Detection and genetic profiling of infectious hypodermal and haematopoietic necrosis virus (IHHNV) infections in wild berried freshwater prawn, Macrobrachium rosenbergii collected for hatchery production.
Infectious hypodermal and haematopoietic necrosis virus (IHHNV) has been detected widely in penaeid culture facilities in Asia and the Americas. IHHNV infection on sub-adult and postlarvae of the giant freshwater prawn, Macrobrachium rosenbergii which had caused up to 80% mortalities was first reported in Southeast Taiwan in 2006. In Malaysia, although, there has been no report on IHHNV infections in M. rosenbergii, preliminary work suggests that there is an urgent need to setup a screening protocol for IHHNV for both wild and cultured populations. In this study, polymerase chain reaction based screening was carried out on 30 randomly sampled berried wild M. rosenbergii before and after spawning. All samples did not showed any sign of IHHNV infection. However, the results showed that 20% of the samples were IHHNV positive. Sequence analysis of the amplified band using NCBI-BLAST showed that the putative IHHNV sequence had 98% nucleotide sequence (388 bp) identity with the IHHNV isolate AC-05-005 non-structural protein 1 gene and seven other IHHNV strains in the data bank further affirming the suggestion on the presence of IHHNV in wild freshwater prawn populations in Malaysia.


Pulmonary inflammation and cellular responses following exposure to benzalkonium chloride: Potential impact of disrupted pulmonary surfactant homeostasis.
Benzalkonium chloride (BKC) is a prototypical quaternary ammonium disinfectant. Previously, we suggested a no lethal dose level (0.005%) and an LD50 range (0.5-0.05%) of BKC following a single pharyngeal aspiration. Herein, we exposed BKC repeatedly by pharyngeal aspiration for 14 days (0.005 and 0.01%, female mice, total five times with interval of two days, 5 mice/group) and 28 days (0, 0.001, 0.005, and 0.01%, male and female mice, weekly, 16 mice/sex/group). Death following 14 days-repeated exposure did not occur. Meanwhile, chronic pathological lesions were observed in the lung tissues of mice exposed to BKC for 28 days. The total number of bronchial alveolar lavage cells increased, and pulmonary homeostasis of immunologic messenger molecules was disturbed. Following, we investigated BKC-induced cellular responses using human bronchial epithelial cells. The cytotoxicity increased rapidly with concentration. Lysosomal volume, NO production, and lipid peroxidation increased in BKC-treated cells, whereas intracellular ROS level decreased accompanying structural and functional damage of mitochondria. We also found that BKC affected the expression level of immune response, DNA damage, and amino acid biosynthesis-related molecules. More interestingly, lamellar body- and autophagosome-like structures were notably observed in cells exposed to BKC, and necrotic and apoptotic cell death were identified accompanying cell accumulation in the G2/M phase. Therefore, we suggest that repeated respiratory exposure of BKC causes pulmonary inflammation and lung tissue damage and that dead and damaged cells may contribute to the inflammatory response. In addition, the formation process of lamellar body-like structures may function as a key toxicity mechanism.


Development of antinociceptive tolerance and changes of opioid receptor ligand binding in central nervous system of the mouse forced to single and repeated swimming in the cold water.
The present study was designed to characterize underlying mechanism involved in the development of tolerance in the production of antinociceptive effect induced by repeated cold water swimming stress (CWSS) using the tail-flick test. Mice were forced to swim at 4 degrees C for 3min and the tail-flick test was performed 5, 10, 20, and 30min after the swimming. The profound antinociception was induced by a single CWSS. However, when the mice were exposed to CWSS repeatedly seven times, they showed a tolerance in the production of antinociception. In the opioid receptor binding study, Bmax of delta opioid receptor (DOR) was decreased in the brainstem, midbrain and the spinal cord areas by both a single and repeated CWSS, without altering Kd value. However, Bmax values of mu opioid receptor (MOR) and kappa opioid receptor (KOR) were increased in the brainstem, midbrain and spinal cord regions by repeated CWSS, without changing Kd values. Our results suggest that the development of tolerance in the production of antinociception in mice forced to the repeated CWSS may be, at least, due to the reduction of DOR number in the brainstem, midbrain and the spinal cord regions.


Catalpol synergistically potentiates the anti-tumour effects of regorafenib against hepatocellular carcinoma via dual inhibition of PI3K/Akt/mTOR/NF-κB and VEGF/VEGFR2 signaling pathways.
Hepatocellular carcinoma (HCC) is the most common primary liver cancer characterized by dysregulation of several crucial cellular signaling pathways such as PI3K/p-Akt/mTOR/NF-κB and VEGF/VEGFR2 pathways. Novel therapies targeting these pathways have been discovered such as regorafenib which is small molecular multi-kinase inhibitor mainly targets VEGF/VEGFR2. Catalpol is an iridoid glycoside richly found in rehmannia glutinosa which is a fundamental herb used extensively in traditional Chinese medicine. It is evidenced that catalpol has many pharmacological effects on nervous and cardiovascular systems, in addition to exhibiting hypoglycemic, anti-inflammatory, anti-proliferative and anti-tumour activities. However, its effect on HCC isn't clear enough. So, this study aimed to investigate the anti-tumour effects of catalpol either alone or in combination with regorafenib on HCC. In vitro experiments were performed using HepG2 and HUH-7 hepatocellular carcinoma cell lines. MTT assays evaluated anti-proliferative effects of catalpol and/or regorafenib. Combination index was calculated via compusyn software to detect synergism. Tumour biomarkers were measured using ELISA technique. Results showed that catalpol has anti-tumour effects against HCC via targeting PI3K/p-Akt/mTOR/NF-κB and VEGF/VEGFR2 pathways. In addition, results revealed that our novel combination of catalpol and regorafenib showed potent synergistic anti-tumour effect via suppressing both of PI3K/p-Akt/mTOR/NF-κB and VEGF/VEGFR2 signaling pathways and their downstreams. Catalpol and/or regorafenib markedly suppressed PI3K/p-Akt/mTOR/NF-κB and VEGF/VEGFR2 signaling pathways and consequently showed potent anti-tumour effects against HCC. Results encourage further pre-clinical and clinical studies of this novel combination as a promising targeted therapy for HCC management.


Blood pressure and resting heart rate in 3-17-year-olds in Germany in 2003-2006 and 2014-2017.
To track blood pressure (BP) and resting heart rate (RHR) in children and adolescents is important due to its associations with cardiovascular outcomes in the adulthood. Therefore, the aim of this study was to examine BP and RHR over a decade among children and adolescents living in Germany using national examination data. Cross-sectional data from 3- to 17-year-old national survey participants (KiGGS 2003-06, n = 14,701; KiGGS 2014-17, n = 3509) including standardized oscillometric BP and RHR were used for age- and sex-standardized analysis. Measurement protocols were identical with the exception of the cuff selection rule, which was accounted for in the analyses. Different BP and RHR trends were observed according to age-groups. In 3- to 6-year-olds adjusted mean SBP and DBP were significantly higher in 2014-2017 compared to 2003-2006 (+2.4 and +1.9 mm Hg, respectively), while RHR was statistically significantly lower by -3.8 bpm. No significant changes in BP or in RHR were observed in 7- to 10-year-olds over time. In 11- to 13-year-olds as well as in 14- to 17-year-olds lower BP has been observed (SBP -2.4 and -3.2 mm Hg, respectively, and DBP -1.8 and -1.7 mm Hg), while RHR was significantly higher (+2.7 and +3.7 bpm). BP trends did not parallel RHR trends. The downward BP trend in adolescents seemed to follow decreasing adult BP trends in middle and high-income countries. The increase in BP in younger children needs confirmation from other studies as well as further investigation. In school-aged children and adolescents, the increased RHR trend may indicate decreased physical fitness.


Changes of urine isolates of Escherichia coli and Klebsiella pneumoniae biofilm affect monocytes' response.
The Gram negative rods as Escherichia coli and Klebsiella pneumoniae belong to the most common etiology agents of urinary tract infections. The aim of our study was to assess the diversity of biofilm formed in different urinary tract diseases and their impact on monocytes' adherence and activation. The bacteria were obtained from patients with different kidney problems. Some of the patients were after renal transplantation, some of them were not. Changes in the size and granularity of monocytes, as well as their adherence to biofilm, were assessed using FACSVerse flow cytometer after 1 h co-incubation of monocytes and bacterial biofilm in 37 °C. The obtained results were validated against monocytes incubated without bacteria. The isolates from patients with chronic kidney disease formed the most adherent biofilm regardless the presence or absence of inflammatory reaction. Adherence of monocytes also increased during therapy with immunosuppressive agents, but monocytes' response was different when cyclosporine or tacrolimus were used. Additionally the presence of inflammatory reaction in patients with kidney disease modified the monocytes response when the immunosuppressive drugs were used. Considering the obtained results, we conclude that the changes of monocytes' morphology in response to biofilm formed by Gram negative rods could become a tool to detect urinary tract infection, especially in those groups of patients, where the knowledge of ongoing inflammation is important and the standard tools fail to detect it.


Extraembryonic Endoderm (XEN) Cells Capable of Contributing to Embryonic Chimeras Established from Pig Embryos.
Most of our current knowledge regarding early lineage specification and embryo-derived stem cells comes from studies in rodent models. However, key gaps remain in our understanding of these developmental processes from nonrodent species. Here, we report the detailed characterization of pig extraembryonic endoderm (pXEN) cells, which can be reliably and reproducibly generated from primitive endoderm (PrE) of blastocyst. Highly expandable pXEN cells express canonical PrE markers and transcriptionally resemble rodent XENs. The pXEN cells contribute both to extraembryonic tissues including visceral yolk sac as well as embryonic gut when injected into host blastocysts, and generate live offspring when used as a nuclear donor in somatic cell nuclear transfer (SCNT). The pXEN cell lines provide a novel model for studying lineage segregation, as well as a source for genome editing in livestock.


