Deficiency of polycystin-2 reduces Ca2+ channel activity and cell proliferation in ADPKD lymphoblastoid cells.
Polycystin-2 (PC2), encoded by the PKD2 gene, mutated in 10-15% of autosomal-dominant polycystic kidney disease (ADPKD) patients, is a Ca2+-permeable cation channel present in kidney epithelia and other tissues. As PC2 was found expressed in B-lymphoblastoid cells (LCLs) and Ca2+ signaling pathways are important regulators of B cell function activities, we investigated whether PC2 plays some role in B-LCLs. In LCLs, PC2 was found mainly in ER membranes but ~8 times less than in kidney HEK293 cells. The same reductions were found in PKD2 and PKD1 RNA; thus, PKD genes maintained, in LCLs, the same reciprocal proportion as they do in kidney cells. In LCLs obtained from subjects carrying PKD2 mutations (PKD2-LCLs) and showing reduced PC2 levels, intracellular Ca2+ concentrations evoked by platelet-activating factor (PAF), were significantly lower than in non-PKD-LCLs. This reduction was also found in PKD1-LCLs but without PC2 reductions. Likewise, cell proliferation, which is controlled by Ca2+, was reduced in PKD2- and PKD1-LCLs. Moreover, in LCLs with PKD2 nonsense mutations, aminoglycoside antibiotics reduced the PC2 defect by promoting readthrough of stop codons. Therefore, PC2 and PC1 are functionally expressed in LCLs, which provide a model, easily obtainable from ADPKD patients, to study PKD gene expression and function.


Rituximab-induced direct inhibition of T-cell activation.
Rituximab, an anti-CD20 monoclonal antibody, is reported to increase the T-cell-dependent infection risk. The current study was designed to investigate whether rituximab interferes with T-cell activation. Patients with non-Hodgkin lymphoma receiving 4-6 courses of 375 mg/m(2) rituximab underwent detailed assessment of T-cell activation pre- and post-rituximab. A similar analysis assessed the in vitro effect of rituximab on T-cell activation in response to allogeneic dendritic cells (allo-DCs) and other stimuli. Patients receiving rituximab exhibited a significant decline in IL-2 and IFN-γ levels in peripheral blood, most prominent after repeated rituximab courses. Evaluation at 3 months after rituximab therapy showed restoration of inflammatory cytokine production. Similarly, in vitro stimulation of peripheral blood mononuclear cells in the presence of rituximab resulted in a significant decrease in T-cell activation markers, inflammatory cytokine production and proliferative capacity. These effects were also observed using B-cell-depleted T cells (CD3(+)CD25(-)CD19(-)) and were accompanied with disappearance of CD3(+)CD20(dim) T-cell population. Rituximab administration results in transient, dose-dependent T-cell inactivation. This effect is obtained even in B-cell absence and may increase the infection risk.


Beneficial impact of the homelands movement on health outcomes in central Australian aborigines.
This study compares prevalence of obesity, hypertension and diabetes in two groups of Aboriginal adults: those living in homelands versus centralised communities in central Australia. It also compares weight gain, incidence of diabetes, mortality and hospitalisation rates between the groups over a seven-year period. Baseline survey of 826 Aboriginal adults in rural central Australian communities in 1987-88 with a follow-up survey of 416 (56% response rate, excluding deaths). Each time, they had a 75 g oral glucose tolerance test (OGTT), and blood pressure and anthropometry measurement. Deaths and hospitalisations for all of the original cohort were recorded for the seven-year period. Homelands residents had a lower baseline prevalence of diabetes (risk ratio [RR] = 0.77, 0.59-1.00), hypertension (RR = 0.66, 0.54-0.80) and overweight/obesity (RR = 0.70, 0.59-0.83). The incidence of diabetes was lower among homelands residents (RR = 0.70, 0.46-1.06). They were less likely to die than those living in centralised communities (RR = 0.56, 0.37-0.85) and less likely to be hospitalised for any cause (RR = 0.79, 0.71-0.87), particularly infections (RR = 0.70, 0.61-0.80), injury involving alcohol (RR = 0.61, 0.47-0.79) and other injury (RR = 0.75, 0.60-0.93). Mean age at death was 58 and 48 years for residents of homelands and centralised communities respectively. Aboriginal people who live in homelands communities appear to have more favourable health outcomes with respect to mortality, hospitalisation, hypertension, diabetes and injury, than those living in more centralised settlements in Central Australia. These effects are most marked among younger adults.


ERCC1 C8092A (rs3212986) polymorphism as a predictive marker in esophageal cancer patients treated with cisplatin/5-FU-based neoadjuvant therapy.
At present, no consensus exists on the beneficial effect of preoperative cisplatin/5-fluorouracil (5-FU)-based chemotherapy versus primary surgery in the management of patients with esophageal cancer. The aim of this study was to evaluate the impact of some relevant genetic polymorphisms, within drug-related and DNA repair genes, on the clinical outcome of esophageal cancer patients subjected to cisplatin/5-FU-based neoadjuvant treatment. DNA from 143 esophageal cancer patients, 63 receiving neoadjuvant therapy and 80 receiving primary surgery, was analyzed for the following polymorphisms: the GSTM1 null, GSTT1 null, and GSTP1 Ile105Val (rs16953) in glutathione S-transferase (GST) family, 2 in thymidylate synthase (TS) gene, and the ERCC1 Asn118Asn (rs11615), ERCC1 C8092A (rs3212986), XPD/ERCC2 Asp312Asn (rs1799793), and XPD/ERCC2 Lys751Gln (rs13181) of the nucleotide excision repair pathway. We found that the ERCC1 rs3212986, although not associated with therapeutic response, is an independent predictive marker of better outcome in a cisplatin/5-FU-based neoadjuvant setting (hazard ratio: 0.38, 95% confidence interval: 0.2-0.73, P=0.008). In contrast, no association with clinical outcome was observed for this polymorphism in the primary surgery group. Our study indicates the ERCC1 rs3212986 as a predictive marker in the cisplatin/5-FU-based neoadjuvant setting, and also suggests its use as a marker to select the appropriate therapeutic approach in esophageal cancer patients.


Variation in the phosphorus content of bone samples obtained from the last three ribs of cattle.
Variation in the phosphorus content and specific gravity of bone samples taken from the 11th, 12th and 13th ribs of cattle was examined in relation to the selection of a site for the acquisition of such samples by biopsy, in experiments where changes in skeletal phosphorus storage required to be monitored. The degree of mineralisation of the 11th rib was significantly higher than that of the 12th, which in turn was greater than that of the 13th. It was concluded that valid comparisons may be made between bone samples obtained during an experimental regime, provided they are taken from the same numbered rib; it is recommended that the 13th rib be avoided in such studies.


Isolation of the receptor for Amaranthus leucocarpus lectin from murine peritoneal macrophages.
The receptor for Amaranthus leucocarpus lectin from CD-1 resident macrophages was purified with affinity chromatography with biotin labeled A. leucocarpus lectin and using avidin-agarose as affinity matrix. The receptor is a glycoprotein of 70 kDa that contains 18% of sugar by weight; it is mainly composed of galactose and N-acetyl-D-galactosamine in its saccharidic portion, and lacks sialic acid; the protein is rich in glycine, serine and alanine and lacks cysteine residues. The amino terminus of the receptor is blocked. By ionic strength chromatography on a mono P column in anionic form we purified three isoforms from the affinity purified receptor, each showing quantitative differences in glycosylation. The A. leucocarpus lectin receptor is identified only in resting, not activated, macrophages suggesting that it plays a role in activation mechanisms of macrophages.


Tunable alignment of macromolecules by filamentous phage yields dipolar coupling interactions.
Dipolar coupling interactions represent an extremely valuable source of long-range distance and angle information that was previously not available for solution structure determinations of macromolecules. This is because observation of these dipolar coupling data requires creating an anisotropic environment for the macromolecule. Here we introduce a new method for generating tunable degrees of alignment of macromolecules by addition of magnetically aligned Pf1 filamentous bacteriophage as a cosolute. This phage-induced alignment technique has been used to study 1H-1H, 1H-13C, and 1H-15N dipolar coupling interactions in a DNA duplex, an RNA hairpin and several proteins including thioredoxin and apo-calmodulin. The phage allow alignment of macromolecules over a wide range of temperature and solution conditions and thus represent a stable versatile method for generating partially aligned macromolecules in solution.


TIMP-2 mediated inhibition of angiogenesis: an MMP-independent mechanism.
Tissue inhibitors of metalloproteinases (TIMPs) suppress matrix metalloproteinase (MMP) activity critical for extracellular matrix turnover associated with both physiologic and pathologic tissue remodeling. We demonstrate here that TIMP-2 abrogates angiogenic factor-induced endothelial cell proliferation in vitro and angiogenesis in vivo independent of MMP inhibition. These effects require alpha 3 beta 1 integrin-mediated binding of TIMP-2 to endothelial cells. Further, TIMP-2 induces a decrease in total protein tyrosine phosphatase (PTP) activity associated with beta1 integrin subunits as well as dissociation of the phosphatase SHP-1 from beta1. TIMP-2 treatment also results in a concomitant increase in PTP activity associated with tyrosine kinase receptors FGFR-1 and KDR. Our findings establish an unexpected, MMP-independent mechanism for TIMP-2 inhibition of endothelial cell proliferation in vitro and reveal an important component of the antiangiogenic effect of TIMP2 in vivo.


Unrelated female-to-male bone marrow transplantation would be preferred over cord blood transplantation in male patients.
Allogeneic hematopoietic stem cell transplantation from female donors to male recipients (female-to-male allo-HCT) is a well-established risk factor for a greater incidence of non-relapse mortality (NRM) and chronic graft-versus-host disease (GVHD). In contrast, unrelated cord blood transplantation (UCBT) is associated with a lower incidence of chronic GVHD. In this study, survival outcomes were compared between the UCBT and unrelated female-to-male bone marrow transplantation (UFMBMT) groups. We evaluated male allo-HCT recipients who underwent UCBT or UFMBMT between 2012 and 2020 in Japan. There were 2517 cases in the UCBT group, 456 cases in the HLA-matched UFMBMT group and 457 cases in the HLA-mismatched UFMBMT group. HLA-mismatched UFMBMT was significantly associated with a decreased risk of relapse (hazard ratio [HR] 0.74; 95% confidence interval [CI] 0.57-0.98], P = 0.033) and HLA-matched UFMBMT had the tendency of a decreased risk of relapse (HR 0.78; 95% CI 0.61-1.01, P = 0.059). HLA-matched UFMBMT was also associated with favorable OS (HR 0.82; 95% CI 0.69-0.97, P = 0.021). The relationship between the donor sources and relapse was similarly observed in the lymphoid malignancy cohort. The difference of graft-versus leukemia effect by H-Y immunity according to donor sources might contribute to the difference in clinical impact. It might be desirable for patients who could sufficiently wait for donor coordination to select BMT rather than UCBT, even if only unrelated female donors are available for male recipients.


