic strategy for DR.


Food deprivation dissociates pancreatic glucagon's effects on satiety and hepatic glucose production at dark onset.
We compared the effects of different durations of pretest food deprivation on pancreatic glucagon's (PG) satiating and glycogenolytic actions in order to test the hypothesis that stimulation of hepatic glucose production causes PG's satiety effect. Rats were maintained on a 12:12 LD cycle (lights off: 1015) and deprived of food 45 min or 8, 12, 18, or 24 hr before intraperitoneal injection of 400 micrograms/kg PG. Testing began at 1015, the beginning of the dark phase. Food intake was not inhibited after 45 min of pretest food deprivation (30 min change, 2.5 +/- 4.0%, p greater than 0.05), but was inhibited after 8 or more hr food deprivation. The largest inhibitory effect, 16.2 +/- 3.8%, p less than 0.01, occurred after 8 hr food deprivation. In separate experiments, rats were food deprived 45 min or 8 hr, similarly injected, and killed 10 min after refeeding for blood and liver samples. Hepatic glycogen content at meal onset was higher in rats deprived 45 min than in rats deprived 8 hr (3.2 +/- 0.3 vs. 1.7 +/- 0.3% liver weight, p less than 0.01), and PG injection produced a higher level of hepatic vein blood glucose in the less deprived rats (196 +/- 5 vs. 168 +/- 12 mg/dl, p less than 0.05). Thus, in rats tested at the beginning of the dark phase of the LD cycle after 45 min or 8 hr food deprivation, there is an inverse relation between PG's potencies to inhibit food intake and to stimulate hepatic glucose production.(ABSTRACT TRUNCATED AT 250 WORDS)


The Simpson grading: defining the optimal threshold for gross total resection in meningioma surgery.
Classification of the extent of resection into gross and subtotal resection (GTR and STR) after meningioma surgery is derived from the Simpson grading. Although utilized to indicate adjuvant treatment or study inclusion, conflicting definitions of STR in terms of designation of Simpson grade III resections exist. Correlations of Simpson grading and dichotomized scales (Simpson grades I-II vs ≥ III and grade I-III vs ≥ IV) with postoperative recurrence/progression were compared using Cox regression models. Predictive values were further compared by time-dependent receiver operating curve (tdROC) analyses. In 939 patients (28% males, 72% females) harboring WHO grade I (88%) and II/III (12%) meningiomas, Simpson grade I, II, III, IV, and V resections were achieved in 29%, 48%, 11%, 11%, and < .5%, respectively. Recurrence/progression was observed in 112 individuals (12%) and correlated with Simpson grading (p = .003). The risk of recurrence/progression was increased after STR in both dichotomized scales but higher when subsuming Simpson grade ≥ IV than grade ≥ III resections (HR: 2.49, 95%CI 1.50-4.12; p < .001 vs HR: 1.67, 95%CI 1.12-2.50; p = .012). tdROC analyses showed moderate predictive values for the Simpson grading and significantly (p < .05) lower values for both dichotomized scales. AUC values differed less between the Simpson grading and the dichotomization into grade I-III vs ≥ IV than grade I-II vs ≥ III resections. Dichotomization of the extent of resection is associated with a loss of the prognostic value. The value for the prediction of progression/recurrence is higher when dichotomizing into Simpson grade I-III vs ≥ IV than into grade I-II vs ≥ III resections.


Free flap surgery: the Welsh Regional Unit experience.
The evolution and uses of free tissue transfer since 1976 are documented. Two hundred free flaps have been performed with an overall success rate of 91%. The factors which may influence survival are the type of flap used, the recipient region and the timing of surgery following trauma. Twenty-five percent of cases required re-exploration postoperatively, of which 78% were successfully salvaged. Venous thrombosis was the commonest problem and appears better tolerated than arterial occlusion. Eighty-two percent of venous thromboses were salvaged compared with only 50% of arterial failures.


Emulsion macromonomer cross-linking. A preparative method for oxidation-responsive nanoparticles with a controlled network structure.
We here report on a preparative, template-based method for oxidation-responsive, poly(propylene sulfide) cross-linked nanoparticles. In this study we demonstrate that preformed, narrow polydispersity, and end-functional polysulfides can be dispersed to yield stable emulsions, which can then be converted into stable nanoparticles through photochemically initiated cross-linking. The nanoparticle size is substantially templated on that of the precursor emulsions; the nanoparticles bulk is an elastomeric material with a homogeneous cross-linking density. The nanoparticles show a peculiar, two-stage behavior upon exposure to oxidants, which is likely composed of a first agglomeration phase followed by swelling.


[Clinical presentation and prognosis of brain stem infarcts. An evaluation of the Stroke Databank of the German Stroke Foundation].
Due to the great variety of clinical classification systems and syndromes, a representative overview of the etiology and prognosis of brain stem infarctions is missing. From the German Stroke Data Bank we therefore investigated 455 patients with visible brainstem infarction on cerebral imaging in comparison to patients with other infarct localizations. Follow-up after 3 and 12 months assessed functional outcome and recurrence of cerebral ischemia. Of 455 patients with acute brainstem infarction, 115 had additional infarctions in other vascular territories. In the remaining 340 patients with isolated brainstem infarction, the classification was: small vessel disease in 36.2%, macroangiopathy in 22.6%, and cardioembolism in 11.2%. After 3 months, 10% of the patients with isolated brainstem infarction had died and 55.6% were functionally independent. Mortality was 43.5% in patients with combined brainstem infarction. Our study highlights the frequency of small vessel disease as well as the relatively favorable prognosis in isolated brainstem infarction and preserved consciousness.


[Effect of stimulation of the nucleus raphe dorsalis on cortical hypersynchronous activity in the rat].
Stimulation of the nucleus raphe dorsalis (B7) with low frequency electrical current in freely moving albino rats provoked an increase of hypersynchronous activity in the epileptogenic focus. The time course of this effect points to an action of the liberated 5-hydroxytryptamine.