Evaluation of micronucleus induction of sand dust storm fine particles (PM(2.5)) in human blood lymphocytes.
Sand dust storms are common phenomena in the arid and semi-arid regions. Previous studies have demonstrated that the airborne air fine particulate matter (PM(2.5), particulates with an aerodynamic diameter ≤2.5μm) and its extracts can induce human genetic damage of lymphocytes such as micronucleus formation, chromosomal aberration and so on. However, little is known about the health risks associated with sand dust storm PM(2.5) and its extracts. The aim of the present study is to investigate the micronucleus induction of sand dust storm PM(2.5) (include its organic and inorganic extract) from two different towns on human lymphocytes. The samples of normal PM(2.5) and sand dust storm PM(2.5) were collected in Wuwei (Gansu Province) and Baotou (Inner Mongolia), China. The cytochalasin-B cytokinesis-block test was employed and the cells were treated with 0, 33, 100, 300μgml(-1) sand dust storm PM(2.5) or normal ambient air PM(2.5) suspension (physiological saline as solvent control), or inorganic extract (0, 75, 150, 300μgml(-1), physiological saline as solvent control) or organic extract (0, 20, 40, 80μgml(-1), DMSO as solvent control) at the beginning of the cell culture. Both sand dust storm and normal PM(2.5) and their extract treatment cultures revealed an increase in the frequency of micronucleus. With the increase of treatment concentrations the frequency of micronucleus increased and the nuclear division index (NDI) values declined in a dose-response manner (P<0.01). In the same concentrates, the frequency of micronucleus of normal ambient air PM(2.5) and its extract were significant higher than those of sand dust storm PM(2.5) (P<0.01) except the treatment of Wuwei sample at higher doses, the treatment of inorganic extract of PM(2.5) at the highest dose (300μgml(-1)) and the treatment of organic extract of PM(2.5) at the higher dose (40 and 80μgml(-1)) either in Baotou or in Wuwei (P>0.05). The toxicity of sand dust storm PM(2.5) and its extract at high dose is very potent. The frequency of micronucleus of normal PM(2.5) (include its organic extract) from Baotou were higher than those of Wuwei especially in low and middle dose (P<0.05), but the treatment results of sand dust storm PM(2.5) (include its all extract) was not significantly different between the towns (P>0.05).


The spatial-temporal evolution of heavy metal accumulation in the offshore sediments along the Shandong Peninsula over the last 100 years: Anthropogenic and natural impacts.
The anthropogenic and natural impacts on the temporal and spatial variations of heavy metals in sediments under the Shandong Peninsula coastal current are still unclear. Here, the concentrations\burial fluxes of Cr, Cu, Zn, As, and Pb in three sediment cores retrieved from the Bohai Sea and the Yellow Sea along the Shandong Peninsula were analyzed to study the spatial-temporal variability of heavy metal accumulation over the last century. The results showed that the buried heavy metal fluxes were relatively low at the end of the Shandong Peninsula coastal current. The enrichment factor (EF) and geoaccumulation index (Igeo) indicated that those metals did not severely pollute the sediments except As that reached a moderate enrichment. Principal component analysis (PCA) revealed that Cr, Cu, Zn, and Pb were mainly derived from natural weathering and As was determined by anthropogenic contamination. The strength of the Shandong Peninsula coastal current, the Yellow River estuary location, and sediment discharge load significantly influenced the concentrations of natural-origin heavy metals by affecting sediment grain size and the source-sink process. The emission of pollutants from agricultural and industrial activities in the Shandong Peninsula region resulted in As enrichment since the 1950s. Moreover, the EF values of heavy metals in sediment cores from China's coastal seas showed apparent spatial variations of heavy metal pollution but had coherent temporal variability with China's economic development process. Heavy metals pollution has weakened in most coastal seas since the 2000s, likely due to the extensive industrial upgrading and the implementation of pollution control. These results have a reference significance for studying the evolution and source-sink process of the heavy metals in offshore sediments and tracing anthropogenic impacts in different periods.


A qualitative exploration of the norms and intentions of nurses toward the clinical use of herbal medicine in Ghana.
The purpose of the study was to determine the norms and intentions of nurses towards the clinical use of herbal medicine. Information on nurses' demographics, norms and intentions was gathered through individual face-to-face interviews. Interviews were analysed using the process of content analysis. Beliefs of the nurses and motivational factors formed their norms. The nurses believed herbal medicine was God-given and was used by their ancestors with good outcomes. Some were self-motivated to serve herbal medicine while others counted on patient's recovery upon the use of herbal medicine to motivate them. Positive and negative intentions were discovered; thus, preparedness and unpreparedness to serve herbal medicine in the future. Though some nurses believe herbal medicine is God-given, used by their ancestors and motivated to serve, others were unwilling because of inadequate training. Training of professional nurses on herbal medicine may improve their negative intentions.


Laparotomy for penetrating gastric trauma - A South African experience.
Penetrating gastric injury (PGI) is common and although primary repair is sufficient for most injuries, several areas surrounding the peri-operative management remain contentious. This study reviews our experience in the management of PGI and review the clinical outcome at a major trauma centre in South Africa. A retrospective study was conducted from January 2012 to April 2020 at a major trauma centre in South Africa. 210 cases were included (184 male, median age: 30 years). Mechanism of injury was 59% stab wounds (SWs) and 41% gunshot wounds (GSWs). The AAST grade was predominantly (92%) grade 2 for all cases. 20% (41/210) were isolated gastric injuries. All cases underwent primary repair and there were no cases of suture line failure. Eleven cases (5%) had one or more injuries not identified at the index laparotomy: 7 were unidentified gastric injuries and the remaining 4 were unidentified non gastric injuries. There was no association between unidentified injuries and mechanism of injury or outcome. Fifty-seven (27%) cases experienced one or more complications. Eighty-two cases (39%) required intensive care unit admission. The overall median length of hospital stay was 7 (IQR 4-11) days. The overall mortality was 14%. GSW injuries were more likely to have additional organ injury, higher ISS and PATI scores, longer length of hospitalization, higher likelihood of ICU stay, greater morbidity and mortality than SW injuries. There was a slight increase in the wound sepsis rate as number of associated extra gastric injuries increased but this was not statistically significant. There was no difference in wound overall sepsis rate between SW and GSW injuries (2% vs 8%, p=0.121). Primary repair alone is sufficient for most PGI, but laparotomy is associated with high incidence of unidentified injury and surgeons must to be cognisant of the likelihood of these occult injuries.


Experience with use of extracorporeal life support for severe refractory status asthmaticus in children.
Severe status asthmaticus (SA) in children may require intubation and mechanical ventilation with a subsequent increased risk of death. In the patient with SA and refractory hypercapnoeic respiratory failure, use of extracorporeal life support (ECLS) has been anecdotally reported for carbon dioxide removal and respiratory support. We aimed to review the experience of a single paediatric centre with the use of ECLS in children with severe refractory SA, and to compare this with international experience from the Extracorporeal Life Support Organization (ELSO) registry. All paediatric patients (aged from 1 to 17 years) with primary International Classification of Diseases (ICD)-9 diagnoses of SA receiving ECLS for respiratory failure from both the Children's Healthcare of Atlanta at Egleston (Children's at Egleston) database and the ELSO registry were reviewed. Thirteen children received ECLS for refractory SA at the Children's at Egleston from 1986 to 2007. The median age of the children was 10 years (range 1 to 16 years). Patients generally received aggressive use of medical and anaesthetic therapies for SA before cannulation with a median partial pressure of arterial carbon dioxide (PaCO2) of 130 mmHg (range 102 to 186 mmHg) and serum pH 6.89 (range 6.75 to 7.03). The median time of ECLS support was 95 hours (range 42 to 395 hours). All 13 children survived without neurological sequelae. An ELSO registry review found 64 children with SA receiving ECLS during the same time period (51 excluding the Children's at Egleston cohort). Median age, pre-ECLS PaCO2 and pH were not different in non-Children's ELSO patients. Overall survival was 60 of 64 (94%) children, including all 13 from the Children's at Egleston cohort. Survival was not significantly associated with age, pre-ECLS PaCO2, pH, cardiac arrest, mode of cannulation or time on ECLS. Significant neurological complications were noted in 3 of 64 (4%) patients; patients with neurological complications were not significantly more likely to die (P = 0.67). Single centre and ELSO registry experience provide results of a cohort of children with refractory SA managed with ECLS support. Further study is necessary to determine if use of ECLS in this setting produces better outcomes than careful mechanical ventilation and medical therapy alone.


Effect of switching from pioglitazone to the sodium glucose co-transporter-2 inhibitor dapagliflozin on body weight and metabolism-related factors in patients with type 2 diabetes mellitus: An open-label, prospective, randomized, parallel-group comparison trial.
The effects of dapagliflozin (DAP) and pioglitazone (PIO) on body weight and glycaemic control were compared in patients with type 2 diabetes mellitus. Seventy-one patients on PIO were either switched to DAP (n = 36) at 5 mg per day or continued on PIO (n = 35). Primary endpoints were superiority of body weight loss and non-inferiority of HbA1c level after 24 weeks with DAP. Body weight decrease was greater with DAP than with PIO (75.3 ± 14.9 to 71.3 ± 15.1 kg vs. 74.7 ± 13.8 to 75.2 ± 13.9 kg; P < 0.01). Change in the HbA1c level was comparable (P = 0.64). The level of N-terminal prohormone of brain natriuretic peptide (NT-proBNP) and urinary albumin : creatinine ratio (ACR) decreased only with DAP (NT-proBNP, P < 0.01; ACR, P = 0.02), and the change in NT-proBNP correlated negatively with baseline NT-proBNP level (ρ = -0.68, P < 0.01) and log-converted ACR (ρ = -0.35, P < 0.05). DAP promotes body weight loss in type 2 diabetes mellitus and may decrease fluid retention, thus reducing the occurrence of cardiovascular events.


Spatially controlled nano-structuring of silicon with femtosecond vortex pulses.
Engineering material properties is key for development of smart materials and next generation nanodevices. This requires nanoscale spatial precision and control to fabricate structures/defects. Lithographic techniques are widely used for nanostructuring in which a geometric pattern on a mask is transferred to a resist by photons or charged particles and subsequently engraved on the substrate. However, direct mask-less fabrication has only been possible with electron and ion beams. That is because light has an inherent disadvantage; the diffraction limit makes it difficult to interact with matter on dimensions smaller than the wavelength of light. Here we demonstrate spatially controlled formation of nanocones on a silicon surface with a positional precision of 50 nm using femtosecond laser ablation comprising a superposition of optical vector vortex and Gaussian beams. Such control and precision opens new opportunities for nano-printing of materials using techniques such as laser-induced forward transfer and in general broadens the scope of laser processing of materials.


