Prolonged Opioid Use Following Distal Radius Fracture Fixation: Who Is at Risk and What are the Consequences?
Opioid pain medication is most commonly prescribed after distal radius fracture fixation, and there is high variability in the quantity and duration prescribed. Comorbidities, including substance use and depression, have been associated with higher consumption habits, and increased sizes of postoperative opioid prescriptions have been previously linked to an increasing risk of chronic opioid use and opioid use disorder. The purpose of this study was to investigate opioid prescription patterns after distal radius fracture fixation and identify patient-specific risk factors associated with increased opioid prescription refills. A retrospective review of 34,629 opioid-naïve patients was conducted using the IBM MarketScan database. The database was queried to identify patient records from January 2009 to December 2017. Demographic, comorbidity, complication data, and prescription pharmacy claims were analyzed. Patients were sorted according to the duration of postoperative prescription refills of opioid pain medication. Seventy-three percent of the patients required no additional refills outside the perioperative window. Twenty percent required additional refill prescriptions, and 6.4% of patients continued to fill the opioid medication beyond 6 months after surgery. Multiple factors increased the risk of increased opioid use, including medical and surgical complications, substance use, diabetes, cardiovascular disease, and obesity. Patients with a longer duration of opioid use after surgery had higher rates of medical and surgical complications. Perioperative prescription quantities were 62.9, 78.6, and 83.3 tablets for no refill, refill (<6M), and prolonged-use groups (>6M), respectively. Patients who underwent distal radius fracture fixation were at greater odds for prolonged opioid use after surgery in the presence of comorbid cardiovascular, renal, metabolic, and mental health illnesses and postoperative medical and surgical complications. A greater understanding of patient-specific factors for prolonged opioid consumption after distal radius fracture fixation can help providers identify at-risk patients who would benefit from a tailored approach to counseling and multimodal pain management. Patients should be educated on these risks associated with their surgery and be provided with alternative medical options and health care resources to optimize pain control and reduce their need for opioid medication as their primary tool for pain relief. Therapeutic III.


Preclinical Validation of an Advanced Therapy Medicinal Product Based on Cytotoxic T Lymphocytes Specific for Mutated Nucleophosmin (NPM1mut) for the Treatment of NPM1mut-Acute Myeloid Leukemia.
Acute myeloid leukemia (AML) with nucleophosmin (NPM1) genetic mutations is the most common subtype in adult patients. Refractory or relapsed disease in unfit patients or after allogeneic hematopoietic stem cell transplantation (allo-HSCT) has a poor prognosis. NPM1-mutated protein, stably expressed on tumor cells but not on normal tissues, may serve as an ideal target for NPM1-mutated AML immunotherapy. The study aim was to investigate the feasibility of producing mutated-NPM1-specific cytotoxic T cells (CTLs) suitable for somatic cell therapy to prevent or treat hematologic relapse in patients with NPM1-mutated AML. T cells were expanded or primed from patient or donor peripheral blood mononuclear cells by NPM1-mutated protein-derived peptides, and tested for leukemia antigen-targeted cytotoxic activity, cytokine production and hematopoietic precursor inhibitory effect. We found that mutated-NPM1-specific CTLs, displaying specific cytokine production and high-level cytotoxicity against patients' leukemia blasts, and limited inhibitory activity in clonogenic assays, could be obtained from both patients and donors. The polyfunctional mutated-NPM1-specific CTLs included both CD8+ and CD4+ T cells endowed with strong lytic capacity. Our results suggest that mutated-NPM1-targeted CTLs may be a useful therapeutic option to control low-tumor burden relapse following conventional chemotherapy in older NPM1-mutated AML patients or eradicate persistent MRD after HSCT.


Neuropeptide modulation of apomorphine-induced stereotyped behavior.
The nucleus accumbens contains many neuropeptides whose functions are presently unknown. The purpose of this study was to determine the extent to which these neuropeptides act in conjunction with the mesolimbic dopamine system. Microinjections of cholecystokinin, neurotensin, met-enkephalin, somatostatin, bombesin, as well as glutamate and muscimol, were made into the medial nucleus accumbens after systemic injection of apomorphine. Cholecystokinin and neurotensin, in nanogram doses, potentiated apomorphine-induced stereotypy. Met-enkephalin reduced, while somatostatin and bombesin were without effect on, apomorphine-induced stereotypy. In addition, both glutamate and muscimol potentiated this effect. These results suggest that several neuropeptides and amino acids act in the nucleus accumbens to modulate apomorphine-induced stereotyped behaviors.


Laparoscopic adrenal surgery.
Laparoscopic adrenalectomy (LA) was performed in 6 patients (4 right and 2 left). A transperitoneal approach in a lateral position was used. Pheochromocytoma was present in two patients and Conn's syndrome, with a solitary functioning adenoma, was the diagnosis in four. Early vascular control was obtained in the two patients with pheochromocytoma, resulting in very stable intraoperative blood pressure. Operative time for LA was 152 +/- 26 min and was associated with a short length of stay (2.0 +/- 0.6 days) and minimal intraoperative blood loss (82 +/- 30 ml). There were no conversions to laparotomy and one complication was noted. LA is a safe and effective operation for patients requiring adrenalectomy for hormone-secreting tumors.


Multi-Degree-of-Freedom Robots Powered and Controlled by Microwaves.
Microwaves have become a promising wireless driving strategy due to the advantages of transmissivity through obstacles, fast energy targeting, and selective heating. Although there are some studies on microwave powered artificial muscles based on different structures, the lack of studies on microwave control has limited the development of microwave-driven (MWD) robots. Here, a far-field MWD parallel robot controlled by adjusting energy distribution via changing the polarization direction of microwaves at 2.47 GHz is first reported. The parallel robot is based on three double-layer bending actuators composed of wave-absorbing sheets and bimetallic sheets, and it can implement circular and triangular path at a distance of 0.4 m under 700 W transmitting power. The thermal response rate of the actuator under microwaves is studied, and it is found that the electric-field components can provide a faster thermal response at the optimal length of actuator than magnetic-field components. The work of the parallel robot is demonstrated in an enclosed space composed of microwave-transparent materials. This developed method demonstrates the multi-degree-of-freedom controllability for robots using microwaves and offers potential solutions for some engineering cases, such as pipeline/reactors inspection and medical applications.


Decisions beyond boundaries: when more information is processed faster than less.
Bounded rationality models usually converge in claiming that decision time and the amount of computational steps needed to come to a decision are positively correlated. The empirical evidence for this claim is, however, equivocal. We conducted a study that tests this claim by adding and omitting information. We demonstrate that even an increase in information amount can yield a decrease in decision time if the added information increases coherence in the information set. Rather than being influenced by amount of information, decision time systematically increased with decreasing coherence. The results are discussed with reference to a parallel constraint satisfaction approach to decision making, which assumes that information integration is operated in an automatic, holistic manner.


Cavopulmonary support with a modified cannulation technique in a failing Fontan patient.
Failing Fontan patients present a unique challenge for mechanical circulatory support. We report on a 17-year-old patient with Fontan failure and preserved ventricular function who underwent mechanical cavopulmonary support using a novel cannulation technique.


A study on egg quality and hatching traits of indigenous and exotic chickens reared in Silte zone, Southern Ethiopia.
The objective of this study was to evaluate egg quality and hatchability of indigenous and exotic chickens in the midland, lowland, and highland agroecological zones of the Silte zone. One district was selected from each agroecological zone, and a total of 399 households (133 from each district) were randomly chosen from six purposefully selected Kebles to collect data on egg hatchability. For external and internal egg quality evaluation, 300 eggs (150 from indigenous and 150 from exotic chickens from each agroecology) were collected. The study found that Sasso chickens had better egg quality in terms of egg weight, yolk width, yolk height, albumen height, yolk index, and Haugh unit compared to indigenous chickens in both the highland and lowland areas. In the highland area, Sasso chickens had higher values for egg weight, yolk width, yolk height, albumen height, yolk index, and Haugh unit compared to the lowland area. This suggests that Sasso chickens performed better in terms of egg quality in both the highland and lowland areas compared to indigenous chickens. The hatchability percentages of Sasso and Koekoek chickens were 70.8 ± 14.1 and 69.7 ± 12.7, respectively, in the midland area. This suggests that Sasso and Koekoek chickens performed well in terms of hatchability, followed by indigenous chicken eggs. However, approximately 68% of respondents did not use exotic chicken eggs for hatching. The study suggests that practicing hatching of exotic chicken eggs could be beneficial in increasing the productivity of indigenous chickens.


Global patterns and climatic drivers of above- and belowground net primary productivity in grasslands.
Understanding patterns and determinants of net primary productivity (NPP) in global grasslands is ongoing challenges, especially for belowground NPP (BNPP) and its fraction (fBNPP). By developing a comprehensive field-based dataset, we revealed that, along with gradients of mean annual precipitation, actual evapotranspiration, and aridity, aboveground NPP (ANPP), BNPP, and total NPP (TNPP) exhibited hump-shaped patterns, whereas fBNPP showed an opposite trend. ANPP and TNPP showed positive correlations with mean annual temperature, but fBNPP was negatively correlated with it. The relationship between BNPP and climatic factors was considerably weak, indicating that BNPP was relatively stable regardless of the climate conditions. We also observed that the sensitivities of ANPP and BNPP to interannual temperature variability and those of BNPP to interannual precipitation fluctuations exhibited large variations among different study sites, and differed from those at the spatial scale. In contrast, the temporal sensitivities of ANPP to interannual precipitation variability were highly similar across all the individual sites and much smaller than those at the spatial scale. Overall, these results highlight that precipitation, temperature and evapotranspiration all play vital roles in shaping ANPP pattern and its partitioning to belowground and that the patterns of BNPP along climatic gradients do not mirror those of the ANPP.


Clinical outcomes of pancreatic ductal adenocarcinoma resection following neoadjuvant chemoradiation therapy vs. chemotherapy.
We compared the clinical outcomes of pancreatic ductal adenocarcinoma (PDAC) resection after neoadjuvant chemoradiation therapy (NACRT) vs. chemotherapy (NAC). The study population comprised 81 patients with UICC stage T3/4 PDAC, treated initially by NACRT with S-1 in 40 and by NAC with gemcitabine + S-1 in 41. This was followed by pancreatectomy with routine nerve plexus resection in 35 of the patients who had received NACRT and 32 of those who had received NAC. We compared the survival curves and clinical outcomes of these two groups. The rates of clinical response, surgical resectability, and margin-negative resection were similar. The NACRT group patients had significantly higher rates of Evans stage ≥IIB tumors (29 vs. 0 %, respectively, p = 0.010) and negative lymph nodes (49 vs. 16 %, respectively, p = 0.021) than the NAC group patients. There was no difference in disease-free survival between the groups, but the disease-specific survival of the NAC group patients was better than that of the NACRT group patients (p = 0.034). Patients undergoing pancreatectomy with nerve plexus resection following NACRT had significantly higher rates of intractable diarrhea and ascites but consequently received significantly less adjuvant chemotherapy and therapeutic chemotherapy for relapse. NACRT followed by pancreatectomy with nerve plexus resection is superior for achieving local control, but postoperative diarrhea and ascites may prohibit continuation of adjuvant chemotherapy or chemotherapy for relapse (UMIN4148).


