Role of IL-15 in HIV-1-associated hypergammaglobulinaemia.
IL-15 is a novel cytokine, produced by monocytes/macrophages, with biological activities similar to IL-2 but with no significant sequence homology. IL-15 also stimulates human B cells to proliferation and immunoglobulin secretion. We measured serum levels of IL-15 in 84 HIV-1-infected individuals at different stages of disease in reference to 41 healthy blood donors. Our results show a marked elevation of IL-15 serum levels during HIV-1 infection. Moreover, we found that this increase correlated with serum levels of IgG (r = 0.376, P < 0.0001), and partly with serum IgM (r = 0.265, P = 0.015). A significant increase of IL-15 production by cultured peripheral blood mononuclear cells (PBMC) and purified monocytes in the presence of HIV-1 virus suggests that monocytes/macrophages may be a source of higher IL-15 serum levels in HIV-1-infected individuals. These findings indicate a participation of IL-15 in the hypergammaglobulinaemia frequently associated with HIV-1 infection.


Measuring degradation of zinc phosphide residues in possum stomach contents.
Zinc phosphide (ZnP) has been identified as a potentially cost-effective vertebrate pesticide for possum (Trichosurus vulpecula) control in New Zealand. We established methodology for analysis of microencapsulated ZnP formulations (MZP) and investigated the half-life of residual ZnP in the stomach contents of poisoned possums. An interlaboratory study was conducted to compare results of ZnP analysis in stomach contents. The half-life of ZnP was 3.4 days for ZnP in possum stomach contents and 6.7 days in vomit. Subsequent estimates were made of 34 and 67 days, respectively, for residual ZnP to decline to concentrations below the 1 microg/g method detection limit.


Arachis virus Y, a new potyvirid from Brazilian forage peanut (Arachis pintoi).
The complete nucleotide sequence of a new member of the family Potyviridae, which we propose to name "Arachis virus Y" (ArVY), is reported from forage peanut plants (Arachis pintoi) exhibiting virus-like symptoms. The ArVY positive-sense RNA genome is 9,213 nucleotides long and encodes a polyprotein with 2,947 amino acids that is predicted to be cleaved into 10 mature proteins. The complete single open reading frame (ORF) of ArVY shares 47% and 34% nucleotide and amino acid sequence identity, respectively, with the closest related virus, soybean yellow shoot virus. Electron microscopic analysis revealed elongated viral particles typical of those found in plant cells infected with potyviruses.


The impact of FDI on environmental pollution in China: evidence from spatial panel data.
With the rapid development of the economy, China's environmental problems remain prominent, and ecological environmental protection has far to go. Many factors work together to affect environmental pollution. In this study, based on the spatial correlation of environmental situation between adjacent regions, spatial autoregressive models are constructed to examine the impacts of foreign direct investment (FDI) on environmental pollution in China. We find an inverted U-shaped relationship between FDI and environmental situation. The study further investigates the mediating effect of economic scale, technology, and industrial structure between FDI and environmental situation. The results show that regions with a larger economic scale and better industrial structure experience a greater FDI impact on environmental situation, but technological level does not serve as a moderator in this study. Our findings have important implications for environmental pollution control and provide important insights for China into a new stage of high-quality development.


A soluble endoplasmic reticulum factor as regenerative therapy for Wolfram syndrome.
Endoplasmic reticulum (ER) stress-mediated cell death is an emerging target for human chronic disorders, including neurodegeneration and diabetes. However, there is currently no treatment for preventing ER stress-mediated cell death. Here, we show that mesencephalic astrocyte-derived neurotrophic factor (MANF), a neurotrophic factor secreted from ER stressed cells, prevents ER stress-mediated β cell death and enhances β cell proliferation in cell and mouse models of Wolfram syndrome, a prototype of ER disorders. Our results indicate that molecular pathways regulated by MANF are promising therapeutic targets for regenerative therapy of ER stress-related disorders, including diabetes, retinal degeneration, neurodegeneration, and Wolfram syndrome.


Dopamine antagonists alter response allocation but do not suppress appetite for food in rats: contrast between the effects of SKF 83566, raclopride, and fenfluramine on a concurrent choice task.
Dopamine is important for enabling organisms to overcome work-related response costs. One way of investigating this function has been with concurrent choice procedures using food reinforcement. In the present study, rats were given a choice between pressing a lever for preferred Bioserve pellets, or approaching and consuming a less-preferred laboratory chow that was concurrently available. In previous work with this task, dopamine antagonists and accumbens dopamine depletions decreased lever pressing but increased chow consumption. The present study assessed three drugs (two dopamine antagonists and one appetite suppressant) using the lever pressing/chow feeding task. Under baseline conditions, rats pressed the lever at high rates (1,300-1,500 responses) to obtain the preferred food, and little of the laboratory chow was eaten (1-2 g). Selective D1 and D2 antagonists (SKF 83566 and raclopride) reduced fixed ratio 5 lever pressing, but substantially increased chow consumption. In contrast, the serotonergic appetite suppressant fenfluramine reduced both lever pressing and chow consumption. With the dopamine antagonists, lever pressing and chow consumption were inversely correlated across treatments, while these two measures were unrelated in the fenfluramine experiment. Dopamine antagonists and accumbens dopamine depletions do not simply reduce appetite. Rats with accumbens dopamine depletions, or rats treated with low doses of selective or non-selective dopamine antagonists, remain directed toward the acquisition and consumption of food. These results demonstrate that fundamental aspects of food reinforcement are left intact after treatment with low doses of dopamine antagonists.


Incidence rate and risk factors of status epilepticus after stroke.
Purpose To evaluate the incidence rate and risk factors for status epilepticus (SE) after stroke (PSSE), including ischaemic stroke (IS), intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH). Methods A meta-analysis was performed using relevant research from databases such as PubMed, Embase, Cochrane Online Library, and Clinicaltrials.gov. The quality of the studies was evaluated by using the quality evaluation criteria of the Agency for Healthcare Research and Quality (AHRQ). All data were pooled by STATA 12.0 software for meta-analysis. Results The review considered 1650 articles, and 17 articles with 2821 instances of SE among 1088087 instances of stroke were included. The incidence rate of SE after stroke was 6.90 per 1000 total strokes (95% CI: 5.58-8.22). By subgroup analysis of SE, the rates were 33.85‰ (95% CI: 13.77-53.94) for non-convulsive status epilepticus (NCSE) and 2.42‰ (95%CI: 1.66-3.19) for generalized convulsive status epilepticus (GCSE). Age, sex, and presence of atrial fibrillation showed no significant difference between the SE group and the non-SE group after stroke. Hypertension and diabetes are associated with a decreased rate of SE. However, African American race, alcohol abuse, and renal disease are associated with an increased rate of SE. Significance There were approximately 6.9 patients with status epilepticus per 1000 strokes. NCSE is more common after stroke and needs more attention. African American race, alcohol abuse and renal disease may be risk factors for PSSE.


The impact of cultural immersion service learning on BSN graduates: A quasi-experimental evaluation.
The cultural immersion service-learning model evaluated in this study sought to facilitate cultural consciousness of culturally congruent nursing care among predominantly White nursing students attending a university that was racially and culturally homogeneous. Evidence supports the use of cultural immersion service learning during undergraduate nursing programs in developing the skills necessary for effective transcultural healthcare; yet, little is known about its impact beyond the semester of the experience. This project used a quasi-experimental design to determine if transcultural self-efficacy of BSN graduates among five campuses differed. One campus of the five conducted a mandatory cultural immersion service-learning experience during the graduates' junior year. From a population of 94 BSN graduates of which 30 (32%) graduates participated in the cultural immersion service-learning experience, 53 completed the Transcultural Self-Efficacy Tool. Eighteen (34%) of the graduates who participated in the cultural immersion service-learning experience participated in this study. The transcultural self-efficacy was significantly greater in those graduates who participated in the cultural immersion service-learning experience; yet, no difference was found among graduates of the four campuses not offering the experience. The cultural immersion service-learning experience seems to provide nursing students from racially and ethnically homogeneous communities with an experiential learning context which facilitates the development of transcultural self-efficacy.


Vinpocetine-based therapy is an attractive strategy against oxidative stress-induced hepatotoxicity in vitro by targeting Nrf2/HO-1 pathway.
Vinpocetine (Vin), a synthetic-derivative of Vincamine, monoterpenoid indole alkaloid, has been reported to have various medicinal benefits. The purpose of our study was to investigate the pivotal role of "nuclear factor erythroid 2-related factor-2" (Nrf2)-mediated antioxidant protection of Vin against H2O2 and paracetamol (APAP)-induced liver toxicity. For this purpose, a normal human hepatic cell line (L02 cells) was incubated with cytotoxic concentrations of H2O2 or APAP in the presence or absence of Vin. To evaluate the responses, MTS Cell Viability assay, immunoblotting, biochemical assays, and molecular docking approach were used. Viability analysis showed that treatment of L02 cells with Vin prevented the cytotoxicity induced by H2O2 and APAP. It was evidenced by the fact that Vin dumped H2O2- and APAP-cytotoxicity and reactive oxygen species (ROS) generation. The immunoblotting analysis shows that Vin increased Nrf2 expression along with the expression of target protein, heme oxygenase-1 (HO-1), and increased intracellular glutathione (GSH) level. Interestingly, we found that Vin could protect the protein expression-level of Nrf2, which indicated the prospective interaction between Vin and Keap1 protein. Additionally, molecular docking-study revealed that Vin competed with Nrf2 for Keap1-binding site, with hydrogen and stearic interactions. Collectively, Vin effectively protects against H2O2 and APAP-induced cytotoxicity via executing Nrf2-mediated restoration of antioxidative/oxidative balance. Meanwhile, Vin interrupts protein-protein interaction between Nrf2 and Keap1, which might also contribute to decrease Nrf2 degradation and stabilize protein expression. Thus, Vin-based adjuvant therapy may represent a smart drug regimen to mitigate drug-induced oxidative stress and liver injuries.