Usefulness of reminiscence therapy for community mental health.
Reminiscence therapy workshops for health-care professionals (total, n = 105: four trainees in their 20, seven in their 30s, 13 in their 40s, 30 in their 50s, 41 in their 60, five in their 70s, one in their 80s, and four of unknown age) were held, and group work with reminiscence therapy was provided to local residents (total, n = 151; mean age, 73.6 ± 10.6 years). Comparison of pre- and post-workshop questionnaires showed that rates of interest and understanding of trainees increased after the workshop. Concerning group work, 89.2% of the participants felt that reminiscence therapy would prove helpful in their life. Reminiscence therapy may be useful in improving mental health in local residents.


Alterations in intercellular junctions of the uterine epithelium during the preimplantation phase in the rabbit.
In the rabbit, the pseudopregnant uterus has been used as a model for studying alterations characteristic of the preimplantation phase. Alterations in intercellular junctions of the uterine epithelium were investigated during early pseudopregnancy (day 0 to day 6) by means of the freeze-fracture technique. In the uterine epithelium of oestrous females the zonula occludens belongs to the "tight" type of tight junctions. During pseudopregnancy an impressive proliferation of tight junctional belts can be observed. The basal strands proliferate, forming loops perpendicular to the luminal surface, whereas the more or less parallel arrangement of the luminal strands is maintained. At day 4 of pseudopregnancy macular tight junctions begin to develop on the lower portions of the lateral plasmalemma and are extensive by day 6 post hCG. Small gap junctions are infrequent between cells of the uterine epithelium and show no significant changes during the preimplantation phase. The physiological significance of the present morphological observations is discussed in the light of changes occurring during the preimplantation period.


Neonates at risk. Screening for deafness--practical or not?
Over a six-year period, 3,507 neonates in King George V Memorial Hospital, classified as being at risk for deafness, were screened for hearing. Although 144 failed to respond in the nurseries, 88 of them were cleared at a later test. The remainder, whether suspect, untraceable or still to return, would all be outside the neonatal period by now. No sensorineural impairment of hearing was detected in all neonates in the programme.


Foreword.
There is a significant body of evidence describing the benefits of using systemic anti-cancer therapy (SACT) agents, such as chemotherapy, biological, hormone and antibiotics, to treat people diagnosed with cancer (Cancer Research UK, 2017). However, the potential improvements in survival outcomes must be regularly weighed against the risk of adverse health effects associated with exposure to them. For patients, the risks are balanced against the need to treat the cancer. For health professionals, the risks simply result from the occupational exposure that can occur when caring for patients receiving these drugs. Collectively referred to as cytotoxic agents, SACTs are known to be toxic; they are considered carcinogenic to humans, and are classified as hazardous (National Institute for Occupational Safety and Health (NIOSH), 2010).


Reframing physically active learning as movement-centred pedagogy: a European priority action framework.
Physically active learning (PAL) has emerged as a promising way of eliciting health and education-based outcomes for pupils. Concurrently, research suggests large variability in how PAL is perceived, operationalized, and prioritized in practice across Europe. Therefore, this study aimed to co-develop a framework for action to support the adoption and implementation of PAL. Adopting a design thinking approach, 40 international stakeholders representing 13 countries engaged in an idea generation workshop during a two-day PAL international conference. Participants included professionals from research (n = 20), practice (n = 4) and policy (n = 1) or a combination (n = 15). Their experience with PAL ranged from none to 19 years (with an average of 3.9 years). Participants were allocated into one of six heterogeneous and multidisciplinary groups and led through interactive tasks to identify: the landscape for PAL across Europe, barriers to the adoption and implementation of PAL, and key objectives for research, policy and practice to improve the adoption and implementation of PAL. All discussions were audio recorded and prioritized objectives were transcribed verbatim and analysed using inductive qualitative content analysis. Five interlinked and mutually reinforcing themes were identified: (1) Integration of the health and education paradigms (2) Coherent national policy and decision making (3) Building confident and competent teachers (4) Adopting a whole school approach for PAL (5) Strengthening the evidence base for PAL. The priority action framework identifies five key areas for action to facilitate PAL adoption and implementation across Europe. Central to the success of border uptake of PAL is the integration of the health and education paradigms. To achieve this aim, reframing PAL as movement-centered pedagogy would provide a more holistic and inclusive perspective.


First report of the nematicidal activity of Flammulina velutipes, its spent mushroom compost and metabolites.
The aim of the present work was to evaluate the nematicidal potential of Flammulina velutipes and its spent mushroom compost. Additionally, the nematicidal activity of enzymes and metabolites was analyzed. Isolated F. velutipes and its SMC had significant nematicidal effect on Panagrellus sp. larvae. The percentages of reduction in relation to the control group were: 69, 57.5 and 70% for SMC and 56, 24.5 and 26.6% for the isolated fungus, for 24, 48 and 72 h, respectively. The active SMC crude extract showed nematicidal action with reduction percentages of 43 and 57% for 24 and 48 h of incubation, respectively. The boiled crude extract also showed nematicidal action, however, the reduction percentages were lower than those of the active extract. This demonstrated that the nematicidal action was due to enzyme activities and other metabolites. The results demonstrated that SMC, the isolated fungus, the crude extract and the boiled crude extract showed a significant percentage of reduction on Panagrellus sp. larvae. SMC evidenced a higher nematicidal activity than the isolated fungus. In addition, nematophagous activity of F. velutipes was observed for the first time.