Irritable Bowel Syndrome and Female Patients.
Irritable bowel syndrome is probably the most common functional gastrointestinal disorder and is characterized by abdominal pain along with altered bowel function. It is a disorder of female predominance. This article focuses on how being female influences the pathophysiology, diagnosis, management, and treatment of this common disorder and discusses the evidence and important controversies related to these areas.


After the sun: a nanoscale comparison of the surface chemical composition of UV and soil weathered plastics.
Once emitted into the environment, macro- (MaP), micro- (MP) and nanoplastics (NP) are exposed to environmental weathering. Yet, the effects of biogeochemical weathering factors occurring in the soil environment are unknown. As the transport, fate, and toxicity of MP and NP depend directly on their surface properties, it is crucial to characterize their transformation in soils to better predict their impact and interactions in this environment. Here, we used scanning transmission x-ray micro spectroscopy to characterize depth profiles of the surface alteration of environmental plastic debris retrieved from soil samples. Controlled weathering experiments in soil and with UV radiation were also performed to investigate the individual effect of these weathering factors on polymer surface alteration. The results revealed a weathered surface on a depth varying between 1 µm and 100 nm in PS, PET and PP environmental plastic fragments naturally weathered in soil. Moreover, the initial step of surface fragmentation was observed on a PS fragment, providing an insight on the factors and processes leading to the release of MP and NP in soils. The comparison of environmental, soil incubated (for 1 year) and UV weathered samples showed that the treatments led to different surface chemical modifications. While the environmental samples showed evidence of alteration involving oxidation processes, the UV weathered samples did not reveal oxidation signs at the surface but only decrease in peak intensities (indicating decrease of the number of chemical C bonds). After a one-year incubation of samples in soil no clear aging effects were observed, indicating that the aging of polymers can be slow in soils. The online version contains supplementary material available at 10.1186/s43591-023-00066-2.


Type II collagen autoimmunity in a mouse model of human rheumatoid arthritis.
Type II collagen (CII) is expressed exclusively in the joint articular. Although the relationship between anti-CII immunity and human rheumatoid arthritis (RA) has been studied for a long time, definitive conclusions have not been reached. CII, as an autoantigen, has been studied extensively in small animal models, such as mice, and the collagen-induced arthritis (CIA) model has increased our understanding of the pathogenesis of human RA. In the present report, we summarize the available information on anti-CII immunity and discuss recent updates regarding pathogenesis in the CIA model, including the role of Th17 cells.


Viability assessment of livers donated after circulatory determination of death during normothermic regional perfusion.
Abdominal normothermic regional perfusion (A-NRP) allows in-situ reperfusion and recovery of abdominal organs metabolism in donors after circulatory death (DCD). Besides improving liver transplantation outcomes, liver injury and function can be assessed during A-NRP. To refine liver viability assessment during A-NRP, prospectively collected data of controlled DCD donors managed at our Institution between October 2019 and May 2022 were retrospectively analyzed. Baseline characteristics, procedural variables and A-NRP parameters of donors whose liver was successfully transplanted were compared to those of donors whose liver was discarded. Twenty-seven donors were included and in 20 (74%) the liver was accepted (positive outcome). No differences between study groups were observed concerning baseline characteristics and warm ischemia times (WIT). Initial lactate levels were positively correlated with functional WIT (r2 = 0.4, p = 0.04), whereas transaminase levels were not. Blood flow during A-NRP was comparable, whereas oxygen consumption (VO2 ) was significantly higher in the positive outcome group after 1 h. Time courses of lactate, AST and ALT were significantly different between study groups (p < 0.001). Donors whose liver was accepted showed faster lactate clearance, a difference which was amplified by normalizing lactate clearance to oxygen delivery (DO2 ) and VO2 . Lactate clearance was correlated to transaminase levels and DO2 -normalized lactate clearance was the parameter best discriminating between study groups. DO2 -normalized lactate clearance may represent an element of liver viability assessment during A-NRP.


Ultra-high-performance liquid chromatography-tandem mass spectrometry measurement of climbazole deposition from hair care products onto artificial skin and human scalp.
A sensitive and specific ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed and validated for the measurement of climbazole deposition from hair care products onto artificial skin and human scalp. Deuterated climbazole was used as the internal standard. Atmospheric pressure chemical ionization (APCI) in positive mode was applied for the detection of climbazole. For quantification, multiple reaction monitoring (MRM) transition 293.0>69.0 was monitored for climbazole, and MRM transition 296.0>225.1 for the deuterated climbazole. The linear range ran from 4 to 2000 ng mL(-1). The limit of detection (LOD) and the limit of quantification (LOQ) were 1 ng mL(-1) and 4 ng mL(-1), respectively, which enabled quantification of climbazole on artificial skin and human scalp at ppb level (corresponding to 16 ng cm(-2)). For the sampling of climbazole from human scalp the buffer scrub method using a surfactant-modified phosphate buffered saline (PBS) solution was selected based on a performance comparison of tape stripping, the buffer scrub method and solvent extraction in in vitro studies. Using this method, climbazole deposition in in vitro and in vivo studies was successfully quantified.


Self-Heating and Failure in Scalable Graphene Devices.
Self-heating induced failure of graphene devices synthesized from both chemical vapor deposition (CVD) and epitaxial means is compared using a combination of infrared thermography and Raman imaging. Despite a larger thermal resistance, CVD devices dissipate >3x the amount of power before failure than their epitaxial counterparts. The discrepancy arises due to morphological irregularities implicit to the graphene synthesis method that induce localized heating. Morphology, rather than thermal resistance, therefore dictates power handling limits in graphene devices.


Directed assembly and reactivity of olefins within a one-dimensional ladder-like coordination polymer based on a dinuclear Zn(II) platform.
A ladder-like coordination polymer involving a dinuclear Zn Schiff-base complex possesses organic linkers that undergo [2+2] photodimerisation in the solid state.


Proximal pancreatectomy: a comparison of electrocautery and contact and noncontact Nd:YAG laser techniques in the dog.
Proximal pancreatectomy with duodenal preservation is technically difficult. It has often been performed experimentally in pancreatic transplantation studies. Preservation of the pancreaticoduodenal vessels and duodenum provides an excellent method of testing various operative techniques in pancreatic surgery which may lead to further clinical applications. The present study has compared the conventional noncontact Nd:YAG laser technique with electrocautery and a new contact Nd:YAG laser technique for proximal pancreatectomy. There were five dogs in each group, and the pancreatic duct was left open to drain into the abdominal cavity after pancreatic transection in all of the animals. Resection with the contact laser caused significantly less blood loss (109 +/- 74 ml) than the noncontact laser (228 +/- 81 ml), (p less than 0.05). A greater number of ligatures were used in the noncontact laser group (11 +/- 3 ligatures) as compared with the electrocautery group (2.2 +/- 1.6 ligatures) and the contact laser group (5.2 +/- 2.8 ligatures), (p less than 0.005). Noncontact laser and electrocautery resection techniques resulted in necrotizing pancreatitis and death in two animals. The new contact laser system provides a safe and effective method of performing pancreatic surgery.


Decolorization of the metal textile dye Lanaset Grey G by immobilized white-rot fungi.
In this paper we studied the ability of four Tunisian-isolated fungi (i.e. Coriolopsis gallica, Bjerkandera adusta, Trametes versicolor and Trametes trogii) immobilized into Ca-alginate beads to decolorize the metal textile dye Lanaset Grey G (LG). The effect of different operational conditions, such as initial dye concentration, temperature, pH, beads/medium ratio and agitation, on dye decolorization by the immobilized fungi was investigated. Maximal decolorization percentages of 88.7%, 89.3%, 82.1% and 81.3% for C. gallica, B. adusta, T. versicolor and T. trogii were attained, respectively, when operating at an initial LG concentration of 150 mg/L, pH values of 5.0-6.0, temperatures of 40-45 °C and a beads/medium ratio of 20% (w/v) in static conditions after 72 h of incubation. Subsequently, the re-usability of the immobilized fungi was evaluated. After three decolorization cycles, the decolorization percentage of free cell cultures dropped to values below 36%, while decolorization percentages of about 75%, 70%, 60% and 68% were obtained by the immobilized cultures of C. gallica, B. adusta, T. versicolor and T. trogii, respectively.


Cortical excitability differences between flexor pollicis longus and APB.
Although abductor pollicis brevis (APB) and flexor pollicis longus (FPL) share a common peripheral nerve supply, these muscles subserve different functions and may be differently affected in neurodegenerative disease such as amyotrophic lateral sclerosis (ALS). As a consequence, differences in cortical excitability may potentially develop in relation to these functional differences. Cortical excitability was assessed using the threshold tracking transcranial magnetic stimulation (TMS) technique in 15 healthy controls with motor responses recorded over the APB and FPL using surface electrode recordings. Short-interval intracortical inhibition (SICI) was significantly reduced from the FPL compared to APB (SICIFPL 6.9±1.8%; SICIAPB 10.7±1.4%, P<0.01). In addition, the FPL motor evoked potential amplitude (MEPFPL 14.7±2.3%; MEPAPB 21.7±3.9%; P<0.01) and cortical silent period duration (CSPFPL 174.7±6.7ms; CSPAPB 205.4±3.9ms, P<0.01) were significantly smaller. The findings in the present study indicate that cortical inhibition and corticomotoneuronal output is reduced when recording over the FPL. The differences in cortical excitability may develop as a consequence of varied function and could potentially explain the dissociated muscle atrophy evident in ALS.


Molecular cloning of a cytosolic ascorbate peroxidase cDNA from cell cultures of sweet potato and its expression in response to stress.
A cDNA encoding a cytosolic ascorbate peroxidase (APX), swAPX1, was isolated from cell cultures of sweet potato ( Ipomoea batatas) by cDNA library screening, and its expression in the context of various environmental stresses was investigated. swAPX1 contains an ORF of 250 amino acids (27.5 kDa) encoding a protein with a pI value of 5.32. The swAPX1 ORF does not code for a transit peptide, suggesting that the product is a cytosolic isoform. RNA blot analysis showed that swAPX1 gene is expressed in cultured cells and mature leaves, but not in stems, non-storage or storage roots of sweet potato. The level of swAPX1 RNA progressively increased during cell growth in suspension cultures. In leaf tissues, the gene responded differentially to various abiotic stresses, as revealed by RT-PCR analysis. swAPX1 was highly induced in leaves by wounding, and treatment with methyl viologen (50 microM), hydrogen peroxide (440 mM), abscisic acid (ABA; 100 microM) or exposure to high temperature (37 degrees C). In addition, the gene was strongly induced in the leaves following inoculation with a bacterial pathogen ( Pectobacterium chrysanthemi). These results indicate that swAPX1 may be involved in hydrogen peroxide-detoxification and thus help to overcome the oxidative stress induced by abiotic and biotic stresses.