A higher body mass index in Chinese inpatients with chronic schizophrenia is associated with elevated plasma orexin-A levels and fewer negative symptoms.
Objective: Orexin-A is involved in numerous physiological functions, such as feeding behavior and energy balance. Yet, the associations among the orexin system, weight changes and the clinical symptoms of schizophrenia patients remain uncertain, especially in inpatients with chronic schizophrenia (CS). The purpose of this study was to investigate the relationship between the orexin-A levels, body mass index (BMI) and clinical symptoms of CS inpatients.Methods: Altogether, 324 inpatients were enrolled in our study. The clinical symptoms of all inpatients were measured using a 30-item Positive and Negative Syndrome Scale (PANSS), and then we calculated the BMI of each subject and tested the orexin-A levels by ELISA methods.Results: The orexin-A levels of the CS inpatients in the obesity group (1.24 ± 1.45 ng/ml, n = 52) were significantly higher than those in the non-overweight group (0.85 ± 1.18 ng/ml, n = 176) and the overweight group (0.97 ± 1.15 ng/ml, n = 96). Spearman's correlation analysis showed that higher BMIs were associated with higher plasma orexin-A levels and fewer negative symptoms. Furthermore, the multiple regression analysis indicated that the orexin-A level could be a contributor to BMI (F = 30.21, p < 0.001). However, there was no correlation between plasma orexin-A concentrations and clinical symptoms in our research.Conclusion: A higher plasma orexin-A level may be a factor influencing the BMI of inpatients with CS, and fewer negative symptoms seem to be correlated with higher BMI, but the causality among BMI, orexin-A and clinical symptoms of schizophrenia requires further clinical research.


Polymorphism of the sterol regulatory element-binding protein-2 gene and its association with serum lipid levels in the Guangxi Hei Yi Zhuang and Han populations.
Information about the association of sterol regulatory element-binding protein-2 (SREBP-2) gene polymorphism at the 1784G>C locus and serum lipid parameters is limited and contradictory. The present study was undertaken to compare the difference in the SREBP-2 gene polymorphism and its association with serum lipid levels between the Guangxi Hei Yi Zhuang and Han populations. Genotyping of the SREBP-2 gene in 768 subjects of Hei Yi Zhuang and 798 participants of Han Chinese aged 15 to 89 was performed by polymerase chain reaction and restriction fragment length polymorphism. The frequency of G allele was 88.9% in Hei Yi Zhuang and 84.7% in Han (P < 0.001). The frequencies of GG, GC, and CC genotypes were 78.9%, 20.1%, and 1.0% in Hei Yi Zhuang, and 70.4%, 28.6%, and 1.0% in Han (P < 0.001), respectively. The frequencies of G allele and GG genotype in Han, but not in Hei Yi Zhuang, were higher in males than in females, or in high total cholesterol (TC >5.18 mmol/L) subgroup than in normal TC subgroup (P < 0.01 for all). In high TC subgroup, TC, triglycerides, low-density lipoprotein cholesterol, and apolipoprotein B levels in Han were lower in GG genotype than in GC/CC genotype (P < 0.05-0.01). There were significant differences in the genotypic and allelic frequencies of the SREBP-2 gene polymorphism at the 1784G>C locus between the Hei Yi Zhuang and Han populations. The individuals carrying the G allele have more favorable lipid profiles than those carrying the C allele in Han but not in Hei Yi Zhuang.


Comparison of ventilation and cardiovascular parameters between prone thoracoscopic and Ivor Lewis esophagectomy.
Thoracoscopic esophagectomy in the prone position is associated with better surgical ergonomics compared to the left lateral decubitus position due to the effects of gravity pooling blood outside the operative field and the reduced need for lung retraction. The aim of this study was to evaluate the physiological effects of prone thoracoscopic esophagectomy with single-lumen intubation on ventilation, respiratory gas exchange, and cardiovascular parameters. Thirty-two consecutive patients underwent esophagectomy either through a prone thoracoscopic approach or through a right thoracotomic approach. Samples of arterial and central venous blood, as well as ventilation and cardiovascular parameters were obtained at baseline, during induction of anesthesia, throughout the operation, and after extubation. Patients undergoing prone thoracoscopic esophagectomy showed higher oxygenation levels (p < 0.001), and a significantly lower mean pulmonary shunt fraction (p = 0.001). Perioperative hemodynamics remained stable throughout the surgical procedures. Thoracoscopic esophagectomy in the prone position with two-lung ventilation was associated with a significant improvement of global oxygen delivery and a significant reduction of the pulmonary shunt when compared to the Ivor Lewis operation.


Pharmacodynamics of NN2211, a novel long acting GLP-1 derivative.
To evaluate the effects of NN2211, a GLP-1 derivative, on glucose and insulin homeostasis in healthy volunteers by use of a nonlinear mixed-effects modeling approach. NN2211 is a GLP-1 derivative intended for the treatment of type 2 diabetes. In the present study, eight dose levels of NN2211 were tested in healthy human volunteers. Since NN2211 is only intended to have an effect when glucose levels are above baseline (thus limiting the risk of hypoglycaemia), no effects would be expected in healthy volunteers. In order to demonstrate effect in a phase 1 study including only healthy subjects, a glucose dose was administered i.v. 9 h after NN2211 dosing; the insulin response would then be expected to be improved (higher) in the subjects dosed with NN2211. In the present work, the pharmacodynamic glucose and insulin response was modeled by fitting glucose and insulin data simultaneously with a nonlinear model incorporating known carbohydrate regulation mechanisms. After an initial model-building phase, the first-order approximation to the likelihood available in NONMEM was used to model the data. Placebo-dosed subjects were included in the analysis. It was possible to satisfactorily fit both insulin and glucose data simultaneously. The analysis demonstrated a dose proportional effect of NN2211 on the parameters controlling beta cell insulin secretion.


E2F5 promotes proliferation and invasion of gastric cancer through directly upregulating UBE2T transcription.
The underlying mechanisms of E2F5 upregulation and its pro-tumor functions have not been elucidated in gastric cancer (GC). Here, the expression, prognostic value, mutation status, and promoter methylation of E2F5 were evaluated. The effects of E2F5 depletion on cell proliferation and invasion in GC, were also assessed through in vitro experiments. Additionally, gene set enrichment analysis (GSEA) was applied to analyze the potential downstream regulator of E2F5. The study also assessed the correlation and transcription regulation between E2F5 and UBE2T. Finally, the roles of UBE2T in E2F5-related pro-tumor functions were examined. The findings revealed that E2F5 was upregulated and showed remarkable association with pathological variables and prognosis. Hypomethylation of the E2F5 promoter predicted poor prognosis and partially caused E2F5 upregulation in GC. E2F5 knockdown significantly inhibited the proliferation and invasion of GC cells. E2F5 had a significant positive correlation with UBE2T in GC. Mechanistically, E2F5 promoted UBE2T transcription and UBE2T overexpression reversed the effects of E2F5 depletion on the proliferation and invasion of cells in GC. Taken together, this study originally confirmed the upregulation of E2F5 in GC, revealed that E2F5 can directly upregulate UBE2T transcription, and subsequently promote the malignant progression, which highlights that the E2F5/UBE2T axis can potentially be used in the diagnosis and treatment of GC.


Moving targets in space: Movement distance as a predictor for experiences of movement agency.
Previous research indicates that the experience of agency over one's actions and movements is influenced by movement predictability as well as movement distance (Hon, Seow, & Pereira, 2018). Addressing previous limitations, we present a compelling test of the relation between movement distance and movement agency. Participants in two studies moved targets predictably or unpredictably, and for short, medium, or long distances. Following prior research, distractor cues moved in the opposite direction of the targets. Results showed that movement agency scores were higher for predictable compared to unpredictable movements. Results also consistently showed that when movements were predictable, longer distances by either the target or the distractor cues increased agency relative to shorter distances. Our findings replicate and extend previous findings showing that stimulus movement distances influence judgments of movement agency.


[The treatment outcomes of children with Gustilo-Anderson grade II and grade III open fractures of the long bone].
We evaluated the treatment results in thirty-two children who had grade 2 and 3 open fractures according to classification of Gustilo-Anderson. There were 21 (%65) male and 11 female (%35) patient and the mean age was 9 years (range, 4-14 years). There were 18 (%56) grade-2, 7 (%22) grade-3A, 5 (%15) grade-3B, and 2 (%6) grade-3C open fracture. All fractures were irrigated and debrided, and then fixed with external fixators. The average duration of follow-up was 11 months (range, 6-28 month). All fractures healed. Inadequate recovering was detected in four patients who had nerve injury, in addition the joint limiting contracture occurred on six patients. Fracture union without segmental bone loss is not a significant problem in open fractures in children, and that joint contractures, compartment syndrome and nerve injuries negatively affect the late outcomes.


Improving psychosocial assessment in oncology.
A project that encouraged nurses to give greater emphasis to cancer patients' psychological, social and spiritual concerns, and not only to the condition's physical effects, reflects one target outlined in The NHS Cancer Plan.