Proposal of a new scoring system for equalization problems during freediving.
Scuba diving and freediving are popular activities around the world, and their growth has increased the frequency of related pathology. A good ability to equalize is of paramount importance for diving. This is especially true for freediving, during which dive time is limited to just one breath. Even though equalization disorders are quite common in divers, a scoring system does not exist to date. In this paper we propose a new scoring system for equalization problems of freedivers: the EP score, shorthand for "equalization problems." We administered the EP score assessment to 40 Italian freediving spearfishermen who were divided in two groups: Group A comprised 20 freedivers complaining of equalization problems and multiple barotraumas but totally asymptomatic in their everyday lives. These individuals had already received medical treatment and nasal surgery without improvement and then had undergone Eustachian tube balloon dilation. Group B comprised 20 healthy freedivers without any history of equalization disorders. We performed a statistical analysis to evaluate the reliability of this scoring system and to evaluate its usefulness in diagnosis and follow-up. Our data show substantial statistical differences between healthy freedivers and freedivers complaining of equalization disorders (Z-Score = -5.396 at p ⟨ 0.05); data do not show any statistical difference between healthy freedivers and patients successfully treated by Eustachian tube balloon dilation (U-value = 152.5 and Z-Score= -1.271 at p ⟨ 0.05). The EP score assessment seems to be a reliable tool to quantify equalization disorders during freediving and to evaluate how the difficulty varies over time and after treatment. Since equalization disorders could be present in different populations, the EP score assessment could be applicable to a wider group.


Clinical and echocardiographic assessment of pregnant women with valvular heart diseases--maternal and fetal outcome.
The study aimed to compare the outcome of pregnancy in women with valvular heart diseases. Two hundred and fifty-nine pregnant women with cardiac diseases, aged 18-42, were observed. Group I-158 patients with mitral valve disease: 30 patients with mitral stenosis; 44 patients with mitral regurgitation, 33 patients with combined mitral valve disease, 51 patients with mitral valve prolapse; Group II-54 patients with aortic valve disease: 32 patients with aortic stenosis, 22 with aortic regurgitation; Group III-47 patients after valve replacement (36 mechanical; 11 homograft valves). Medical history and physical examination, NYHA class assessment, ECG, and echocardiography were performed during consecutive trimesters of pregnancy and after delivery. Clinical deterioration was observed in 38 patients-in 25 women of Group I, 6 women of Group II, and 7 women of Group III. Newborns outcome : 250 healthy (10 prematures, 12 with intrauterine growth retardation), 6 aborted, 2 stillbirths, 1 neonatal death. Method of delivery : 200 vaginally, 53 cesarean sections. (1). Pregnants with critical mitral valve stenosis form a high-risk group of life-threatening complications. (2) In women with severe aortic stenosis, pregnancy could lead to sudden clinical status deterioration. (3) Cardiac complications can be expected in patients with left ventricular enlargement and its depressed function. (4) Key factors influencing successful course of pregnancy and labour in patients with prosthetic valves: adequate left ventricular function, properly functioning valves, and effective anticoagulation.


Chaperone activities of bovine and camel beta-caseins: Importance of their surface hydrophobicity in protection against alcohol dehydrogenase aggregation.
Beta-casein (beta-CN) showing properties of intrinsically unstructured proteins (IUP) displays many similarities with molecular chaperones and shows anti-aggregation activity in vitro. Chaperone activities of bovine and camel beta-CN were studied using alcohol dehydrogenase (ADH) as a substrate. To obtain an adequate relevant information about the chaperone capacities of studied caseins, three different physical parameters including chaperone constant (k(c), microM(-1)), thermal aggregation constant (k(T), degrees C(-1)) and aggregation rate constant (k(t), min(-1)) were measured. Bovine beta-CN displays greater chaperone activity than camel beta-CN. Fluorescence studies of 8-anilino-1-naphthalenesulfonic acid (ANS) binding demonstrated that bovine beta-CN is doted with larger effective hydrophobic surfaces at all studied temperatures than camel beta-CN. Greater relative hydrophobicity of bovine beta-CN than camel beta-CN may be a factor responsible for stronger interactions of bovine beta-CN with the aggregation-prone pre denatured molecular species of the substrate ADH, which resulted in greater chaperone activity of bovine beta-CN.


An amino acid substitution in a capsid protein enhances phage survival in mouse circulatory system more than a 1000-fold.
In experiments with germ free mice, free from adaptive antibodies to the bacterial virus lambda phage, titers of the virus in the circulatory system have been reported to decrease by more than 10(9)pfu within 48 h of intraperitoneal intravenous or oral administration. Based on these observations, serial passage techniques have been used to select lambda phage mutants, with 13,000-16,000-fold greater capacity to remain in the mouse circulatory system 24h after intraperitoneal injection. In these prior studies the "long-circulating" phage, designated lambdaArgo phage, had at least three mutations including one in the major phage capsid (E) protein, which resulted in the change of glutamic acid to a lysine at residue 158. In the current study, we demonstrate that this single specific substitution in the E protein is sufficient to confer the "long-circulating" phenotype. The isogenic pair of phage developed in this study consisting of the long-circulating marker-rescued lambdaArgo phage, and the parental wild type phage can be used for studies of viral recognition mechanisms of the innate immune system and for the development of more effective antibacterial therapeutic phage strains.


Laser surgery and fire hazards in ear, nose, and throat surgeries.
Operating room fires are rare but can be devastating. These fires can occur during almost any surgical procedure but are more likely during airway surgery, during head and neck surgery, and if volatile flammable liquids are used. Each team in the operating room (ie, anesthesia, surgery, and nursing) has special expertise and responsibility in preventing and responding to a fire. Fires can be prevented by ongoing education and an interdisciplinary discussion of risks and responsibilities prior to each high-risk case.