High resolution ultra high pressure liquid chromatography-time-of-flight mass spectrometry dereplication strategy for the metabolite profiling of Brazilian Lippia species.
Plants belonging to the Lippia genus have been widely used in ethnobotany throughout South and Central America and in tropical Africa as foods, medicines, sweeteners and in beverage flavouring. Various taxonomic problems involving some genera from Verbenaceae, including Lippia, have been reported. In this study, the metabolite profiling of fifteen extracts of various organs of six Lippia species was performed and compared using UHPLC-PDA-TOF-MS. Fourteen phenolic compounds that were previously isolated from L. salviaefolia Cham. and L. lupulina Cham. were used as references. The annotation of the remaining LC peaks was based on concomitant online high mass accuracy measurements and subsequent molecular formula assignments following these different steps: (i) elimination of non-coherent putative molecular formulae by heuristic filtering, (ii) verification of the occurrence of remaining molecular formulae in databases, (iii) cross search with reported compounds in the Lippia genus, (iv) match with reported UV spectra, (v) estimation of the chromatographic retention behaviour based on the log P parameter of reference compounds. This strategy is generic and time-saving, avoids isolation/purification procedures, enables an efficient LC peak annotation of most of the studied compounds and is well adapted for plant chemotaxonomic studies. Within this study, the interconversion of four flavanone glucoside isomers was additionally highlighted by analytical HPLC isolation and immediate analysis using fast UHPLC gradients. Dereplication results and hierarchical data analysis demonstrated that L. salviaefolia, L. balansae, L. velutina and L. sidoides displayed significant chemical similarities, while the compositions of L. lasiocalicyna and L. lupulina differed substantially.


Assessment of Dasatinib Versus Nilotinib as Upfront Therapy for Chronic Phase of Chronic Myeloid Leukemia in Qatar: A Cost-Effectiveness Analysis.
The economic outcome research of approved tyrosine kinase inhibitors for treating the chronic phase of chronic myeloid leukemia in developing is scarce. The aim of this study was to assess the cost-effectiveness of dasatinib and nilotinib for newly diagnosed chronic myeloid leukemia patients. A decision tree model was developed linking clinical effectiveness (defined as major molecular response) and/or complete cytogenetic response, utility, and cost data over a 12-month period. Patients are recruited from Qatar Cancer Registry. The probability of primary clinical outcome is calculated from DASISION (dasatinib) and ENESTnd (nilotinib) trials. Direct healthcare costs were derived from the national healthcare payer system, whereas adverse effects data were derived from local incident reporting system. In the first-line treatments of chronic myeloid leukemia patients, nilotinib has greater major molecular response (39% nilotinib vs 12% dasatinib) and complete cytogenetic response (24% nilotinib vs 16% dastinib) response outcomes, and more adverse effects than dasatinib (13.3% vs 4%). Moreover, nilotinib is more cost-effective with annual costs (USD63,589.59) and after 12 months of follow-up. Despite the lower acquisition annual cost of dasatinib (USD59,486.30), the incremental cost-effectiveness ratio of nilotinib (vs dasatinib) per major molecular response/complete cytogenetic response achieved was USD15,481.10 per year. There were no cases in both arms that progressed to accelerated or blast phase. At a threshold of 3 times gross domestic product per capita of Qatar and according to World Health Organization recommendation, the nilotinib use is still cost-effective. Upfront therapy of chronic myeloid leukemia-chronic phase patients by nilotinib plan appears to be more cost-effective than dasatinib.


Role of GSTM1 (Present/Null) and GSTP1 (Ile105Val) polymorphisms in susceptibility to acute lymphoblastic leukemia among the South Indian population.
Acute lymphoblastic leukaemia (ALL) is the most common pediatric malignancy worldwide. The origin of this disease may be explained by a combination of genetic and environmental factors. Glutathione-s-transferases are a multi-gene family of enzymes involved in the detoxification of a wide variety of environmental carcinogens. A total of 92 immunophenotyped cases (below 25 years of age) and 150 cord blood controls were here analysed by PCR for GSTM1(Present/Null) and RQ-PCR allelic discrimination assay for GSTP1(Ile105Val). We found a significant increased risk for ALL with the GSTM1 null genotype (OR: 1.96, 95%CI=1.08-3.57), but no significant risk was found with the GSTP1 (Ile/Val) genotype (OR: 1.32, 95%CI = 0.74-2.37) and the GSTP1 Val/Val genotype (OR: 1.41, 95%CI=0.5-3.96) alone. Combined analysis of GSTM1 and GSTP1 showed significant higher risk associated with the GSTM1 (null/null) and GSTP1 [(Ile/Val)/ (Val/Val)] genotype (OR=2.78: 95%CI=1.16-6.69).


Laparoscopic versus open right hepatectomy: a comparative study.
The safety of laparoscopic major liver resections is still uncertain. The aim of this study was to compare our results for laparoscopic right hepatectomy (LRH) with those for open right hepatectomy (ORH). Patients undergoing LRH were compared with retrospectively selected patients from our ORH database. The 2 groups were well matched for sex, age, American Society of Anesthesiologists score, body mass index, liver disease, and tumor size. Surgical and postsurgical outcomes were compared. Seventy-two patients were analyzed: 22 in the LRH group and 50 in the ORH group. Operating time was similar. Blood loss was significantly less in laparoscopic resections (P = .038). Specific morbidity rates were not different, general morbidity was lower after laparoscopy (P = .04), and the severity of postsurgical complications was not different. Mean hospital stay was significantly shorter after laparoscopy (P = .009). Laparoscopy improved surgical and postsurgical outcomes for ORH in selected patients. This is the first comparative study to demonstrate an advantage of laparoscopy for a major liver resection. Prospective randomized studies with a greater number of cases are needed to confirm the role of laparoscopy in major liver resections.


Immunogenicity and safety of intradermal trivalent influenza vaccination in nursing home older adults: a randomized controlled trial.
To compare the immunogenicity and safety between full-dose (15 μg) intramuscular (i.m.) and full-dose (15 μg) intradermal (i.d.) immunization of the trivalent influenza vaccine in nursing home older adults. A single-center, randomized, controlled, open-label, parallel group trial from October 2013 to April 2014. Nine nursing homes in Hong Kong. Hundred nursing home older adults (mean age: 82.9 ± 7.4 years). Fifty received i.d. (Intanza) and 50 received i.m. (Vaxigrip) vaccination. Baseline measurements included demographics, comorbidity, frailty and nutritional status. Day 21 and day 180 immunogenicity (seroconversion rate, seroprotection rate, geometric mean titer [GMT] fold increase in antibody titer) using hemagglutination-inhibition and adverse events were measured. Noninferiority and superiority of i.d. compared with i.m. vaccination in immunogenicity were analyzed. The study was registered on ClinicalTrials.gov; identifier: NCT 01967368. At day 21, noninferiority in immunogenicity of the i.d. vaccination was demonstrated. The seroconversion rate of the H1N1 strain was significantly higher in the i.d. group. At day 180, immunogenicity of both groups fell but the GMT of all strains in i.d. group was higher and the difference was significant for H3N2 strain. The seroconversion rate and GMT fold increase of H3N2 strain was significantly higher in the i.d. group. Local adverse events was significantly more in i.d. group, but they were mild and resolved in 72 hours. I.d. vaccination is noninferior, and even superior in some parts of immunogenicity assessment, to i.m. vaccination without compromising safety in nursing home older adults. I.d. vaccination is a good alternative to i.m. vaccination in this population.


Determination of creatinine in urine by tandem mass spectrometry.
Electrospray tandem mass spectrometry (TMS) is a very powerful tool that enables one to perform high sample throughput analysis. This paper describes a method to determine creatinine in urine by tandem mass spectrometry with direct sample infusion into an ion source. Samples (50 microl) were diluted with internal standard (IS) (450 microl of 0.667 mmol/l deuterated creatinine). Diluted samples were introduced into mass spectrometer with no prior pretreatment and after purification on ion-exchange 96-column cartridge. Tandem mass spectrometry analyses were performed in selected reaction monitoring mode. Creatinine and creatinine-d(3) were monitored using precursor and product ion settings (m/z 114 to 86 and m/z 117 to 89, respectively). The time of an analysis was 3.015 min. Both TMS methods were compared mutually and with the results obtained by enzymatic and Jaffe method. Linearity was obtained in the range 0.06-60 mmol/l. Detection limit was 0.2 mumol/l and recoveries were in the range 95.1-98.3% for both the assays with and without ion-exchange column. Results of both assays are in good agreement with those obtained by enzymatic and Jaffe method based on log-transformed Bland-Altman plots. Electrospray tandem mass spectrometry method utilizing both approaches with and without ion-exchange column is acceptable according to CLIA criteria. Tandem mass spectrometry allows rapid, sensitive and selective determination of creatinine in untreated urine.


Disseminated herpes simplex virus and varicella zoster virus coinfection in a patient taking thalidomide for relapsed multiple myeloma.
Disseminated herpes simplex virus (HSV) and varicella zoster virus (VZV) have been reported individually in immunosuppressed adults. We present a case of coinfection with disseminated HSV and VZV infection in a patient taking thalidomide for relapsed multiple myeloma. This is the first report of opportunistic infection associated with thalidomide.


Mild Cognitive Impairment Is Associated with Poorer Nutritional Status on Hospital Admission and after Discharge in Acutely Hospitalized Older Patients.
In acutely hospitalized older patients (≥65 years), the association between mild cognitive impairment (MCI) and malnutrition is poorly described. We hypothesized that (1) MCI is associated with nutritional status on admission and after discharge; (2) MCI is associated with a change in nutritional status; and (3) a potential association is partly explained by frailty, comorbidity, medication use, and age. We combined data from a randomized controlled trial (control group data) and a prospective cohort study (ClinicalTrials.gov: NCT01964482 and NCT03052192). Nutritional status was assessed on admission and follow-up using the Mini Nutritional Assessment-Short Form. MCI or intact cognition (noMCI) was classified by three cognitive performance tests at follow-up. Data on frailty, comorbidity, medication use, and age were drawn from patient journals. MCI (n = 42) compared to noMCI (n = 47) was associated with poorer nutritional status with an average difference of -1.29 points (CI: -2.30; -0.28) on admission and -1.64 points (CI: -2.57; -0.70) at 4-week follow-up. Only age influenced the estimates of -0.85 (CI: -1.86; 0.17) and -1.29 (CI: -2.25; -0.34), respectively. In acutely hospitalized older patients, there is an association between MCI and poorer nutritional status upon admission and four weeks after discharge. The association is partly explained by higher age.


[Treatment concepts for fractures of the thoracolumbar junction and lumbar spine].
Thoracolumbar vertebral fractures are not only characterized by frequent osteoligamentous instability, but also often by irreversible damage to to the intervertebral disk. Treatment guidelines can be formulated based on an accurate classification system. In addition to reconstructing the axis of rotation, it is crucial that the width of the spinal canal be restored when neurological deficits are present. Both indirect dorsal compression and ventral endoscopically guided direct decompression are equally of decisive importance. To achieve long-term stability with as little corrective loss as possible, the ventral column absorbing pressure is surgically stabilized by diligently resecting a destroyed intervertebral disk and vertebral fragments and replacing it with a corticocancellous bone graft or cage. The goal should always be to keep the fusion length as short as possible.