PROMISE I: Early feasibility study of the LimFlow System for percutaneous deep vein arterialization in no-option chronic limb-threatening ischemia: 12-month results.
We report the 6- and 12-month outcomes of the PROMISE I early feasibility study after treatment of no-option chronic limb-threatening ischemia (CLTI) with percutaneous deep vein arterialization (pDVA) using the LimFlow System. Thirty-two patients with no-option CLTI, previously offered major amputation, were enrolled in this single-arm early feasibility study of the LimFlow pDVA System. No-option CLTI was defined as being ineligible for surgical or endovascular arterial revascularization. Patients were assessed for clinical status, pain, wound healing, and duplex ultrasound at 30 days, 6 months, and 12 months post-treatment. Primary endpoint analysis was amputation-free survival (AFS) at 30 days and 6 and 12 months. AFS was defined as freedom from above-ankle amputation of the index limb and freedom from all-cause mortality. Secondary endpoints evaluated included technical success of the procedure, and wound healing at 6 and 12 months. Of 32 enrolled patients, 31 (97%) were successfully treated with the LimFlow System at the time of the procedure, and two (6.3%) were lost to follow-up. The 30-day, 6-month, and 12-month AFS rates were 91%, 74%, and 70% respectively. The wound healing status of fully healed or healing was 67% at 6 months, and 75% at 12 months. Reintervention was performed in 16 patients (52%) with 14 (88%) of the maintenance reinterventions occurring within the first 3 months. The majority of reinterventions (n = 12; 75%), involved the arterial inflow tract proximal to the stented LimFlow circuit, and no in-stent stenoses were determined to have been the cause of reintervention. The LimFlow pDVA System was utilized in treating patients with no-option CLTI. A high technical success rate was observed, with a significant percentage of patients surviving free of major amputation at 12 months. These results suggest early safety and provide an initial assessment of the efficacy of the LimFlow pDVA System that supports the expansion of carefully executed studies to determine whether this is a viable option that can be used in this critically disadvantaged and growing patient population.


Guanine crystal formation by bacteria.
Guanine crystals are organic biogenic crystals found in many organisms. Due to their exceptionally high refractive index, they contribute to structural color and are responsible for the reflective effect in the skin and visual organs in animals such as fish, reptiles, and spiders. Occurrence of these crystals in animals has been known for many years, and they have also been observed in eukaryotic microorganisms, but not in prokaryotes. In this work, we report the discovery of extracellular crystals formed by bacteria and reveal that they are composed of guanine monohydrate. This composition differs from that of biogenic guanine crystals found in other organisms, mostly composed of β anhydrous guanine. We demonstrate the formation of these crystals by Aeromonas and other bacteria and investigate the metabolic traits related to their synthesis. In all cases studied, the presence of the bacterial guanine crystals correlates with the absence of guanine deaminase, which could lead to guanine accumulation providing the substrate for crystal formation. Our finding of the hitherto unknown guanine crystal occurrence in prokaryotes extends the range of organisms that produce these crystals to a new domain of life. Bacteria constitute a novel and more accessible model to study the process of guanine crystal formation and assembly. This discovery opens countless chemical and biological questions, including those about the functional and adaptive significance of their production in these microorganisms. It also paves the road for the development of simple and convenient processes to obtain biogenic guanine crystals for diverse applications.


Genome-wide analysis of Panax MADS-box genes reveals role of PgMADS41 and PgMADS44 in modulation of root development and ginsenoside synthesis.
Panax root is an important material used in food and medicine. Its cultivation and production usually depend on root shape and ginsenoside content. There is limited understanding about the synergistic regulatory mechanisms underlying root development and ginsenoside accumulation in Panax. MADS-box transcription factors possibly play a significant role in regulation of root growth and secondary metabolites. In this study, we identified MADS-box transcription factors of Panax, and found high expression levels of SVP, ANR1 and SOC1-like clade genes in its roots. We confirmed that two SOC1-like genes, PgMADS41 and PgMADS44, bind to expansion gene promoters (PgEXLB5 and PgEXPA13), which contribute to root growth, and to SE-4, CYP716A52v2-4, and β-AS-13 promoters, which participate in ginsenoside Ro biosynthesis. These two genes were found to increase lateral root number and main root length in transgenic Arabidopsis thaliana by improving AtEXLA1, AtEXLA3, AtEXPA5, and AtEXPA6 gene expression. As a non-phytohormone regulatory tool, Ro can stimulate adventitious root growth by influencing their expression and ginsenoside accumulation. Our study provides new insights into the coordinated regulatory function of SOC1-like clade genes in Panax root development and triterpenoid accumulation, paving the way towards understanding root formation and genetic improvement in Panax.


Opposite effects of Trichostatin A on activation of mast cells by different stimulants.
Mast cells (MCs) are activated upon stimulation via TLRs or FcepsilonRI, contributing to immune protection and/or leading to allergic diseases. In the present study, the effects of Trichostatin A (TSA) on the activation of MCs were analyzed with bone marrow-derived (BM) MCs. TSA increased the transcription and protein secretion of IL-6 in case of LPS-stimulation, in contrast to the suppressive effect on IgE-mediated activation of BMMCs. Chromatin immunoprecipitation assay showed IgE-mediated signaling-specific suppression of transcription factors recruitment to the IL-6 promoter. TSA-treatment inhibited nuclear translocation of NF-kappaB following IgE-mediated, but not LPS-induced activation in MCs.


The Judgment of the German Federal Constitutional Court regarding assisted suicide: a template for pluralistic states?
The article presents the judgment of the German Federal Constitutional Court from 26 February 2020 on assisted suicide. The statements regarding human dignity, human rights and the relationship between citizens and the state are examined. Furthermore, the consequences resulting from this interpretation of human dignity for states that are pluralistic and based on human rights will be laid out. The court's judgment limits the power of parliaments and poses a challenge to many laws in states that see themselves as pluralistic, human rights-based states.


Developmental, audiological, and speech perception functioning in children after cochlear implant surgery.
To examine changes in audiological, speech perception, and developmental functioning subsequent to cochlear implantation in children with severe to profound hearing impairment, and to identify factors related to those changes. Prospective, longitudinal analysis to compare functioning of pediatric patients who underwent cochlear implantation before and 1 year after surgery. Outpatient pediatric cochlear implantation program in an academic institution (The Listening Center, The Johns Hopkins University School of Medicine, Baltimore, Md). Patients Forty consecutive pediatric patients between 1(1/2) and 9 years of age who received a cochlear implant between April 1, 1996, and August 31, 1998, and who also underwent psychological, audiological, and speech perception evaluations immediately before and 1 year after implantation. Scores on the Bayley Scales of Infant Development-Second Edition, Stanford-Binet Intelligence Scale-Fourth Edition, Developmental Profile II, Child Behavior Checklist, speech perception categories, and audiological pure-tone thresholds. Mean (SD) duration of hearing impairment was 37.78 (27.94) months, mean (SD) age at surgery was 50.72 (27.66) months. Significant improvements were found 1 year after surgery in audiological, speech perception, and developmental functioning, but not in nonverbal intelligence or behavior. Greater benefits in audiological and developmental functioning were associated with younger age (<48 months) at implantation. Patients showed significant improvement in audiological status, overall developmental functioning, and speech perception skills in a short time after surgery. Greatest improvement in speech perception was for children with the least initial impairment, and greatest developmental gains were associated with young age at implantation.


A method for postural critical factors checking: The case of library chairs.
According to ergonomic researches regarding a good sitting posture, it is essential to ensure a natural back-curve in order to prevent musculoskeletal disorders. A brief observation among the Scientific Technology Library inside the University of Salerno showed that students used to complain about neck and lumbar pain, especially after a study day. On the light of this background, a sitting posture comfort analysis had been performed on chairs inside the library to check the critical factors that influence the postural comfort and, consequently, the learning. A prolonged sitting posture, that is common during the daily study activity, had been simulated with fifteen volunteer students performing 1-hour tests (divided into four 15-minutes tasks). Subjective perceptions had been gathered through questionnaires rating on a 5-point Comfort scale, both the expected comfort at the beginning of the experiment and the Localized Postural Comfort at the end of each task have been investigated. Then, postural angles had been gathered through photographic acquisition and Kinovea®. CaMAN software had been used to calculate the objective (dis)comfort indexes. Finally, subjective and objective data had been statistically processed and compared. Lumbar area scored the lowest perceived comfort while the perceived comfort was independent of participants and tasks, but dependent on time. After this comfort-driven analysis, critical factors of the chair-design were checked, and a proposal for a future re-design was hypothesized.


How to Sequence and Assemble Plant Genomes.
Although nanopore sequencer is a great tool, many plant scientists have suffered from bad sequencing results, even though they have exactly followed the official protocol in preparing a library. This is because the protocol is not optimized for plant genomic DNA. The protocol may be good for sequencing animal or bacterial genomes, but not for plants. However, if the protocol is properly modified, one can obtain lots of long reads and achieve a telomere-to-telomere assembly. Here I present a protocol to that end.


No impact of rifamycin selection on tuberculosis treatment outcome in HIV coinfected patients.
Rifabutin has been substituted for rifampicin when treating tuberculosis (TB)/HIV coinfection. However, despite reports of anti-TB treatment failure and acquired rifamycin resistance, long-term clinical outcome data are lacking. Observational analyses performed in a UK TB/HIV cohort demonstrated no difference in severe adverse events, anti-TB treatment completion, relapse frequency or subsequent rifamycin resistance when rifampicin and rifabutin were compared, using different combinations of antiretroviral therapy. Our data support the wider use of rifabutin in TB/HIV coinfection.


"Care is increasingly absent from the pathway of unaccompanied minors". Legal experts of the French ombudsperson work with professionals supporting unaccompanied minors on different levels. They can also have a watchdog role with legislative authorities and judicial bodies. They note in particular increasing difficulty for these youngsters in accessing appropriate care. Interview with Nathalie Lequeux, legal expert and coordinator at the French children's rights centre.