Morphological plasticity of hyperelongated cells caused by overexpression of translation elongation factor P in Synechococcus elongatus PCC7942.
Translation elongation factors (EFs) are proteins that play important roles during the elongation stage of protein synthesis. In prokaryotes, at least four EFs function in repetitive reactions (EF-Tu, EF-Ts, EF-G, and EF-P). EF-P plays a vital role in the specialized translation of consecutive proline amino acid motifs. It was also recently recognized that EF-P acts throughout translation elongation. Here, we demonstrated for the first time that cell division and morphology are intimately linked to the control of EF-P in the model cyanobacterium Synechococcus elongatus PCC7942. We constructed the overexpression of a wild-type gene product for EF-P (Synpcc7942_2565) as a tool to identify EF-P functionality. The overexpression of EF-P resulted in the morphological plasticity of hyperelongated cells. During the stationary phase, EF-P overexpressors displayed cell lengths of 150 μm or longer, approximately 35 times longer than the control. Total cellular protein and amino acid content were also increased in overexpressors. To explore the molecular mechanisms underlying hyperelongation, gene expression analysis was performed. The results revealed that cell division genes, including ftn6, minD, mreB, mreC, and ftsZ, were modulated in overexpressors. Strikingly, ftn6 was severely down-regulated. Little is known regarding EF-P in prokaryotic photosynthetic organisms. Our results suggest that cyanobacterial EF-P participates in the acceleration of protein synthesis and also regulates cell division processes. These findings suggest new ways to modify translation and metabolism in cyanobacteria. Phenotypic and metabolic alterations caused by overexpressing EF-P may also be beneficial for applications such as low-cost, green molecular factories. KEY POINTS: • Cell division and cell morphology in the cyanobacterium Synechococcus elongatus PCC7942 are closely linked with the control of translation elongation factor P (EF-P). • Overexpression of EF-P leads to morphological plasticity in hyperelongated cells. • Cyanobacterial EF-P is involved in the acceleration of protein synthesis and the regulation of cell division processes.


Description of Amblyomma monteiroae n. sp. (Acari: Ixodidae), a parasite of the great horned owl (Strigiformes: Strigidae) in southern Brazil.
In 2020, adult hard ticks (males and females) were collected from great horned owls [Bubo virginianus (Gmelin, 1788)] in the coastal region in southern Brazil. The engorged females were allowed to oviposit in the laboratory and hatched larvae could be obtained. Analyses of the external morphology of the adult ticks revealed that they represent a new species, which was named Amblyomma monteiroae n. sp. Partial sequences of the mitochondrial 16S rRNA gene and the nuclear second internal transcribed spacer (ITS2) were generated from a male and a female. Their 16S rRNA haplotypes were identical to each other and closest (96% identity) to corresponding sequences of Amblyomma parvitarsum Neumann, 1901, and 90% identical to Amblyomma neumanni Ribaga, 1902. Their ITS2 haplotypes were 95.8 to 96.0 identical to the single ITS-2 partial sequence of A. parvitarsum available in GenBank. In the phylogenetic trees inferred by both 16S rRNA and ITS2 partial sequences, A. monteiroae n. sp. formed a clade with A. parvitarsum, with A. neumanni branching sister to this clade. Amblyomma monteiroae n. sp. is genetically and morphologically related to A. parvitarsum. Both tick species are unique in combining the following morphological characters: scutum extensively ornate; eyes rounded and bulging; coxa I with two moderate pointed spurs, the external longer than the internal; a single triangular short spur on coxae II-III; presence of two spines on the tibia of legs II-IV; hypostomal dentition 3/3, trochanters without spurs. However, the males of the two species can be separated by specific features in palps and festoons, whereas the females differ in specific features of the coxal spurs. The larva of A. monteiroae n. sp. can be morphologically distinguished from A. parvitarsum only by morphometry, with the former species being slightly smaller. Currently, A. monteiroae n. sp. is restricted to southern Brazil, and the only known host is B. virginianus (Strigiformes: Strigidae). The present study increases the Amblyomma Brazilian fauna to 34 species.


Therapeutic efficacy of halofuginone and spiramycin treatment against Cryptosporidium serpentis (Apicomplexa: Cryptosporidiidae) infections in captive snakes.
The therapeutic effect of halofuginone hydrobromide (Steronol) and spiramycin solubilized (Spirasol) applied to clinical Cryptosporidium serpentis infections in captive snakes was investigated. Pathological changes induced by C. serpentis were typical for snake cryptosporidiosis. Spiramycin induced no significant change in the pattern of shedding of fecal Cryptosporidium oocysts; biopsies and necropsies revealed cryptosporidiosis in gastric mucosa of all spiramycin-treated animals. In all, 8 of 21 (38%) halofuginone-treated snakes stopped shedding C. serpentis oocysts; examination of gastric tissue of 6 of these 8 animals revealed cryptosporidiosis in 2 snakes. Hepatotoxic and nephrotoxic pathological changes induced by halofuginone included focal or multifocal, severe, acute liver necrosis; severe liver hemosiderosis; and bilateral, severe, acute diffuse cortical and tubular necrosis and iron deposition. Postprandial regurgitation associated with midbody swelling, observed in 4 halofuginone-treated and 2 spiramycin-treated snakes at 15 and 21 weeks after drug withdrawal, did not coincide with oocyst-positive feces. Neither halofuginone nor spiramycin treatment produced a satisfactory therapeutic outcome when applied against clinical C. serpentis infections in snakes.


Histomorphometric and micro-CT analyses of calvarial bone grafts used to reconstruct the extremely atrophied maxilla.
Calvarial bone grafts are successful in the reconstruction of the severely atrophied maxilla as a pre-implant procedure. However, not much is known about graft incorporation at the microscopic level. This study aimed to assess calvarial bone conversion 4 months after being grafted in the edentulous maxillary bone. In 13 patients (age:65.3 ± 8.7 years) the atrophic maxilla was reconstructed with autologous calvarial bone. Biopsies were taken from fresh calvarial bone grafts and from the reconstructed maxillae after 4 months of healing. Micro-CT, histomorphometric, and histological analysis were performed. From three patients biopsies were obtained after 9, 11, or 45 months. The micro-CT analysis revealed that in the maxilla the calvarial bone was well preserved even after 45 months. Histology showed progressive incorporation of grafted bone within a maxillary bone. Osteoid and osteocytes were present in all biopsies indicating new bone formation and vital bone. Histomorphometrically, the percentage of grafted bone volume over total volume decreased from 79.8% (IQR78.7-83.3) in fresh calvarial grafts to 59.3% (IQR44.8-64.6) in healed grafts. The biopsies were taken after 9, 11, and 45 months showed similar values. Calvarial bone grafts result in stable and viable bone, good incorporation into native maxillary bone, and a minor decrease in bone volume after healing. Consequently, they provide a solid base for implant placement in severely atrophied edentulous maxillary bone.


Conformational Flexibility Enables the Function of a BECN1 Region Essential for Starvation-Mediated Autophagy.
BECN1 is essential for autophagy, a critical eukaryotic cellular homeostasis pathway. Here we delineate a highly conserved BECN1 domain located between previously characterized BH3 and coiled-coil domains and elucidate its structure and role in autophagy. The 2.0 Å sulfur-single-wavelength anomalous dispersion X-ray crystal structure of this domain demonstrates that its N-terminal half is unstructured while its C-terminal half is helical; hence, we name it the flexible helical domain (FHD). Circular dichroism spectroscopy, double electron-electron resonance-electron paramagnetic resonance, and small-angle X-ray scattering (SAXS) analyses confirm that the FHD is partially disordered, even in the context of adjacent BECN1 domains. Molecular dynamic simulations fitted to SAXS data indicate that the FHD transiently samples more helical conformations. FHD helicity increases in 2,2,2-trifluoroethanol, suggesting it may become more helical upon binding. Lastly, cellular studies show that conserved FHD residues are required for starvation-induced autophagy. Thus, the FHD likely undergoes a binding-associated disorder-to-helix transition, and conserved residues critical for this interaction are essential for starvation-induced autophagy.


Contractile function assessment by intraventricular balloon alters the ability of regional ischaemia to evoke ventricular fibrillation.
In drug research using the rat Langendorff heart preparation, it is possible to study left ventricular (LV) contractility using an intraventricular balloon (IVB), and arrhythmogenesis during coronary ligation-induced regional ischaemia. Assessing both concurrently would halve animal requirements. We aimed to test the validity of this approach. The electrocardiogram (ECG) and LV function (IVB) were recorded during regional ischaemia of different extents in a randomized and blinded study. IVB-induced proarrhythmia was anticipated, but in hearts with an ischaemic zone (IZ) made deliberately small, an inflated IVB reduced ischaemia-induced ventricular fibrillation (VF) incidence as a trend. Repeating studies in hearts with large IZs revealed the effect to be significant. There were no changes in QT interval or other variables that might explain the effect. Insertion of an IVB that was minimally inflated had no effect on any variable compared with 'no IVB' controls. The antiarrhythmic effect of verapamil (a positive control drug) was unaffected by IVB inflation. Removal of an inflated (but not a non-inflated) IVB caused a release of lactate commensurate with reperfusion of an endocardial/subendocardial layer of IVB-induced ischaemia. This was confirmed by intracellular (31) phosphorus ((31) P) nuclear magnetic resonance (NMR) spectroscopy. IVB inflation does not inhibit VF suppression by a standard drug, but it has profound antiarrhythmic effects of its own, likely to be due to inflation-induced localized ischaemia. This means rhythm and contractility cannot be assessed concurrently by this approach, with implications for drug discovery and safety assessment.