Delayed effect of blood pressure fluctuations on heart rate in patients with end-stage kidney disease.
The time delay of the baroreflex may be affected by decreased autonomic activity in uremia. To assess the magnitude and the time delay of heart rate response in patients with end-stage renal disease, continuous beat-to-beat intervals (IBI) and systolic blood pressure (SBP) recordings were monitored in hemodialysis (HD) patients (n = 72), in patients after renal transplantation (TX) (n = 41) and in age-matched controls (C) (n = 34). A 2-term prediction model was computed, in which each IBI change was represented as a function of SBP difference values of two immediately preceding beats. Baroreflex slope and the frequency domain variables low frequency (LF) α index, phase shift, and lag time were also calculated. b₁ coefficient, representing the dependence of IBI difference with the first previous SBP difference was lower in HD than in Cs, but increased after TX. b₁ correlated with age, baroreflex slope, and LF α, and b₂ (the 2nd term), with both the phase shift between SBP and IBI and lag time. The latter was lower in Cs than in HD or transplanted patients. These findings show that the time delay of the heart rate response to SBP variations is increased in renal insufficiency. The prolonged delay may contribute to the circulatory instability in uremic patients.


[Dependent relative: Effects on family health].
The purpose of this work is to analyse the effects on informal caregiver's health and lifestyle when living with a dependent person at home. A comparison will be made between this situation and other situations involving commitment of time and energy, taking into account gender and age differences in each stage of the life cycle. Cross-sectional study analysing secondary data. The method used for collecting information is the computer assisted personal interview carried out in selected homes by the Ministry of Health, Social Services and Equality. The study included 19,351 participants aged over 25 years who completed the 2011-2012 Spanish National Health Survey. This research is based on demographic information obtained from a Spanish National Health Survey (2011/12). Using an empirical framework, the Logit model was select and the data reported as odds ratio. The estimations were repeated independently by sub-groups of age and gender. The study showed that the health of people who share their lives with a dependent person is worse than those who do not have any dependent person at home (they are 5 times at higher risk of developing health problems). The study found that being a woman, advance age, low educational level and does not work, also has an influence. Being a caregiver reduces the likelihood of maintaining a healthy lifestyle through physical exercise, relaxation, or eating a balanced diet. Living with a dependent person reduces the likelihood of maintaining healthy lifestyles and worsens the state of health of family members. Significant differences in gender and age were found.


You have to be twice as good and work twice as hard: a mixed-methods study of perceptions of sexual harassment, assault and women's leadership among female faculty at a research university in the USA.
The purpose of this study was to examine the perceptions of institutional policies and practices for the prevention of and response to gender inequities as experienced by female faculty working in the health sciences at a US research university. Data from the institution's Faculty Campus Climate Survey (n = 260 female faculty) were coupled with qualitative interviews (n = 14) of females in leadership positions, exploring campus climate, and institutional policies and practices aimed at advancing women. Two-thirds (59%) of the female faculty respondents indicated witnessing sexual harassment and 28% reported experiencing sexual harassment. Several organizational themes emerged to address this problem: culture, including cultural change, transparency, and accountability. The findings reveal the ways in which university culture mimics the larger societal context. At the same time, the distinct culture of higher education processes for recruitment, career advancement - specifically tenure and promotion - are identified as important factors that require modifications in support of reductions in gender inequalities.


Functional up-regulation of P2X3 receptors in dorsal root ganglion in a rat model of bone cancer pain.
Cancer-induced bone pain remains a clinical challenge due to the poor understanding of the mechanisms. Recent study revealed extracellular adenosine triphosphate (ATP) and P2X receptors may be implicated in nociceptive signalling under cancer pain state. Therefore, here we investigated the potential role of P2X(3) receptor in a rat model of bone cancer pain. Walker 256 tumour cells were inoculated into the left tibia of Wistar rats. The model was verified by X-ray imaging, pathology and behaviour examinations. The expression of P2X(3) receptors in dorsal root ganglia (DRG) was examined. Functional significance of altered P2X(3) receptors was investigated by measuring influx upon α,β-meATP stimulation in acutely dissociated DRG neurons. Moreover, A-317491, an antagonist of P2X(3) receptors, was administrated intrathecally or locally to evaluate its analgesia effect in the cancer pain animals. The P2X(3) receptor was up-regulated for about 50% in DRG neurons in rats with bone cancer at both protein and mRNA levels and correlated with the pain behaviour in bone cancer rats. A 51.9% increase of α,β-me ATP (10 μM, for 4 s) evoked transient response currents and a higher percentage of neurons responsive to the application of α,β-me ATP was detected in bone cancer rats. Intrathecal or local injection of A-317491 significantly attenuated pain behaviour induced by bone cancer. These results suggest that the P2X(3) receptor is functionally up-regulated in DRG in cancer rats. P2X(3) receptor is a promising target for therapeutic intervention in cancer patients for pain management.


Pigeons integrate visual motion signals differently than humans.
Perceiving motion is a fundamental ability for animals. Primates integrate local 1D motion across orientation and space to compute a rigid 2D motion. It is unknown whether the rule of 2D motion integration is universal within the vertebrate clade; comparative studies of animals with different ecological backgrounds from primates may help answer that question. Here we investigated 2D motion integration in pigeons, using hierarchically structured motion stimuli, namely a barber-pole illusion and plaid motion. The pigeons were trained to report the direction of motion of random dots. When a barber-pole or plaid stimulus was presented, they reported the direction perpendicular to the grating orientation for barber-pole and the vector average of two component gratings for plaid motion. These results demonstrate that pigeons perceive different directions than humans from the same motion stimuli, and suggest that the 2D integrating rules in the primate brain has been elaborated through phylogenetic or ecological factors specific to the clade.


Coping response and family communication of cancer risk in men harboring a BRCA mutation: A mixed methods study.
Providing genetic counseling and genetic testing to at-risk blood relatives (cascade screening) is important for improving BRCA cancer outcomes. Intra-familial communication of risk is critical for cascade screening efforts yet relatively little is known about men's role in communicating BRCA risk. We sought to examine men's coping response to their BRCA status and intra-familial communication of risk to inform the development of tailored interventions that could promote cascade screening. We employed a sequential mixed-methods design. First, we measured coping response (quantitative) using the Multidimensional Impact of Cancer Risk Assessment (MICRA). MICRA scores were compared between BRCA+ men, BRCA- men and BRCA+ women. Subsequently, we used template analysis to analyze qualitative interviews exploring coping and intra-familial communication of risk. The Theory of Planned Behavior (TPB) served as a guiding framework for identifying intervention targets. BRCA+ men (n = 36) had significantly higher levels of distress (p < 0.001), uncertainty (p < 0.001) and negative experiences (p < 0.05) compared to BRCA- male counterparts (n = 23). BRCA+ men had significantly lower distress (p < 0.001) and uncertainty (p < 0.001) than BRCA+ women (n = 406). Qualitative analysis of in-depth interviews with BRCA+ men (n = 35) identified promoters and barriers to active coping response and intra-familial communication of risk. Mapping results onto the TPB identified targets for tailoring person-centered approaches for men addressing beliefs/attitude, subjective norms, and perceived behavioral control. Men and women appear to have different coping responses to learning their BRCA status. Developing tailored (sex-based), theory informed interventions may help promote intra-familial communication of BRCA risk and support cascade screening.


A new osteophyte segmentation algorithm using partial shape model and its applications to rabbit femur anterior cruciate ligament transection via micro-CT imaging.
Osteophyte is an additional bony growth on a normal bone surface limiting or stopping motion at a deteriorating joint. Detection and quantification of osteophytes from CT images is helpful in assessing disease status as well as treatment and surgery planning. However, it is difficult to distinguish between osteophytes and healthy bones using simple thresholding or edge/texture features due to the similarity of their material composition. In this paper, we present a new method primarily based active shape model (ASM) to solve this problem and evaluate its application to anterior cruciate ligament transection (ACLT) rabbit femur model via CT imaging. The common idea behind most ASM based segmentation methods is to first build a parametric shape model from a training dataset and apply the model to find a shape instance in a target image. A common challenge with such approaches is that a diseased bone shape is significantly altered at regions with osteophyte deposition misguiding an ASM method and eventually leading to suboptimum segmentations. This difficulty is overcome using a new partial ASM method that uses bone shape over healthy regions and extrapolates it over the diseased region according to the underlying shape model. Finally, osteophytes are segmented by subtracting partial-ASM derived shape from the overall diseased shape. Also, a new semi-automatic method is presented in this paper for efficiently building a 3D shape model for an anatomic region using manual reference of a few anatomically defined fiducial landmarks that are highly reproducible on individuals. Accuracy of the method has been examined on simulated phantoms while reproducibility and sensitivity have been evaluated on CT images of 2-, 4- and 8-week post-ACLT and sham-treated rabbit femurs. Experimental results have shown that the method is highly accurate ( R2 = 0.99), reproducible (ICC = 0.97), and sensitive in detecting disease progression (p-values: 0.065,0.001 and < 0.001 for 2- vs. 4, 4- vs. 8- and 2- vs. 8-weeks, respectively).


Small vessel disease disrupts EEG postural brain networks in 'unexplained dizziness in the elderly'.
To examine the hypothesis that small vessel disease disrupts postural networks in older adults with unexplained dizziness in the elderly (UDE). Simultaneous electroencephalography and postural sway measurements were undertaken in upright, eyes closed standing, and sitting postures (as baseline) in 19 younger adults, 33 older controls and 36 older patients with UDE. Older adults underwent magnetic resonance imaging to determine whole brain white matter hyperintensity volumes, a measure of small vessel disease. Linear regression was used to estimate the effect of instability on electroencephalographic power and connectivity. Ageing increased theta and alpha desynchronisation on standing. In older controls, delta and gamma power increased, and theta and alpha power reduced with instability. Dizzy older patients had higher white matter hyperintensity volumes and more theta desynchronisation during periods of instability. White matter hyperintensity volume and delta power during periods of instability were correlated, positively in controls but negatively in dizzy older patients. Delta power correlated with subjective dizziness and instability. Neural resource demands of postural control increase with age, particularly in patients with UDE, driven by small vessel disease. EEG correlates of postural control saturate in older adults with UDE, offering a neuro-physiological basis to this common syndrome.