Mediation role of low birth weight on the factors associated with newborn mortality and the moderation role of institutional delivery in the association of low birth weight with newborn mortality in a resource-poor setting.
To assess low birth weight's (LBW) mediation role on the factors associated with newborn mortality (NM), including stillbirth and the role of institutional delivery in the association between LBW and NM. I used the 2011-2015 event histories health demographic data collected by Iganga-Mayuge Health Demographic and Surveillance Site (HDSS). The dataset consisted of 10 758 registered women whose birth occurred at least 22 weeks of the gestation period and records of newborns' living status 28 days after delivery. The Iganga-Mayuge HDSS is in Eastern Uganda, which routinely collects health and demographic data from a registered population of at least 100 000 people. The study's key outcomes or endogenous factors were perinatal mortality (PM), late NM and LBW (mediating factor). The factors that were directly associated with PM were LBW (OR=2.55, 95% CI 1.15 to 5.67)), maternal age of 30+ years (OR=1.68, 95% CI 1.21 to 2.33), rural residence (OR=1.38, 95% CI 1.02 to 1.85), mothers with previous experience of NM (OR=3.95, 95% CI 2.86 to 5.46) and mothers with no education level (OR=1.63, 95% CI 1.21 to 2.18). Multiple births and mother's prior experience of NM were positively associated with NM at a later age. Institutional delivery had a modest inverse role in the association of LBW with PM. LBW mediated the association of PM with residence status, mothers' previous NM experience, multiple births, adolescent mothers and mothers' marital status. Of the total effect attributable to each of these factors, LBW mediated +25%, +22%, +100%, 25% and -38% of rural resident mothers, mothers with previous experience of newborn or pregnancy loss, multiple births, adolescent mothers and mothers with partners, respectively. LBW mediated multiple factors in the NM pathways, and the effect of institutional delivery in reducing mortality among LBW newborns was insignificant. The findings demonstrate the need for a holistic life course approach that gears the health systems to tackle NM.


Mobility of norbornane-type substrates and water accessibility in cytochrome P-450cam.
The behaviour of norbornane-type substrates bound to oxidised cytochrome P-450cam (CYP 101) in 60% (w/w) glycerol-containing phosphate buffer was investigated using electronic absorption spectroscopy. The high-pressure dependence study revealed that the value of the spin-state reaction-volume change decreased from -70 to -22.8 cm3/mol with decreasing high-spin state content from 99 to 63%. Simultaneously, the values for the enthalpy and entropy determined from the low-temperature dependence of the spin-state transition decreased from 73.7 to 24.3 kJ/mol and from 310.4 to 88.9 J/mol K, respectively. Under our experimental conditions the pH-value of the buffer remained at low temperatures and high pressures in the range of pH 7-8, in which no pH-value-induced spin-state conversion occurred. Therefore, the secondary effect of the temperature and pressure-induced pH change can be disregarded as being responsible for the observed spin-state transition effects. Substrate dissociation constants were determined. From the temperature-jump experiments (297 K to 180 K) we found a higher mobility in the active site for the substrates in the sequence (1R)-camphor, (1S)-camphor, camphane, (1R)- and (1S)-camphorquinone, norcamphor, and norbornane. Our findings can be explained by the incomplete fit of the methyl groups of the norbornane-type substrate to the protein, in particular to the I-helix, predominantly determining the substrate mobility and water accessibility to the protein.


A systematic review, umbrella review, and quality assessment on clinical translation of stem cell therapy for knee osteoarthritis: Are we there yet?
The success of stem cell therapy for knee osteoarthritis (KOA) in preclinical animal models has accelerated the pace of clinical translation. However, it remains uncertain whether the current scientific evidence supports the clinical application of stem cells in treating KOA. A comprehensive evaluation of the safety and efficacy of stem cell therapies and scientific evidence quality is necessary. Using "stem cells" and "knee osteoarthritis" as the search terms, several databases, including PubMed, Web of Science, Cochrane, Embase, and Clinicaltrials.gov, were searched on August 25, 2022, and updated on February 27, 2023. Clinical studies that reported adverse reactions (ARs) of stem cell therapy in KOA patients were included without limiting the type of studies. Quantitative systematic reviews of stem cell therapy for KOA that conducted meta-analysis were included. Two researchers conducted literature screening and data extraction independently, and the evidence quality was evaluated according to the Institute of Health Economics and AMSTAR 2 criteria. Fifty clinical studies and 13 systematic reviews/meta-analyses (SRs/MAs) were included. Nineteen ARs were reported in 50 studies, including five knee-related ARs, seven common ARs, and seven other ARs. Some studies reported over 10% prevalence of knee pain (24.5%; 95% CI [14.7%, 35.7%]), knee effusion (12.5%; 95% CI [4.8%, 22.5%]), and knee swelling (11.9%; 95% CI [3.5%, 23.5%]). Additionally, two studies have reported cases of prostate cancer and breast tumors, respectively. However, these two studies suggest that stem cell therapy does not bring significant ARs to patients. SRs/MAs results revealed that stem cell therapy relieved pain in patients over time but did not improve knee function. However, current clinical studies have limited evidence regarding study objectives, test designs, and patient populations. Similarly, SRs/MAs have inadequate evidence regarding study design, risk of bias assessment, outcome description, comprehensive discussion, and potential conflicts of interest. The inefficacy of stem cells, the risk of potential complications, and the limited quality of evidence from current studies precluded any recommendation for using stem cell products in patients with KOA. Clinical translation of stem cell therapies remains baseless and should be cautiously approached until more robust evidence is available. PROSPERO registration number: CRD42022355875.


New treatment modalities for brain tumors in dogs and cats.
Despite advancements in standard therapies, intracranial tumors remain a significant source of morbidity and mortality in veterinary and human medicine. Several newer approaches are gaining more widespread acceptance or are currently being prepared for translation from experimental to routine therapeutic use. Clinical trials in dogs with spontaneous brain tumors have contributed to the development and human translation of several novel therapeutic brain tumor approaches.


Comparison of annual eGFR decline among primary kidney diseases in patients with CKD G3b-5: results from a REACH-J CKD cohort study.
Disease-specific trajectories of renal function in advanced chronic kidney disease (CKD) are not well defined. Here, we compared these trajectories in the estimated glomerular filtration rate (eGFR) by CKD stages. Patients with multiple eGFR measurements during the 5-year preregistration period of the REACH-J study were enrolled. Mean annual eGFR declines were calculated from linear mixed effect models with the adjustment variables of baseline CKD stage, age, sex and the current CKD stage and the level of proteinuria (CKDA1-3). Among 1,969 eligible patients with CKDG3b-5, the adjusted eGFR decline (ml/min/1.73 m2/year) was significantly faster in diabetic kidney disease (DKD) patients and polycystic kidney disease (PKD) patients than in patients with other kidney diseases (DKD, - 2.96 ± 0.13; PKD, - 2.82 ± 0.17; and others, - 1.95 ± 0.05, p < 0.01). The declines were faster with higher CKD stages. In DKD patients, the eGFR decline was significantly faster in CKDG5 than CKDG4 (- 4.10 ± 0.18 vs - 2.76 ± 0.20, p < 0.01), while these declines in PKD patients were similar. The eGFR declines in PKD patients were significantly faster than DKD patients in CKDG4 (- 2.92 ± 0.23 vs - 2.76 ± 0.20, p < 0.01) and in CKDA2 (- 3.36 ± 0.35 vs - 1.40 ± 0.26, p < 0.01). Our study revealed the disease-specific annual eGFR declines by CKD stages and the level of proteinuria. Comparing to the other kidney diseases, the declines in PKD patients were getting faster from early stages of CKD. These results suggest the importance of CKD managements in PKD patients from the early stages.


Sialylation of cell surface glycoconjugates modulates cytosolic galectin-mediated responses upon organelle damage : Minireview.
Sialylation is an important terminal modification of glycoconjugates that mediate diverse functions in physiology and disease. In this review we focus on how altered cell surface sialylation status is sensed by cytosolic galectins when the integrity of intracellular vesicles or organelles is compromised to expose luminal glycans to the cytosolic milieu, and how this impacts galectin-mediated cellular responses. In addition, we discuss the roles of mammalian sialidases on the cell surface, in the organelle lumen and cytosol, and raise the possibility that intracellular glycan processing may be critical in controlling various galectin-mediated responses when cells encounter stress.


Depression in the workplace: a systematic review of evidence-based prevention strategies.
Depression is one of the most common mental disorders, causing enormous personal and economic burden. In its early stages, however, it is the most manageable of mental disorders. The workplace, where a large proportion of the adult population can be reached, might be a good setting for prevention interventions that target depression directly. Identify evidence-based indicated/secondary prevention strategies for depression in the workplace. Systematic review of articles published until February 2010 using PubMed, EbscoHost and the Cochrane Library. Studies were selected based on different inclusion criteria, such as diagnosis of depression with validated screening instruments and presence of a control group. A total of 9,173 articles were found. One evaluated intervention study in the workplace met all inclusion criteria (French APRAND programme). The intervention, which combined the provision of diagnosis and psychoeducation, had a positive effect on people with depression, with a significant trend towards chances of recovery or remission after 1 year. The remaining studies did not meet the predefined inclusion criteria of this systematic review. The findings are quite sobering given the high prevalence of depression and the individual and societal burden caused by it. More tailor-made interventions in the workplace targeting depression directly are needed.


CD47 blockade enhances therapeutic efficacy of cisplatin against lung carcinoma in a murine model.
Cisplatin (CDDP) is the first generation of platinum-based drug and is widely used to treat many cancers due to its potency. The present study aims to explore the effects of CDDP on lung carcinoma and its relationship with macrophage phagocytosis. In in vitro study, murine and human lung cancer cell lines were applied and treated with CDDP, CD47 antibody (aCD47), or CDDP plus aCD47. In in vivo study, a tumor xenograft animal model was treated with CDDP, aCD47, or CDDP plus aCD47. Real-time PCR was applied to determine the mRNA expressions. Enzyme-linked immunosorbent assay (ELISA), Western blotting, and Immunofluorescent staining were applied to determine the protein expressions. Flow cytometry was applied to analyze cell apoptosis, phagocytosis, and specific cell populations. CDDP enhanced the expressions of CD47 in lung cancer cells. Interestingly, the blockage of CD47 enhanced the macrophages' phagocytic activity on the CDDP-treated tumor cells. The treatment of CDDP and aCD47 exhibited anti-tumor effects and prolonged the LLC tumor-bearing mice survival time. Mechanistic studies revealed that the treatment of CDDP and aCD47 regulated the phagocytic activity of macrophage, percentage of CD8+ T cells, and cytokines (tumor growth factor (TGF)-β, interleukin (IL)12p70, and interferon (IFN)-γ) in the tumor-bearing model. CD47 blockade enhanced therapeutic efficacy of cisplatin against lung carcinoma in vivo and in vitro.