[Two staged Starnes operation for Ebstein's anomaly with pulmonary atresia in early infancy--a report of a successful case].
Severe tricuspid valve regurgitation and decreased pulmonary blood flow in neonatal Ebstein's anomaly with pulmonary atresia, may result in cardiac respiratory failure and hypoxemia. The poor natural course and lack of standard surgical treatment make treatment for neonatal Ebstein's anomaly very difficult. The Blalock-Taussig operation was performed for hypoxemia in Ebstein's anomaly associated with pulmonary atresia and severe tricuspid regurgitation on 36th day after birth. On the 63rd day after birth, tricuspid valve orifice closure and right atrium plication (Starnes procedure) were accomplished under cardiopulmonary bypass. Heart failure became controllable and the patient condition was satisfactory at one year after surgery.


Randomized Placebo-Controlled Trial of Methylphenidate or Galantamine for Persistent Emotional and Cognitive Symptoms Associated with PTSD and/or Traumatic Brain Injury.
We report findings from a 12-week randomized double-blinded placebo-controlled trial of methylphenidate or galantamine to treat emotional and cognitive complaints in individuals (n=32) with a history of PTSD, TBI, or both conditions. In this small pilot study, methylphenidate treatment was associated with clinically meaningful and statistically significant improvement compared with placebo on the primary outcome, a measure of cognitive complaints (Ruff Neurobehavioral Inventory-Postmorbid Cognitive Scale), as well as on the secondary outcomes reflecting post-concussive (Rivermead Post Concussive Symptom Questionnaire) and post-traumatic stress symptoms (Posttraumatic Stress Disorder Checklist). Treatment was well tolerated. These results suggest the need for a larger RCT to replicate and confirm these findings. Design considerations for such a trial should include the need for multiple sites to facilitate adequate recruitment and extension of the treatment and follow-up periods.


Limited Environmental Serine and Glycine Confer Brain Metastasis Sensitivity to PHGDH Inhibition.
A hallmark of metastasis is the adaptation of tumor cells to new environments. Metabolic constraints imposed by the serine and glycine-limited brain environment restrict metastatic tumor growth. How brain metastases overcome these growth-prohibitive conditions is poorly understood. Here, we demonstrate that 3-phosphoglycerate dehydrogenase (PHGDH), which catalyzes the rate-limiting step of glucose-derived serine synthesis, is a major determinant of brain metastasis in multiple human cancer types and preclinical models. Enhanced serine synthesis proved important for nucleotide production and cell proliferation in highly aggressive brain metastatic cells. In vivo, genetic suppression and pharmacologic inhibition of PHGDH attenuated brain metastasis, but not extracranial tumor growth, and improved overall survival in mice. These results reveal that extracellular amino acid availability determines serine synthesis pathway dependence, and suggest that PHGDH inhibitors may be useful in the treatment of brain metastasis. SIGNIFICANCE: Using proteomics, metabolomics, and multiple brain metastasis models, we demonstrate that the nutrient-limited environment of the brain potentiates brain metastasis susceptibility to serine synthesis inhibition. These findings underscore the importance of studying cancer metabolism in physiologically relevant contexts, and provide a rationale for using PHGDH inhibitors to treat brain metastasis.This article is highlighted in the In This Issue feature, p. 1241.


Purification and structural analysis of the modulator of the glucocorticoid-receptor complex. Evidence that modulator is a novel phosphoglyceride.
Modulator is the low molecular weight heat-stable inhibitor of glucocorticoid-receptor complex activation. We have purified modulator to apparent homogeneity from heated rat liver cytosol. This was accomplished using Sephadex G-15 gel filtration, Dowex 1 anion-exchange chromatography, and preparative silica high-performance liquid chromatography. The modulator preparation was judged to be homogeneous by analytical silica high-performance liquid chromatography, two-dimensional silica thin-layer chromatography, and proton nuclear magnetic resonance spectroscopy. The apparent concentration of modulator in rat liver cytosol is 6.5 microM. The purified modulator inhibits heat activation of the rat liver glucocorticoid-receptor complex and stabilizes the steroid binding ability of the unoccupied rat liver glucocorticoid receptor in a dose-dependent manner. At a concentration of 5-6.5 microM, modulator inhibits receptor activation and stabilizes the unoccupied receptor by 50%. At a concentration of 500-630 microM, sodium molybdate also inhibits receptor activation and stabilizes the unoccupied receptor by 50%. Thus, modulator appears to be the endogenous factor that exogenous sodium molybdate mimics in vitro. Chemical analysis of the purified modulator following two-dimensional silica thin-layer chromatography indicates that modulator is an aminophospholipid. Physical analysis of the purified modulator by infrared and nuclear magnetic resonance spectroscopy, as well as mass spectrometry, demonstrates that modulator is an ether aminophosphoglyceride.


Human Galectin-9 Potently Enhances SARS-CoV-2 Replication and Inflammation in Airway Epithelial Cells.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has caused a global economic and health crisis. Recently, plasma levels of galectin-9 (Gal-9), a β-galactoside-binding lectin involved in immune regulation and viral immunopathogenesis, were reported to be elevated in the setting of severe COVID-19 disease. However, the impact of Gal-9 on SARS-CoV-2 infection and immunopathology remained to be elucidated. Here, we demonstrate that Gal-9 treatment potently enhances SARS-CoV-2 replication in human airway epithelial cells (AECs), including primary AECs in air-liquid interface (ALI) culture. Gal-9-glycan interactions promote SARS-CoV-2 attachment and entry into AECs in an ACE2-dependent manner, enhancing the binding affinity of the viral spike protein to ACE2. Transcriptomic analysis revealed that Gal-9 and SARS-CoV-2 infection synergistically induce the expression of key pro-inflammatory programs in AECs including the IL-6, IL-8, IL-17, EIF2, and TNFα signaling pathways. Our findings suggest that manipulation of Gal-9 should be explored as a therapeutic strategy for SARS-CoV-2 infection. COVID-19 continues to have a major global health and economic impact. Identifying host molecular determinants that modulate SARS-CoV-2 infectivity and pathology is a key step in discovering novel therapeutic approaches for COVID-19. Several recent studies have revealed that plasma concentrations of the human β-galactoside-binding protein galectin-9 (Gal-9) are highly elevated in COVID-19 patients. In this study, we investigated the impact of Gal-9 on SARS-CoV-2 pathogenesis ex vivo in airway epithelial cells (AECs), the critical initial targets of SARS-CoV-2 infection. Our findings reveal that Gal-9 potently enhances SARS-CoV-2 replication in AECs, interacting with glycans to enhance the binding between viral particles and entry receptors on the target cell surface. Moreover, we determined that Gal-9 accelerates and exacerbates several virus-induced pro-inflammatory programs in AECs that are established signature characteristics of COVID-19 disease and SARS-CoV-2-induced acute respiratory distress syndrome (ARDS). Our findings suggest that Gal-9 is a promising pharmacological target for COVID-19 therapies.


Diurnal changes in the rate of cholesterogenesis in hepatocytes from fed and starved rats: effects of precursors and pancreatic hormones in vitro.
The activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase) varied with a diurnal periodicity in hepatocytes prepared at different times from rats accustomed to a controlled feeding and lighting schedule. The rates of sterol synthesis varied in a similar manner but the maximum rate was not synchronous with maximum HMG-CoA reductase activity. The diurnal increase in HMG-CoA reductase activity and sterol synthesis rate started before food was offered to donor animals. Neither insulin nor glucagon had any effect on the diurnal pattern of hepatic sterol synthesis in vitro. Pyruvate inhibited sterol synthesis in hepatocytes prepared during the feeding period but had no effect at other times of day. When food was withheld from donor animals at the beginning of the normal feeding period both HMG-CoA reductase activity and the rate of sterol synthesis rapidly decreased. During this period neither insulin nor lipogenic substrates, alone or in combination, were able to restore the rates of sterol synthesis to normal values. In hepatocytes prepared from animals starved for a longer period (43 h) the decrease in the activity of HMG-CoA reductase was much less than that in the rate of sterol synthesis. In contrast to hepatocytes from fed or short-term-starved animals, the rate of sterol synthesis in these hepatocytes could be increased by glucose or pyruvate.


Von Hipple-Lindau disease complicated with central retinal vein occlusion: a case report.
Central Retinal Vein Occlusion (CRVO) is a rare complication of von Hipple-Lindau (VHL) disease. This report presents the first case of VHL disease complicated with CRVO caused by VHL c.208G > A mutation. A 20 s man whose left eye visual acuity gradually declined for half a year. The visual acuity of the left eye is counting fingers. Fundus examination revealed that retinal hemangioblastoma was also found in addition to typical CRVO signs such as tortuous expansion of retinal veins and flame-shaped hemorrhage of the retina. Liver tumor, cerebral infarction and erythrocytosis were found during systemic examination, and the diagnosis of polycythemia was confirmed by bone marrow smear. Furthermore, both family history and genetic analysis indicated that the patient had VHL disease caused by VHL c.208G > A. In this patient, a large number of bone marrow erythrocytes proliferated due to VHL disease, which led to the increase of blood viscosity and erythrocyte vascular adhesion, resulting in the obstruction of central retinal vein blood flow, and finally CRVO. For CRVO and its pathogenic factor polycythemia, patient received laser retinal photocoagulation and phlebotomies. After a 1-year follow-up, the vision in the left eye improved to 0.2 logMAR. This is a rare case of polycythemia complicated by CRVO in patient with VHL disease. It reminds us that the systemic disease factors should be fully considered in the diagnosis of young patients with CRVO, and that treatment requires a coordinated effort of physicians.


Increase of ethanol productivity by cell-recycle fermentation of flocculating yeast.
Using the recombinant flocculating Angel yeast F6, long-term repeated batch fermentation for ethanol production was performed and a high volumetric productivity resulted from half cells not washed and the optimum opportunity of residual glucose 20 g l(-1) of last medium. The obtained highest productivity was 2.07 g l-(1) h(-1), which was improved by 75.4% compared with that of 1.18 g l(-1) h(-1) in the first batch fermentation. The ethanol concentration reached 8.4% corresponding to the yield of 0.46 g g(-1). These results will contribute greatly to the industrial production of fuel ethanol using the commercial method with the flocculating yeast.