Emerging biomarkers of delayed graft function in kidney transplantation.
Delayed Graft Function (DGF) is one of the most common early complications in kidney transplantation, associated with poor graft outcomes, prolonged post-operative hospitalization and higher rejection rates. Given the severe shortage of high-quality organs for transplantation, DGF incidence is expected to raise in the next years because of the use of nonstandard kidneys from Extended Criteria Donors (ECD) and from Donors after Circulatory Death (DCD). Alongside conventional methods for the evaluation of renal allograft [e.g. serum creatinine Glomerular Filtration Rate (GFR), needle biopsy], recent advancements in omics technologies, including proteomics, metabolomics and transcriptomics, may allow to discover novel biomarkers associated with DGF occurrence, in order to identify early preclinical signs of renal dysfunction and to improve the quality of graft management. Here, we gather contributions from basic scientists and clinical researchers to describe new omics studies in renal transplantation, reporting the emerging biomarkers of DGF that may implement and improve conventional approaches.


The canonical Wnt pathway in embryonic axis polarity.
The canonical Wnt pathway plays crucial roles in multiple developmental processes, including in axis specification. Throughout the animal kingdom, this pathway has been reported to drive patterning of axes as different as the animal-vegetal axis in echinoderms to the dorsal-ventral axis in vertebrates. Intriguingly enough, this pathway appears structurally and functionally well conserved during evolution. However, differences between these phyla are observed that explain how a same pathway can mediate establishment of two such apparently distinct axes. This review compares the axis specification processes used in two evolutionarily distant embryos, the sea urchin and Xenopus.


Denervation and beta2-adrenoceptor-agonist administration on craniofacial bone density.
Beta2-agonist medications are thought to have adverse effects on bone density. Surgical denervation and intramuscular beta2-agonist injections appear to have opposing effects on skeletal muscles. The present study has been designed to assess the effects of denervation of the masseter, intramuscular injection of a beta2-agonist and the combination of both procedures, on bone density in the craniofacial skeleton in rats. Sprague-Dawley rats were prepared as four groups: 1. surgical sham + saline injection into the masseter (sham); 2. surgical denervation of the masseter (den.); 3. surgical denervation of the masseter + intramuscular formoterol injection into the affected muscle (den.+form.); 4. intramuscular formoterol injection into the masseter (form.). All specimens were submitted for CT examination and volumetric calculations of the mineralised bone tissue were performed. The sham and form. groups had a greater volume of mineralised bone in the zygoma on the experimental side compared with the control side. The maxilla on the experimental side had a higher volume of mineralised bone in the den.+form. and form. groups compared with the sham and den. groups. The control side of the maxilla had a higher volume of mineralised bone in the den.+form. and form. groups compared with the den. group only. Intramuscular administration of formoterol appears to induce a bilateral increase in bone mineral density in the maxilla and the zygoma, likely explained as a secondary effect of the well-described increase in muscle mass and strength associated with beta2-agonist administration.


Estrogenic regulation of cholesterol biosynthesis and cell growth in DLD-1 human colon cancer cells.
The main molecules of cholesterol homeostasis are 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoAR), the key enzyme of the biosynthetic pathway, and the low-density lipoprotein receptor (LDL-R), which is responsible for the uptake of plasma lipoproteins. The increase in the endogenous cholesterol biosynthesis results in stimulation of DNA synthesis, while the inhibition of cholesterogenesis suppresses cell growth. Estrogens have been reported to regulate hepatic LDL-R expression and modulate cell proliferation in different tissues. In order to clarify the mechanisms of estrogenic growth control in colorectal carcinoma, we have investigated the effects of 17beta-estradiol exposure on LDL-R gene expression and its protein, as well as on HMG-CoAR gene expression, its protein as well as enzyme activity in the DLD-1 human colon cancer cell line. The effect of 17beta-estradiol on both cell growth and apoptosis in this cell line was also investigated. LDL-R and HMG-CoAR gene expressions were determined using quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) in DLD-1 cells at different times and doses of 17beta-estradiol exposure. LDL-R and HMG-CoAR protein expression was detected by Western immunoblotting. HMG-CoAR activity was evaluated using a radiometric assay. Cell proliferation was measured by colorimetric MTT test and incorporation of [3H]-thymidine in DNA. Apoptotic death was estimated by DNA fragmentation analysis. Estrogens induced an early increase of LDL-R, at both mRNA and protein level, and later decreased HMG-CoAR activity and protein expression. DLD-1 cells treated with 17beta-estradiol exhibited inhibition of DNA synthesis and apoptosis. The results of this study suggest that estrogens regulate LDL-R and HMG-CoAR and influence cell growth and apoptosis in colon cancer cells.


Diffusion imaging with a multi-echo MISSTEC sequence.
An imaging method is presented to measure the water-diffusion coefficient. The sequence (MISSTEC) uses the simultaneous acquisition of a spin echo and several stimulated echoes with the same intensity except for diffusion weighting. The optimal number of stimulated echoes was calculated to minimize the diffusion coefficient error (D). D values obtained in vitro and in vivo were in good agreement with those from the spin-echo sequence (IntraVoxel Incoherent Motion [IVIM] method). The total acquisition time is half that of the classic IVIM method.


Children learn spurious associations in their math textbooks: Examples from fraction arithmetic.
Fraction arithmetic is among the most important and difficult topics children encounter in elementary and middle school mathematics. Braithwaite, Pyke, and Siegler (2017) hypothesized that difficulties learning fraction arithmetic often reflect reliance on associative knowledge-rather than understanding of mathematical concepts and procedures-to guide choices of solution strategies. They further proposed that this associative knowledge reflects distributional characteristics of the fraction arithmetic problems children encounter. To test these hypotheses, we examined textbooks and middle school children in the United States (Experiments 1 and 2) and China (Experiment 3). We asked the children to predict which arithmetic operation would accompany a specified pair of operands, to generate operands to accompany a specified arithmetic operation, and to match operands and operations. In both countries, children's responses indicated that they associated operand pairs having equal denominators with addition and subtraction, and operand pairs having a whole number and a fraction with multiplication and division. The children's associations paralleled the textbook input in both countries, which was consistent with the hypothesis that children learned the associations from the practice problems. Differences in the effects of such associative knowledge on U.S. and Chinese children's fraction arithmetic performance are discussed, as are implications of these differences for educational practice. (PsycINFO Database Record (c) 2018 APA, all rights reserved).


Cryofreezing for slow-pathway modification in patients with slow-fast AVNRT: Efficacy, safety, and electroanatomical relation between sites of transient AV block and sites of successful cryoablation.
Cryoablation has emerged as an alternative to radiofrequency ablation for treating atrioventricular nodal reentrant tachycardia (AVNRT). The aim of this prospective study was to evaluate the efficacy and safety of cryoapplication at sites within the mid/high septal region of Koch's triangle and the relation between sites of transient AV block (AVB) and sites of successful cryoablation. Included were 45 consecutive patients undergoing slow-fast AVNRT cryoablation. Initial delivery of cryoenergy was to the mid-septal to high septal region of Koch's triangle. Transient AVB occurred during cryoenergy delivery in 62% (28/45) of patients. Median distance between sites at which cryofreezing successfully eliminated slow pathway conduction and sites of AVB was 4.0 (3.25-5.0) mm. Sites of successful cryoablation tended to be to the left and inferior to the AVB sites. The atrial/ventricular electrogram ratio was significantly lower at sites of successful cryoablation than at AVB sites (0.25 [0.17-0.56] vs. 0.80 [0.36-1.25], p < .001). Delayed discrete or fractionated atrial electrograms were recorded more frequently at sites of successful cryoablation than at AVB sites (78% vs. 20%, p < .001). No persistent AV conduction disturbance occurred, and 96% (43/45) of patients showed absence of recurrence at a median follow-up time of 25.0 months. Cryoablation of slow-fast AVNRT and targeting the mid/high septal region of Koch's triangle was highly successful. AVB frequently emerged near the site at which the slow pathway was eliminated but always resolved by regulating the energy delivery under careful monitoring, and it may be distinguishable by its local electrogram features.


Hypereosinophilia and metastatic anaplastic carcinoma of unknown primary.
The differential diagnosis of eosinophilia may sometimes be difficult. Eosinophilia may occur in a diverse array of conditions from parasitic infestations to malignacies. Idiopathic hypereosinophilic syndrome has also been described. A 65-year-old male patient presenting with eosinophilia of obscure etiology is described in the present report. Three years after the diagnosis of eosinophilia, metastatic anaplastic carcinoma of unknown primary was detected. Differential diagnosis is disscussed briefly. It is stressed that patients with hypereosinophilia of unknown etiology must be screened for malignancy regularly during follow up.


Toxic plants: a chemist's perspective.
Chemistry has long been an integral part of toxicology, as the two fields originated in much the same way: the investigation of plants with interesting properties. In this chapter I review the role that chemistry has played in understanding toxic and medicinal plants. After some introductory remarks, three broad areas are addressed: the role of natural products in understanding plant taxonomy and evolution, recent developments in chemical synthesis, especially efforts to discover and efficiently synthesize novel structures based upon naturally occurring toxins, and finally, developments in the new field of systems toxicology, which seeks to integrate all aspects of an organism's response to toxic insult.


Paleo-immunology of human anti-carbohydrate antibodies preventing primate extinctions.
Two human natural anti-carbohydrate antibodies appeared in critical evolutionary events that brought primates and hominins to brink of extinction. The first is the anti-Gal antibody, produced in Old-World monkeys (OWM), apes and humans. It binds the carbohydrate-antigen 'α-gal epitope' (Galα1-3Galβ1-4GlcNAc-R) on carbohydrate-chains (glycans) synthesized by non-primate mammals, lemurs and New-World monkeys (NWM). The second is anti-N-glycolylneuraminic-acid (anti-Neu5Gc) antibody binding Neu5Gc on glycans synthesized by OWM, apes and most non-primate mammals. Ancestral OWM and apes synthesized α-gal epitopes and were eliminated ~20-30 million-years-ago (mya). Only few accidentally mutated offspring lacking α-gal epitopes, produced anti-Gal and survived. Hominin-populations living ~3 mya synthesized Neu5Gc and were eliminated, but few mutated offspring that accidently lost their ability to synthesize Neu5Gc, produced natural anti-Neu5Gc antibody. These hominins survived and ultimately evolved into present-day humans. It is argued that these two near-extinction events were likely to be the result of epidemics caused by highly virulent and lethal enveloped viruses that killed parental-populations. These viruses presented α-gal epitopes or Neu5Gc synthesized in host-cells of the parental-populations. Mutated offspring survived the epidemics because they were protected from the lethal virus by the natural anti-Gal or anti-Neu5Gc antibodies they produced due to loss of immune-tolerance to α-gal epitopes or to Neu5Gc, respectively.