Predictors of Anastomotic Complications After Resection and Anastomosis for Tracheal Stenosis.
Resection and anastomosis is an effective option for the management of complex tracheal stenosis, however, it's not without the complications. This study aims at evaluating various factors predicting anastomotic complications after trachea resection and anastomosis. This is a retrospective analysis of database from a dedicated thoracic surgical unit in New Delhi, India over 7 years. An analysis of demographic details, perioperative variables including complications were carried out. Analysis of various factors predicting anastomotic complications was performed. Out of 65 patients in the study, 49 (75.3%) were males and 16 (24.7%) were females. Median age of the patients was 31 years. Stenosis was cervical in 80%, cervico-thoracic in 15.4% and thoracic in 4.6% of patients. Median length of stenosis was 2.9 cm (1-4.2). 53 (81.6%) patients had some kind of preoperative intervention, where as rest 12 (18.4%) patients had no intervention at all. Out of 65 patients, 26 (40%) had crico-tracheal anastomosis while 39 (60%) had tracheo-tracheal anastomosis. Median length of resected tracheal segment was 3.3 cm (1-5). Overall complication rate (anastomotic + non-anastomotic) was 18.4% in which anastomosis related were in 4 (6.1%) patients. Resection of tracheal segment ≥ 3.5 cm, presence of diabetes mellitus and pre-operative use of corticosteroids were statistically significant factors for the onset of complications. Perioperative mortality rate was 1.5% (n = 1). Length of resection > 3.5 cm, presence of diabetes mellitus and pre-operative prolonged use of corticosteroids were significant predictors for the anastomotic complications.


The association between plasma proneurotensin and glucose regulation is modified by country of birth.
The prevalence of type 2 diabetes (T2D) has increased dramatically in Middle Eastern populations that represent the largest non-European immigrant group in Sweden today. As proneurotensin predicts T2D, the aim of this study was to investigate differences in proneurotensin levels across populations of Middle Eastern and Caucasian origin and to study its associations with indices of glucose regulation. Participants in the age 30 to 75 years, living in Malmö, Sweden, and born in Iraq or Sweden, were recruited from the census register. Anthropometrics and fasting samples were collected and oral glucose tolerance tests conducted assessing insulin secretion (DIo) as well as insulin sensitivity (ISI). A total of 2155 individuals participated in the study, 1398 were Iraqi-born and 757 were Swedish-born participants. Higher fasting proneurotensin levels were observed in Iraqi- compared to Swedish-born participants (137.5 vs. 119.8 pmol/L; p < 0.001) data adjusted for age, sex and body mass index. In Iraqi participants only, plasma proneurotensin was associated with impaired glucose regulation assessed as ISI, DIo and HbA1c, and significant interactions between country of birth and proneurotensin were observed (Pinteraction ISI = 0.048; Pinteraction DIo = 0.014; PinteractionHbA1c = 0.029). We report higher levels of proneurotensin in the general Middle Eastern population. The finding that Middle Eastern origin modifies the relationship of proneurotensin with indices of glucose regulation suggests that proneurotensin may be a stronger determinant of T2D in Middle Eastern as compared to Caucasian populations. These findings may explain part of the excess T2D risk in the Middle Eastern population but needs to be explored further.


Factors associated with the evolution of lung function in patients with alpha-1 antitrypsin deficiency in the Spanish registry.
The present study intends to describe the characteristics of patients diagnosed with severe alpha-1 antitrypsin deficiency (AATD) in Spain, to observe the rate of decline in forced expiratory volume in 1 second (FEV1) with and without substitutive therapy, and to identify factors associated with a rapid rate of decline in FEV1. A retrospective study of the evolution of individuals with AATD was carried out based on data collected from the Spanish registry. The primary response variable was the annual rate of decline in FEV1, calculated using the baseline and last postbronchodilator FEV1 values in an endpoint analysis. 303 patients with severe AATD and Pi ZZ phenotype were identified. Follow-up spirometric data were collected for 117 subjects. Being a smoker or ex-smoker versus never smoker (odds ratio [OR]=10.31; 95% confidence interval (CI)=1.8-58.8; p=0.008) and having a higher baseline postbronchodilator FEV1 (% predicted) (OR=1.03; 95% CI=1.005-1.06; p=0.018) were independently associated with a more rapid rate of decline in FEV1. There was also a trend towards a relationship between low body mass index (BMI) and a greater rate of deterioration in lung function (OR=1.14; 95% CI=0.98-1.33; p=0.085). Being a smoker or ex-smoker, greater baseline lung function, and low BMI were the main risk factors associated with an accelerated rate of decline in FEV1. This finding warrants the close observation of younger patients with a better-preserved FEV1.


Risk Factors for and Intraoperative Management of Intolerance to Flow Reversal in TCAR.
In patients deemed high risk for carotid endarterectomy (CEA) who are indicated for treatment of carotid artery stenosis (CAS), transcarotid artery revascularization (TCAR) has been demonstrated as a safe and effective alternative to trans-femoral carotid artery stenting (TF-CAS). Compared to CEA, where approx. 12% of patients undergoing awake intervention do not tolerate internal carotid artery (ICA) clamping, only 1-2% of patients were observed to have intolerance to flow reversal during TCAR based on data from the ROADSTER1/2 trials. This study reviewed awake interventions from those trials to assess factors associated with intolerance to flow reversal and review how those cases were managed. This is a retrospective review of prospectively collected data from Reverse Flow Used During Carotid Artery Stenting Procedure (ROADSTER) multicenter trial along with the subsequent post-approval (ROADSTER-2) trial. The subset of patients from both trials undergoing awake TCAR was analyzed to compare demographics, procedural details, and anatomic factors between patients who did and did not experience intolerance to reversal of flow to assess for predisposing factors. Patients were deemed intolerant to flow reversal at the discretion of the operator, often related to changes in completion of neurologic tasks, hemodynamic stability, or patient reported symptoms. A total of 103 patients from ROADSTER and 194 patients from ROADSTER-2 underwent TCAR under local/regional anesthesia. Of these, 8 patients had intolerance to flow reversal, though all cases were successfully completed. While intraoperative hemodynamic data was only available for 5 of the 8 intolerant patients, none experienced hypotension. 4 cases were completed under low flow reversal, 3 cases were successfully weaned from low to high flow over several minutes, and 1 case required general anesthesia. No significant association was found between intolerance to flow reversal and comorbidities including diabetes mellitus (DM), hypertension (HTN), hyperlipidemia (HLD), congestive heart failure (CHF), prior MI or angina, pre-op CAS-related symptoms, prior stroke, prior CAS or CEA, prior neck radiation, tandem stenosis, high cervical stenosis, or hostile neck. A trend towards significance was seen with chronic obstructive pulmonary disease (COPD) and contralateral carotid artery occlusion (P = 0.086 and 0.139, respectively). Despite intolerance to flow reversal, TCAR cases were successfully completed by adjusting reversal-of-flow rate and do not typically require conversion to GETA. While factors contributing to intolerance of flow reversal during TCAR remain poorly understood, this study identified a trend towards significance with an association of preexisting COPD and contralateral carotid artery occlusion. Given the low number of patients who experienced this issue, a larger sample size is required to better elucidate these trends.


Respiratory function and sleep in children with myotonic dystrophy type 1.
Myotonic dystrophy type 1 (DM1) is a rare neuromuscular disease in children causing sleep and respiratory disorders that are poorly described in the literature compared to adult forms. This retrospective observational study was performed at the Armand Trousseau University Hospital, Assistance Publique-Hôpitaux de Paris (APHP), Paris, France. We retrospectively collected data from lung function tests, nocturnal gas exchange recordings, and polysomnography of 24 children with DM1. 39% of the children with DM1 reported respiratory symptoms indicative of sleep disordered breathing. Three patients (12%) presented with a restrictive respiratory pattern, 10 (42%) with a sleep apnoea syndrome, mainly of obstructive origin (2/10 with severe obstructive sleep apnea syndrome), and 11 (45%) with nocturnal alveolar hypoventilation. Non-invasive ventilation (NIV) was indicated in 9 (37.5%) children, although tolerance was poor. No significant deterioration in respiratory function or nocturnal gas exchange was observed during the NIV-free period. This study provides new and useful insights into DM1 disease evolution in children to better adapt for respiratory follow-up and management. This highlights the need for future research to better understand the origin of respiratory and sleep disorders in patients with DM1.


Significance of PPD Test for the Relationship Between BCG Vaccine and COVID-19 in Patients on Kidney Transplant Waiting List.
The aim of this study was to determine the relationship between purified protein derivative of tuberculin (PPD) values, an indicator of BCG protection, and COVID-19 disease in patients with end-stage renal disease (ESRD) on the kidney transplant waiting list. Age, sex, dialysis type, ERSD etiologies, and PPD values of patients on the renal transplant waiting list were recorded. SARS-CoV-2 PCR data, whether the patients were previously infected with the virus, and, if infected, the severity of the disease were noted. Data were statistically compared. PCR of 87 (47.02%) of 185 patients were studied; 107 of the patients were male and 78 were female, with a mean age of 52.8 years. The test result was positive for 28 patients. Of the patients for whom PCR was studied, 41 had a negative PPD result, while 46 had a positive PPD result. There was no correlation with SARS-CoV-2 PCR positivity in patients with a PPD ≤ 5 mm and > 5 mm. However, patients with pneumonic infiltration who required hospitalization had a significantly higher PPD value. The PPD measurement, which is an indicator of BCG protection, might be a significant parameter for predicting the course of the disease in SARS-CoV-2 pneumonia.