Comparison of two encapsulated curcumin particular systems contained in different formulations with regard to in vitro skin penetration.
Curcumin is known for its anti-inflammatory, antioxidative, and anticarcinogenic properties. However, the strong lipophilic compound is not easily applicable, neither in water, nor directly in o/w formulations. So far, loading of nano or micro scaled carriers has enabled only an uptake up to 30% of curcumin. In the present article, curcumin was successfully encapsulated into two different safe and inexpensive polymers, ethyl cellulose and methyl cellulose blended ethyl cellulose with a loading capacity of ~ 46-48%. In addition, the in vitro skin penetration of the two curcumin encapsulated particular systems, which were applied each in three different formulations, an o/w, w/o lotion, and water suspension, was investigated on porcine ear skin using Laser scanning microscopy. It was found that in comparison to water suspensions, o/w and w/o lotions enhanced, especially the follicular penetration of the encapsulated curcumin particles into porcine skin, whereas the w/o enhanced the penetration better than the o/w lotion. Furthermore, the application of ethyl cellulose blended with methyl cellulose improved the penetration of curcumin in all formulations. High loaded encapsulated curcumin systems, prepared from a simple and highly efficient encapsulation system can be used to transport curcumin effectively into the skin.


Biomarkers of anti-angiogenic therapy in metastatic colorectal cancer (mCRC): original data and review of the literature.
Tumour angiogenesis via vascular endothelial growth factor (VEGF) is essential for promoting tumour progression and is overexpressed in colorectal cancer. The humanised monoclonal anti-VEGF antibody bevacizumab (Avastin®, Genentech Inc., South San Francisco, CA) has shown activity in metastatic colorectal cancer (mCRC) combined with conventional chemotherapy. The search for biomarkers to predict response to anti-angiogenic therapy in mCRC is of great interest. We investigated several potential predictive anti-angiogenic markers including circulating endothelial progenitor cells (EPC) in patients with mCRC receiving bevacizumab containing treatment within a randomised multicenter phase 2 study of the German AIO GI tumour study group. We collected sequential blood samples and tumour tissues from patients participating in a clinical trial for patients with mCRC. We performed flow cytometry of mononuclear cells isolated from peripheral blood to assess CD 133 + or CD 34 + /KDR + EPC before the first bevacizumab containing chemotherapy and after 21 days. Circulating VEGF blood levels before a bevacizumab containing chemotherapy regimen and after 21 days and VEGF expression in tumour tissue were examined. Patients with mCRC and a partial remission after six months of immuno-chemotherapy containing bevacizumab showed a reduction of CD 34 negative KDR positive cells as early as 3 weeks after start of therapy. In contrast, no remarkable change in the number of CD 34 /KDR positive or CD 34 /CD133 positive cells was seen. Furthermore, there was no correlation between treatment response and VEGF expression within the tumour tissue. The mAb bevacizumab reduced serum-VEGF levels in patients independent of their treatment response to bevacizumab. We examined circulating endothelial progenitor cells (EPC), serum-VEGF levels and the tumour tissue VEGF expression of patients with mCRC under a bevacizumab containing chemotherapy. The patients with a partial remission after six months of immuno-chemotherapy showed a reduction of CD 34 negative KDR positive cells as early as 3 weeks after start of therapy. Neither serum nor tissue markers were of significant predictive value in our pilot study. Furthermore, we review the current data on biomarkers for anti-angiogenic therapy of mCRC.


Economic evaluation of antiaromatase agents in the second-line treatment of metastatic breast cancer.
An economic evaluation was conducted comparing anastrozole, exemestane, letrozole and megestrol for the second-line treatment of postmenopausal patients with hormone-sensitive metastatic breast cancer who had failed tamoxifen. An economic model was developed based on data from phase III megestrol-controlled clinical trials of antiaromatase agents (AA) and estimates of resource utilization from both Statistic Canada's Population Health Model for breast cancer and expert opinion. In megestrol-controlled trials, anastrozole and exemestane equivalently improved survival compared to megestrol, while letrozole did not. Compared to megestrol, exemestane and anastrozole both cost Canadian $9000 per life-year gained, and letrozole saved Canadian $300 annually, with no life-year gain. Cost-effectiveness results were robust under sensitivity analysis testing. However, the model was dependent on any difference between AAs with respect to survival benefit and drug acquisition price. Based on available data and this cost-effectiveness analysis, exemestane and anastrozole are appropriate choices for second-line hormonal treatment of metastatic breast cancer.


Monitoring arsenic using genetically encoded biosensors in vitro: The role of evolved regulatory genes.
Toxic pollutant (TP) detection in situ using analytical instruments or whole-cell biosensors is inconvenient. Designing and developing genetically coded biosensors in vitro for real-world TP detection is a promising alternative. However, because the bioactivity and stability of some key biomolecules are weakened in vitro, the response and regulation of reporter protein become difficult. Here, we established a genetically encoded biosensor in vitro with an arsenical resistance operon repressor (ArsR) and GFP reporter gene. Given that the wildtype ArsR did not respond to arsenic and activate GFP expression in vitro, we found, after screening, an evolved ArsR mutant ep3 could respond to arsenic and exhibited an approximately 3.4-fold fluorescence increase. Arsenic induced expression of both wildtype ArsR and ep3 mutant in vitro, however, only ep3 mutant regulated the expression of reporter gene. Furthermore, the effects of cell extracts, temperature, pH, incubation, and equilibrium time were investigated, and the equilibration of reaction mixtures for 30 min at 37 °C was found to be essential for in vitro arsenic detection prior to treatment with arsenic. Based on our data, we established a standard procedure for arsenic detection in vitro. Our results will facilitate the practical application of genetically encoded biosensors in TP monitoring.


Abatement of cockroach allergen (Bla g 1) in low-income, urban housing: A randomized controlled trial.
Clinically relevant reductions in exposure to cockroach allergen, an important risk factor for asthma in inner-city households, have proven difficult to achieve in intervention trials. This study investigated a method for the abatement of cockroach allergen in low-income, urban homes. The goal was to reduce mean Bla g 1 concentrations below the previously proposed thresholds for allergic sensitization and asthma morbidity. A prerandomized, nonmasked trial with 16 intervention and 15 control homes was conducted. Study inclusion was based on 50 to 500 cockroaches trapped in a 3-day period. The interventions consisted of occupant education, placement of insecticide bait, and professional cleaning. Vacuumed dust and multiple swab samples were collected at 0, 1, 2, 4, and 6 months in intervention homes and at 0 and 6 months in control homes. Room maps containing cockroach and allergen data were used to guide and monitor the interventions. From 0 to 6 months among intervention homes, geometric mean Bla g 1 concentrations (U/g dust) decreased from 633 to 24 on kitchen floors (96% reduction), from 25 to 4.3 on living room floors/sofas (83% reduction), from 46 to 7.3 on bedroom floors (84% reduction), and from 6.1 to 1.0 in bedroom beds (84% reduction). These reductions, with the exception of that on the bedroom floor (P =.06), were statistically significant relative to changes in control homes. Substantial reductions in cockroach allergen levels can be achieved in inner-city homes. In this study, allergen levels were reduced below the sensitization threshold (2 U/g) in beds, arguably the most relevant site for exposure, and below the asthma morbidity threshold (8 U/g) on bedroom floors and living room floors/sofas. The level on kitchen floors, although reduced 96%, remained above the asthma morbidity threshold. Future studies will test the intervention's effectiveness in asthma prevention trials.


'Being human' and the 'moral sidestep' in drug policy: Explaining government inaction on opioid-related deaths in the UK.
With drug-related deaths at record levels in the UK, the government faces two potential sources of pressure to implement more effective policies. One source is the individuals and families who are most likely to suffer from such deaths; i.e. working class people living in de-industrialised areas. The other source is experts who argue for different policy on the basis of research evidences. This article aims to explain why, in the face of these two potential sources of pressure, the UK government has not implemented effective measures to reduce deaths. The article uses critical realist discourse analysis of official documents and ministerial speeches on recent British drug policy (2016-2018). It explore this discourse through the theoretical lens of Archer's (2000) ideas on 'being human' and by drawing on Sayer's (2005) work on the 'moral significance of class'. Members of economically 'residual' groups (including working class people who use heroin) are excluded from articulating their interests in 'late welfare capitalism' in a project of depersonalising 'class contempt' through which politicians cast the people most likely to die as passive, 'vulnerable' 'abjects'. Conservative politicians dismiss 'evidence-based' ideas on the reduction of drug-related death through a 'moral sidestep'. They defend policy on the basis of its relevance to conservative moral principles, not effectiveness. This is consistent with the broader moral and political pursuit of partial state shrinkage which Conservative politicians and the social groups they represent have pursued since the 1970s.


Linkage disequilibrium between the HLA-DQA2 alleles and the HLA/DR/DQ complex.
A statistically significant association was observed between alleles of the HLA-DQA2 and of the DR/DQ complex in a DNA-restriction fragment length polymorphism study of 219 members from 21 multiplex families of patients with hyperthyroid Graves' disease and 773 unrelated individuals selected for homozygosity of the HLA-DQA2 alleles. This data provides evidence for linkage disequilibrium rather than for a hot spot of recombination within the HLA-DQ subregion.


Burden of lymphoma in China, 2006-2016: an analysis of the Global Burden of Disease Study 2016.
The accurate information about lymphoma burden at national and provincial levels remains unknown in China. Following the general analytical strategy used in GBD 2016, the age-, sex-, and province-specific incidence, mortality, and prevalence of lymphoma in China were analyzed. Trends in the incidence, mortality, prevalence, and disability-adjusted life years (DALYs) due to Hodgkin's lymphoma (HL) and non-Hodgkin's lymphoma (NHL) were assessed from 2006 to 2016. It was estimated that there were 75,400 new cases and 40,500 deaths of lymphoma in 2016 in China, of which 6900 new cases and 2900 deaths were due to HL, while 68,500 new cases and 37,600 deaths were due to NHL. The age-standardized incidence rate (ASIR), mortality rate (ASMR), and prevalence rate (ASPR) per 100,000 were 0.46, 0.19, and 1.75 for HL, and 4.29, 2.45, and 14.9 for NHL, respectively. An upward trend with age in incidence and mortality was observed. Males had higher incidence and mortality rates than females in all age groups. Sociodemographic index had a correlation with the ASIR (r = 0.75), ASMR (r = - 0.74), ASPR (r = 0.84), and age-standardized DALYs (r = - 0.75) of HL, as well as with the ASIR (r = 0.80), ASPR (r = 0.83), and age-standardized DALYs (r = - 0.33) of NHL. From 2006 to 2016, the age-standardized DALYs of HL decreased significantly, while the age-standardized DALYs of NHL increased from 2006 to 2013 and remained stable from 2013 to 2016. The burden of lymphoma in China showed unexpected patterns varied by sex, age, and provinces, with an increased trend of NHL and a decreased trend of HL from 2006 to 2016.