PF4/heparin antibody testing and treatment of heparin-induced thrombocytopenia in the intensive care unit.
The diagnosis of heparin-induced thrombocytopenia (HIT) may be challenging in critically ill patients, as heparin exposures are ubiquitous, and thrombocytopenia is common. Unwarranted ordering and incorrect interpretation of heparin antibody tests can expose a patient to adverse drug events and imposes a significant economic burden on our health care system. A prospective, observational study was performed over 4 months on all adult patients located in 5 intensive care units, with a heparin antibody test ordered. A platelet factor 4/heparin enzyme-linked immunosorbent assay (ELISA) test was ordered in 131 patients. In total, 110 patients had a low 4Ts score (0-3), and of these 103 had a negative ELISA result. In patients with a low 4Ts score, 0 (0%) of 110 had an optical density value >1.0. One hundred twenty-nine patients (98%) had another possible cause of thrombocytopenia identified. In critically ill patients, low 4Ts scores indicate a low probability of HIT, and heparin antibody testing in these patients is not useful.


Fabrication, optimisation and in vitro evaluation of docetaxel and curcumin Co-loaded nanostructured lipid carriers for improved antitumor activity against non-small cell lung carcinoma.
To develop docetaxel (DT) and curcumin (CUR) co-loaded nanostructured lipid carriers (DTCR-NLCs) for ratiometric co-targeting to non-small cell lung carcinoma (NSCLC) cells. The DTCR-NLCs were developed by employing a high-pressure homogenisation technique and optimised by employing a rotatable central composite design response surface methodology (RCCD-RSM) via the design of experiments (DoE) approach. The optimised DTCR-NLCs had a particle size (D90) of 150.2 ± 5.2 nm, Pdi of 0.263 ± 0.15, zeta potential of +26.3 ± 5.2 mv. The % drug loading (% DL) of DT and CUR was observed to be 1.38 ± 0.98 and 2.99 ± 1.24, respectively. Dissolution studies depicted a pH-independent drug release (≈98% drug release at 144 h). The DTCR-NLCs were stable and haemocompatible. MTT cell viability assay of DTCR-NLCs demonstrated considerably increased cytotoxicity towards NCI-H460 cells. The developed DTCR-NLCs heralds the future of an efficacious and safer Taxane therapy for NSCLC.


The listening loop: a model of choice about cues within primary care consultations.
As well as hearing a story at the start of an interaction, listening in medicine involves picking up and checking out patients' cues. Despite this, cues are frequently missed or ignored by doctors. To explore the perceptions of general practitioners (GPs) about initiating listening and choosing not to listen during interactions. Qualitative study constant comparison. Methods General practitioners with over 5 years' experience in practice in a semi-rural area of England took part in a single, semistructured, audiotaped interview which was piloted initially. Interviews were transcribed and analysed according to the precepts of constant comparison. In total, 23 of 24 eligible doctors participated. The data emphasise the importance of spotting cues during interactions. Factors influencing judgements on whether or not to attend to cues included pressure of work, the doctor's mood or feelings about the patient, and the context of the interaction. Methods of limiting, blocking or resisting listening included reassuring, changing the subject, interrupting, being directive or making a plan, reducing sympathy and using body language. A tramline metaphor of choice in listening emerged (the listening loop: a definite period of listening by the GP within the interaction, generally separate to hearing the patient's initial story). The listening loop offers a simple model of listening that emphasises choice and judgement in response to patients' cues within interactions. Emphasising this choice highlights both picking up cues and pragmatic limits and resistance to attending to them, with implications for teaching.


Shaping the niche in macrophages: Genetic diversity of the M. tuberculosis complex and its consequences for the infected host.
Pathogenic mycobacteria of the Mycobacterium tuberculosis complex (MTBC) have co-evolved with their individual hosts and are able to transform the hostile environment of the macrophage into a permissive cellular habitat. The impact of MTBC genetic variability has long been considered largely unimportant in TB pathogenesis. Members of the MTBC can now be distinguished into three major phylogenetic groups consisting of 7 phylogenetic lineages and more than 30 so called sub-lineages/subgroups. MTBC genetic diversity indeed influences the transmissibility and virulence of clinical MTBC isolates as well as the immune response and the clinical outcome. Here we review the genetic diversity and epidemiology of MTBC strains and describe the current knowledge about the host immune response to infection with MTBC clinical isolates using human and murine experimental model systems in vivo and in vitro. We discuss the role of innate cytokines in detail and portray two in our group recently developed approaches to characterize the intracellular niches of MTBC strains. Characterizing the niches and deciphering the strategies of MTBC strains to transform an antibacterial effector cell into a permissive cellular habitat offers the opportunity to identify strain- and lineage-specific key factors which may represent targets for novel antimicrobial or host directed therapies for tuberculosis.


A retrospective analysis of paroxysmal sympathetic hyperactivity following severe pediatric brain injury.
There are several gaps in the literature related to the prognosis and care of children who have experienced a brain injury then develop paroxysmal sympathetic hyperactivity (PSH). The objective of the present study was to explore the characteristics and prognosis of children who have experienced severe brain injury and developed PSH. A secondary analysis was conducted using an established clinical dataset of children who had experienced severe brain injury and were admitted to an academic children's rehabilitation center (n= 83). Those children with PSH had a significantly longer acute care length of stay (p= 0.024) and total length of stay (p= 0.034) compared with those without PSH. There was no significant difference in cognitive and motor function or transition to rehabilitation between those with and those without PSH after controlling for age and etiology of injury. The findings from the present study reveal factors regarding the elusive phenomenon of PSH among children.


Metals and magnets in medicine: hysteria, hypnosis and medical culture in fin-de-siècle Paris.
It is well known that the end of the nineteenth century represented a 'golden age' of hysteria and hypnosis research under Jean-Martin Charcot in Paris, but the extent to which metals and magnets figured in this strange and provocative world has been very incompletely told. This paper offers itself as a first corrective to this neglect. In 1876 a certain elderly physician and mesmerist, Victor Burq, asked the Parisian Société de Biologie formally to establish the validity of his so-called 'metallotherapy' (later 'metalloscopy') treatment for hysteria. The paper argues that Charcot's participation in the investigation of Burq's work--undertaken in conjunction with two other leading French neurologists, Amédée Dumontpallier and Jules Bernard Luys--served as a major catalyst in arousing the great neurologist's interest in hypnosis in the first place, and was subsequently responsible for several of his key beliefs about the underlying physiological link between hypnosis and hysteria. It is also shown how these early metalloscopy studies--and especially the discovery by Charcot and his colleagues of so-called metalloscopic 'transfer'--opened the door to the rise of a neo-mesmeric, and increasingly occult, branch of hypnosis research in French psychiatry, which has to date, in the secondary literature, gone almost wholly unremarked.


[The effect of eukaryotic expression plasmid ARHI on gastric cancer].
To study the effect of expressed aplasia ras homolog member I (ARHI) on the malignant biological behaviors of gastric cancer including the proliferation, migration and invasion of the cell. The eukaryotic expression plasmid of ARHI was constructed and transfected into MKN-28 cell with lipofectamine 2000 as pEGFP-ARHI group, transfected with pEGFP-N1 as pEGFP-N1 group, and untreated MKN-28 as control group. The expression of ARHI was detected by Western blotting and fluorescence microscope. CCK-8 assay was used to analyze the cell proliferation, the wound-healing assay and transwell assay were performed to investigate the effects on migration and invasion. Compared with the pEGFP-N1 group and control group, proliferation, invasion and migration of the pEGFP-ARHI group were depressed (P < 0.05). Recombination eukaryotic expression pEGFP-ARHI could partially reverse the malignant phenotypes of gastric cancer cell MKN-28.


Development and psychometric testing of a patient-reported inventory to measure patient-centred care in dietetic practice.
To develop and psychometrically test a conceptually grounded patient-reported inventory to measure patient-centred care (PCC) in dietetics. Development of the inventory involved conducting a literature search and selecting previously validated scales to reflect the conceptual model of PCC that was developed by the research team. Next, a cross-sectional survey of patients attending individual consultations with Accredited Practicing Dietitians working in primary care was undertaken. To evaluate the factor structure of the inventory, exploratory factor analysis was performed using principal component analysis. Cronbach's α, inter-item correlations and corrected-item total correlations were computed to test the internal consistency reliability. A total of 133 patients completed the survey. Five factors were extracted, accounting for 78.4% of the variance. All items demonstrated significant loadings (i.e. ≥0.45) and most items had significant loadings on only one factor. High Cronbach's α values (ranging 0.87-0.97), inter-item correlations (0.46-0.89) and corrected item-total correlations (0.61-0.90) indicated good internal consistency of the inventory, but also potential item redundancy. This study provides the first patient-reported measure of PCC in dietetic practice, which has promising preliminary validity and reliability. With further testing, there is potential for this inventory to be used in future dietetic practice, research and education.


Breech presentation at term: morbidity and mortality according to the type of delivery at Port Royal Maternity hospital from 1993 through 1999.
To compare neonatal morbidity and mortality at Port Royal Maternity between 1993 and 1999 for infants with a singleton breech presentation born after 37 weeks, according to planned mode of delivery. Retrospective study of 501 patients of whom vaginal delivery was planned in 322 (64%) or/and cesarean in 179 (36%). Severe neonatal morbidity was similar in the two groups (13/322, 4.0% versus 8/179, 4.5%; P=0.82); severe trauma morbidity was not significantly higher in the "planned vaginal delivery" group (3/322, 0.9% versus 1/179, 0.06%; P=0.16); there were no long-term sequelae. Mortality was not higher when vaginal delivery was planned. We have not found in this series any excess of morbidity or mortality attributable to vaginal delivery of breech presentations. This work does not indicate that we should change our obstetrical practice in the light of other recently-published studies.


Schistosoma mansoni: detection of circulating antigens in murine schistosomiasis by antigen-capture sandwich ELISA using a monoclonal antibody.
A monoclonal antibody (MAb) 5H11/B1 that reacts with a repeating epitope on an excretory-secretory (E + S) antigen of adult worms of Schistosoma mansoni was used in the detection of circulating antigen (CA) in sera from S. mansoni-infected mice using an antigen-capture sandwich ELISA. Trichloroacetic acid (TCA) pretreatment of sera from mice infected for 8 or 16 weeks precipitated immune complexes and/or dissociated CA and allowed its detection. Sera obtained 8 weeks after infection contained high levels of CA. Upon treatment with praziquantel (100 mg/kg body wt), this level was significantly less within 1 week. A strong correlation was found between the worm count determined by perfusion and the level of antigenemia detected by the 5H11/B1 assay in light and heavy infection (r = 0.80). Based on the results of both TCA pretreatment and sodium periodate treatment, the 5H11/B1 sandwich ELISA assay detects a repeating carbohydrate epitope on an E + S antigen. This system appears to be a sensitive assay for the detection of schistosomal antigenemia in murine schistosomiasis. Studies on the detection of antigenemia in human schistosomiasis using this assay are in progress.