What helps or undermines adolescents' anticipated capacity to cope with mental illness stigma following psychiatric hospitalization.
Better understanding of the individual and environmental factors that promote adolescents' use of more or less adaptive coping strategies with mental illness stigma would inform interventions designed to bolster youth resilience. This cross-sectional study draws on data from research on adolescents' well-being after discharge from a first psychiatric hospitalization to explore the relationships between anticipated coping in reaction to a hypothetical social stigma scenario, and various factors conceptualized as 'coping resource' and 'coping vulnerability' factors. Focusing on coping strategies also identified in the companion article, we hypothesize that primary and secondary control engagement coping would relate to more coping resource and less coping vulnerability factors, and the opposite would be true for disengagement, aggression/confrontation and efforts to disconfirm stereotypes. Data were elicited from interviews with 102 adolescents within 7 days of discharge. Hypothesized coping resource factors included social resources, optimistic illness perceptions, better hospital experiences and higher self-esteem. Vulnerability factors included more previous stigma experiences, desire for concealment of treatment, more contingent self-worth, higher symptom levels and higher anticipated stress. Multivariate ordinary least squares (OLS) regression was used to analyze associations between coping strategy endorsement and correlates. Although some coping correlates 'behaved' contrary to expectations, for the most part, our hypotheses were confirmed. As expected, youth anticipating reacting to the stigmatizing situation with greater disengagement, aggression/confrontation or efforts to disconfirm stenotypes rated significantly lower on 'coping resources' such as self-esteem and higher on vulnerability factors such as symptom severity. The opposite was true for youth who anticipated exercising more primary and secondary control engagement coping. This study begins to identify factors that promote more and less adaptive coping strategies among youth at high risk for social stigma. Some factors that can be modified in the shorter term point to useful directions for clinical interventions.


One stage treatment of anal abscesses and fistulas. A clinical appraisal on the basis of two different classifications.
In a five year period 227 patients with anal abscesses and/or fistulas of suspected cryptoglandular origin were observed and treated by one surgeon. In 201 patients the primary opening or the crypt of origin of the abscesses and/or fistulas were identified. These lesions were evaluated according to two classifications [1,2]. The aim was to verify whether primary abscesses and/or fistulas may spontaneously loop all the external sphincters and the puborectalis muscle as reported by Parks et al. [1] or whether the formation of tracks which loop all the striated sphincteric complex (Parks' supra- and extra-sphincteric fistulas) derives exclusively by the incorrect treatment of more superficial lesions, as suggested by Eisenhammer. Not one of the primary suppurative lesions (acute or chronic) looped the striated sphincteric complex (external sphincter-puborectalis muscle). Supra- and extrasphincteric tracks were observed only in the lesions which recurred after previous surgical treatment. The one-stage treatment of primary abscesses and fistulas (fistulotomy drainage or one-stage lay-open) with a few exceptions is a definitive (2% recurrence rate) and safe (4% prolonged impairment of continence rate) procedure.


Middle manager role of the chief medical resident: an organizational psychologist's perspective.
The role of the chief resident in internal medicine is examined through the eyes of an organizational psychologist who, over a 3-year period, met with each of 6 groups of chief residents for an average of 1 hour a week over the 12 months of the job. Based on this experience, the chief resident job is conceptualized as a middle management role with 4 distinct types of tasks: up work, down work, lateral work, and internal work. Core challenges facing the chief residents at each stage of the chief resident year are also identified. The paper concludes with a description of "lessons" learned in 5 areas (sliding up or sliding down, losing contact, splitting, scapegoating, and losing sight of the system) for improving the effectiveness of the chief resident role.


Load dependency in force-length relations in isolated single cardiomyocytes.
The previously reported pressure-volume (PV) relationship in frog hearts shows that end-systolic PV relation (ESPVR) is load dependent, whereas ESPVR in canine hearts is load independent. To study intrinsic cardiac mechanics in detail, it is desirable to study mechanics in a single isolated cardiomyocyte that is free from interstitial connective tissue. Previous single cell mechanics studies used a pair of carbon fibers (CF) attached to the upper surface of opposite cell ends to stretch cells. These studies showed that end-systolic force-length (FL) relation (ESFLR) is load independent. However, the range of applicable mechanical load using the conventional technique is limited because of weak cell-CF attachment. Therefore, the behavior of ESFLR in single cells under physiologically possible conditions of greater load is not yet well known. To cover wider loading range, we contrived a new method to hold cell-ends more firmly using two pairs of CF attached to both upper and bottom surfaces of cells. The new method allowed stretching cells to 2.2 μm or more in end-diastolic sarcomere length. ESFLR virtually behaves in a load independent manner only with end-diastolic sarcomere length less than 1.95 μm. It exhibited clear load dependency with higher preload, especially with low afterload conditions. Instantaneous cellular elastance curves showed that decreasing afterload enhanced relaxation and slowed time to peak elastance, as previously reported. A simulation study of a mathematical model with detailed description of thin filament activation suggested that velocity dependent thin filament inactivation is crucial for the observed load dependent behaviors and previously reported afterload dependent change in Ca(2+) transient shape.


Impaired renal allograft function: a comparative study with angiography and histopathology.
We reviewed 47 renal transplant recipients who had undergone angiography and transplant biopsy to evaluate impaired allograft function. Angiographic criteria for rejection were seen in all allografts with hyperacute rejection, accelerated rejection and chronic rejection, and in 13 of 17 allografts with acute cellular rejection. Angiography was normal in allografts with vasomotor nephropathy or transplant glomerulopathy. Angiography is an accurate method for the diagnosis of most causes of post-transplant dysfunction.


[Painful diagnostic and therapeutic interventions].
There are many modes to prevent pain during minor surgical procedures or painful interventions. Besides mental preparation and support there are various effective locoregionalanalgetic and sedative regimens from (analgo-)sedation to total anaesthesia adequate for age. If safety rules are followed and medical indication is adequate, the presented regimens are safe and effective tools with respect to stress prevention in the discussed field. There are many modes to prevent pain during minor surgical procedures or painful interventions. Besides mental preparation and support there are various effective locoregionalanalgetic and sedative regimens from (analgo-)sedation to total anaesthesia adequate for age. If safety rules are followed and medical indication is adequate, the presented regimens are safe and effective tools with respect to stress prevention in the discussed field.


Dislocation after total hip arthroplasty: a randomized clinical trial of a posterior approach and a modified lateral approach.
We compared the dislocation rate of total hip arthroplasty between posterior approach and lateral approach in a prospective randomized trial. One hundred ninety-six hips were randomly chosen for a posterior approach with a posterior soft tissue repair (99 hips) or a lateral approach (97 hips). The average duration of follow-up was 37.9 months. Three hips (3%) dislocated in the lateral group, whereas none from the posterior group dislocated. At the final follow-up, the Harris hip score and limping were similar in the 2 groups. The joint stability obtained by the posterior soft tissue repair in the posterior approach group seemed to produce more favorable result when compared to the stability obtained from the lateral approach group.


Rapid Semiconducting Supramolecular Mg(II)-Metallohydrogel: Exploring Its Potential in Nonvolatile Resistive Switching Applications and Antiseptic Wound Healing Properties.
An effective strategy was employed for the rapid development of a supramolecular metallohydrogel of Mg(II) ion (i.e., Mg@PEHA) using pentaethylenehexamine (PEHA) as a low-molecular-weight gelator in aqueous medium under ambient conditions. The mechanical stability of the synthesized Mg@PEHA metallohydrogel was characterized by using rheological analysis, which showed its robustness across different angular frequencies and oscillator stress levels. The metallohydrogel exhibited excellent thixotropic behavior, which signifies that Mg@PEHA has a self-healing nature. Field emission scanning electron microscopy and transmission electron microscopy images were utilized to explore the rectangular pebble-like hierarchical network of the Mg@PEHA metallohydrogel. Elemental mapping through energy-dispersive X-ray spectroscopy analysis confirmed the presence of primary chemical constituents in the metallohydrogel. Fourier transform infrared spectroscopy spectroscopy provided insights into the possible formation strategy of the metallohydrogel. In this work, Schottky diode structures in a metal-semiconductor-metal geometry based on a magnesium(II) metallohydrogel (Mg@PEHA) were constructed, and the charge transport behavior was observed. Additionally, a resistive random access memory (RRAM) device was developed using Mg@PEHA, which displayed bipolar resistive switching behavior at room temperature. The researchers investigated the switching mechanism, which involved the formation or rupture of conduction filaments, to gain insights into the resistive switching process. The RRAM device demonstrated excellent performance with a high ON/OFF ratio of approximately 100 and remarkable endurance of over 5000 switching cycles. RRAM devices exhibit good endurance, meaning they can endure a large number of read and write cycles without significant degradation in performance. RRAM devices have shown promising reliability in terms of long-term performance and stability, making them suitable for critical applications that require reliable memory solutions. Significant inhibitory activity against the drug-resistant Klebsiella pneumonia strain and its biofilm formation ability was demonstrated by Mg@PEHA. The minimum inhibitory concentration value of the metallohydrogel was determined to be 3 mg/mL when it was dissolved in 1% DMSO. To study the antibiofilm activity, an MTT assay was performed, revealing that biofilm inhibition (60%) commenced at 1 mg/mL of Mg@PEHA when dissolved in 1% DMSO. Moreover, in the mouse excisional wound model, Mg@PEHA played a crucial role in preventing postoperative wound infections and promoting wound healing.