A Combined Approach To Crooked Nose Deformity.
Crooked nose deformity is a complex anatomical deformity; therefore, repair remains a challenge. Here, we introduce a new technique for crooked nose deformity repair. Twenty-two patients underwent intraoperative evaluations and measurements, followed by surgery using the open rhinoplasty technique. Our method involves three major steps. First is the creation of an asymmetric medial oblique osteotomy using piezoelectric ultrasonic surgery and double lateral osteotomies, wherein the asymmetric bony ascending part of the maxillary bone at the base of the nasal vault is fractured, pushed in, and delivered to the face. Second is septoplasty with L-strut preservation. The L-strut is removed as a 1-cm block caudally from the septal stump of the keystone area. A (or double) fabricated batten cartilage graft is placed on the concave side of the deviation and sutured to cover the septal stump. The L-strut is then replaced and sutured on the batten graft, redirecting the septum toward the midline. Third is an overlapping cruroplasty on the side of the long asymmetrical lower lateral cartilage to equalize both wings and correct tip deviation. Our new technique was effective for the treatment of crooked nose deformity. Our technique of K-stone batten plasty with delivery to the face and overlapping cruroplasty may be an effective surgical method for crooked nose deformity. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .


[The evolution of kidney transplantation over the last 20 years].
Kidney transplantation is an efficient treatment of end stage renal disease, decreasing patient mortality by comparison with mortality in dialysis and improving patient quality of life. The number of patients living in France with a functioning transplant is almost as high as the number of patients on dialysis (33,000 versus 37,500 in 2009). The constant progress in immunosuppressive treatments has made graft survival improve. According to the "Agence de biomédecine", the national institution in charge of transplantation regulation and management, overall graft survival is 68% at 10 years but 80% for living donor transplantation. Transplantation indications have been extended with time to more difficult patients: retransplanted patients and elderly patients, to the point that age per se is no more a contraindication to transplantation. Increase in transplant activity has followed increase in kidney harvesting in marginal donors, called "extended criteria donors": older, hypertensive, having atherosclerotic pathologies. Kidney from these donors are attributed to recipients of similar age. With organ shortage, new sources of donors are proposed, non heart beating donors and living donors. Living donor transplantation is the best transplantation with the best results but it is insufficiently developed in France (8-10% of the total annual number of renal transplantations versus 30-50% in the Scandinavian and Anglo-Saxon countries). Extension of the definition of the living donor through the successive revisions of the Law of Bioethics should hopefully improved this situation.


Possible Role of Accessory Proteins in the Viral Replication for the 20I/501Y.V1 (B.1.1.7) SARS CoV-2 Variant.
The emergence of new severe acute respiratory syndrome coronavirus-2 (SARS CoV-2) has been a global concern. The B.1.1.7 variant of SARS CoV-2 is reported to cause higher transmission. The study investigates the replication cycle and transcriptional pattern of the B.1.1.7 to hypothesis the possible role of different genes in viral replication. It was observed that the B.1.1.7 variant required a longer maturation time. The transcriptional response demonstrated higher expression of ORF6 and ORF8 compared to nucleocapsid transcript till the eclipse period which might influence higher viral replication. The number of infectious viruses titer is higher in the B.1.1.7, despite a lesser copy number than B.1, indicating higher transmissibility. The experimental evidence published linked ORF6 and ORF8 to play important role in replication and we also observed their higher expression. This leads us to hypothesis the possible role of ORF6 and ORF8 in B.1.1.7 higher replication which causes higher transmission.


Chirality of gold nanocluster affects its interaction with coagulation factor XII.
Probing the interaction of nanomaterials (NMs) with proteins is the basic step for biological safety assessment. Many physiochemical factors of NMs play important roles in binding with proteins as they determine the binding process. Among them, the chirality-related biological effects and nanotoxicology have not been fully understood. As NMs are mainly exposed to human circulatory system with intentional or unintentional exposure, understanding the interaction mechanism of plasma functional proteins with chiral NMs is of great importance. Herein, we show the interaction of chiral gold nanoclusters (AuNCs), L- and D-cysteine coated AuNC (i.e., L-AuNC and D-AuNC, respectively) with human coagulation factor XII (FXII, an important plasma zymogen initiating the inner coagulation system). D-AuNC exhibited weak binding affinity for FXII, induced FXII aggregation due to significant conformational change, which then activated the FXII for further cleavage. In contrast to D-AuNC, the binding affinity of L-AuNC for FXII was strong and their bioconjugate was quite stable without aggregation. L-AuNC induced the structural change and autoactivation of FXII to a lower extent. Moreover, the enzymatic activity of FXIIa (the activated form of FXII) was influenced upon incubation with L- AuNCs and D-AuNCs with different molecular mechanisms. The finding will expand the understanding of the nanobiological effects of chiral NMs and suggest the potential application in nanomedicine.


Cytotoxic activity of some Asarum plants.
The cytotoxic activity against some tumor cell lines of 16 commonly used species of Asarum was evaluated in this study. All of these plants were widely used in Asian countries as traditional medicines or folk medicines. Their inhibitory activities against four tumor cell lines (HL-60, BGC-823, KB and Bel-7402) were compared. It was observed that 10 of the tested extracts (eight ethanol extracts and two water extracts) among 32 extracts of these plants showed cytotoxic activity. Those 95% ethanol extractions from A. caudigerellum, A. forbesii, A. inflatum and A. maximum exhibited the highest cytotoxic activity, and 95% ethanol extracts or water extracts of A. sieboldii var. seoulense, A. himalaicum, A. splendens and A. crispulatum showed selective activity against one or two cells among the tested tumor cells. This is the first report of Asarum plants possessing cytotoxic activity against tumor cell lines.


Abnormal amino acid composition of nails in Bazex's paraneoplastic acrokeratosis.
Bazex's paraneoplastic acrokeratosis is a syndrome with psoriasiform acral hyperkeratosis and nail changes associated with carcinoma of the upper respiratory or alimentary tract. We report here a case where amino acid analysis of the hyperkeratotic and friable nails differed from normal and other diseased nails investigated by us, but they were similar to those reported in trichothiodystrophy or the BIDS syndrome.


Correlation of Press Ganey Scores With Early Patient Satisfaction After Anterior Cruciate Ligament Reconstruction.
Patient satisfaction metrics are commonly used to assess the quality of health care and affect reimbursement. The Press Ganey Ambulatory Surgery (PGAS) is a satisfaction survey that has emerged as a prominent quality assessment tool; however, no data exist on whether PGAS scores correlate with early postsurgical satisfaction during the PGAS survey administration period in patients who underwent anterior cruciate ligament reconstruction (ACLR). To determine if PGAS scores correlate with measures of satisfaction and patient-reported outcomes (PROs) at 2 weeks postoperatively in ACLR patients. Cohort study (diagnosis); Level of evidence, 3. A retrospective review of patients who underwent ACLR at a single institution was performed. Patients who completed the PGAS survey and PROs at 2 weeks postoperatively were included in the study. Surgical satisfaction was measured with the Surgical Satisfaction Questionnaire (SSQ-8), and PROs included 6 Patient-Reported Outcomes Measurement Information System domains. Bivariate analysis between PGAS and PRO scores was conducted using the Spearman rank correlation coefficient (r S). Of the 716 patients who received the PGAS survey after ACLR, 81 patients completed the survey, and 39 patients also completed PROs and were included in the study. Total converted (mean scaled score) and "top box" (percentages of questions with highest rating selected) PGAS scores showed no significant correlations with the SSQ-8 (r S =-0.24; P = .14). There were no significant correlations between SSQ-8 and PGAS domain scores except for a negative correlation with Facility domain top box scores (r S =-0.33; P = .04), meaning that patients with higher surgical satisfaction had lower PGAS Facility scores. Total PGAS (converted and top box scores) and PGAS domain scores showed no significant correlation with any of the other PROs. PGAS scores showed no significant positive correlation with surgical satisfaction, function, pain, mental health, activity, or expectations of surgery in patients 2 weeks after ACLR. This suggests little to no relationship between PGAS score and surgical satisfaction in the early recovery period after ACLR.


The role of radiotherapy in the treatment of childhood intracranial germinoma: long-term survival and late effects.
The aim of the present report was to evaluate the role of radiotherapy in the treatment of childhood intracranial germinoma in view of long-term survival and functional outcome. Nine children with histologically verified intracranial germinomas treated in Slovenia between 1983 and 1995 were reviewed. The four boys and five girls were 8.8-16.9 years old (median, 11.3 years). Five tumors were suprasellar, three were in the pineal region, and one patient had bifocal disease. Two patients had disseminated tumor. All patients received radiotherapy: six to the tumor bed, one to the whole brain, and two to the whole central nervous axis (CNA). The doses to the tumor bed ranged from 30 to 46 Gy (median, 44 Gy) and to the CNA were 24 and 34.5 Gy. Five patients received neoadjuvant cyclophosphamide and three patients, all with beta-human chorionic gonadotropin secreting tumors, received neoadjuvant cisplatin-based chemotherapy. Six patients are alive 12.8-21.8 years (median, 19 years) from diagnosis. The causes of death in three patients were disseminated disease, toxicity of salvage chemotherapy, and secondary etoposide-induced leukemia. All patients with suprasellar tumors presented with overt endocrinopathy. Results of psychological evaluation were subnormal in one out of five patients tested. Estimate of mental deterioration due to therapy ranged from 0% to 30% (median, 15%). Emotional disorder was registered in four patients and psycho-organic syndrome in three. Our results on long-term survival and functional outcome confirm the efficacy and relative safety of limited-field and reduced-dose radiotherapy for childhood intracranial germinoma when supplemented with chemotherapy.


CD4 T cells are required for both development and maintenance of disease in a new mouse model of reversible colitis.
Current therapies to treat inflammatory bowel diseases have limited efficacy, significant side effects, and often wane over time. Little is known about the cellular and molecular mechanisms operative in the process of mucosal healing from colitis. To study such events, we developed a new model of reversible colitis in which adoptive transfer of CD4(+)CD45RB(hi) T cells into Helicobacter typhlonius-colonized lymphopenic mice resulted in a rapid onset of colonic inflammation that was reversible through depletion of colitogenic T cells. Remission was associated with an improved clinical and histopathological score, reduced immune cell infiltration to the intestinal mucosa, altered intestinal gene expression profiles, regeneration of the colonic mucus layer, and the restoration of epithelial barrier integrity. Notably, colitogenic T cells were not only critical for induction of colitis but also for maintenance of disease. Depletion of colitogenic T cells resulted in a rapid drop in tumor necrosis factor α (TNFα) levels associated with reduced infiltration of inflammatory immune cells to sites of inflammation. Although neutralization of TNFα prevented the onset of colitis, anti-TNFα treatment of mice with established disease failed to resolve colonic inflammation. Collectively, this new model of reversible colitis provides an important research tool to study the dynamics of mucosal healing in chronic intestinal remitting-relapsing disorders.