Chromatin structure and epigenetics.
In eukaryotic cells, the DNA molecule is found in the form of a nucleoprotein complex named chromatin. The basic unit of the chromatin is the nucleosome, which comprises 147 base pairs of DNA wrapped around an octamer of core histones (made of two molecules of each H2A, H2B, H3, and H4 histones). Each nucleosome is linked to the next by small segments of linker DNA. Most chromatin is further condensated by winding in a polynucleosome fibre, which may be stabilized through the binding of histone H1 to each nucleosome and to the linker DNA. The modulation of the structure of the chromatin fibre is critical for the regulation of gene expression since it determines the accessibility and the sequential recruitment of regulatory factors to the underlying DNA. Depending on the different transcriptional states, the structure of the chromatin may be altered in its constituents (e.g. the presence of repressors, activators, chromatin remodelling complexes, and/or incorporation of histone variants), and in covalent modifications of its constituents (such as DNA methylation at cytosine residues, and posttranslational modifications of histone tails). Here, we give an overview of the molecular mechanisms involved in chromatin regulation and the epigenetic transmission of its state, both in normal and pathological scenarios.


Decision-Making in Gynaecological Oncology Multidisciplinary Team Meetings: A Cross-Sectional, Observational Study of Ovarian Cancer Cases.
Multidisciplinary team (MDT) meetings are widely used across the UK to provide expert decisions and improve cancer outcomes. However, little is known about the underlying mechanisms of MDT decision-making. We investigated how decisions are made regarding the management of advanced ovarian cancer in gynaecological oncology MDT meetings. A cross-sectional observational study was performed, focussing on 41/ 223 MDT case discussions across six hospitals. The validated MDT-MODe tool was adapted to increase relevance to gynaecological oncology. Case information and contributions from seven disciplines were rated on a five-point Likert scale. Spearman's correlation investigated relationships between factors and an exploratory factor analysis examined the underlying structure of MDT discussion. Forty-one MDT decisions were made for patients with FIGO Stage III/IV ovarian cancer. MDT case discussions were structured by four factors: "Clinical Presentation," "Patient Factors," "Chair's Direction" and "Input from Other Specialties." Nurses were often quiet but facilitated discussion of patient factors. Junior doctors were not involved in MDT decision-making. The decision-making process in MDT meetings is driven by four underlying factors, the most significant of which represents patient history, tumour markers, images and radiologist input. Patient factors were underrepresented, and nurses should be empowered to overcome this.


The analysis of interaural time differences in the chick brain stem.
The brain stem auditory system of the chick has proven to be a useful model system for analyzing how the brain encodes temporal information. This paper reviews some of the work on a circuit in the brain stem that compares the timing of information coming from the two ears to determine the location of a sound source. The contralateral projection from the cochlear nucleus, nucleus magnocellularis (NM), to nucleus laminaris (NL) forms a delay line as it proceeds from medial to lateral across NL. NL neurons function like coincidence detectors in that they respond maximally when input from the two ears arrive simultaneously. This arrangement may allow NL to code sound space by the relative level of activity across the nucleus. The head anatomy of the chick allows for enhancement of the functional interaural time differences. Comparing the functional interaural time differences to the length of the neural delay line suggests that each NL can encode approximately one hemifield of sound space. Finally it is suggested that inhibitory input into the NM-NL circuit may provide a means to dynamically adjust the gain of the circuit to allow accurate coding of sound location despite changes in overall sound intensity.


Toenail Metal Exposures in Fishermen from Bodo City, Nigeria.
We conducted exposure assessment using toenails from 20 fishermen living in Bodo City, a community of the Niger delta region in Nigeria. This community has been affected by over 4000 oil spills and environmental disasters. Fishing is the primary source of food and income for individuals in this community. Previous research in Bodo City found elevated metal levels in fish. Toenails were used as a biomarker to investigate the feasibility for use in risk assessment studies in developing countries. The toenails collected had significantly higher manganese levels (median 5.8 µg/g) and lead levels (median 0.98 µg/g) than those reported in more developed countries, comparable levels to those from other low-middle incomes countries. These exposure levels are likely a direct result of exposures from the environmental disasters the community has experienced and would be related to increased risks for many diseases previously associated with heavy metal exposures.


Llama DNA Immunization and Isolation of Functional Single-Domain Antibody Binders.
Genetic immunization is a simple, cost-effective, and powerful tool for inducing innate and adaptive immune responses to combat infectious diseases and difficult-to-treat illnesses. DNA immunization is increasingly used in the generation of monoclonal antibodies against targets for which pure proteins are unavailable or are difficult to express and purify (e.g., ion channels and receptors, transmembrane proteins, and emerging infectious pathogens). Genetic immunization has been successfully utilized in small inbred laboratory animals (mostly rodents); however, low immunogenicity of DNA/RNA injected into large mammals, including humans, is still a major challenge. Here, we provide a method for the genetic immunization of llamas, using a combination of biolistic transfection with a gene gun and intradermal injection with a DERMOJET® device, to elicit heavy-chain IgG responses against epidermal growth factor receptor (EGFR). We show the technique can be used to generate single-domain antibodies (VHHs) with nanomolar affinities to EGFR. We provide methods for gene gun bullet preparation, llama immunization, serology, phage-display library construction and panning, and VHH characterization.


The changes of AHI after long-term CPAP in patients with comorbid OSA and cardiovascular disease.
To evaluate the effect of long-term continuous positive airway pressure (CPAP) treatment on disease severity of obstructive sleep apnea (OSA). We analyzed results from the Sleep Apnea and Cardiovascular Events (SAVE) study involving participants recruited at the Guangdong Provincial People's Hospital, China. Participants were aged 45-75 years with a history of cardiac or cerebrovascular disease. OSA was confirmed by home sleep apnea testing (HSAT). Participants were randomized to receive CPAP plus standard cardiovascular care (CPAP group) or standard care alone (UC group) and followed for several years. At the study conclusion, surviving participants were invited to repeat HSAT. Changes in OSA indicators were compared by independent samples t-tests and subgroup analysis was implied among groups stratified by OSA severity. One hundred two adults were recruited (51 per group) and followed for 48.0 ± 14.5 months. Daily CPAP usage in the CPAP group was 4.1 ± 1.9 h. AHI decreased from baseline to end-of-study in both CPAP and UC groups (- 5.0 (- 12.5,2.0), P = 0.000; - 4.0 (- 12.5,1.5), P = 0.007, respectively), with no between-group difference (P = 0.453). An improvement in nadir SpO2 showed from baseline to end-of-study in the CPAP but not UC group (2.3% ± 6.1%, P = 0.011 and - 0.7% ± 7.6%, P = 0.511, respectively; between-group difference P = 0.032). Subgroup analysis shows that CPAP could improve AHI in patients with moderate OSA (- 8.0 (- 11.8, - 2.8) in CPAP group, - 2.0 (- 0.8,6.0) in UC group, P = 0.022) and improve nadir SpO2 in patients with severe OSA (5.0 (- 0.8, - 0.8,7.0) in CPAP group, 0.0 (- 8.5,2.5) in UC group, P = 0.032). Long-term CPAP use did not result in clinically significant changes in AHI or ODI overall but showed variable effects stratified by OSA severity. Registry: Clinical Trials.gov, title: Continuous Positive Airway Pressure Treatment of Obstructive Sleep Apnea to Prevent Cardiovascular Disease (SAVE), URL: www. gov , identifier: NCT00738179.


Education level predicts mortality and morbidity in hospitalised patients with atrial fibrillation.
Education level has been long considered a life-quality modifier, but little is known about its relation to life expectancy in patients with cardiovascular disease. This study aims to assess possible correlations between education level and survival in patients with atrial fibrillation (AF). This retrospective cohort study used data from a randomised trial of 1082 hospitalised patients with AF (mean age of 75 ± 11 years) who were followed up after discharge. Patients were divided into three groups based on their education level: i) none or primary (NPEL), ii) secondary (SEL), and iii) tertiary education level (TEL). Kaplan-Meier curves and multivariable-adjusted hazard ratios (aHRs) were used to compare survival rates between groups. The primary outcome was all-cause mortality. The composite secondary outcome was cardiovascular mortality or any hospitalisation. After a median 31-month follow-up period, 289 (41.9%) patients died in the NPEL group, 75 (31.1%) in the SEL group, and 29 (19.1%) in the TEL group. The aHRs for all-cause mortality were 0.42 (95% CI, 0.27 to 0.66; p < 0.001) for the TEL group compared with the NPEL group, 0.55 (95% CI, 0.33 to 0.93; p = 0.02) for the TEL group compared with the SEL group, and 0.68 (95% CI, 0.50 to 0.93; p = 0.01) for the SEL group compared with the NPEL group. The corresponding aHRs for the composite secondary outcome were 0.36 (95% CI, 0.23 to 0.52; p < 0.001), 0.49 (95% CI, 0.29 to 0.80; p < 0.001), and 0.67 (95% CI, 0.50 to 9.91; p = 0.01). Higher education levels were independently associated with fewer fatal and non-fatal outcomes in recently hospitalised patients with AF.


Effects of sleep position on time course in remission of positional vertigo in patients with benign paroxysmal positional vertigo.
The findings suggest that it is easy for otoconial debris dislodged from the utricle to fall into the posterior semicircular canal (PSCC) or the horizontal semicircular canal (HSCC) of the undermost ear during sleep, but not to exit from the uppermost ear in patients with benign paroxysmal positional vertigo (BPPV). The aims of the present study were two-fold. (1) To examine the association between the preferred side of head-lying during sleep and the side of the affected ear in patients with both posterior canal BPPV (P-BPPV) and horizontal canal BPPV (H-BPPV). (2) To see whether that position affects the time course in remission of their positional vertigo. One hundred and sixteen patients with P-BPPV and 40 patients with H-BPPV who showed a habitual preference for right or left side sleeping position were included in this study. The side of the affected ear was significantly associated with the head-lying side during sleep in patients with P-BPPV and was closely but not significantly associated with it in patients with H-BPPV. However, the head-lying side during sleep did not affect the remission rate of their positional vertigo.