Milk Production and Energetic Metabolism of Heat-Stressed Dairy Goats Supplemented with Propylene Glycol.
Heat-stressed dairy animals increase their reliance on glucose. This elevated glucose demand is partially met by increasing the conversion of glucogenic amino acids (AA) in the liver. Propylene glycol (PG) is a glucogenic precursor and was not tested in dairy goats under thermoneutral (TN) and heat stress (HS) conditions simultaneously. We hypothesize that if HS-goats are fed with PG, they would get more glucose and consequently spare more glucogenic AA for milk protein synthesis rather than gluconeogenesis. Eight multiparous dairy goats (40.8 ± 1.1 kg body weight; 84 ± 1 days in milk) were used in a replicated 4 × 4 Latin square design of 4 periods; 21 d each (14 d adaptation, 5 d for measurements, and 2 d of transition). Goats were allocated to one of 4 treatments in a 2 × 2 factorial arrangement. Factors were control (CO) without PG or 5% of PG, and thermoneutral (TN; 15 to 20 °C) or heat stress (HS; 12 h/d at 37 °C and 12 h/d at 30 °C) conditions. Feed intake, rectal temperature, respiratory rate, milk yield, milk composition, and blood metabolites were measured. Compared to TN, HS goats had lower (p < 0.01) feed intake (-34%), fat-corrected milk (-15%), and milk fat (-15%). Heat-stressed goats also tended (p < 0.10) to produce milk with lower protein (-11%) and lactose (-4%) contents. Propylene glycol increased blood glucose (+7%; p < 0.05), blood insulin (+37%; p < 0.10), and body weight gain (+68%; p < 0.05), but decreased feed intake (-9%; p < 0.10) and milk fat content (-23%; p < 0.01). Furthermore, blood non-esterified fatty acids (-49%) and β-hydroxybutyrate (-32%) decreased (p < 0.05) by PG. In conclusion, supplementation of heat-stressed dairy goats with propylene glycol caused milk fat depression syndrome, but reduced body weight loss that is typically observed under HS conditions. Supplementation with lower doses of PG would avoid the reduced feed intake and milk fat depression, but this should be tested.


Human umbilical cord tissue-derived mesenchymal stromal cells as adjuvant therapy for myocardial infarction: a review of current evidence focusing on pre-clinical large animal models and early human trials.
Although biologically appealing, the concept of tissue regeneration underlying first- and second-generation cell therapies has failed to translate into consistent results in clinical trials. Several types of cells from different origins have been tested in pre-clinical models and in patients with acute myocardial infarction (AMI). Mesenchymal stromal cells (MSCs) have gained attention because of their potential for immune modulation and ability to promote endogenous tissue repair, mainly through their secretome. MSCs can be easily obtained from several human tissues, the umbilical cord being the most abundant source, and further expanded in culture, making them attractive as an allogeneic "of-the-shelf" cell product, suitable for the AMI setting. The available evidence concerning umbilical cord-derived MSCs in AMI is reviewed, focusing on large animal pre-clinical studies and early human trials. Molecular and cellular mechanisms as well as current limitations and possible translational solutions are also discussed.


Complete Genome Sequence of Rhodopseudomonas palustris RCB100, an Anoxygenic Phototroph That Degrades 3-Chlorobenzoate.
The purple nonsulfur bacterium Rhodopseudomonas palustris RCB100 anaerobically degrades 3-chlorobenzoate (3-CBA), a halogenated pollutant. R. palustris RCB100 uses 3-CBA as a carbon source, while most R. palustris strains cannot. We report the complete genome sequence of strain RCB100 to help gain insight into how this bacterium degrades 3-CBA.


Prevalence and Risk Factors of Preoperative Deep Vein Thrombosis in Patients with End-Stage Knee Osteoarthritis.
The purpose of this study is to determine the prevalence and the risk factors of DVT in end-stage OA patients. From March 2015 to June 2017, 521 patients with knee degenerative osteoarthritis undergoing knee arthroplasty were enrolled; 458 patients (87.9%) were admitted for primary total knee arthroplasty and 63 patients (12.1%) were admitted for unicompartmental knee arthroplasty. Parameters were compared using χ2 or t-test for both the groups. Binary logistic regression analysis was used to determine risk factors. The incidence of preoperative DVT was 6.7% (n = 35). Age in preoperative DVT group was significantly more than the non-DVT group (72.54 ± 6.53 vs. 68.65 ± 7.35, P = 0.002). Preoperative D-dimer >0.5 μg/mL (P < 0.001) was also associated with preoperative DVT in knee osteoarthritis patients. The incidence increased with age significantly (2.17% in <65 years, 6.86% in ≥65 <75 years, and 12.26% in ≥75 years) (P = 0.008). Thus, age (P = 0.041, OR 1.075, 95% CI [1.002-1.110]) and D-dimer >0.5 μg/mL (P < 0.001, OR 4.441, 95% CI [1.942-10.153]) were the independent risk factors for preoperative DVT in knee osteoarthritis patients. The incidence of DVT in end-stage osteoarthritis was 6.7%. The results suggest that older people aged over 75 and D-dimer > 0.5 μg/mL were risk factors for DVT among patients admitted to the hospital for total knee arthroplasty. Instrumental screening should be encouraged, especially in subgroups at higher risk for preoperative DVT.


Engineering the oleaginous yeast Yarrowia lipolytica to produce limonene from waste cooking oil.
Limonene is an important biologically active natural product widely used in the food, cosmetic, nutraceutical and pharmaceutical industries. However, the low abundance of limonene in plants renders their isolation from plant sources non-economically viable. Therefore, engineering microbes into microbial factories for producing limonene is fast becoming an attractive alternative approach that can overcome the aforementioned bottleneck to meet the needs of industries and make limonene production more sustainable and environmentally friendly. In this proof-of-principle study, the oleaginous yeast Yarrowia lipolytica was successfully engineered to produce both d-limonene and l-limonene by introducing the heterologous d-limonene synthase from Citrus limon and l-limonene synthase from Mentha spicata, respectively. However, only 0.124 mg/L d-limonene and 0.126 mg/L l-limonene were produced. To improve the limonene production by the engineered yeast Y. lipolytica strain, ten genes involved in the mevalonate-dependent isoprenoid pathway were overexpressed individually to investigate their effects on limonene titer. Hydroxymethylglutaryl-CoA reductase (HMGR) was found to be the key rate-limiting enzyme in the mevalonate (MVA) pathway for the improving limonene synthesis in Y. lipolytica. Through the overexpression of HMGR gene, the titers of d-limonene and l-limonene were increased to 0.256 mg/L and 0.316 mg/L, respectively. Subsequently, the fermentation conditions were optimized to maximize limonene production by the engineered Y. lipolytica strains from glucose, and the final titers of d-limonene and l-limonene were improved to 2.369 mg/L and 2.471 mg/L, respectively. Furthermore, fed-batch fermentation of the engineered strains Po1g KdHR and Po1g KlHR was used to enhance limonene production in shake flasks and the titers achieved for d-limonene and l-limonene were 11.705 mg/L (0.443 mg/g) and 11.088 mg/L (0.385 mg/g), respectively. Finally, the potential of using waste cooking oil as a carbon source for limonene biosynthesis from the engineered Y. lipolytica strains was investigated. We showed that d-limonene and l-limonene were successfully produced at the respective titers of 2.514 mg/L and 2.723 mg/L under the optimal cultivation condition, where 70% of waste cooking oil was added as the carbon source, representing a 20-fold increase in limonene titer compared to that before strain and fermentation optimization. This study represents the first report on the development of a new and efficient process to convert waste cooking oil into d-limonene and l-limonene by exploiting metabolically engineered Y. lipolytica strains for fermentation. The results obtained in this study lay the foundation for more future applications of Y. lipolytica in converting waste cooking oil into various industrially valuable products.


A sequentially responsive nanogel via Pt(IV) crosslinking for overcoming GSH-mediated platinum resistance.
Chemotherapy efficiency of platinum(II) (Pt(II)) is often attenuated owing to the low intracellular drugs concentration and glutathione (GSH)-mediated detoxification. To address these problems, we fabricated a step-by-step responsive nanogel (~160 nm) by copolymerization between four functional monomers. Hydrophilic methoxypolyethylene glycols (mPEG) distributedrandomly on the surface of particles endowed the nanogel with "stealth" property in blood circulation, while the chemical crosslinking inside particles by platinum(IV) (Pt(IV)) linker remarkably increased the stability of nanogel in vivo. These advantages of nanogels leaded to higher accumulation at tumor region (6.4% ID/g), followed by triggering the dePEGylation effect by the cleavage of ortho ester at tumoral extracellular pH. Meanwhile, the exposed phenylboric acid (PBA) could significantly increase cellular uptake and intracellular drugs levels by targteing sialic acid residues on the cells membrane. More importantly, this nanogels could further deplete intracellular glutathione (GSH) by the dual-regulation of platinum(IV) and arylboronic ester, resulting in enhanced platinum(II) toxicity both in vitro and in vivo, eventually achieving superior inhibition rate (79.14%) in A549/DDP tumor. Thus, the sequentially responsive nanogel could be considered as an effective strategy for cancer treatment.


Acute respiratory failure during therapy for salicylate intoxication.
The case of a patient who developed severe acute respiratory failure during therapy for salicylate intoxication is described. The individual with aspirin overdose is at risk for this complication because of the potential for treatment modalities to cause or worsen lung edema initiated by the effects of salicylates on the pulmonary capillary bed.


Optimization of RNA extraction methods from human metabolic tissue samples of the COMET biobank.
Constitution of biobank of human tissues requires careful handling and storage of biological material, to guarantee the quality of samples. Tissue preparation is also critical for further applications such as transcriptomic profiling. In this study, our aim was to evaluate the impact of different disruption techniques (FastPrep-24 instrument, GentleMACS dissociator, and syringe/needle) and homogenizing buffers (RLT versus QIAzol) on RNA purity and quality of metabolic tissues (adipose tissues, liver and skeletal muscle) present in the COMET Biobank. For all homogenization methods used and tissue types, the A260/280 ratios reached values ≥ 1.8, which are in the range of what is found in human tissues and cell lines, while the A260/230 ratios were however ≤ 1.8, with the lowest value obtained with GentleMACS Dissociator. In addition, GentleMACS Dissociator combined with QIAzol reagent gave the highest RIN value and 28S/18S ratio for all tissues tested, except for muscle. Performing RT-qPCR, Ct values for different housekeeping genes can be influenced by extraction methods and RNA quality of samples. In conclusion, we have demonstrated that different disruption techniques and homogenizing buffers impact the purity and some quality markers of RNA, and can also impact quantification of mRNAs by RT-qPCR in human metabolic tissues.