Early life adversity predicts brain-gut alterations associated with increased stress and mood.
Alterations in the brain-gut system have been implicated in various disease states, but little is known about how early-life adversity (ELA) impacts development and adult health as mediated by brain-gut interactions. We hypothesize that ELA disrupts components of the brain-gut system, thereby increasing susceptibility to disordered mood. In a sample of 128 healthy adult participants, a history of ELA and current stress, depression, and anxiety were assessed using validated questionnaires. Fecal metabolites were measured using liquid chromatography tandem mass spectrometry-based untargeted metabolomic profiling. Functional brain connectivity was evaluated by magnetic resonance imaging. Sparse partial least squares-discriminant analysis, controlling for sex, body mass index, age, and diet was used to predict brain-gut alterations as a function of ELA. ELA was correlated with four gut-regulated metabolites within the glutamate pathway (5-oxoproline, malate, urate, and glutamate gamma methyl ester) and alterations in functional brain connectivity within primarily sensorimotor, salience, and central executive networks. Integrated analyses revealed significant associations between these metabolites, functional brain connectivity, and scores for perceived stress, anxiety, and depression. This study reveals a novel association between a history of ELA, alterations in the brain-gut axis, and increased vulnerability to negative mood and stress. Results from the study raise the hypothesis that select gut-regulated metabolites may contribute to the adverse effects of critical period stress on neural development via pathways related to glutamatergic excitotoxicity and oxidative stress.


Genetics and treatment options for recurrent acute and chronic pancreatitis.
Worldwide research efforts demonstrate a major role of gene-environment interactions for the risk, development, and progression of most pancreatic diseases, including recurrent acute and chronic pancreatitis. New findings of pancreas disease-associated risk variants have been reported in the CPA1, GGT1, CLDN2, MMP1, MTHFR, and other genes. These risk genes and their regulatory regions must be added to the known pathogenic variants in the PRSS1, SPINK1, CFTR, CTRC, CASR, UBR1, SBDS, CEL, and CTSB genes. This new knowledge promises to improve disease management and prevention through personalized medicine. At the same time, however, knowledge of an increasing number of pathogenic variants, and their complicated effects when present in combination, results in increasing difficulty in interpretation and development of recommendations. Direct-to-consumer marketing of genetic testing results also adds complexity to disease management paradigms, especially without interpretation and, in many cases, proven accuracy. While improvements in the ability to rapidly and accurately interpret complex genetic tests are clearly needed, some results, such as pathogenic CFTR variants, including a new class of bicarbonate-defective mutations, and PRSS1 variants have immediate implications that direct management. In addition, discovery of pancreatitis-associated genetic variants in patients with glucose intolerance may suggest underlying type 3c diabetes, which also has implications for treatment and disease management.


MRI-Related Risk Factors for Distal Radioulnar Joint Instability.
Instability of the dorsal radioulnar ligament (DRUL) is caused by multiple factors from bony and soft tissue structures. Studies of DRUJ instability based on MRI have rarely been reported. This study aims to investigate related instability factors in the distal radioulnar joint (DRUJ) after trauma based on MRI imaging. The MRI imaging was performed on 121 post-traumatic patients with or without DRUJ instability from April 2021 to April 2022. All patients demonstrated pain or attenuated wrist ligamentous tissue quality with physical examination. The interesting variables, including age, sex, the distal radioulnar transverse shape, the triangular fibrocartilage complex (TFCC), DRUL, the volar radioulnar ligament (VRUL), distal interosseus membrane (DIOM), the extensor carpi ulnaris (ECU), and pronator quadratus (PQ), were analyzed using univariable and multivariable logistic regression model. The different variables were compared in radar plots and bar chart. An average age of 121 patients was 42.16 ± 16.07 years. The 50.4% DRUJ instability existed in all patients and the distal oblique bundle (DOB) presented in 20.7% of patients. The TFCC (p = 0.03), present DIOM (p = 0.001), and PQ (p = 0.006) were identified to be significant in final multivariable logistic model. The percentage of patients with ligament injuries were general higher in DRUJ instability group. The patients with absent DIOM had a higher rate in DRUJ instability, TFCC, and ECU injury. There was higher stability in shape of C-type, intact TFCC, and present DIOM. DRUJ instability is closely associated with TFCC, DIOM, and PQ. It could provide a potential for early detection of potential instability risk and taking necessary preventive measures.


Urinary metabolomic analysis to identify potential markers for the diagnosis of tuberculosis and latent tuberculosis.
Tuberculosis (TB) is a serious infectious disease with high infection and mortality rates. 5%-10% of the latent tuberculosis infections (LTBI) are likely to develop into active TB, and there are currently no clinical biomarkers that can distinguish between LTBI, active TB and other non-tuberculosis populations. Therefore, it is necessary to develop rapid diagnostic methods for active TB and LTBI. In this study, urinary metabolome of 30 active TB samples and the same number of LTBI and non-TB control samples were identified and analyzed by UPLC-Q Exactive MS. In total, 3744 metabolite components were obtained in ESI- mode and 4086 in ESI + mode. Orthogonal partial least square discriminant analysis (OPLS-DA) and hierarchical cluster analysis (HCA) showed that there were significant differences among LTBI, active TB and non-TB. Six differential metabolites were screened in positive and negative mode, 3-hexenoic acid, glutathione (GSH), glycochenodeoxycholate-3-sulfate, N-[4'-hydroxy-(E)-cinnamoyl]-l-aspartic acid, deoxyribose 5-phosphate and histamine. The overlapping pathways differential metabolites involved were mainly related to immune regulation and urea cycle. The results showed that the urine metabolism of TB patients was disordered and many metabolic pathways changed. Multivariate statistical analysis revealed that GSH and histamine were selected as potential molecular markers, with area under curve of receiver operating characteristic curve over 0.75. Among the multiple differential metabolites, GSH and histamine changed to varying degrees in active TB, LTBI and the non-TB control group. The levels of GSH and histamine in 48 urinary samples were measured by ELISA in validation phase, and the result in our study provided the potential for non-invasive biomarkers of TB.


Improving the accuracy of meta-analysis for datasets with missing measures of variance: Elevated [CO2] effect on plant growth as a case study.
Ongoing increases in atmospheric carbon dioxide (CO2) are expected to stimulate biomass and yield of plants possessing the C3 photosynthetic pathway; however, the extent of stimulation is likely to vary both intra- and inter-species specifically. Meta-analytic approaches can be applied to decrease variation and uncertainty by delineating and characterizing variation, allowing results to be used in modeling plant responses to elevated [CO2]. However, the use of meta-analysis in this effort could be limited by missing measures of variance, including standard deviations (SDs) of the compiled dataset. Here, we examined whether there were differences in effect sizes of elevated [CO2] on plant growth using various weighting and imputation approaches. Our results showed that the efficacy of different weighting functions and data interpolation methods on meta-analysis outcomes depended on the SDs provided by the studies. Comparing different methodologies for [CO2] fumigation as a case study, if the ratio of missing SD was low, the overall trend of effect values and 95% confidence interval (CI) were not changed. For datasets of greenhouse and growth chamber [CO2] methodologies, which had a high ratio of missing SDs, effect sizes and 95% confidence intervals using different weighing and imputation methods were influenced relative to that of the raw dataset, with reduced effect sizes and broader CI. Overall these results suggest that application of meta-analysis to discern general biological responses could be influenced by the number of missing SDs. As such, efforts should be made to check the proportion of missing SDs of the compiled dataset and if necessary, to apply various weighting functions and imputation methods to fully discern meta-analysis implications. Our findings could improve the assessment of methodological choices for future [CO2] experimentation and discerning long-term trends for agricultural productivity and food security.


Placental site nodule.
The immunohistological features of a case of placental site nodule, a cytologically alarming but clinically benign lesion, are reported.


A human X-Y homologous region encodes "amelogenin".
Results of cloning and sequencing of genomic sequences from the X and Y chromosomes that encode the tooth enamel gene amelogenin (both AMG and AMGL) are described. Three exons are defined on both the X and Y sequences. The nucleotide sequences reported here offer basic information for investigating human amelogenin.


Community philanthropy as practice: A case study of Thousand Currents.
As philanthropy has emerged to play a prominent role in supporting community well-being efforts, important critiques have been raised about the undemocratic nature of philanthropy that appears to privilege private interests over community needs. In response to these concerns, Community Philanthropy (CP) has emerged as a philanthropic model that prioritizes community asset-building, agency, and trust in order to "shift power" to beneficiary communities (Hodgson & Pond (2018). How community philanthropy shifts power. Grantcraft. Retrieved August 14, 2021, from https://grantcraft.org/content/guides/how-community-philanthropy-shifts-power). Despite its promise, questions remain about how CP can practically achieve the goals of sharing power, building trust, and showing solidarity toward community self-determination for well-being. To address these gaps, we examine the case of Thousand Currents, a public foundation that has pioneered a CP inspired grantmaking model. Thousand Currents provides long-term unrestricted grants to grassroots partners (grantees), learns about partner concerns, acts upon partner feedback, and is self-reflexive about its positional power as a funder. The foundation achieves its grantmaking objectives by taking deliberate fundraising and staffing decisions. Our case study showcases how other foundations can take steps towards actualizing CP.


Cost-effective circadian mechanism: rhythmic degradation of circadian proteins spontaneously emerges without rhythmic post-translational regulation.
Circadian protein oscillations are maintained by the lifelong repetition of protein production and degradation in daily balance. It comes at the cost of ever-replayed, futile protein synthesis each day. This biosynthetic cost with a given oscillatory protein profile is relievable by a rhythmic, not constant, degradation rate that selectively peaks at the right time of day but remains low elsewhere, saving much of the gross protein loss and of the replenishing protein synthesis. Here, our mathematical modeling reveals that the rhythmic degradation rate of proteins with circadian production spontaneously emerges under steady and limited activity of proteolytic mediators and does not necessarily require rhythmic post-translational regulation of previous focus. Additional (yet steady) post-translational modifications in a proteolytic pathway can further facilitate the degradation's rhythmicity in favor of the biosynthetic cost saving. Our work is supported by animal and plant circadian data, offering a generic mechanism for potentially widespread, time-dependent protein turnover.