Repetitive DNAs highlight the role of chromosomal fusions in the karyotype evolution of Dascyllus species (Pomacentridae, Perciformes).
The Dascyllus genus consists of 11 species spread over vast regions of the Indo-Pacific, showing remarkable reductions in the diploid chromosome numbers (2n). The present study analyzed the karyotypes and other chromosomal characteristics of D. trimaculatus (2n = 48; 2st + 46a; NF = 50), D. carneus (2n = 48; 2st + 46a; NF = 50) and D. aruanus (2n = 30; 18m + 2st + 10a; NF = 50) from the Thailand Gulf (Pacific Ocean) and D. melanurus (2n = 48; 2st + 46a; NF = 50) from the Andaman Sea (Indian Ocean), employing conventional cytogenetic analyses and the chromosomal mapping of repetitive DNAs, using 18S and 5S rDNA, telomeric sequences and (CA)15, (GA)15, and (CAA)10 microsatellites as probes. The C-positive heterochromatin was found in the centromeric regions of most chromosomal pairs and 18S rDNA phenotypes were single in all species. However, in D. aruanus (2n = 30), which harbors nine metacentric pairs; the 5S rDNA sites were located in the centromeric region of the shortest one. The mapping of the telomeric sequences in D. aruanus revealed the presence of interstitial telomeric sites (ITS) in the centromeric region of four metacentric pairs, with one of these pairs also displaying an additional ITS in the long arms. Distinct chromosomal markers confirmed the reduction of the 2n by chromosomal fusions, highlighting the precise characterization of these rearrangements by the cytogenetic mapping of the repetitive DNAs.


P63 and Ki-67 expression in radicular cyst.
The aim of the current study was to identify the expression of P63 and its relation to odontogenic epithelial cell proliferation, severity of the inflammatory infiltrate and size of radicular cysts (RCs). In this retrospective cross-sectional study, 30 cases of paraffin-embedded RCs were randomly selected from the archive. P63 and Ki-67 expression was assessed by immunohistochemistry. Epithelial P63 expression was absent in four (13.3%), weak in 10 (33.3%), and moderate in 16 (53.3%) cases. In the connective tissue wall of RC, P63 expression was absent in two (6.7%) cases, weak in 24 (80.0%) cases, and moderate in four (13.3%) cases. Ki-67 was found to be weakly expressed in 12 (40.0%) cases, moderately expressed in 13 (43.3%), and strongly expressed in five (16.7%) cases. No correlation was found between Ki-67 expression in odontogenic epithelium and P63 expression in the odontogenic epithelium (rho = 0.110, p = .563) or fibrous capsule (rho = 0.160, p = .399). Nevertheless, we found a positive correlation between Ki-67 expression in the odontogenic epithelium and the size of the RC (rho = 0.450, p = .013). The inflammatory infiltrate was negatively correlated with P63 expression in the odontogenic epithelium (rho = -0.428, p = .018), and with the size of cysts (rho = -0.728, p < .001). There is a high expression of P63 throughout the odontogenic epithelium and connective tissue capsule of the RC. P63 expression in the odontogenic epithelium is negatively correlated with the degree of the inflammatory infiltrate but not with epithelial cell proliferation or the size of the cyst.


Endothelial estrogen receptor {alpha} plays an essential role in the coronary and myocardial protective effects of estradiol in ischemia/reperfusion.
To assess the coronary endothelial protective effects of 17β-estradiol (E2) and the role of estrogen receptor (ER) α in ischemia/reperfusion (I/R). E2 exerts protective effects in cardiac I/R. However, the implication in vivo of the endothelium and the cellular targets of the anti-ischemic effects of E2 are unknown. Mice were subjected to I/R (30 minutes of I and 1 hour of R) in vivo, after which acetylcholine-induced relaxation of isolated coronary segments was assessed ex vivo. I/R induced a coronary endothelial dysfunction in untreated ovariectomized mice that was prevented by long-term treatment with E2 in wild-type, but not in ERα(-/-), mice. Chimeric mice inactivated for ERα in the hematopoietic compartment remained protected by E2. Further inactivation of endothelial ERα abolished the protective action of E2 on coronary endothelial function in Tie2-Cre(+) ERα(f/f) mice. More importantly, E2 significantly limited infarct size in wild-type mice but not in mice deficient in endothelial ERα, even in the presence of hematopoietic ERα. Endothelial ERα plays a crucial role in the E2-induced prevention of endothelial dysfunction after I/R. To our knowledge, we demonstrate for the first time, by using unique genetically modified mice, that targeting endothelial protection per se can confer cardiomyocyte protection in I/R.


Diagnosis of adhesive capsulitis: comparison of contrast-enhanced MRI with noncontrast-enhanced MRI.
To compare the diagnostic performance of contrast-enhanced (CE) magnetic resonance imaging (MRI) and non-CE MRI for adhesive capsulitis (AC). CE MRI of 50 AC and 53 non-AC patients were reviewed by two radiologists independently. Axillary capsular thickening and T2 hyperintensity (sensitivity=92-94%; specificity=53-64%) and enhancement of the axillary capsule and rotator interval (sensitivity=92-98%; specificity=38-64%) were helpful in diagnosing AC. Interobserver reliability was highest with axillary joint capsule enhancement (κ=0.92). Non-CE and CE MRI are helpful in confirming the clinical diagnosis of AC. CE-MRI may improve assessment of the rotator interval and diagnostic confidence in patients with AC.


A study of GJB2 and delGJB6-D13S1830 mutations in Brazilian non-syndromic deaf children from the Amazon region.
Hearing impairment affects about 1 in 1000 newborns. Mutations in the connexin 26 (GJB2) gene rank among the most frequent causes of non-syndromic deafness in different populations, while delGJB6-D13S1830 mutation located in the DFNB30 locus is known to cause sensorineural hearing loss. Despite the many studies on the involvement of GJB2 mutations in hearing impairment in different populations, there is little information on genetic deafness in Brazil, especially in the Amazon region. To determine the prevalence of GJB2 mutations and delGJB6-D13S1830 in 77 sporadic non-syndromic deaf patients. The coding region of the GJB2 gene was sequenced and polymerase chain reaction was performed to detect the delGJB6-D13S1830 mutation. Mutant allele 35delG was found in 9% of the patients (7/77). Mutations M34T and V95M were detected in two distinct heterozygous patients. Non-pathogenic mutation V27I was detected in 28.6% of the patients (22/77). None of the deaf patients carried the delGJB6-D13S1830 mutation. Mutant alleles on gene GJB2 were observed in 40% (31/77) of the subjects in the sample. Pathogenic variants were detected in only 12% (9/77) of the individuals. More studies are required to elucidate the genetic causes of hearing loss in miscegenated populations.


Randomized controlled trial of reinsemination strategies in dairy cows diagnosed nonpregnant using color flow Doppler ultrasonography on d 21 after insemination.
The objective of this study was to quantify the reproductive performance of 4 reinsemination strategies in cows diagnosed nonpregnant using corpus luteum color flow Doppler ultrasonography on d 21 after last insemination. A total of 2,140 color flow Doppler ultrasonography exams from 845 Holstein cows from 10 commercial dairy herds were used in this study. Farms were visited every 2 wk by the research team. On d 7 after insemination, cows were enrolled in a randomized controlled trial to be assigned 1 of 4 treatments if they were subsequently diagnosed nonpregnant on d 21. All cows were then examined on d 21 using Doppler ultrasonography to diagnose nonpregnancy. Treatment A (CON) was the control group: nonpregnant cows were programmed to receive a standard Ovsynch protocol starting on d 32. Nonpregnant cows in treatment B (GnRH) were injected i.m. with GnRH on d 21 after insemination and reinseminated immediately. Cows in treatment C (2×GnRH) received an i.m. injection of GnRH on d 11 after insemination. If diagnosed nonpregnant on d 21 after insemination, they were injected i.m. with GnRH on d 21 after insemination and inseminated immediately. Cows in treatment D (Resynch) received an i.m. injection of GnRH on d 14 after insemination. If diagnosed nonpregnant on d 21 after insemination, they were injected i.m. with PGF2α on d 21 after insemination and injected i.m. with GnRH on d 24. Then, a standard Ovsynch protocol was started on d 32. Statistical analyses were performed using mixed logistic regression models accounting for cow clustering and herd effect. A theoretical simulation was performed for each treatment to quantify the proportion of cows remaining nonpregnant 42 d after initial insemination. Of the 2,140 color flow Doppler ultrasonography exams in the study, 870 (40.6%) had a Doppler score of D0 (n = 444) or D1 (n = 426), which were indicative of nonpregnancy and used for data analysis. Overall, the number of exams assigned to each treatment was as follows: CON = 223 (25.6%), GnRH = 214 (24.6%), 2×GnRH = 220 (25.3%), and Resynch = 213 (24.5%). The final mixed multivariable logistic regression model included treatment, parity, days in milk at enrollment, and herd. Conception risk at first insemination following enrollment was 31.4, 20.6, 31.9, and 48.7% for treatments CON, GnRH, 2×GnRH, and Resynch, respectively. Based on the simulation, if 100 cows were diagnosed nonpregnant at their color flow Doppler ultrasonography exam on d 21 after last insemination, the total number of cows remaining nonpregnant 42 d after the initial insemination would be 69, 72, 58, and 51 for treatments CON, GnRH, 2×GnRH, and Resynch, respectively. Thus, the treatments used in groups 2×GnRH and Resynch for cows diagnosed nonpregnant on d 21 after insemination yielded better results than those used in the other groups.


Use of a mixed-method approach to evaluate the implementation of retention promotion strategies in the New York State WIC program.
This research assessed the implementation of strategies piloted at 10 Special Supplemental Nutrition Program for Women, Infants and Children (WIC) clinics aimed at increasing retention in the program, by enhancing participants' shopping experiences. Under WIC Retention Promotion Study: Keep, Reconnect, Thrive (WIC RPS), clinics were recruited and assigned to implement one or a combination of strategies: a standardized Shopping Orientation (SO) curriculum, a Guided Shopping Tour (GST), and a Pictorial Foods Card (PFC) from November 2012 through August 2013. This paper presents results from the process evaluation of the retention strategies, using a mixed-methods comparative case study design employing WIC administrative data, interviews, and focus groups. Qualitative data were inductively coded, analyzed and mapped to the following implementation constructs: organizational capacity, fidelity, allowable adaptations, implementation challenges, and participant responsiveness, while quantitative data were analyzed using SAS to assess reach and dose. Several sites implemented the SO and PFC interventions with the necessary fidelity and dose needed to assess impact on participants' shopping experiences. Sites that were assigned the GST strategy struggled to implement this strategy. However, use of the standardized SO enabled staff to use a "consistent list of shopping tips" to educate participants about the proper use of checks, while use of the PFC increased participants' awareness of the variety of WIC-allowable foods. During follow-up telephone calls, 91 percent of participants reported the shopping tips as helpful. Future analyses will assess the impact of enhanced shopping experience on retention at intervention sites.