Necrotizing fasciitis from an iliopsoas muscle abscess caused by a toothpick: A case report and literature review.
Psoas muscle abscess is rare and can become more complicated to treat after they have progressed to necrotizing fasciitis. The data of secondary psoas muscle abscess cause by ingested toothpick are limited in the literature. We have done an extensive literature review and found a number of 8 cases (including our new case) of ingested toothpicks causing iliopsoas muscle abscess. We present a 70-year-old man with unremarkable medical history experienced left flank pain for several days with radiated to left thigh and unable to walk. He initially exhibited drowsiness at emergency department with fever and chillness. Computed tomography showed iliopsoas abscess and necrotizing fasciitis. This patient received emergent surgical debridement and a toothpick was found lodged in the deep portion of the left psoas muscle. He was tolerated to the treatment and discharged on 58 days after the operation. A review of the literature revealed only eight reported cases since 1946 (including ours) of ingested toothpicks migrating into the iliopsoas muscle and causing abscess formation or necrotizing fasciitis. Three of the cases did not exhibit gut perforation, possibly because of self-healing of the wound. Gastrointestinal symptoms are not always apparent when the perforation site is over the retroperitoneal space. Thorough debridement is essential if the origin of infection is unknown. Ingestion of a foreign body may be asymptomatic, the present case and a review of the literature indicated that ingested toothpicks can cause severe morbidity or even mortality. The diagnosis of psoas abscesses associated with toothpicks is difficult, and such cases should not be overlooked. Appropriate early surgical intervention is recommended.


Environmental Risks for Spondyloarthropathies.
Spondyloarthropathies, also known as spondyloarthritis, encompasses a spectrum of diseases classified by it's axial and peripheral musculoskeletal manifestations. Extra-articular features are common in SpA making these systemic rheumatologic diseases involve the skin, eye, gut, and other organ systems.Research has identified risk factors for the development of spondyloarthritis, particularly regarding genetic susceptibility and the strong association with HLA-B27. Multiple studies have elucidated clinical risk factors associated with SpA disease activity and severity. In this review, we aim to explore the environmental risk factors for spondyloarthritis.


Insights into the underpinning effect of graphene in Cu1Mn10 on enhancing the low-temperature catalytic activity for CO oxidation.
CO emission is a critical issue of industrial processes such as steel-smelting, cement manufacturing, and waste incineration. Catalytic oxidation based on Cu-Mn binary catalysts shows great potential for efficient removal of CO, whereas their practical applicability is limited by the inferior low-temperature catalytic activity and the high catalyst cost owing to a substantial quantity of Cu. In this study, doping graphene is designed to adjust the electron transfer capability to improve the low-temperature catalytic activity as well as reduce the amount of Cu, and thereby Cu1Mn10 catalysts doped with slight amounts of graphene (x%G-Cu1Mn10, x is 1∼5) were fabricated. It was found that the introduction of graphene could form effective electron transport channels to enhance the intermetallic interaction and oxygen vacancy generation, thus improving the low-temperature catalytic performance of the Cu1Mn10 catalyst. Among all the catalysts, 4%G-Cu1Mn10 exhibited the highest activity, achieving CO conversion of 92% at 110 °C at a weight hourly space velocity of 120,000 mL/(g∙h). The introduction of graphene also enabled the catalyst with excellent catalytic activity and stability at a relative humidity of 70%. Attractively, 4%G-Cu1Mn10 can be further loaded into the polyester fabric, presenting great application potentials in the effective elimination of CO during the dust removal process since the flue gas temperature in the dust collector is just around the T90% and the catalyst that is inside of fabric fiber rather than on the fabric surface can be rarely influenced by the dust. In general, doping graphene provides a facile method to enhance the low-temperature activities of the Cu-Mn binary catalysts and cut down the use of valuable Cu, showing great application potential.


The usefulness of olfactory fear conditioning for the study of early emotional and cognitive impairment in reserpine model.
Due to the ability for depleting neuronal storages of monoamines, the reserpine model is a suitable approach for the investigation of the neurobiology of neurodegenerative diseases. However, the behavioral effects of low doses of reserpine are not always detected by classic animal tests of cognition, emotion, and sensory ability. In this study, the effects of reserpine (0.5-1.0mg/kg) were evaluated in olfactory fear conditioning, inhibitory avoidance, open-field, elevated plus-maze, and olfactory discrimination. Possible protective effects were also investigated. We found that single administration of reserpine impaired the acquisition of olfactory fear conditioning (in both doses) as well as olfactory discrimination (in the higher dose), while no effects were seen in all other tests. Additionally, we demonstrated that prior exposure to environmental enrichment prevented effects of reserpine in animals tested in olfactory fear conditioning. Altogether, these findings suggest that a combined cognitive, emotional and sensory-dependent task would be more sensitive to the effects of the reserpine model. In addition, the present data support the environmental enrichment as an useful approach for the study of resilience mechanisms in neurodegenerative processes.


Phenolic compounds of 'Galega Vulgar' and 'Cobrançosa' olive oils along early ripening stages.
In this study, the lipophilic and hydrophilic phenol composition of virgin olive oils (VOO) obtained from olives from two of the most important Portuguese cultivars ('Galega Vulgar' and 'Cobrançosa'), harvested at different ripening stages and under two irrigation schemes (rain fed and irrigated), was evaluated. Phenolic alcohols (hydroxytyrosol and tyrosol), phenolic acids and derivatives and flavonoids (luteolin and apigenin), as well as tocopherols were quantified. Lipophilic (>300mgkg(-1)) and hydrophilic phenols (>600mgkg(-1)) were present in high contents in both VOO, for early ripening stages. Gamma-tocopherol content is higher in 'Galega Vulgar' VOO. Total phenols showed a decrease between ripening index 2.5 and 3.5. The dialdehydic form of elenolic acid linked to hydroxytyrosol (3,4-DHPEA-EDA), also known as oleacein, was the major phenolic compound identified in both oils. The concentration of free hydroxytyrosol and tyrosol in both VOO is very low while their esterified derivatives, like 3,4-DHPEA-EDA and p-HPEA-EDA, are much more abundant.


Analysis of Antimicrobial Activity of Monocytic Myeloid-Derived Suppressor Cells in Infection with Mycobacterium tuberculosis and Human Immunodeficiency Virus.
Myeloid-derived suppressor cells (MDSC) encompass a subset of myeloid cells, which suppress both innate and adaptive immune functions. Since Mycobacterium tuberculosis (M. tuberculosis) can infect these cells, interest has emerged to study the antimicrobial response of MDSC to mycobacteria causing tuberculosis. Reactive oxygen species (ROS) are critical mediators to control intracellular replication of M. tuberculosis and MDSC express high levels of these effector molecules. Here we describe the flow cytometric assessment of total cellular ROS produced by MDSC in response to infection with M. tuberculosis and compare it with the ROS activity of non-MDSC myeloid cells. To further understand the dynamics of host-pathogen interactions, we provide details on methods for measurement of the intracellular replication of M. tuberculosis within MDSC. Of note, these procedures were adopted for primary MDSC and non-MDSC subsets isolated from human immunodeficiency virus (HIV)-uninfected or HIV-infected individuals, in vitro infected with M. tuberculosis to mimic M. tuberculosis mono- or HIV-M. tuberculosis coinfection, respectively.


High dorsal drainage routes of Spiegel's lobe.
The venous drainage from Spiegel's lobe to the terminal portion of the hepatic veins has been described in the literature, but its morphology remains unclear. We examined 42 dissected liver specimens and 38 cast specimens. In 8 of the 42 dissected liver specimens and 5 of the 38 cast specimens we found atypical but thick (over 3 mm) caudate veins that drained Spiegel's lobe and emptied into the terminal portion (along the most proximal 5-mm course) of the middle hepatic vein (MHV) or the inferior vena cava (IVC) near the MHV terminal (less than 10 mm from the MHV). We termed these the superior caudate vein. This vein ran upward between the caudate portal branches of the left and hilar bifurcation origins or through the territory of the left origin. The superior caudate vein, consistently coexisted with the typical vein(s). We also found several analogues of the superior caudate vein, such as the cranially shifted opening of the typical caudate vein and relatively thick proximal tributaries of the MHV from Spiegel's lobe. Although the superior caudate vein, if present, seemed to have a large role in the venous drainage of the lobe, its incidence seemed to be too low for clinical relevance.


Exaggerated arthropod assault: Eosinophilic dermatosis in a patient with small lymphocytic lymphoma.
Dermatologic reactions are commonly encountered in clinical practice. Providers must be aware of both the common and uncommon etiologies leading to these eruptions, particularly in patients with underlying malignancies. Establishing the appropriate etiology directs treatment of these conditions, which may be therapy directed at the malignancy itself.


Differential excision from DNA of the C-8 deoxyguanosine reaction products of N-hydroxy-2-aminofluorene and N-acetoxy-N-acetyl-2-aminofluorene by endonuclease S1 from Aspergillus oryzae.
Calf thymus DNA was modified in vitro with [G-3H]N-hydroxy-2-aminofluorene and [G-3H]N-acetoxy-N-acetyl-2-aminofluorene and the nuclease S1 digestion was studied under identical conditions. The ratios of the maximum reaction rate (V) and the Michaelis constant (Km), V/Km, indicate that 2-aminofluorene(AF)-modified DNA is hydrolyzed 3 times more slowly than N-acetyl-2-aminofluorene(AAF)-modified DNA under similar reaction conditions. The AF-modified DNA was slightly more susceptible to partial digestion by nuclease S1 than unmodified control DNA. These results suggest that the local regions of denaturation induced by AF substitution are smaller than those associated with AAF modification.


Emerging roles of mitochondria in animal regeneration.
The regeneration capacity after an injury is critical to the survival of living organisms. In animals, regeneration ability can be classified into five primary types: cellular, tissue, organ, structure, and whole-body regeneration. Multiple organelles and signaling pathways are involved in the processes of initiation, progression, and completion of regeneration. Mitochondria, as intracellular signaling platforms of pleiotropic functions in animals, have recently gained attention in animal regeneration. However, most studies to date have focused on cellular and tissue regeneration. A mechanistic understanding of the mitochondrial role in large-scale regeneration is unclear. Here, we reviewed findings related to mitochondrial involvement in animal regeneration. We outlined the evidence of mitochondrial dynamics across different animal models. Moreover, we emphasized the impact of defects and perturbation in mitochondria resulting in regeneration failure. Ultimately, we discussed the regulation of aging by mitochondria in animal regeneration and recommended this for future study. We hope this review will serve as a means to advocate for more mechanistic studies of mitochondria related to animal regeneration on different scales.