Axillary adenopathy detected on breast MRI following COVID-19 vaccination: outcomes and follow-up recommendations.
This retrospective study presents 110 patients with suspected COVID-19 vaccine-related axillary adenopathy on breast MRI. Our study aimed to assess the outcomes of axillary adenopathy detected on breast MRI performed within one year after COVID-19 vaccination. The median time between the COVID-19 vaccine and breast MRI was shorter in patients with detected adenopathy compared to patients without detected adenopathy (6 weeks [2-17] versus 15 [7-24] weeks, p < 0.001). Unilateral axillary adenopathy detected on breast MRI had a low malignancy rate (3.3%), and no cases of malignant axillary adenopathy were diagnosed without a known breast cancer in the ipsilateral breast. Our findings suggest that unilateral axillary adenopathy identified on breast MRI ipsilateral to a recent COVID-19 vaccination can be considered benign in the absence of a suspicious breast finding or known breast cancer. Regardless of vaccine status and timing, unilateral axillary adenopathy detected on MRI evaluation with a known malignancy or suspicious breast finding should be considered suspicious. This will avoid unnecessary scheduling constraints, patient anxiety, and cost, without delaying diagnosis of metastatic breast cancer.


Experience with implementation of a nurse practitioner-led newborn circumcision clinic.
The Nurse Practitioner (NP)-Led Newborn Circumcision Clinic (NCC), developed in 2016, provides clamp-style circumcision to newborns without general anesthesia. There is a paucity of research regarding outcomes, satisfaction, and the cost benefit of such NP-led clinics. The purpose of this descriptive study was to describe the impact of the NCC including family satisfaction, clinical and demographic characteristics, and cost. This study utilized a mixed-method approach to describe the impact of the NP-led NCC using survey methodology to describe family satisfaction, a single center retrospective chart review to describe clinical and demographic characteristics and outcomes, and investigation of charges in NCC versus operating room (OR) circumcisions. Descriptive statistics were used to present survey results and chart review data. Results of the patient satisfaction survey revealed 89.8% of patients rated the overall quality of care as excellent or very good. Of the 234 patients reviewed, the median age and weight of patients was 4.30 weeks and 4.39 kg, respectively. Of the patients with comorbidities (30.3%), the most common were related to prematurity (12.8%). The most common reason for referral was concern for anatomical abnormality of the penis (53.8%). The median length of procedure was 20 minutes. No patients in our cohort experienced penile amputations, infections, strictures, intraoperative bleeding, or wounds. Ten patients (4.3%) had bleeding events during the recovery period which were treated with a topical medication (StatSeal). Two patients (0.9%) had bleeding after discharge requiring Emergency Department evaluation and application of a pressure dressing. Two patients (0.9%) required circumcision revision. Investigation of charges revealed a savings of 92.9% for circumcisions in the NCC versus OR. This study reveals that the NP-led NCC has high family satisfaction, few adverse outcomes, and cost benefits as compared to OR circumcision. There are a limited number of publications presenting outcome data for circumcisions and even fewer for NP- led circumcision clinics. Furthermore, a lack of standardized definitions for adverse events makes comparison difficult. Critical to the success of the NP-led NCC is appropriately selecting patients, a NP training program, and intra-professional collaboration. This ambulatory clinic offers another option for select infants who were not immediately circumcised in the newborn period. By expanding opportunities for NPs to practice to the full extent of their education and expertise, our institution continues to develop opportunities to improve access to care, control costs, and increase patient and family satisfaction.


Refinements in embryo manipulation applied to CRISPR technology in livestock.
The implementation of CRISPR technology in large animals requires further improvements in embryo manipulation and transfer to be applied with commercial purposes. In this study we report (a) developmental competence of CRISPR/Cas microinjected zygotes subjected to in vitro culture in large scale programs in sheep; (b) pregnancy outcomes after early-stage (2-8-cell) embryo transfer into the oviduct or the uterine horn; and (c) embryo survival and birth rate after vitrification/warming of CRISPR/Cas microinjected zygotes. Experiment 1 consisted of a retrospective analysis to evaluate embryo developmental rate of in vitro produced zygotes subjected to CRISPR/Cas microinjection (n = 7,819) compared with a subset of non-microinjected zygotes (n = 701). Development rates to blastocyst on Day 6 were 20.0% for microinjected zygotes and 44.9% for non-injected zygotes (P < 0.05). In Experiment 2, CRISPR/Cas microinjected zygotes were transferred on Day 2 after in vitro fertilization (2-8 cell embryos) into the oviductal ampulla (n = 262) or into the uterine horn (n = 276) in synchronized recipient ewes at prefixed time (i.e., approximately two days after ovulation). Pregnant/transferred recipients (24.0% vs. 25.0%), embryo survival/transferred embryos (6.9% vs. 6.2%), and born lambs/pregnant embryos (72.2% vs. 100.0%) did not differ significantly in the two groups. In Experiment 3, CRISPR/Cas microinjected zygotes were maintained under in vitro culture until blastocyst stage (Day 6), and subjected to vitrification/warming via the Cryotop method (n = 474), while a subset of embryos were left fresh as control group (n = 75). Embryos were transferred into the uterine horn of recipient females at prefixed time 8.5 days after the estrous synchronization treatment (i.e., approximately six days after ovulation). Pregnancy rate (30.8% vs. 48.0%), embryo survival rate (14.8% vs. 21.3%), and birth rate (85.7% vs. 75.0%) were not different (PNS) between vitrified and fresh embryos, respectively. In conclusion, the current study in sheep embryos reports (a) suitable developmental rate after CRISPR/Cas microinjection (i.e., 20%), even though it was lower than non-microinjected zygotes; (b) similar outcomes when Day 2-embryos were placed into the uterine horn instead of the oviduct, avoiding both time-consuming and invasive oviduct manipulation, and extended in vitro culture during one week; (c) promising pregnancy and birth rates obtained with vitrification of CRISPR/Cas microinjected embryos. This knowledge on in vitro embryo development, timing of embryo transfer, and cryopreservation of CRISPR/Cas microinjected zygotes have practical implications for the implementation of genome editing technology in large animals.