Dietary assessment in children using electronic methods: telephones and tape recorders.
Selection of dietary assessment methodology is important in dietary intervention studies. Few studies have reported the relative merits of various assessment methods or the feasibility of electronic methods in pediatric populations. Parent-child dyads performed telephone recalls (no. = 32) and tape recorded dietary records (no. = 33). Traditional recalls were first conducted to familiarize parents and children with the telephone recall procedure, to introduce two-dimensional food models, and to instruct on the use of the tape recorder. Parents monitored and documented as unobtrusively as possible the child's intake on the day before the telephone recall and also on the day of the taped record. Children were called at random to reduce bias. Simple correlation coefficients (r) were calculated for nine nutrients and calories for both methods. For telephone recalls, values ranged from a low of r = .64 for saturated and polyunsaturated fat to r = .85 for cholesterol and r = .93 for iron. Tape-recorded data yielded r = .80 or above, except calories with r = .68 (p less than .001 for all values, 1-tail tests). Mean nutrient values were within expected ranges, e.g., 1,800 kcal +/- 500, with saturated fat about 14% of calories per day. Comparisons between parents and childrens reports of food frequencies and portion sizes revealed the best correlations for beverages, bread-cereals-crackers, meat-fish-poultry, and mixed dishes. We conclude that preadolescent children are able to provide dietary intake data using electronic methods in a manner that compares favorably with their parents' written records.


[Paranoid personality disorder and criminal offense].
Currently, all of the studies that focus on the relationship between paranoia and criminal offenses exclusively concern subjects suffering from a delusional paranoid disorder. However, subjects with single paranoid personality disorder, without any associated delusional disorder, are not uncommon in forensic practice. This study aims to describe the offenses committed by subjects suffering from a single paranoid personality disorder and to compare them with the offenses committed by the subjects affected by a paranoid delusional disorder associated with paranoid personality disorder. Our initial hypothesis is that both populations have a comparable criminological profile. Based on a 17 year-long experience carried out in the framework of a forensic assessment, we have selected all subjects presenting a paranoid personality disorder, whether single or associated with paranoid delusional disorder. The selected individuals were divided into two groups according to whether they presented paranoid delusional disorder or not. The offenses were grouped into criminal categories. The alpha risk was fixed at 1%. Data analysis is done by SAS software version 9.4. In a sample of 106 subjects presenting a paranoid personality disorder, including 4 women and 102 men, we found 79 subjects with a single paranoid personality and 27 with an associated paranoid delusional disorder. The average age at the time of the offense was 41 for those with single personality disorders and 49 for those with paranoid delusional disorders. Both groups had forensic antecedents (41%, 11/27 of paranoid delusional disorder and 51%, 40/79 of single paranoid personality disorder). Psychiatric history was more frequent in the paranoid delusional disorder group (59%, 16/27) than in the single paranoid personality disorder group (13%, 10/79). History of addiction was comparable in terms of alcohol abuse (26% in both groups) and other substances (7.5%, 2/27 of paranoid delusional disorder and 9%, 7/79 of single paranoid personality disorder). Comparison of the two groups highlighted significant differences in the type of criminal offenses committed (Fisher's exact test: P=0.0003, alpha risk <0.0001). The offenses committed by delusional authors essentially came down to verbal or physical violence, including homicide (44%, 12/27), and were usually focused on a designated persecutor. Sexual violence was rare. On the other hand, paranoid personality disorder was associated with a wider variety of offenses. Sexual offenses (including 28 rapes, 35%, 28/79) were thus almost as frequent as murder, and attempted murder (38%, 30/79). This diversity of committed offenses was found in their forensic antecedents. In these subjects, the logic of omnipotence may had over ruled the logic of revenge. We conducted a retrospective study on 106 subjects with paranoid personality disorder, including 27 subjects with associated paranoid delusional disorder. The comparison of the two groups demonstrated significant differences in offenses. Verbal and physical but non-sexual violence, committed in a delusional logic, was found among delusional subjects, while the forms of violence were more multiform in the single paranoid personality disorder group, frequently including sexual violence. This is, as far as we know, the first study describing the medico-legal acting-out of paranoid personalities. These results, which will need to be confirmed by future studies, point out the importance of the criminological risk that may be associated with paranoid personality disorder, without any associated delusional disorder.


Determination of free and protein-bound methadone and its major metabolite EDDP: enantiomeric separation and quantitation by LC/MS/MS.
To measure free and protein-bound R- and S-enantiomers of methadone and its major metabolite, 2-ethylidine-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) in serum. To determine free fraction, samples were filtered using ultrafiltration membranes with a molecular weight cut-off of 10,000 Da and extracted using liquid-liquid extraction. The solvent extract was evaporated and reconstituted in mobile phase for analysis by LC/MS/MS. Total analyte was determined by extracting unfiltered samples. Enantiomeric separation was by chiral chromatography. LC conditions resulted in baseline separation of R- and S-EDDP, and 85% resolution of methadone enantiomers. Precision of spiked specimens for both R- and S-methadone and R- and S-EDDP was less than 10% at 100 nM, and did not exceed 20% at 10 nM. Using minimal sample clean-up and a total instrument run-time of 10 min, a rapid, sensitive and highly specific method was developed for quantitation of free and total R- and S-enantiomers of methadone and EDDP.


Feeding behavior as seen through the prism of brain microdialysis.
The knowledge of feeding behavior mechanisms gained through brain microdialysis is reviewed. Most of the chemical changes so far reported concern to the limbic system in rodents. A picture showing increases and decreases of extracellular neurotransmitters correlating to different aspects of feeding behavior is gradually emerging. Depending on the region, the same neurotransmitter may signal opposite aspects of feeding. Dopamine (DA) in the nucleus accumbens (NAC) correlates with food reward, stimulus saliency, and goal directed hyperlocomotion but in the ventromedial hypothalamus DA correlates with satiety and hypolocomotion. The findings accumulated in the last 25 years suggest that the control of a particular function relies on the interaction of several neurotransmitters rather than on a single neurotransmitter. The poor sensitivity of most analytical techniques hinders time and spatial resolution of microdialysis. Therefore, neurochemical correlates of short lasting behaviors are hard to figure out. As new and more sensitive analytical techniques are applied, new neurochemical correlates of feeding show up. Sometimes the proper analytical techniques are simply not available. As a consequence, critical signals such as neuropeptides are not yet completely placed in the puzzle. Despite such limitations, brain microdialysis has yielded a great deal of knowledge on the neurochemical basis of feeding.


Superb microvascular imaging (SMI) detects increased vascularity of the torn anterior cruciate ligament.
Ultrasound with superb microvascular imaging (SMI) is a novel microvascular imaging technology which may be useful to assess the vascularity of the torn anterior cruciate ligament (ACL) as a potential measure of healing potential following surgery. This study aimed to quantify the vascularity of the torn and intact ACL using ultrasound with SMI. 23 patients (mean age ± standard deviation, 27.1 ± 12.8 years), who were diagnosed with an ACL tear with an intact contralateral ACL were enrolled (ACL injury group). Ten healthy volunteers (36.1 ± 4.9 years) who had intact ACLs in both knees were also recruited (ACL healthy controls). The vascularity of the ACL was assessed using SMI within 15 mm from the tibial insertion in both knees. The amount of the vascular signal was assessed using a semi-quantitative grading scale (vascularity grade: grade 0-3) and a quantified ratio of vascularized area with respect to total area of the region of interest (vascularity ratio). In the ACL injury group, a significantly higher vascularity grade and ratio were observed in the torn ACL (vascularity grade 0-3: 1, 8, 7, and 7 patients, respectively; vascularity ratio: 1.3 ± 1.4%) than the contralateral intact ACL (vascularity grade 0-3: 21, 1, 1, and 0 patients, respectively; vascularity ratio: 0.1 ± 0.5%) (P < 0.001), whereas no significant difference was observed between both ACLs in the ACL healthy control group. SMI was useful to assess the increased vascularity in torn ACL, which may reflect the potential for, or state of, ACL maturation following reconstruction or repair. Level III.


Can patiromer allow for intensified renin-angiotensin-aldosterone system blockade with losartan and spironolactone leading to decreased albuminuria in patients with chronic kidney disease, albuminuria and hyperkalaemia? An open-label randomised controlled trial: MorphCKD.
Chronic kidney disease (CKD) is associated with significantly increased morbidity and mortality. No specific treatment of the underlying condition is available for the majority of patients, but ACE-inhibitors (ACE-I) and angiotensin II-receptor blockers (ARB) slows progression in albuminuric CKD. Adding a mineralocorticoid receptor-antagonist (MRA) like spironolactone has an additive effect. However, renin-angiotensin-aldosterone system (RAAS)-blockade increases the risk of hyperkalaemia which is exacerbated by the presence of CKD. Thus, hyperkalaemia may prevent optimal use of RAAS-blockade in some patients.This project hypothesises that adding a potassium binder (patiromer) allows for improved RAAS-blockade including the use of MRA, thereby reducing albuminuria in patients with albuminuric CKD where full treatment is limited by hyperkalaemia.If successful, the study may lead to improved treatment of this subgroup of patients with CKD. Furthermore, the study will examine the feasibility of potassium binders in patients with CKD. An open-label, randomised controlled trial including 140 patients with estimated glomerular filtration rate (eGFR) 25-60 mL/min/1.73 m2, a urinary albumin/creatinine ratio (UACR) >500 mg/g (or 200 mg/g if diabetes mellitus) and a current or two previous plasma-potassium >4.5 mmol/L. Patients who develop hyperkaliaemia >5.5 mmol/L during a run-in phase, in which RAAS-blockade is intesified with the possible addition of spironolactone, are randomised to 12-month treatment with maximal tolerated ACE-I/ARB and spironolactone with or without patiromer.The primary endpoint is the difference in UACR measured at randomisation and 12 months compared between the two groups. Secondary endpoints include CKD progression, episodes of hyperkalaemia, blood pressure, eGFR, markers of cardiovascular disease, diet and quality of life. This study is approved by The Central Denmark Region Committees on Health Research Ethics (REFNO 1-10-72-110-20) and is registered in the EudraCT database (REFNO 2020-001595-15). Results will be presented in peer-reviewed journals, at meetings and at international conferences.