Bilateral dorsal cochlear nucleus lesions prevent acoustic-trauma induced tinnitus in an animal model.
Animal experiments suggest that chronic tinnitus ("ringing in the ears") may result from processes that overcompensate for lost afferent input. Abnormally elevated spontaneous neural activity has been found in the dorsal cochlear nucleus (DCN) of animals with psychophysical evidence of tinnitus. However, it has also been reported that DCN ablation fails to reduce established tinnitus. Since other auditory areas have been implicated in tinnitus, the role of the DCN is unresolved. The apparently conflicting electrophysiological and lesion data can be reconciled if the DCN serves as a necessary trigger zone rather than a chronic generator of tinnitus. The present experiment used lesion procedures identical to those that failed to decrease pre-existing tinnitus. The exception was that lesions were done prior to tinnitus induction. Young adult rats were trained and tested using a psychophysical procedure shown to detect tinnitus. Tinnitus was induced by a single unilateral high-level noise exposure. Consistent with the trigger hypothesis, bilateral dorsal DCN lesions made before high-level noise exposure prevented the development of tinnitus. A protective effect stemming from disruption of the afferent pathway could not explain the outcome because unilateral lesions ipsilateral to the noise exposure did not prevent tinnitus and unilateral lesions contralateral to the noise exposure actually exacerbated the tinnitus. The DCN trigger mechanism may involve plastic circuits that, through loss of inhibition, or upregulation of excitation, increase spontaneous neural output to rostral areas such as the inferior colliculus. The increased drive could produce persistent pathological changes in the rostral areas, such as high-frequency bursting and decreased interspike variance, that comprise the chronic tinnitus signal.


Libman-Sacks endocarditis with an unusual presentation.
Systemic lupus erythematosus is relatively common medical disorder with female predominance. This disorder can affect any organ system. Cardiac involvement is variable which can include pericardium, myocardium and endocardium. The endocardial involvement commonly affects mitral and aortic valves. This report discusses lupus endocarditis in young man with atypical presentation.


DNA profiling: a valuable tool for quality control of sample logistics including occurrences of suspected sample confusion in a blood donation centre.
A molecular method for analysing whole-blood samples should be established for quality control of plasma sample logistics. DNA profiles of retention samples (plasma) were compared to profiles of recent donations (whole blood). DNA extraction, amplification and detection were performed using the Qiagen DNA Blood Mini kit, the AmpFFISTR Profiler Plus Kit and capillary electrophoresis, respectively. Matched pairs of full profiles were obtained for all samples investigated, therefore no deviation from the standardized procedures was detected. Modified extraction and amplification protocols enabled DNA profiling to be used for the quality control of plasma samples. Hence, DNA profiling can be used in the blood bank as a safe and easy method for quality control of sample logistics.


Preservation of pancreas in the University of Wisconsin solution supplemented with AP39 reduces reactive oxygen species production and improves islet graft function.
Ischemia-reperfusion injury (IRI) results in increased rates of delayed graft function and early graft loss. It has recently been reported that hydrogen sulfide (H2 S) protects organ grafts against prolonged IRI. Here, we investigated whether the preservation of pancreas in University of Wisconsin (UW) solution supplemented with AP39, which is a mitochondrial-targeted H2 S donor, protected pancreatic islets against IRI and improved islet function. Porcine pancreata were preserved in the UW solution with AP39 (UW + AP39) or the vehicle (UW) for 18 h, followed by islet isolation. The islet yields before and after purification were significantly higher in the UW + AP39 group than in the UW group. The islets isolated from the pancreas preserved in UW + AP39 exhibited significantly decreased levels of reactive oxygen species (ROS) production and a significantly increased mitochondrial membrane potential as compared to the islets isolated from the pancreas preserved in the vehicle. We found that the pancreas preserved in UW + AP39 improved the outcome of islet transplantation in streptozotocin-induced diabetic mice. These results suggest that the preservation of pancreas in UW + AP39 protects the islet grafts against IRI and could thus serve as a novel clinical strategy for improving islet transplantation outcomes.


Investigations of the Optical and Thermal Properties of the Pyrazoloquinoline Derivatives and Their Application for OLED Design.
In this study, the photo-optical properties of the series of new 1H-pyrazolo[3,4-b]quinoline derivatives were investigated. Pyrazoloquinoline studies were conducted to explain the electroluminescent effect in organic LEDs. Absorption and photoluminescence spectra for the materials under consideration were examined, and quantum chemical calculations were made. Differential scanning calorimetric and thermogravimetric measurements were carried out for the manufactured materials. The phase situation of the materials was determined, and glassy transitions were detected for three of the investigated materials. Degradation temperatures were obtained. Single-layer luminescent diodes based on the ITO/PEDOT:PSS/active layer/Al scheme were fabricated. Current-voltage and brightness-voltage characteristics of the diodes were determined, ignition voltage was calculated, and electroluminescence types were determined.


Palaeohistory of the spruce in Switzerland.
Pollen and carbon dating suggest that the Post-Glacial spread of the spruce (Picea) in Switzerland has been influenced by human activity. This is different from the situation in the eastern Alps.


Retrorenal colon: implications for percutaneous diskectomy.
It has been recommended that computed tomography (CT) with the patient prone be performed in every patient undergoing percutaneous diskectomy; this would enable detection of a retrorenal location of the colon, which could interfere with the percutaneous procedure. In this evaluation of 346 prone CT studies, only one patient (0.29%) was found to have retrorenal or retropsoas bowel that would have been perforated at diskectomy. Because of this extremely low prevalence, the performance of prone CT in every patient undergoing percutaneous lumbar diskectomy is not believed to be necessary.


Tapping the immunological repertoire to produce antibodies of predetermined specificity.
We understand the structure of antibodies in detail, but know little about the molecular basis of the immunogenicity of proteins. Recent experiments have shown that chemically synthesized peptides representative of virtually any part of the surface of a protein can elicit antibodies reactive with the native molecule. Such peptides can serve as synthetic vaccines, and antibodies, useful in the study of changes in protein structure, can be generated. As these antibodies react with regions of the protein known in advance to the experimenter, they can be said to be of predetermined specificity.


Corticostriatal plasticity is necessary for learning intentional neuroprosthetic skills.
The ability to learn new skills and perfect them with practice applies not only to physical skills but also to abstract skills, like motor planning or neuroprosthetic actions. Although plasticity in corticostriatal circuits has been implicated in learning physical skills, it remains unclear if similar circuits or processes are required for abstract skill learning. Here we use a novel behavioural task in rodents to investigate the role of corticostriatal plasticity in abstract skill learning. Rodents learned to control the pitch of an auditory cursor to reach one of two targets by modulating activity in primary motor cortex irrespective of physical movement. Degradation of the relation between action and outcome, as well as sensory-specific devaluation and omission tests, demonstrate that these learned neuroprosthetic actions are intentional and goal-directed, rather than habitual. Striatal neurons change their activity with learning, with more neurons modulating their activity in relation to target-reaching as learning progresses. Concomitantly, strong relations between the activity of neurons in motor cortex and the striatum emerge. Specific deletion of striatal NMDA receptors impairs the development of this corticostriatal plasticity, and disrupts the ability to learn neuroprosthetic skills. These results suggest that corticostriatal plasticity is necessary for abstract skill learning, and that neuroprosthetic movements capitalize on the neural circuitry involved in natural motor learning.


Urinary excretion of electrolytes during prolonged physical activity in normal man.
Nine normal young male students were studied during 2 days of relative rest, during 2 days of physical training and again during the succeeding 2 days of relative rest. Twenty-four hour urine collections showed that sodium and potassium excretion were lower during the exercise days, while urinary aldosterone excretion was increased. No differences in the 24-h urinary excretion of creatinine, calcium, and magnesium were found between the resting and exercise days. Hemoglobin concentration, hematocrit and red cell counts were decreased at 14 h and 42 h after exercise; these findings together with the increased serum bilirubin concentration could result from hemolysis. Plasma renin activity, angiotensin II and aldosterone concentration were increased 14 h after exercise but returned to baseline 42 h after exercise. Our data shows that one should take into account previous exercise when interpreting results of certain of these tests.


Childhood trauma increases the risk of post-traumatic stress disorder in response to first-episode psychosis.
To investigate the relationship between childhood trauma, post-traumatic stress symptoms due to the experience of childhood trauma, and post-traumatic stress symptoms due to the experience of psychosis. The current study assessed childhood trauma and post-traumatic stress disorder (PTSD) symptoms as a result of both childhood trauma and psychosis using the Impact of Events Scale - Revised, in a group of 36 people with first-episode psychosis. Reported rates of clinical level post-psychotic PTSD symptoms, childhood trauma and childhood trauma-related clinical level PTSD symptoms were 47% (95% CI 31-64%), 64% (95% CI 48-80%) and 39% (95% CI 23-55%), respectively. Reporting childhood trauma increased the risk of developing post-psychosis PTSD 27-fold (95% CI 2.96-253.80, p = 0.01). Having childhood trauma-related PTSD increased the risk of developing post-psychosis PTSD 20-fold (95% CI 3.38-123.25, p = 0.01). These risks were not explained by illness factors such as duration of untreated psychosis, age of onset or severity of psychotic symptoms. Those without post-psychotic PTSD symptoms at clinical levels were unlikely to report childhood trauma (6%; 95% CI 3-8%). These results suggest the cognitive, social and biological consequences of childhood trauma can prevent effective recovery from the trauma of acute first-episode psychosis resulting in post-psychotic PTSD. Treatment strategies for post-psychotic PTSD must address childhood trauma and related PTSD.


Prognostic Value of Soluble Programmed Cell Death Ligand-1 (sPD-L1) in Various Cancers: A Meta-analysis.
The prognostic value of soluble programmed cell death ligand-1 (sPD-L1) in patients with cancer has been inconsistent across previous studies. This meta-analysis aimed to investigate the prognostic significance of sPD-L1 in human tumors. A comprehensive search of PubMed, Web of Science, Embase, and Cochrane databases from inception to January 6, 2020 was conducted. Studies of sPD-L1 measured by enzyme-linked immunosorbent assay (ELISA) that had available hazard ratios (HRs) for survival outcomes based on high or low sPD-L1 levels were included. The primary endpoint was long-term survival, namely, overall survival (OS), and the second endpoint was short-term survival, including progression-free survival (PFS), disease-free survival (DFS), recurrence-free survival (RFS), and cancer-specific survival (CSS). A total of 21 studies, with 2413 patients, were included in this meta-analysis. Elevated sPD-L1 was associated with worse OS [HR = 2.46, 95% confidence interval (CI) 1.74-3.49, P < 0.001]. Moreover, high sPD-L1 was predictive of worse PFS/DFS/RFS/CSS (HR = 2.22, 95% CI 1.47-3.35, P < 0.001). High sPD-L1 was consistently correlated with poor OS and PFS/DFS/RFS/CSS irrespective of study design, sample, and cut-off value of sPD-L1. However, there was non-significant correlation between sPD-L1 and sex, age, clinical stage, Eastern Cooperative Oncology Group Performance Status, tumor differentiation, or serum lactate dehydrogenase. This meta-analysis showed that sPD-L1 was correlated with poor prognosis in human tumors. In addition, sPD-L1 could be used as a predictive factor of inferior outcomes during multiple malignancy treatments.