Atypical promyelocytic leukemia (M3) with immature primary granules and t(15;17).
An unusual case of acute myeloid leukemia with a standard t(15;17) is described. While light microscopy morphology was suggestive of acute myeloid leukemia M5a and light microscopy cytochemistry showed 80% of blasts to be strongly positive with Sudan Black B--more consistent with a diagnosis of M4--ultrastructural analysis demonstrated that the predominant cells were promyelocytes with immature primary granules hardly visible with the Romanovsky stains by light microscopy. Because typical cytologic and clinical features of M3 or M3 variant were lacking this atypical case would not have been recognized but for the presence of t(15;17) and the demonstration of promyelocytic features by electron microscopy.


Explore the reaction mechanism of the Maillard reaction: a density functional theory study.
The mechanism of Maillard reaction has been investigated by means of density functional theory calculations in the gaseous phase and aqueous solution. The Maillard reaction is a cascade of consecutive and parallel reaction. In the present model system study, glucose and glycine were taken as the initial reactants. On the basis of previous experimental results, the mechanisms of Maillard reaction have been proposed, and the possibility for the formation of different compounds have been evaluated through calculating the relative energy changes for different steps of reaction under different pH conditions. Our calculations reveal that the TS3 in Amadori rearrangement reaction is the rate-determining step of Maillard reaction with the activation barriers of about 66.7 and 68.8 kcal mol(-1) in the gaseous phase and aqueous solution, respectively. The calculation results are in good agreement with previous studies and could provide insights into the reaction mechanism of Maillard reaction, since experimental evaluation of the role of intermediates in the Maillard reaction is quite complicated.


Management of cricopharyngeal achalasia in an 8-month child using endoscopic cricopharyngeal myotomy.
A term baby was transferred to our tertiary care center with desaturations and inability to manage upper airway secretions. Rigid bronchoscopy and swallowing study revealed cricopharyngeal (CP) achalasia. A gastrostomy tube insertion and Botulinum Toxin-A injection were performed at 6 weeks of age. Improvement of symptoms was observed, however were short-lived requiring recurrent injections. Given the symptom severity, at 8 months, a successful endoscopic CP myotomy was performed. Patient was able to tolerate oral feeds as early as 2 months post-operatively. This is the youngest patient, to our knowledge, treated with endoscopic CP myotomy. Intraoperative pictures and video are presented.


Circadian clocks and mood-related behaviors.
Circadian clocks are present in nearly all tissues of an organism, including the brain. The brain is not only the site of the master coordinator of circadian rhythms located in the suprachiasmatic nuclei (SCN) but also contains SCN-independent oscillators that regulate various functions such as feeding and mood-related behavior. Understanding how clocks receive and integrate environmental information and in turn control physiology under normal conditions is of importance because chronic disturbance of circadian rhythmicity can lead to serious health problems. Genetic modifications leading to disruption of normal circadian gene functions have been linked to a variety of psychiatric conditions including depression, seasonal affective disorder, eating disorders, alcohol dependence, and addiction. It appears that clock genes play an important role in limbic regions of the brain and influence the development of drug addiction. Furthermore, analyses of clock gene polymorphisms in diseases of the central nervous system (CNS) suggest a direct or indirect influence of circadian clock genes on brain function. In this chapter, I will present evidence for a circadian basis of mood disorders and then discuss the involvement of clock genes in such disorders. The relationship between metabolism and mood disorders is highlighted followed by a discussion of how mood disorders may be treated by changing the circadian cycle.


Ozonation performance of WWTP secondary effluent of antibiotic manufacturing wastewater.
The ozonation performance of wastewater treatment plant secondary effluent of oxytetracycline (OTC) manufacturing wastewater was investigated in terms of ozone dosage and initial pH levels when OTC contributed to a negligible fraction in the chemical oxygen demand (COD) ingredients of the medium-organic-strength wastewater with low biodegradability. A particular emphasis was placed on ammonia, OTC, and residual antibacterial activity (RAA) (evaluated using the objective pathogenic bacterium Staphylococcus aureus). It appears that an ozone dosage of 657 mg L⁻¹ (120 min of reaction) was enough to achieve an OTC abatement of 96%, and COD and biochemical oxygen demand removals of 29% and 33%, respectively, at initial levels of 10.4, 1360, and 300 mg L⁻¹ , respectively. There is a clear correlation between complete OTC depletion and complete RAA disappearance with an increase of ozone dosage. The presence of plentiful non-antibiotic refractory substances influenced the determination of the optimum ozone dosage for biodegradability enhancement and OTC/RAA reduction as well as the ozonation transformation of NH(3). The initial pH adjustment from the original level (pH 9) to pH 11 significantly reduced COD removal while RAA and NH(3) levels were not significantly influenced.


A comparison of osteotomy and joint replacement in the surgical treatment of the arthritic knee.
The relatively small numbers of knees compared in this study make it impossible to draw conclusions with great confidence. On the other hand we believe that the quality of our comparison has been improved by our effort to match the groups of knees under study. Our results lead to the controversial conclusion that, at least in RA and in elderly patients with OA, ICLH arthroplasty is preferable to osteotomy regardless of the pathology and preoperative deformity and that osteotomy should not be used as a temporizing procedure before ICLH arthroplasty. We are unable to say whether or not similar conclusions would apply to other forms of arthroplasty but we suspect that they would. Certainly joint replacement is now widely preferred to osteotomy at the hip and it is difficult to see why the knee should be different. It should not be concluded from these results that replacemnt is to be preferred to osteotomy for the mildly damaged knee. It does however appear that if osteotomy fails (for technical or other reasons), it may then be difficult to obtain a satisfactory result even by replacement. Thus if a patient with a mildly damaged knee is not to be disabled irreparably, it may be better to avoid osteotomy until the day comes when the causes of failure after this operation can be predicted preoperatively and prevented. The data presented here suggest (as do those in many other studies) that one step in this direction is to confine osteotomy to the varus OA knee. Even in this group the surgeon should, we believe, do his utmost to avoid surgery altogether until the parents' disability is unacceptable. In summary therefore, we now advance the view that if the arthritic knee is sufficiently disabling to require major surgery, it should be replaced. If the disability is less severe, the joint should be treated conservatively.