Iron and zinc status of patients with chronic renal failure who are not on dialysis.
The purpose of this study was to assess the zinc and iron status in patients with chronic renal failure (CRF) who were not receiving dialysis. Cross-sectional study. Outclinic patients of the Nephrology Division at Federal University of São Paulo. This study was performed on 29 stable patients with CRF who were not receiving dialysis. The parameters for determining iron and zinc status were transferrin saturation, zinc protoporphyrin, serum ferritin, hematocrit, serum iron, total iron binding capacity, erythrocyte, and plasma zinc levels (measured by atomic absorption spectrophotometry). The serum ferritin level was reduced to 85.5 +/- 67.1 ng/mL and the zinc protoporphyrin level was high (68 +/- 32.9 micromol/mol heme), serum transferrin saturation was 19.9% +/- 7.85%, mean serum iron level was 66.6 +/- 26.3 microg/dL, and mean total iron binding capacity was 336 +/- 45.7 microg/dL. Absolute iron deficiency was found in 34.5% of the patients. Zinc level in erythrocytes was high (50.0 +/- 7.2 microg/g hemoglobin), whereas plasma zinc was at a borderline level (74 +/- 17.7 microg/dL) when compared with normal values. There were significant correlations among plasma zinc and serum iron and transferrin saturation, zinc erythrocyte, and parameters of iron. These results show that absolute iron deficiency can occur in patients who are not receiving dialysis and that there is an abnormal distribution of zinc levels in these patients. Moreover, a possible relationship between iron deficiency and zinc distribution was observed.


Synthesis and X-ray structure analysis of a heptacoordinate titanium(IV)-bis-chelate with enhanced in vivo antitumor efficacy.
Chelate stabilization of a titanium(IV)-salan alkoxide by ligand exchange with 2,6-pyridinedicarboxylic acid (dipic) resulted in heptacoordinate complex 3 which is not redox-active, stable on silica gel and has increased aqueous stability. 3 is highly toxic in HeLa S3 and Hep G2 and has enhanced antitumor efficacy in a mouse cervical-cancer model.


Model simulations of spatial distributions and daily totals of photosynthesis in Eucalyptus grandis canopies.
A simulation model for radiation absorption and photosynthesis was used to test the hypothesis that observed nonuniform distributions of nitrogen concentrations in young Eucalyptus grandis trees result in greater amounts of daily assimilation than in hypothetical trees with uniform N distributions. Simulations were performed for trees aged 6, 9, 12 and 16 months which had been grown in plantations under a factorial combination of two levels of fertilization and irrigation. Observed leaf N distribution patterns yielded daily assimilation rates which were only marginally greater (<5%) than for hypothetical trees with uniform distributions. Patterns of assimilation distribution in individual tree crowns closely resembled those for absorbed radiation, rather than for N. These conclusions were unaffected by three choices of alternative leaf area density distributions. The simulation model was also used to calculate hourly and daily rates of canopy assimilation to investigate the relative importance of radiation absorption and total canopy nitrogen on assimilation. Simulated hourly rates of carbon assimilation were often lightsaturated, whereas daily carbon gain was directly proportional to radiation absorbed by the tree crown and to total mass of N in the leaves. Leaf nitrogen concentrations determined photosynthetic capacity, whereas total leaf area determined the amount of radiation absorbed and thus the degree to which capacity was realized. Observed total leaf area and total crown N were closely correlated. The model predicted that nitrogen use efficiences (NUE, mol CO2 mol-1 N) were 60% higher for unfertilized than for fertilized trees at low levels of absorbed photosynthetically active radiation (PAR). Nitrogen use efficiency was dependent on fertilizer treatment and on the amount of absorbed PAR; NUE declined with increasing absorbed PAR, but decreased more rapidly for unfertilized than for fertilized trees. Annual primary productivity was linearly related to both radiation absorbed and to mass of N in the canopy.


[CIAPIN1 expression in human lung cancer tissues and inhibitory effects of the gene on human pulmonary carcinoma NCI-H446 cells].
To explore CIAPIN1 gene expression in lung carcinoma tissues and its regulatory in the growth of NCI-H446. Fifty-one formalin-fixed paraffin-embedded specimens of primary lung cancer and their non-cancerous counterparts were detected by SABC immunohistochemistry method. Adenoviral vector construction was recombined and the gene was transduced into NCI-H446 cells. The expression of CIAPIN1 protein was identified by Western blot. Trypan blue staining was used to count the alive cells and to draw a cellular growth curve. The changes of cell cycle and apoptosis were analyzed by flow cytometry. The positive rate of CIAPIN1 expression in cancer tissues (39.2%)was much lower than that in non-cancerous counterparts (100%, P<0.05). In Ad-CIAPIN1 group, the growth of transfected NCI-H446 cells in vitro was significantly inhibited. In addition the Ad-CIAPIN1-induced cell apoptosis and a predominant arrest in the G1/S phase (P<0.01) were observed. The down-regulation of CIAPIN1 expression in tumor is associated with the development of lung carcinoma. Transduction of NCI-H446 CIAPIN1-negative cell, with Ad-CIAPIN1 can inhibit cell growth, suggesting that CIAPIN1 can be a new tumor-related suppressor gene.


Shoulder disorders and occupation.
Shoulder pain is very common, and it causes substantial morbidity. Standardised classification systems based upon presumed patho-anatomical origins have proved poorly reproducible and hampered epidemiological research. Despite this, there is evidence that exposure to combinations of physical workplace strains such as overhead working, heavy lifting and forceful work as well as working in an awkward posture increases the risk of shoulder disorders. Psychosocial risk factors are also associated. There is currently little evidence to suggest that either primary prevention or treatment strategies in the workplace are very effective, and more research is required, particularly around the cost-effectiveness of different strategies.


Effects of Crawling before Walking: Network Interactions and Longitudinal Associations in 7-Year-Old Children.
To study the impact of crawling before walking (CBW) on network interactions among body composition, the cardiovascular system, lung function, motor competence and physical fitness, at age 7, and to assess the longitudinal association between CBW and body composition, the cardiovascular system, lung function, motor competence, physical fitness and physical activity parameters, at age 7. CBW, body composition, cardiovascular system, lung function, motor competence, physical fitness and physical activity were assessed in seventy-seven healthy Caucasian children. Network analyses revealed that the crawling group had a greater number of links among all the studied variables compared with the non-crawling group. In the longitudinal study, using multiple regression analyses, crawling was independently associated with fat mass (%), fat-to-muscle ratio and systolic blood pressure, with models explaining up to 56.3%, 56.7% and 29.9% of their variance, respectively. CBW during child's development is a possible modulator in the network interactions between body systems and it could influence future metabolic and cardiovascular health.


Functionalized graphene grids with various charges for single-particle cryo-EM.
A major hurdle for single particle cryo-EM in structural determination lies in the specimen preparation impaired by the air-water interface (AWI) and preferential particle-orientation problems. In this work, we develop functionalized graphene grids with various charges via a dediazoniation reaction for cryo-EM specimen preparation. The graphene grids are paraffin-assistant fabricated, which appear with less contaminations compared with those produced by polymer transfer method. By applying onto three different types of macromolecules, we demonstrate that the high-yield charged graphene grids bring macromolecules away from the AWI and enable adjustable particle-orientation distribution for more robust single particle cryo-EM structural determination.


Single-cell transcriptome analysis reveals cellular and molecular alterations in small cell lung cancer tumors following chemotherapy.
Chemotherapy is the standard therapy for small cell lung cancer (SCLC), but relapse is common and the 2-year survival rate remains low. Given the contribution of the tumor microenvironment (TME) to cancer development and response to treatment, we analyzed here how chemotherapy alters the TME in SCLC using single-cell RNA sequencing. The comparison between neuroendocrine cells and other epithelial cells in five chemotherapy-naive patients identified upregulation of Notch-inhibiting genes, such as DLL3 and HES6. Analysis of genes differentially expressed between five patients receiving chemotherapy and five treatment-naive patients in cells in the TME showed that chemotherapy promoted antigen presentation and senescence in neuroendocrine cells, upregulated ID1 to enhance angiogenic activities of stalk-like endothelial cells and strengthened vascular endothelial growth factor signaling in lymphatic endothelial cells. Chemotherapy also promoted the remodeling of extracellular matrix by fibroblasts and upregulated interferon-mediated antitumor immune responses by B and T cells. Our single-cell transcriptome analysis provides insights into how chemotherapy affects the TME in SCLC, which may guide efforts to make therapy more effective.


High-Performance Phosphorus-Graphite Dual-Ion Battery.
Recently, dual-ion batteries (DIBs) are regarded as a promising alternative to well-developed lithium-ion batteries, and the development of high-performance and abundant-sodium-based DIBs (SDIBs) is being intensively pursued. In this work, a novel SDIB composed of a phosphorus (P)-based anode and graphite (G) cathode is successfully constructed for the first time. This P-G SDIB shows a high working voltage of around 3.9 V, a high reversible capacity of 373 mA h/g, good rate capability, and long cyclability, which are superior to those of the most reported DIBs. The ex situ X-ray diffraction, high-resolution transmission electron microscopy, and X-ray photoelectron spectroscopy tests reveal the insertion/extraction mechanism of Na+ ions into/from P-based anodes via reversible Na-P alloying reactions accompanied with high charge-storage capability. Moreover, the presodiation of P-based composites is found to be an efficient approach to boost the cycling performance of the P-G SDIB by forming a stable NaF-rich solid electrolyte interphase layer to alleviate electrolyte decomposition. Our results demonstrate that P-based SDIBs possess tremendous potential for practical electrochemical energy-storage applications.


Performance of two Picea abies (L.) Karst. stands at different stages of decline : VIII. Photosynthesis and nutrition under polluted and clean air conditions of Germany and New Zealand.
Photosynthetic rates and nutrient contents of spruce needles were measured in a region with high levels of air pollution in NE Bavaria, Germany (FRG), and compared to spruce grown under clean air conditions at Craigieburn, in the South Island of New Zealand (NZ). The absolute rates of CO2 uptake, the slope of the CO2 response curve at 240 μl l-1 internal CO2 concentration, and the change of photosynthetic rates with needle age at ambient and saturated CO2 concentrations were virtually identical at both measuring sites. These results confirm an earlier conclusion, that there is no long-term effect of atmospheric pollutants directly on photosynthetic CO2 uptake rates with persistent exposure at the FRG site to high levels of anthropogenic air pollution. Photosynthetic capacity at saturating CO2 concentration was three times higher in the NZ spruce. Needles with high photosynthetic capacity in NZ had lower nitrogen and higher calcium concentrations per unit dry weight but higher concentrations of nitrogen, phosphorus, potassium, magnesium and calcium per unit leaf area, and twice the specific leaf weight.