Clinical Anatomy of the Puboprostatic Ligament for the Safe Guidance for the Prostate Surgery.
To provide the anatomy of the puboprostatic ligament and related structures to save urogenital competence after prostatectomy. Pelvic areas of 31 adult cadavers were dissected to figure out the shape, number, and location of the puboprostatic ligaments. The puboprostatic ligament was the most important support structure between the pubic bone and prostate gland. Puboprostatic ligaments were bilaterally single (61.3%), bilaterally double (19.4%), or mixed (19.4%). Ligaments were mostly I-shaped (53.8%). If ligaments had extra attachment to or from the arcuate line, the ligaments were λ-shaped (36.3%), or Y-shaped (8.8%). In one case, the ligament had a central fusion with an irregular shape. I-shaped puboprostatic ligaments were observed more frequently in specimens with double ligaments, while λ-shaped puboprostatic ligaments were observed more frequently in the cases with single ligaments. The average distance between both puboprostatic ligaments was 8.1 mm at the pubic site and 14.2 mm at the prostate site. The distance was narrower when the specimen had double puboprostatic ligaments on both sides. The neurovascular bundle ran beneath the puboprostatic ligament. If the ligament was the λ-shaped type, the neurovascular bundle frequently pierced the lateral band of the ligament. Puboprostatic ligaments hold and stabilize the prostate against the pubic bone. It is believed that a pelvis with bilateral, double puboprostatic ligaments would have advantages in urogenital competence. The morphologic data of the shape, multiplicity, and location of the PPLs would help to make a plan to approach the prostate.


Injection of Bone Marrow Aspirate for Glenohumeral Joint Osteoarthritis: A Pilot Randomized Control Trial.
To compare the efficacy of a single, intra-articular, nonconcentrated bone marrow aspirate (BMA) injection in comparison to cortisone for the treatment of glenohumeral joint osteoarthritis (GHJ OA). Inclusion criteria were patients between the ages of 18 and 75 with a diagnosis of GHJ OA on radiograph. Patients were randomized to receive an ultrasound-guided, intra-articular cortisone injection or BMA injection (without concentration). The primary outcome measure was the Western Ontario Osteoarthritis of the Shoulder (WOOS) index at 12 months. Secondary outcome measures were the QuickDASH, EuroQOL 5-dimensions 5-level questionnaire (EQ-5D-5L) and visual analogue scale. The study included 25 shoulders of 22 patients who completed baseline and 12 months' patient-reported outcome measures (12 shoulders received cortisone, 13 shoulders received BMA) after the study was terminated early by changes in Health Canada regulations. Baseline characteristics demonstrated a significant difference in the ages of the 2 groups, with the BMA group being older (61.6 vs 53.8 mean years, P = 0.021). For the BMA group, a significant improvement was seen in the WOOS index (P = 0.002), the QuickDASH (P < 0.001), and the EQ-5D-5L pain dimension (P = 0.004) between baseline and 12 months. No significant difference was seen for any outcome in the cortisone group between baseline and 12 months. No significant difference was demonstrated between changes in the WOOS scores from baseline to 12 months when compared between groups (P = 0.07). However, a significant difference in changes in scores was seen in the QuickDASH (P = 0.006) and the EQ-5D-5L pain scores (P = 0.003) and the EQ-5D-5L health scores (P = 0.032) in favor of BMA. The results of this study demonstrate that patients with GHJ OA treated with BMA have superior changes in the QuickDASH and EQ-5D-5L pain and health scores but not in the WOOS outcomes measures at 12 months post injection when compared to patients treated with cortisone. However, because of the limited number of patients as a result of the early termination of the study, larger randomized studies are required to confirm these findings. Level II, randomized controlled trial.


An Efficient Neural Network Design Incorporating Autoencoders for the Classification of Bat Echolocation Sounds.
Bats are widely distributed around the world, have adapted to many different environments and are highly sensitive to changes in their habitat, which makes them essential bioindicators of environmental changes. Passive acoustic monitoring over long durations, like months or years, accumulates large amounts of data, turning the manual identification process into a time-consuming task for human experts. Automated acoustic monitoring of bat activity is therefore an effective and necessary approach for bat conservation, especially in wind energy applications, where flying animals like bats and birds have high fatality rates. In this work, we provide a neural-network-based approach for bat echolocation pulse detection with subsequent genus classification and species classification under real-world conditions, including various types of noise. Our supervised model is supported by an unsupervised learning pipeline that uses autoencoders to compress linear spectrograms into latent feature vectors that are fed into a UMAP clustering algorithm. This pipeline offers additional insights into the data properties, aiding in model interpretation. We compare data collected from two locations over two consecutive years sampled at four heights (10 m, 35 m, 65 m and 95 m). With sufficient data for each labeled bat class, our model is able to comprehend the full echolocation soundscape of a species or genus while still being computationally efficient and simple by design. Measured classification F1 scores in a previously unknown test set range from 92.3% to 99.7% for species and from 94.6% to 99.4% for genera.


DNA methylation-based classifier differentiates intrahepatic pancreato-biliary tumours.
Differentiating intrahepatic cholangiocarcinomas (iCCA) from hepatic metastases of pancreatic ductal adenocarcinoma (PAAD) is challenging. Both tumours have similar morphological and immunohistochemical pattern and share multiple driver mutations. We hypothesised that DNA methylation-based machine-learning algorithms may help perform this task. We assembled genome-wide DNA methylation data for iCCA (n = 259), PAAD (n = 431), and normal bile duct (n = 70) from publicly available sources. We split this cohort into a reference (n = 399) and a validation set (n = 361). Using the reference cohort, we trained three machine learning models to differentiate between these entities. Furthermore, we validated the classifiers on the technical validation set and used an internal cohort (n = 72) to test our classifier. On the validation cohort, the neural network, support vector machine, and the random forest classifiers reached accuracies of 97.68%, 95.62%, and 96.5%, respectively. Filtering by anomaly detection and thresholds improved the accuracy to 99.07% (37 samples excluded by filtering), 96.22% (17 samples excluded), and 100% (44 samples excluded) for the neural network, support vector machine and random forest, respectively. Because of best balance between accuracy and number of predictable cases we tested the neural network with applied filters on the in-house cohort, obtaining an accuracy of 95.45%. We developed a classifier that can differentiate between iCCAs, intrahepatic metastases of a PAAD, and normal bile duct tissue with high accuracy. This tool can be used for improving the diagnosis of pancreato-biliary cancers of the liver. This work was supported by Berlin Institute of Health (JCS Program), DKTK Berlin (Young Investigator Grant 2022), German Research Foundation (493697503 and 314905040 - SFB/TRR 209 Liver Cancer B01), and German Cancer Aid (70113922).


Structural basis for salinity-induced alteration in oxygen binding by haemocyanin from the estuarine amphipod Chaetogammarus marinus (L.).
In the estuarine amphipod Chaetogammarus marinus, differences in O(2) binding by haemocyanins (Hc) could be related to natural and salinity-related quantitative variation in just one polypeptide subunit (band 2) and not to variations in any of the other seven bands present. Band 2 was always present, irrespective of salinity treatment, and naturally makes up 6%-36% of the total Hc. However, low salinity exposure (S=4 per thousand for 48-49 h, T=15 degrees C) was accompanied by an increase in the prevalence of greater concentrations of band 2 (i.e., range, 20%-36% of total Hc present) and a concomitant increase in Hc-O(2) affinity (half saturation [P(50)] decreased from 1.38 to 1.12 kPa at pH=7.81, T=15 degrees C). A similar salinity-related mechanism (that is, one band altering) has been shown previously for the blue crab Callinectes sapidus, although the functional consequences were different. In contrast with C. marinus, an increase in the proportion of one polypeptide subunit in C. sapidus resulted in a decrease in Hc-O(2) affinity. This study has confirmed that between-individual variation (quantitative rather than qualitative) in just one Hc subunit may have functional consequences, although the significance of such variation is difficult to interpret.


Dacryocystitis. Late complication of orbital floor fracture repair with implant.
Fifteen years after orbital floor fracture repair with a silicone implant, dacryocystitis unresponsive to medical management developed in a 66-year-old woman. On examination, the edge of the implant was palpable at the most medial aspect of the inferior orbital rim in the anatomic area of the nasolacrimal sac. Orbital computed tomography (CT) scan and intraoperative probing and irrigation of the nasolacrimal system confirmed that the implant obstructed the nasolacrimal sac at the floor of the orbit. Removal of the implant combined with dacryocystorhinostomy has led to resolution of the dacryocystitis. To the authors' knowledge, dacryocystitis as a late complication of orbital floor fracture repair with an orbital floor implant has not been previously reported. This case demonstrates that orbital floor implants should not be placed too anteriorly or too medially in the anatomic region of the lacrimal sac and that they should be fixed to prevent implant migration.


Secondary Oral Cancer after Systemic Treatment of Hematological Malignancies and Oral GVHD: A Systematic Review.
(1) Purpose: In this article, the authors decided to systematically review the available literature to identify potential correlations regarding secondary oral carcinoma occurring after hematological systemic treatment and oral chronic graft-versus-host disease. (2) Methods: Medline (PubMed) and Scopus (Elsevier) databases were searched, including articles from the years 2002-2022. The 33 unique results were assessed by a PRISMA flowchart, and we rejected 24 papers and included 9 articles in the review. (3) Results: The majority of patients suffered from the oral form of chronic graft-versus-host disease before the diagnosis of oral malignancy. Two common cancer sites were the tongue and buccal mucosa. The exact percentage of secondary oral carcinoma after hematopoietic stem cell transplantation could not be estimated due to a lack of data. (4) Conclusions: Every physician taking part in the follow-up of patients after hematological treatment should be aware of the possibility of secondary neoplastic disease in the oral cavity, especially in patients with oral graft-versus-host disease. Proper follow-up protocols and monitoring are needed in this patient group as the cause of these cancers appears to be multifactorial.