PHLDA1, another PHLDA family protein that inhibits Akt.
The PHLDA family (pleckstrin homology-like domain family) of genes consists of 3 members: PHLDA1, 2, and 3. Both PHLDA3 and PHLDA2 are phosphatidylinositol (PIP) binding proteins and function as repressors of Akt. They have tumor suppressive functions, mainly through Akt inhibition. Several reports suggest that PHLDA1 also has a tumor suppressive function; however, the precise molecular functions of PHLDA1 remain to be elucidated. Through a comprehensive screen for p53 target genes, we identified PHLDA1 as a novel p53 target, and we show that PHLDA1 has the ability to repress Akt in a manner similar to that of PHLDA3 and PHLDA2. PHLDA1 has a so-called split PH domain in which the PH domain is divided into an N-terminal (β sheets 1-3) and a C-terminal (β sheets 4-7 and an α-helix) portions. We show that the PH domain of PHLDA1 is responsible for its localization to the plasma membrane and binding to phosphatidylinositol. We also show that the function of the PH domain is essential for Akt repression. In addition, PHLDA1 expression analysis suggests that PHLDA1 has a tumor suppressive function in breast and ovarian cancers.


Optimization of mesenchymal stem cell expansion procedures by cell separation and culture conditions modification.
Optimization of the mesenchymal stem cells (MSC) isolation and expansion method. Mononuclear cells (MNC) from bone marrow aspirates were obtained by both density gradient centrifugation (standard method) and gravity sedimentation. Cells were cultured in standard conditions (10% fetal calf serum and normal oxygen tension [21% O(2)]) and expansion results compared to those obtained with the same culture conditions to which platelet lysate (PL) preparations were added; in addition, the 21% O(2) concentration was compared to a lower (5%) concentration (hypoxia) until the fourth cell passage. Time of expansion, number of cells obtained, morphology, cell surface markers, and differentiation potential were evaluated. MSC obtained by any of the different culture conditions expressed comparable immunophenotype and were able to differentiate into osteoblasts, adipocytes, and chondrocytes. When the number of MSC obtained at fourth passage was analyzed, the highest cell numbers were obtained with gravity sedimentation isolation and PL-supplemented culture and the expansion time was the shortest when cells were cultured under hypoxic conditions. MSC isolation by MNC gravity sedimentation together with culture medium supplementation with 5% of PL in a hypoxic atmosphere (5% O(2)) significantly improved MSC yield and reduced expansion time compared to the standard accepted protocols.


Genetic organization of the regions associated with surface polysaccharide synthesis in Vibrio cholerae O1, O139 and Vibrio anguillarum O1 and O2: a review.
Vibrio cholerae and V. anguillarum are recognized as aquatic-borne human and fish pathogens, respectively. Based upon analyses of several genes and the presence of novel genetic elements it seems that these two species are very closely related. Studies in this laboratory have identified an association of IS1358 with rfb and capsule loci in these two species. The most recent findings suggest that IS1358 is associated with the rfb region in V. cholerae O1 and O139 and in V. anguillarum O1 and O2. In addition, the rfb region in both V. cholerae serogroups and in V. anguillarum O1 is limited at one end by gmhD. These features make it feasible to envisage a mechanism by which the evolution of new rfb genes is taking place involving IS1358 and the region around gmhD. Furthermore, it is possible to envisage that there is or has been an exchange of genetic material between these species leading to new rfb/capsule regions. This review examines the genetics and biosynthesis of the O-antigen and capsule of V. cholerae O1 and O139, as well as the V. anguillarum serogroup O1 and the role of IS1358. Throughout this review we have used the new nomenclature for rfb genes proposed by.


A recombinant IL-4-Pseudomonas exotoxin inhibits protein synthesis and overcomes apoptosis resistance in human CLL B cells.
We have determined that CLL B cells consistently express type 3 membrane receptors for the Th2-derived cytokine IL-4 (IL-4R). Furthermore, when added to CLL B cells, IL-4 induces increased apoptosis resistance, increased protein synthesis in CLL B cells and rapid onset activation of STAT1, STAT5 and STAT6. Since the IL-4-IL-4R pathway is intact in CLL B cells and is related to apoptosis resistance, we considered whether we could target this pathway. A recombinant IL-4 Pseudomonas exotoxin fusion protein (IL-4 PE), known to bind to IL-4R, was incubated with CLL B cells. IL-4 PE (10 ng/ml) cultured with CLL B cells resulted in an increase of apoptosis/death from mean levels of 46.6+/-7.0 of non-exposed cells to 69+/-8.6 (n=6). By measuring in vitro protein synthesis, two predominant patterns of sensitivity were observed. In one, CLL B cell clones (n=4) were found to be extremely sensitive to IL-4 PE (IC50's range=6-25 ng/ml). In the second, low concentrations of IL-4 PE induced agonist activity while increasing concentrations induced cytotoxicity in 6 of 21 patient-derived cells. These studies suggest that the IL-4R, on B-CLL cells, can serve as a unique molecular target for directing cytotoxic agents in the therapy of B-CLL.