Sepsis prevalence and associated hospital admission and mortality after ureteroscopy in employed adults.
To determine 30-day inpatient mortality, intensive care unit (ICU) admissions, inpatient admissions/readmissions, and yearly trends in sepsis prevalence and inpatient mortality after ureteroscopy (URS) in employed adults. We performed a retrospective analysis of the IBM MarketScan Commercial Database to identify employed adults aged 18-64 years who underwent URS between 2015 and 2019. Patients were categorized as having no sepsis (controls), non-severe sepsis, or severe sepsis within 30 days of URS. The main outcomes included inpatient mortality, ICU admissions, inpatient admissions, readmissions, and annual rates of sepsis and associated inpatient mortality. Among 109 496 patients undergoing URS, 5.6% developed sepsis (4.1% non-severe, 1.5% severe). The 30-day inpatient mortality rates were 0.03%, 0.3% and 2.5% for controls, non-severe sepsis and severe sepsis, respectively (P < 0.001). In a multivariable analysis, diagnosis of sepsis regardless of severity (hazard ratio [HR] 17.2, 95% confidence interval [CI] 10.5-28.1; P < 0.001) or severe sepsis (HR 49.5, 95% CI 28.9-84.7; P < 0.001) increased the risk of 30-day inpatient mortality compared to no sepsis (controls). ICU admissions on the day of procedure (1.5%, 19.8% and 52.4%), inpatient admission rates (18.3%, 74.9% and 76.9%) and readmission rates (7.1%, 12.0% and 15.9%) were higher with severe sepsis and non-severe sepsis vs controls (all P < 0.001). During the study period, the prevalence of sepsis after URS increased from 4.7% to 6.6% (P < 0.001), while the associated mortality rate decreased from 0.7% to 0.2% (P < 0.001). Among working adults aged 18-64 years, sepsis after URS increases the risk of 30-day inpatient mortality, ICU and hospital admission, and hospital readmission. Although the prevalence of sepsis after URS is increasing over time, associated mortality rates are declining. Urologists should be aware of the potentially deadly consequences of sepsis after URS in younger patients.


People in Custody With a Suicidal History: An Ideation-to-Action Perspective Involving Individuals Incarcerated in Two U.S. Jails.
Despite high suicide mortality in U.S. jails, little is known about the cognitive (ideation) and behavioral (attempt) spectrum of suicide risk in this population. Identifying factors associated with the development of suicidal ideation, as well as the translation of thoughts to acts of suicide, is important for suicide prevention. Using data from a cross-sectional study conducted in 2018-2019, we investigated suicidal ideation and attempt among 548 individuals incarcerated in jail in the United States. Specifically, we compared those with suicidal ideation (n = 212) to those without suicidal ideation (n = 336), as well as compared those who had experienced suicidal ideation and attempted suicide (n = 114) to those who thought about suicide without making an attempt (n = 98), on a range of sociodemographic and clinical factors. Over one-third (38.7%) of participants had a history of suicidal ideation, whereas 23.3% had attempted suicide. In the adjusted analyses, a family history of suicide (OR = 2.09), drug use (OR = 2.26), social support (OR = 0.61), and self-harm (OR = 24.93) were linked to suicidal ideation. No wish to live (OR = 5.26) and interpersonal violence while intoxicated (OR = 2.41) were associated with the progression from suicidal ideation to a suicide attempt. Consistent with extant theoretical and empirical work, findings suggest that factors linked to the development of suicidal cognitions differ from those underlying the progression from suicidal ideation to a (non-lethal) suicide attempt.HIGHLIGHTSSuicidal risk is particularly high among individuals who are incarcerated in jail.Factors linked to suicidal ideation differ from those underlying acts of suicide.Ideators and attempters possess a different set of targets for intervention.


Lens and Peripheral Retinal Relationships During Vitrectomy: Comparison of 23-, 25-, and 27-Gauge Vitrectomy and Curved Endolaser Probes.
This work aims to compare spatial relationships between the crystalline lens and vitrectomy instruments of different gauges. Eight phakic eyes recovered from deceased donors were used after fixation. Valved trocars (27-gauge, 25-gauge, and 23-gauge) were sequentially placed in the superotemporal quadrant 4 mm posterior to the limbus in each eye. Intraocular relationships of vitrectomy and curved endolaser probes were measured for each gauge. There were no significant differences in maneuverability between instruments of different gauges. The mean distance from instrument to lens at the geometric center of the globe was 5.5 mm. Vitrectomy probes of all gauges could access the peripheral retina on both sides of the sclerotomy in the 3 to 4 o'clock position adjacent to the sclerotomy without touching the lens. The instruments could be advanced without lens touch to contact the retina within at least 2 mm of the ora serrata 180° away from the insertion site. Vitrectomy and curved endolaser probes achieved similar maneuverability relative to the lens regardless of gauge. This study confirms that small-gauge vitrectomy instruments have a considerable range of safe access to the peripheral retina in phakic eyes from a single sclerotomy.


Quickly 'learning' to move optimally.
People take account of the variability in their movements in a near-optimal manner in various visuo-motor tasks. Is knowledge of one's variability needed for such near-optimal performance, or could it arise from responding to one's success in previous attempts in some simple manner? We asked subjects to move a pen back and forth across a tablet to make a cursor move as quickly as possible between two targets. The cursor had to stop within the targets. Task difficulty was varied between blocks. Part of the variation in difficulty was explicit (three target sizes) whereas the rest had to be discovered during the movements (two mappings between the movements of pen and cursor). In all cases, subjects sped up after stopping within a target and slowed down after failing to do so. We interpret this as evidence that explicit knowledge of one's variability is not necessary for performing close to optimally.


Quantification of ACE inhibiting peptides in human plasma using high performance liquid chromatography-mass spectrometry.
An HPLC-MRM-MS method was developed for the quantification of 17 small ACE inhibiting (ACEI) peptides in plasma samples collected from human volunteers after the consumption of a peptide-enriched drink. The assay shows the high selectivity and sensitivity necessary to monitor small changes in the levels of the ACEI peptides after consumption of drinks developed to effect lowering of the blood pressure. Four different sample preparation methods were tested and evaluated. The final sample preparation method selected is simple and effective and consists mainly of the removal of proteins by acidification and heating, followed by a large volume injection. Additional sample preparation steps such as solid phase extraction and liquid/liquid partitioning were studied. Although they resulted in cleaner extracts, losses of specific peptides such as SAP were frequently seen. The isotope labeled form of one of the peptides to be quantified, [U(13)C]IPP, was used as an internal standard. The limit of detection of the assay is below 0.01 ng ml(-1). The limit of quantification is between 0.05 and 0.2 ng ml(-1), which is approximately 10% of the expected peptide concentration in plasma based on a normal diet. The intra- and inter-day relative standard deviations for all peptides have shown to be below 25% and the method has an accuracy of better than 75%. The long-term stability is good. At least 200 samples could be analysed before the system had to be cleaned. The assay has been successfully applied to blood samples collected from volunteers during a human trial.


Immunomodulatory Effect of G2013 (α-L-Guluronic Acid) on the TLR2 and TLR4 in Human Mononuclear Cells.
Inhibition of Toll-like receptors (TLRs) signaling has been established as a new method for the development of anti-inflammatory drugs instead of NSAIDs (non-steroid anti-inflammatory drugs). Since the immunomodulatory role of G2013 (α-L-Guluronic acid) was reported in some recent experiments, we decided to assess the effects of G2013 on the protein expression of TLR2 and TLR4, their downstream signaling cascade, and the secretion of pro-inflammatory cytokines in human peripheral blood mononuclear cells (PBMCs). After blood sampling from 16 healthy donors, PBMCs were isolated and treated with/without lipopolysaccharide (LPS), lipopolyteichoic acid (LTA), and G2013. Flow cytometry was done for detecting the protein expression of TLR2 and TLR4. MyD88, IκB, Tollip, and NF-κB mRNA expression were assessed by realtime PCR. ELISA was performed for assessing the concentration of IL-1β and IL-6. G2013 at a concentration of 25 µg/mL (high dose) significantly downregulated NF-κB, IκB and MyD88 mRNA expression and suppressed the secretion of IL-1β by PBMCs. The findings indicate that G2013 may exert its regulatory effect under normal condition via Tollip in a dose dependence pathway. Our results demonstrated that G2013 had no profound impact on the protein expression of TLR2 and TLR4. In conclusion, our findings point to the immunomodulatory effect of G2013 on the TLR2 and TLR4 signaling cascade and cytokine production by PBMCs. These findings could lead to an establishment of new safe anti-inflammatory drugs in the future.


Cholinesterase inhibition and behavioral toxicity of carbofuran on Oreochromis niloticus early life stages.
Nile tilapia Oreochromis niloticus at 9 days post-hatch were exposed in semi-static experiments to the carbamate insecticide carbofuran, which is applied in agricultural systems in Brazil. Although the molecular mechanism of carbofuran toxicity is well known, a detailed understanding of the ecological mechanisms through which carbofuran effects can propagate towards higher levels of biological organization in fish is incomplete. Mortality rates were quantified for larvae exposed for 96 h to 8.3, 40.6, 69.9, 140, 297 and 397 μg/L carbofuran, and the LC(50) 96 h was 214.7 μg/L. In addition, the biochemical biomarker cholinesterase inhibition and behavioral biomarkers related to vision, swimming, prey capture and predator avoidance were quantified in individual larvae, as well as their growth in weight. The behavioral parameters were quantified by analysis of digitally recorded videos of individual larvae within appropriate experimental setups. The activity of the enzyme cholinesterase decreased after exposure to carbofuran with a lowest observed effects concentration (LOEC) of 69.9 μg/L. Visual acuity deficits were detected after carbofuran exposure with a LOEC of 40.6 μg/L. Swimming speed decreased with carbofuran exposure, with a LOEC of 397.6 μg/L. The number of attacks to prey (Daphnia magna nauplii) decreased in larvae exposed to carbofuran, with a LOEC of 397.6 μg/L. Growth in weight was significantly reduced in a dose dependent manner, and all carbofuran groups exhibited a statistically significant decrease in growth when compared to controls (p<0.05). The number of predator attacks necessary to capture larvae decreased after exposure to carbofuran, and the LOEC was 69.9 μg/L. These results show that exposure of sensitive early life stages of tilapia O. niloticus to sublethal concentrations of carbofuran can affect fundamental aspects of fish larval ecology that are relevant to recruitment of fish populations, and that can be better understood by the application of behavioral biomarkers.


Isothermal chemiluminescent assay based on circular stand-displacement polymerization reaction amplification for cel-miRNA-39-3p determination in cell extracts.
A sensitive and specific heterogeneous assay for quantitation of cel-miRNA-39-3p (miRNA-39) was constructed. To improve the assay sensitivity an amplification strategy based on the use of isothermal circular strand-displacement polymerization reaction (ICSDPR), polyperoxidase conjugated with streptavidin and enhanced chemiluminescence was used. The detection limit of the proposed assay was 4 × 10-13 M. The coefficient of variation (CV) for quantitation of miRNA-39 within the working range was below 8%. The study of cross-reactivity of different miRNAs including miRNA-39 demonstrated high specificity of the proposed assay. Comparison of the calibration curves of miRNA-39 dissolved in the buffer and the lysate of MCF-7 cells (prepared by lysis of the cells with phenol/guanidine thiocyanate mixture and purified using silica membrane spin column) has demonstrated a negligible matrix effect. The proposed assay makes it possible to estimate the yield of purification of miRNAs from cells, which is necessary for the quantitative calculation of the intracellular content of miRNAs measured with the isothermal assay coupled with ICSDPR.