Cadaveric Dissection vs Homemade Model: What is the Best Way to Teach Endoscopic Totally Extraperitoneal Inguinal Hernia Repair?
Endoscopic totally extraperitoneal inguinal hernia repair (TEP-IHR) requires practice and training to perform well. We developed a simple, low-cost, inanimate model to teach surgical residents inguinal anatomy and the technique of mesh insertion for a safe, endoscopic TEP-IHR. The objective of this study was to compare our model vs cadaveric dissection for teaching anatomy and mesh insertion. A total of 14 general surgery residents participated in an institutional review board approved, prospective, and randomized study. Participants received a timed, web-based, interactive pretest assessing relevant anatomy and operative-based techniques. They then performed endoscopic TEP-IHRs on either a cadaver or our low-cost model. Participants then received a timed, web-based interactive posttest consisting of the same questions. Participants were surveyed anonymously regarding the degree to which either the model or the cadaver was educationally effective. Both groups of trainees (cadaver = 7, low-cost model = 7) scored higher on the posttest (p<0.05) with similar improvement (cadaver group: pretest = 78% correct, posttest = 87%; low-cost model group: 77% vs 86%). Survey results revealed the trainees preferred for both initial learning and understanding of mesh placement using low-cost models (5 out of 5, 4.8/5, respectively) over cadavers (4.0/5, 3.8/5, respectively; p<0.05). Trainees preferred the cadaver (4.7) over the low-cost model (3.9, p<0.05) in overall experience. No differences were found in the trainees' preference between the cadaver (4.5) and low-cost model (4.7) in the overall educational value. While the overall educational experience of 14 learners favored a cadaver experience to learn TEP-IHR, initial anatomical learning and placing the mesh was better with an inanimate model. Given the educational value of the 2 methods was equivalent, the $1500 cost for cadavers make the inexpensive and repeatable inanimate model an attractive early resource for learning TEP-IHR.


Monitoring of diazinon concentrations and loadings, and identification of geographic origins consequent to stormwater runoff from orchards in the Sacramento River watershed, U.S.A.
Diazinon contamination of California's rivers has resulted in placing several rivers on the federal Clean Water Act 303d list of impaired waterways. Impaired water body listing requires the development of Total Maximum Daily Loads (TMDL). Previous studies identified stormwater related diazinon pulses in California rivers. This study was conducted to monitor diazinon concentrations in the Sacramento River watershed after rainfall events, to ascertain whether pulses could be identified and, if concentrations of concern were observed, to estimate loadings and determine geographic origins of the insecticide. TMDL development requires knowledge of contaminant sources, loadings, and geographic origins. Flow and diazinon concentrations peaked in the Sacramento River at Sacramento after the three largest storms during January and February 1994. Diazinon concentrations peaked consequent to each of three storms. Diazinon concentrations measured in the Sacramento River at Sacramento exceeded the California Department of Fish and Game acute and chronic criteria for protection of aquatic life during January and February for nine and nineteen days, respectively. Multiple exceedances were observed throughout the watershed. Diazinon loading and geographic origin differed with each of the three storms. The design of this study provides a useful template for others attempting to identify loadings and sources of contaminants in surface waters and to rectify aquatic ecosystem contamination from various land use practices.


Primary care costs due to prodromal Alzheimer disease: a real-world study in patients with a 10-year or longer medical history.
The aim of this study was to estimate primary care costs of prodromal signs/symptoms of Alzheimer disease (AD), during a 10-year or longer period preceding AD diagnosis, in relation to costs cumulated in the general population for the same reasons. Nested case-control study involving 1889 AD cases and 18,890 controls aged 60+ from the Italian primary care Health Search Database (HSD). AD incident cases were through the International Classification of Diseases, 9th edition. Costs related to drugs, diagnostic tests and specialist referrals triggered by prodromal AD signs and/or symptoms were quantified and compared with costs cumulated by non-AD counterparts. During the pre-diagnosis 10-year or longer period, prodromal signs and symptoms trigger diagnostic and therapeutic costs 55% higher than those cumulated in general population for the same clinical reasons. After accounting for patients' comorbidity and regional differences, the mean cost related to diagnostic and therapeutic procedures, and those related to specialist referrals, amounted to 854.1 €(SD: 630.6 €) in AD incident cases vs. 527.3 €(SD: 446.2) cumulated in patients not developing AD. Prodromal AD manifestations are associated with primary care costs that resulted higher than those cumulated in the general population aged 60+. It remains to be elucidated if earlier dementia diagnoses would be associated with reduced costs triggered by the same clinical signs and symptoms.


Pancreatic choriocarcinoma presenting as inflammatory pseudocyst.
A primary pancreatic choriocarcinoma was discovered at surgery in a patient with a clinical diagnosis of pancreatic inflammatory pseudocyst. To our knowledge, this is the first example of an extragonadal choriocarcinoma reported as a primary at this site. We consider this neoplasm to be another example of a visceral choriocarcinoma arising from a primary carcinoma through a process of metaplasia. This case illustrates the inherent difficulties in the preoperative evaluation of cystic lesions of the pancreas, and the importance of recognizing endocrinologic manifestations of malignant disease.


Diverse regulation of 3' splice site usage.
The regulation of splice site (SS) usage is important for alternative pre-mRNA splicing and thus proper expression of protein isoforms in cells; its disruption causes diseases. In recent years, an increasing number of novel regulatory elements have been found within or nearby the 3'SS in mammalian genes. The diverse elements recruit a repertoire of trans-acting factors or form secondary structures to regulate 3'SS usage, mostly at the early steps of spliceosome assembly. Their mechanisms of action mainly include: (1) competition between the factors for RNA elements, (2) steric hindrance between the factors, (3) direct interaction between the factors, (4) competition between two splice sites, or (5) local RNA secondary structures or longer range loops, according to the mode of protein/RNA interactions. Beyond the 3'SS, chromatin remodeling/transcription, posttranslational modifications of trans-acting factors and upstream signaling provide further layers of regulation. Evolutionarily, some of the 3'SS elements seem to have emerged in mammalian ancestors. Moreover, other possibilities of regulation such as that by non-coding RNA remain to be explored. It is thus likely that there are more diverse elements/factors and mechanisms that influence the choice of an intron end. The diverse regulation likely contributes to a more complex but refined transcriptome and proteome in mammals.


[Epidemioclinical and ultrasonographic profile of hydatidiform moles in Abidjan].
The purpose of our study was to describe the epidemioclinical and ultrasonographic features of hydatidiform moles (HM) in Abidjan. We conducted a cross-sectional study in the Department of Radiology, University Teaching Hospital of Yopougon over a 6-year period (January 2011-December 2016). In this study we describe the epidemioclinical and ultrasonographic profile of patients with HM. Ultrasonographic exams were performed using a mixed-methods approach (intravaginal and subpubic) based on B-mode and Color Doppler by senior radiologists. Anatomopathological examination of uterine content was performed. Out of 12190 obstetric ultrasound performed, twenty-five cases of HM were diagnosed reflecting a radiological referral rate of 0.2%. The average age of patients was 33.4 years, ranging from 22 to 50 years. There was no dominant age class. The main clinical signs associated with amenorrhea (100%) included abdominal mass 36% and vaginal bleeding 28%. Ultrasound showed hypertrophic uterus in 100% of cases, homogeneous uterus in 96% of cases and myomatous uterus in 4% of cases. MH had an average thickness of 42.7 mm with vesicular appearance in 68% of cases, "honeycomb" appearance in 16%, multicystic appearance in 12% and snowstorm appearance in 4%. MHs were classified as partial in 4% of cases, complete in 92% of cases and invasive in 4% of cases. Hypertrophic ovaries were found in 44% of cases with macrofollicles in 32% of cases and cysts in 8% of cases. Ultrasonographic diagnosis of HM was confirmed by anatomopathological examination in 100% of cases. HMs are rare in Abidjan and are dominated by the complete hydatidiform mole. Its occurrence at the extreme ages wasn't found.


Unlocking the Potential of Kinase Targets in Cancer: Insights from CancerOmicsNet, an AI-Driven Approach to Drug Response Prediction in Cancer.
Deregulated protein kinases are crucial in promoting cancer cell proliferation and driving malignant cell signaling. Although these kinases are essential targets for cancer therapy due to their involvement in cell development and proliferation, only a small part of the human kinome has been targeted by drugs. A comprehensive scoring system is needed to evaluate and prioritize clinically relevant kinases. We recently developed CancerOmicsNet, an artificial intelligence model employing graph-based algorithms to predict the cancer cell response to treatment with kinase inhibitors. The performance of this approach has been evaluated in large-scale benchmarking calculations, followed by the experimental validation of selected predictions against several cancer types. To shed light on the decision-making process of CancerOmicsNet and to better understand the role of each kinase in the model, we employed a customized saliency map with adjustable channel weights. The saliency map, functioning as an explainable AI tool, allows for the analysis of input contributions to the output of a trained deep-learning model and facilitates the identification of essential kinases involved in tumor progression. The comprehensive survey of biomedical literature for essential kinases selected by CancerOmicsNet demonstrated that it could help pinpoint potential druggable targets for further investigation in diverse cancer types.


Biofuel cell for generating power from methanol substrate using alcohol oxidase bioanode and air-breathed laccase biocathode.
We report here an alcohol oxidase (AOx) based third generation bioanode for generating power from methanol substrate in a fuel cell setup using air breathed laccase biocathode. A composite three dimensional microporous matrix containing multiwalled carbon nanotubes, carbon paste and nafion was used as electroactive support for immobilization of the enzymes on toray carbon paper as supporting electrode in the fabrication of the bioelectrodes. Polyethylenimine was used to electrostatically stabilize the AOx (pI 4.3) on the anode operating on direct electrochemistry principle. Osmium tetroxide on poly (4-vinylpyridine) was used to wire the laccase for electron transfer in the biocathode. The enzymatic biofuel cell (EFC) generated an open circuit potential of 0.61 (±0.02) V with a maximum power density of 46 (±0.002) µW cm(-2) at an optimum of 1M methanol, 25 °C and an internal resistance of 0.024 µΩ. The operation and storage half life (t1/2) of the EFC were 17.22 h and 52 days, respectively at a fixed load of 1.85 Ω. The findings have demonstrated the feasibility of developing EFC using AOx based bioanode and laccase based biocathode without applying any toxic free mediator and metal electrode supports for generating electricity.


Tailored self-assembled photocatalytic nanofibres for visible-light-driven hydrogen production.
The creation of efficient artificial systems that mimic natural photosynthesis represents a key current challenge. Here, we describe a high-performance recyclable photocatalytic core-shell nanofibre system that integrates a cobalt catalyst and a photosensitizer in close proximity for hydrogen production from water using visible light. The composition, microstructure and dimensions-and thereby the catalytic activity-of the nanofibres were controlled through living crystallization-driven self-assembly. In this seeded growth strategy, block copolymers with crystallizable core-forming blocks and functional coronal segments were coassembled into low-dispersity, one-dimensional architectures. Under optimized conditions, the nanofibres promote the photocatalytic production of hydrogen from water with an overall quantum yield for solar energy conversion to hydrogen gas of ~4.0% (with a turnover number of >7,000 over 5 h, a frequency of >1,400 h-1 and a H2 production rate of >0.327 μmol h-1 with 1.34 μg of catalytic polymer (that is, >244,300 μmol h-1 g-1 of catalytic polymer)).