A convenient procedure for the catalytic asymmetric 1,3-dipolar cycloaddition of azomethine ylides and alkenes.
[reaction: see text] Silver fluoride and cinchona alkaloids catalyze the diastereo- and enantioselective 1,3-dipolar cycloaddition between azomethine ylides, generated from N-alkylideneglycine esters, and acrylates to give the corresponding endo-adducts. Azomethine ylides derived from aromatic and aliphatic aldehydes react in a highly diastereoselective reaction with good yields and enantioselectivities of the substituted pyrrolidines.


An alternative covariance estimator to investigate genetic heterogeneity in populations.
For genomic prediction and genome-wide association studies (GWAS) using mixed models, covariance between individuals is estimated using molecular markers. Based on the properties of mixed models, using available molecular data for prediction is optimal if this covariance is known. Under this assumption, adding individuals to the analysis should never be detrimental. However, some empirical studies showed that increasing training population size decreased prediction accuracy. Recently, results from theoretical models indicated that even if marker density is high and the genetic architecture of traits is controlled by many loci with small additive effects, the covariance between individuals, which depends on relationships at causal loci, is not always well estimated by the whole-genome kinship. We propose an alternative covariance estimator named K-kernel, to account for potential genetic heterogeneity between populations that is characterized by a lack of genetic correlation, and to limit the information flow between a priori unknown populations in a trait-specific manner. This is similar to a multi-trait model and parameters are estimated by REML and, in extreme cases, it can allow for an independent genetic architecture between populations. As such, K-kernel is useful to study the problem of the design of training populations. K-kernel was compared to other covariance estimators or kernels to examine its fit to the data, cross-validated accuracy and suitability for GWAS on several datasets. It provides a significantly better fit to the data than the genomic best linear unbiased prediction model and, in some cases it performs better than other kernels such as the Gaussian kernel, as shown by an empirical null distribution. In GWAS simulations, alternative kernels control type I errors as well as or better than the classical whole-genome kinship and increase statistical power. No or small gains were observed in cross-validated prediction accuracy. This alternative covariance estimator can be used to gain insight into trait-specific genetic heterogeneity by identifying relevant sub-populations that lack genetic correlation between them. Genetic correlation can be 0 between identified sub-populations by performing automatic selection of relevant sets of individuals to be included in the training population. It may also increase statistical power in GWAS.


Coral reefs benefit from reduced land-sea impacts under ocean warming.
Coral reef ecosystems are being fundamentally restructured by local human impacts and climate-driven marine heatwaves that trigger mass coral bleaching and mortality1. Reducing local impacts can increase reef resistance to and recovery from bleaching2. However, resource managers lack clear advice on targeted actions that best support coral reefs under climate change3 and sector-based governance means most land- and sea-based management efforts remain siloed4. Here we combine surveys of reef change with a unique 20-year time series of land-sea human impacts that encompassed an unprecedented marine heatwave in Hawai'i. Reefs with increased herbivorous fish populations and reduced land-based impacts, such as wastewater pollution and urban runoff, had positive coral cover trajectories predisturbance. These reefs also experienced a modest reduction in coral mortality following severe heat stress compared to reefs with reduced fish populations and enhanced land-based impacts. Scenario modelling indicated that simultaneously reducing land-sea human impacts results in a three- to sixfold greater probability of a reef having high reef-builder cover four years postdisturbance than if either occurred in isolation. International efforts to protect 30% of Earth's land and ocean ecosystems by 2030 are underway5. Our results reveal that integrated land-sea management could help achieve coastal ocean conservation goals and provide coral reefs with the best opportunity to persist in our changing climate.


A concept analysis of routines for improving health behaviors.
Chronic disease patients often have unhealthy routines, especially when away from health care professionals. These patients need clear guidance about establishing and maintaining routines. This study aimed to synthesize a definition of the concept of routines for improving health behaviors based on its uses in the literature. We searched CINAHL, Medline, Scopus, and Google Scholar from January to May, 2022 for articles that included definitions of routines in the context of improving health behavior. We applied no date restriction. The systematic analytic method and Rodgers' evolutionary concept analysis method were used. We charted the attributes, antecedents, and consequences of routines for improving health behaviors, analyzed their uses in the literature, and synthesized the results in a definition of the concept. At total of 24 articles were included. Attributes of the concept were repeated patterns, controllable by the patient, goal-oriented health, and integration into an overarching lifestyle. Antecedents were individual characteristics and environmental factors. Consequences were psychological, physical, and social well-being at individual and environmental levels. This clarified definition of routines for improving health behaviors will provide a starting point for future research and, eventually, a basis for clinical nursing interventions to support patients in developing and maintaining healthy routines to promote better patient outcomes.


PNPLA3 Gene Polymorphisms in HCV/HIV-Coinfected Individuals.
The patatin-like phospholipase domain-containing 3 (PNPLA3) gene has been associated with the development of alcoholic and nonalcoholic steatohepatitis. Using a newly developed and validated assay for PNPLA3, we explored the prevalence of gene polymorphisms in a cohort of HCV/HIV-coinfected individuals to determine whether there was an association with insulin resistance or hepatic fibrosis. A high-resolution melting point (HRM) assay was developed and validated. The assay was used to evaluate samples obtained in the context of a clinical trial performed at ACTG sites across the USA in HIV-infected patients. Clinical features and treatment outcomes were assessed in relation to the PNPLA3 genotype. The HRM methodology demonstrated 100% concordance with results obtained by Sanger sequencing. Among 241 participants tested, 66.0% had the wild-type allele (CC) and the remainder had the aberrant PNPLA3 gene polymorphism in the homozygotic (GG) or heterozygotic (CG) form. Race and ethnicity were associated with PNPLA3 genotype but fibrosis stage, Homeostatic Model Assessment of Insulin Resistance, and HCV treatment outcome were not. The HRM method is an effective, rapid technique for characterizing PNPLA3 genotype. In those with HCV/HIV infection, nearly 40% carry gene polymorphisms associated with the development of NASH or ASH. Prospective studies should focus on this group to determine whether they represent a subset of HIV-infected persons at increased risk of fibrotic progression.