From the laboratory to pharmaceutical care research--Part I.
In pharmaceutical care research (PCR) a mass of robust general rules has not yet been found. Consequently, the challenge of PCR is that mainly through induction researchers have to study objects which are learning and which are open to environmental influences and, by doing so, researchers have to contribute to both theory and practice. Therefore the characteristics reductionism, repeatability and refutability originated from natural sciences cannot be applied to PCR on a 1:1 basis. PCR should be imitable, defensible, consistent and relevant in order to enable other researchers to agree or disagree with the conclusions and to stimulate new research.


Sleep disordered breathing and the risk of severe maternal morbidity in women with preeclampsia: A population-based study.
Obstructive sleep apnea (OSA) may exacerbate the widespread endothelial dysfunction seen in preeclampsia, potentially worsening clinical outcomes. We aimed to assess whether OSA is associated with an increased risk of severe maternal morbidity, cardiovascular morbidity, and healthcare utilization among women with preeclampsia. We performed a retrospective cohort study utilizing data from the National Perinatal Information Center (2010-2014) in the United States.The cohort comprised women with preeclampsia. We estimated the association between OSA and the outcomes using logistic regression analyses and determined odds ratio adjusted for demographic factors and comorbidities (ORadj) and associated 95% confidence intervals (CI). The primary outcome was a composite of mortality and severe maternal morbidity comprising intensive care unit (ICU) admission, acute renal failure, pulmonary edema, pulmonary embolism, congestive heart failure, cardiomyopathy, and stroke. Secondary outcomes comprised the subset of cardiovascular events, as well as increased healthcare utilization (including Cesarean delivery, preterm birth, ICU admission, and prolonged length of hospital stay). In total, 71,159 women had preeclampsia, including 270 (0.4 %) with OSA. Women with preeclampsia and OSA were more likely to experience severe maternal morbidity than women without OSA (ORadj 2.65, 95 % CI [1.94-3.61]). Moreover, women with concomitant OSA had more severe cardiovascular morbidity than women without OSA (ORadj 5.05, 95 % CI [2.28-11.17]). Accordingly, OSA was associated with increased healthcare utilization in women with preeclampsia (ORadj. 2.26, 95 % CI [1.45-3.52]). In women with preeclampsia, OSA increases the risk for severe maternal morbidity, cardiovascular morbidity, and healthcare utilization.


Effects of hemarthrosis on cartilage and synovium in rabbits.
To provide experimental basis for clinic treatment by observing the effects of simple acute hematoma on cartilage and synovium, and improvement of hyaluronic acid (HA) on the damage. Twenty-four New Zealand white rabbits were randomly divided 3 groups according to killed time: hematoma group, HA group and control group. These rabbits were killed at 4 days, 2, 4 and 8 weeks, respectively. Knee articular cartilage and synovium were obtained to detect histology, histochemistry and chondroitin proteoglycans (PG). Morphologies of cartilage and synovium in the control group were normal, while cartilage cells were detected hyperplasia of activation and each layer was disorganized in hematoma groups with 4 days and 2 weeks. Compared to the control group, concentrations of PG in 4 days and 2 weeks groups were significantly reduced (p < 0.05), while no significant difference was detected between 4 weeks group and the control group. Morphology was recovered normal in 8 weeks. Compared to hematoma group, morphology and histochemistry were improved in HA group at each time frame. Simple acute hematoma can lead to temporary change of morphology and biochemistry. Application of HA can reduce damage of hemarthrosis on cartilaginous and shorten the cartilage recovery time.


Peer victimization, prison climate, resilience and psychological distress of incarcerated juvenile offenders in Ghana: A serial mediation examination.
Most Ghanaian research in the area of victimization among children has focused on the school setting. Little research has been done in an attempt to understand inmate-on-inmate victimization within the juvenile correctional facilities in Ghana. This study, therefore, investigated the extent to which peer victimization influences psychological distress among juvenile offenders in the Senior Correctional Center of Ghana. A cross-sectional design was used to purposively sample 115 juvenile offenders for the study. Following mediation analysis performed in PROCESS, the results revealed that prison climate and resilience serially mediated the relationship between peer victimization and psychological distress. Independently, both prison climate and resilience mediated the relationship between peer victimization and psychological distress. It was recommended that anti-bullying programs ought to be institutionalized to create mental health awareness within the correctional facilities. Also, support systems such as the Listener Scheme need to be deployed within the correctional facilities.


Experts Achieve Consensus on a Majority of Statements Regarding Platelet-Rich Plasma Treatments for Treatment of Musculoskeletal Pathology.
To establish consensus statements on platelet-rich plasma (PRP) for the treatment of musculoskeletal pathologies. A consensus process on the treatment of PRP using a modified Delphi technique was conducted. Thirty-five orthopaedic surgeons and sports medicine physicians participated in these consensus statements on PRP. The participants were composed of representatives of the Biologic Association, representing 9 international orthopaedic and musculoskeletal professional societies invited due to their active interest in the study of orthobiologics. Consensus was defined as achieving 80% to 89% agreement, strong consensus was defined as 90% to 99% agreement, and unanimous consensus was indicated by 100% agreement with a proposed statement. There was consensus on 62% of statements about PRP. (1) PRP should be classified based on platelet count, leukocyte count, red blood count, activation method, and pure-plasma versus fibrin matrix; (2) PRP characteristics for reporting in research studies are platelet count, leukocyte count, neutrophil count, red blood cell count, total volume, the volume of injection, delivery method, and the number of injections; (3) the prognostic factors for those undergoing PRP injections are age, body mass index, severity/grade of pathology, chronicity of pathology, prior injections and response, primary diagnosis (primary vs postsurgery vs post-trauma vs psoriatic), comorbidities, and smoking; (4) regarding age and body mass index, there is no minimum or maximum, but clinical judgment should be used at extremes of either; (5) the ideal dose of PRP is undetermined; and (6) the minimal volume required is unclear and may depend on the pathology. Level V, expert opinion.


A rare case of Acrodermatitis continua of Hallopeau successfully treated with topical calcipotriol/betamethasone dipropionate ointment associated with Jaccaud's arthropathy: A case report.
Acrodermatitis continua of Hallopeau (ACH) is a rare and localized form of pustular psoriasis that can lead to irreversible anonychia whereas Jaccoud's arthropathy (JA) is a rare non-articular condition characterized by a deforming non-erosive arthropathy involving the digits. This case describes the first reported association of these two rare conditions in a 73-year-old Filipino male who was treated topically until remission of ACH. Because calcipotriol/betamethasone ointment works better and faster than clobetasol ointment, it may be considered as a preferred first-line treatment for ACH. This case also highlights the evaluation of joint symptoms in the context of psoriatic arthritis and JA, along with a discussion of its management. A multidisciplinary approach involving dermatology, rheumatology, and physiatry is essential in the care of these two rare conditions.


Analysis of barriers, supports and gender gap in the choice of STEM studies in secondary education.
Society is more digitised than ever and there is an urgent need to train people in these sectors, where women are still under-represented. A quantitative descriptive, correlational and explanatory descriptive design was used to identify barriers, supports and gender gaps in Science, Technology, Engineering and Mathematics in Secondary Education by analysing the interest and perception of 1562 students and 432 teachers. Descriptive statistics, Chi-square and Lambda test and Crame's V or Phi test were performed together with a qualitative analysis. The results show that fewer female students want to pursue STEM studies, with girls preferring health and education professions and boys preferring engineering and computer science. Indeed, their motivation is different since we found correlations between being a girl and choosing STEM for helping people and society, while earning money is important for boys. Girls believe more necessary than boys to have qualities to study STEM and less often perceive themselves as intelligent and courageous. Our study revealed that families and teachers encourage more boys than girls towards STEM activities. Teachers believe that girls are influence by preconceived ideas, lack of STEM knowledge and lower self-esteem. Regarding gender equality, almost half state that no objectives are included in the curricula, 43.85% do not include it in subjects and only 30% received training. Consequently, female vocations need to be promoted by teaching how STEM solves real-life problems, fostering creativity, increasing self-confidence, promoting STEM activities and making female role models visible. Teachers should receive more gender training and promote gender-sensitive STEM education.


[B. Parenteral feeding. Metabolic dysfunction in the postoperative and post-traumatic phase].
A fundamental knowledge of postaggression metabolism, i.e., postoperative and posttraumatic metabolism, is necessary for prophylaxis and treatment of its deleterious dysfunctions. These may be due to disturbed regulation of the water, electrolyte, and acid-base balance, the oxygen supply to cells, energy metabolism as well as structural and functional metabolism (with special emphasis on protein metabolism), and vitamin and trace-element metabolism. This schematic synopsis is a preliminary introduction to this topic.


A comparison of microplastic contamination in freshwater fish from natural and farmed sources.
Contamination of aquatic systems mainly by urbanization and poor sanitation, deficient or lack of wastewater treatments, dumping of solid residues, and run off has led to the presence of particles, including manmade polymers, in tissues of many marine and freshwater species. In this study, the prevalence of microplastics (MPs) in freshwater fish from farmed and natural sources was investigated. Oreochromis niloticus from aquaculture farms in the Huila region in Colombia, and two local species (Prochilodus magdalenae and Pimelodus grosskopfii), naturally present in surface waters were sampled. Of the particles identified, fragments were the predominant type in the three tissue types (stomach, gill, and flesh) derived from farmed and natural fishes. MicroFT-IR spectroscopy was conducted on 208 randomly selected samples, with 22% of particles identified as MPs based on spectra with a match rate ≥ 70%. A total of 53% of identified particles corresponded to cellophane/cellulose, the most abundant particle found in all fish. Not all fish contained MPs: 44% of Oreochromis farmed fish contained MPs, while 75% of natural source fish contained MPs in any of its tissues. Overall, polyethylene terephthalate (PET), polyester (PES), and polyethylene (PE) were the prevalent MPs found in the freshwater fish. A broader variety of polymer types was observed in farmed fish. The edible flesh part of fish presented the lower prevalence of MPs compared to gill and stomach (gut), with gut displaying a higher frequency and diversity of MPs. This preliminary study suggests that the incidence and type of MPs varies in farmed verses natural fish sources as well as across different tissue types, with significantly less detected within the edible flesh tissues compared with stomach and gill tissues.