Mechanical and antibacterial efficacy of photo-sonodynamic therapy via methylene blue-loaded nanoparticles over dental implants for treating peri-implantitis.
This study aimed to evaluate the mechanical (i.e., flexural modulus [FM], flexural strength [FS], and surface roughness [Ra]) and antibacterial efficacy of photo-sonodynamic therapy via methylene blue-loaded poly(D,L-lactide-co-glycolide) nanoparticles (MB-loaded PLGA NPs) over dental implants for potential treatment of peri-implantitis. PLGA NPs were synthesized via a solvent displacement method. After the synthesis and confirmation of MB-loaded PLGA NPs via physical (Scanning Electron Microscope [SEM]) and chemical characterization (Fourier transform infrared spectroscopy [FTIR]), the mature dental biofilm of Porphyromonas gingivalis was produced over the surfaces of dental implants. Then, the bacterial viability assessment of the following five study groups was performed: group-I (diode laser treatment); group-II (PDT/MB-loaded PLGA NPs treatment; group-III (ultrasound treatment); group-IV (ultrasound/PLGA NPs-MB treatment); and group-V: control group included the samples without any treatment. Finally, the FS, FM, and Ra of the samples was assessed. Under the SEM, the NPs were spherical homogeneous particles having round morphology ranging approximately 100 nm in size without aggregation. The FTIR spectra of PLGA NPs and MB-loaded PLGA NPs demonstrated absorption peaks at approximately 1000 cm-1 to 1200 cm-1 and around 1500 cm-1 to 1750 cm-1. The greatest level of P. gingivalis killing was exhibited by ultrasound/MB-loaded PLGA-NPs-treated samples. The FS was statistically significantly greater for control group samples than any other group (i.e., 100.28 MPa; p<0.05). The FM and Ra ranged between 3.31 and 3.58 GPa and between 0.18 and 0.20 µm without any statistically significant difference between the control and experimental groups (p>0.05), respectively. Within the limitations of this study, the application of photo-sonodynamic therapy via MB-loaded PLGA NPs demonstrated the greatest antibacterial activity against P. gingivalis without deteriorating the surfaces and compromising the mechanical properties of dental implants.


The historical narrative: tales of professionalism?
The historical narrative is a story told to illustrate a point, however subconsciously. The "giants" of obstetric anesthesia -- Simpson, Snow, Apgar -- and countless other less well-known physicians all contributed to the history of obstetric anesthesia. We remember them by retelling this history to illustrate elements of professionalism and how we as a profession wish to act. The Physician Charter is an excellent first approximation of a workable definition of this quality, which can and does change over time. By using the three principles and 10 professional responsibilities as a template, the past comes alive as a teaching method to each and every obstetric anesthesiologist.


Molecular and elemental marker-based source apportionment of fine particulate matter at six sites in Hong Kong, China.
Source apportionment of PM2.5 was performed using positive matrix factorization (PMF) based on chemical speciation data from 24-h filters collected throughout 2015 at six sampling sites of varying urban influences in Hong Kong. The input data include major inorganic ions, organic and elemental carbon, elements, and organic tracers. Nine factors were resolved, including (1) secondary sulfate formation process, (2) secondary nitrate formation process, (3) industrial emissions, (4) biomass burning, (5) primary biogenic emissions, (6) vehicle emissions, (7) residual oil combustion, (8) dust, and (9) aged sea salt. The PMF-resolved factor contributions in conjunction with air mass back trajectories showed that the two major sources for PM2.5 mass, secondary sulfate (annual: 41%) and secondary nitrate (annual: 9.9%), were dominantly associated with regional and super-regional pollutant transport. Vehicular emissions are the most important local source, and its contributions exhibit a clear spatial variation pattern, with the highest (6.9 μg/m3, 24% of PM2.5) at a downtown roadside location and the lowest (0.4 μg/m3, 2.0% PM2.5) at two background sites away from city centers. The ability of producing a more reliable source separation and identifying new sources (e.g. primary biogenic source in this study) was a direct advantageous result of including organic tracers in the PMF analysis. PMF analysis conducted on the same dataset in this study but without including the organic tracers failed to separate the biomass burning emissions and industrial/coal combustion emissions. PMF analysis without the organic tracers would also over-apportion the contribution of vehicular emissions to PM2.5, which would bias the evaluation of the effectiveness of vehicle-related control measures. This work demonstrates the importance of organic markers in achieving more comprehensive and less biased source apportionment results.


Cytotoxic and anticonvulsant aryloxyaryl Mannich bases and related compounds.
A series of 1-(4-aryloxyphenyl)-3-diethylamino-1-propanone hydrochlorides 3a-3e and related compounds 3f, 3g and 4a-4d were synthesised. In addition, a group of 4-(4-aryloxyphenyl)-3-(4-aryloxyphenylcarbonyl)-1-ethyl-4-piperidinol hydrochlorides 6a-6e were prepared which incorporated most of the structural features of 3a-3e. All of these compounds displayed cytotoxic properties towards murine L1210 cells as well as human Molt 4/C8 and CEM T-lymphocytes. A number of these compounds possessed noteworthy potencies towards seven human colon cancer cell lines. Some correlations were noted between the IC(50) values generated in the different screens and the sigma, pi and molar refractivity constants of the aryl substituents as well as with the volumes and solvent accessible surface areas of various basic groups. Molecular modelling of representative compounds revealed structural features, which may have contributed to the varying potencies noted. In general, the compounds in series 6 were well tolerated when administered to mice. Anticonvulsant properties were demonstrated by a number of compounds in the maximal electroshock (MES) screen when administered intraperitoneally to mice while 4c and 6e afforded protection in the MES test when given orally to rats.