[A common concept of the pathogenesis of intestinal obstruction].
On the basis of personal investigations and literature data the authors make a conclusion of the common nature of pathogenesis of acute ileus and various kinds of shock reactions. This common nature is determined by the character of trigger mechanisms of pathological reactions and formation of defense reactions of the patient.


Multifocal pancreatic PPoma in the setting of MEN1: Case report and review of literature.
Functioning pancreatic neuroendocrine tumors (pNETs) that express pancreatic polypeptide-PPomas-do not yet have a pathognomonic clinical syndrome associated with them due to their overall rarity and diverse symptoms. Moreover, in patients with MEN1, the often multifocal nature of pNETs presents a unique clinical issue. We report a case of a 22-year-old man with a known MEN1 gene mutation who was suffering from severe diarrhea (7-8 bowel movements per day) and was found to have only elevated PP levels on biochemical work-up. Ga68-DOTATATE PET/CT showed multifocal tumors in the body and tail of the pancreas that were not evident on contrast-enhanced CT. The patient underwent a successful laparoscopic radical antegrade modular pancreatosplenectomy (RAMP) and recovered well post-operatively with complete resolution of his diarrhea. Immunohistochemistry showed multiple pure PPomas. This case highlights the unique propensity for multifocal disease in patients with MEN1 mutations and the utility of functional imaging by somatostatin analogs, i.e., Ga68-DOTATATE PET/CT, in order to perform oncologic laparoscopic pancreatic resections. PPomas in the setting of MEN1 mutations are a unique clinical entity due to their diverse associated clinical syndromes and propensity for multifocal disease.


Lessons of COVID-19: A roadmap for post-pandemic science.
The response to the COVID-19 crisis across most research institutions mandated ceasing nonessential research activities in order to minimize the spread of the virus in our communities. With minimal notice, experiments were terminated, cell lines were frozen, mouse colonies were culled, and trainees were prevented from performing bench research. Still, despite the interruption of experimental productivity, the shutdown has proven for many PIs and trainees that doing and thinking science are not activities that are bound to the laboratory. Furthermore, the shutdowns have solidified important emerging trends and forced us to further innovate to get the most out of working remotely. We hope that some of these innovations, hard-gained in this difficult time, will persist and develop into new paradigms-lessons that will improve our science and our relationship to the climate and community beyond the current pandemic.


Probable fatal mastoiditis by the around 2300 year old Heidelberg's Egyptian mummy Djed-Hor.
The universal use of computed tomography (CT) has opened up new possibilities in the noninvasive examination of human mummies, and particularly the detailed study of the fine structures of the temporal bone. The aim of this study was to describe the morphological changes, as seen on CT, found in the right temporal bone of Djed-Hor, an around 2300 year old Heidelberg's Egyptian mummy, and to discuss their possible causal relation to his death. Here we showed the presence of a compress on the auricle, and of probable pus in the mastoid, middle ear, and external ear with erosion of the tegmen tympani probably related to a fatal acute mastoiditis. These typical morphological changes of such a disease were demonstrated in the same way as in living patients of today. This would be the first depiction of a compress on an auricle associated with pus in the ear of an Egyptian mummy.


[Quarantine nematode species and pathotypes potentially dangerous for domestic potato production: populations diversity and the genetics of potato resistance].
The review considers quarantine species and nematode pathotypes potentially dangerous for domestic potato production. Potatoes are affected by more than 30 types of parasitic nematodes, but the review focuses on the most harmful representatives of genera that cause great damage to potato production: Globodera, Ditylenchus, Nacobbus and Meloidogyne. Phytopathological and molecular methods of identification of species and pathotypes and the main achievements in studying the population variability of parasitic potato nematodes were analyzed. It was shown that due to the peculiarities of the life cycle of nematodes and lability of their genomes, the genetic variability of these organisms is very high, which creates a threat of forming new pathogenic genotypes of the parasites. The information about the intra- and interpopulation variability of nematodes is important for studying the ways of introduction and distribution of separate species, as well as for searching for the correlations of molecular markers with the pathotype. Phylogenetic studies based on modern data on genetic variability of populations have allowed to reveal species complexes in Globodera pallida (Stone) Behrens and Nacobbus aberrans (Thorne) Thorne & Allen (sensu lato), including cryptic species. The main components of successful protection preventing a wide distribution of parasitic nematodes are quarantine measures, agricultural techniques, biological methods of protection and cultivation of resistant cultivars. Special attention in the review is paid to the breeding of potato cultivars with durable resistance to various nematode pathotypes, because the cultivation of such varieties is the most ecologically safe and economically advantageous way to prevent epiphytoties. Currently, significant progress has been made in the genetic protection of potato cultivars, especially against cyst-forming nematodes. The review provides data on sources of potato resistance to parasitic nematodes identified in collections of wild and cultivated species. Data on identified R-gens and QTL of resistance that have been introduced into breeding varieties using different methods and approaches are analyzed. The literature data on the study of structural and functional organization of genes for resistance to potato cyst nematodes are given. The results of molecular research on revealing the polymorphisms of loci involved in the control of resistance to cyst and gall nematodes, the development of molecular markers of certain genes and their use in marker-assisted selection for developing of new resistant cultivars, including those with group resistance, are considered.


Four plasma membrane-localized MGR transporters mediate xylem Mg2+ loading for root-to-shoot Mg2+ translocation in Arabidopsis.
Magnesium (Mg2+), an essential structural component of chlorophyll, is absorbed from the soil by roots and transported to shoots to support photosynthesis in plants. However, the molecular mechanisms underlying root-to-shoot Mg2+ translocation remain largely unknown. We describe here the identification of four plasma membrane (PM)-localized transporters, named Mg2+ release transporters (MGRs), that are critical for root-to-shoot Mg transport in Arabidopsis. Functional complementation assays in a Mg2+-uptake-deficient bacterial strain confirmed that these MGRs conduct Mg2+ transport. PM-localized MGRs (MGR4, MGR5, MGR6, and MGR7) were expressed primarily in root stellar cells and participated in the xylem loading step of the long-distance Mg2+ transport process. In particular, MGR4 and MGR6 played a major role in shoot Mg homeostasis, as their loss-of-function mutants were hypersensitive to low Mg2+ but tolerant to high Mg2+ conditions. Reciprocal grafting analysis further demonstrated that MGR4 functions in the root to determine shoot Mg2+ accumulation and physiological phenotypes caused by both low- and high-Mg2+ stress. Taken together, our study has identified the long-sought transporters responsible for root-to-shoot Mg2+ translocation in plants.


Halotolerant and metalotolerant bacteria strains with heavy metals biorestoration possibilities isolated from Uburu Salt Lake, Southeastern, Nigeria.
Environmental contaminations by heavy metals are currently an increasing public health concern globally. One key challenge of these toxic metals is the extremely difficulties involved in their detoxification from the environment and effluents because of their non-degradability. An efficient biologic agent with potentials of remediating these toxic metals may ease these ever-increasing problems. We reported toxic metals tolerance and bioremediation potentials of novel bacteria sp. Strains USL2S, USL4W and USL5W isolated from Uburu salt lake, Ebonyi State, Nigeria. The phenotypic characteristics and the 16S rRNA gene analyses revealed that USL2S strain belongs to the genus Klebsiella, whereas USL4W and USL5W strains belong to the genus Pseudomonas. The bacteria isolates grew well in media containing 5-15 % of sodium chloride. The bacteria isolate showed capacity to tolerate 50.0 mM Hg+2 and Pb+2, 17.0, 12.50 and 4.0mM Ni+2, Cd+2, and Zn+2 respectively in solid media. Pseudomonas putida A4W Strain also tolerated 16.0 mM Cu+2, while Klebsiella sp. Strain USL2S, Pseudomonas putida USL5W Strain tolerated 4.0 mM each. AAS analyses showed 85, 95, and 95 % Hg; 97.13, 98.89, and 97.55 % Pb; 73.33, 77.42 and 69.72 Cd; 88.06, 99.54, and 97.91 % Ni; 100, 100 and 83.62% Cu; 42.30, 84.52 and 98.80 % Zn removal from media broth incorporated with the tested metals by Klebsiella sp. USL2S, Pseudomonas sp. Strain USL5W and Pseudomonas sp. USL4W respectively. We therefore recommend these novel moderately halophilic and metal tolerant isolates as possible biologic agents for effective bioremediation of mercury, lead, cadmium, nickel, copper and zinc in contaminated environments and effluents.


Understanding suicide through studies of diaries: the case of Cesare Pavese.
The diary left by Cesare Pavese covering the 15 years prior to his suicide is examined. The noteworthy pattern is that mention of failure with women was immediately followed in his diary by denigration of his literary work. Other features of his life, such as the loss of his father when he was six, are also discussed.


Radiation therapy to the primary and postinduction chemotherapy MIBG-avid sites in high-risk neuroblastoma.
Although it is generally accepted that consolidation therapy for neuroblastoma includes irradiation of the primary site and any remaining metaiodobenzylguanidine (MIBG)-avid metastatic sites, limited information has been published regarding the efficacy of this approach. Thirty patients with high-risk neuroblastoma were treated at 1 radiation therapy (RT) department after receiving 5 cycles of induction chemotherapy and resection. All patients had at least a partial response after induction therapy, based upon international neuroblastoma response criteria. The primary sites were treated with 24 to 30 Gy whereas the MIBG-avid metastatic sites were treated with 24 Gy. RT was followed by high-dose chemotherapy with autologous stem cell rescue and 6 months of cis-retinoic acid. The 5-year progression-free survival (PFS) and overall survival (OS) rates were 48% and 59%, respectively. The 5-year locoregional control at the primary site was 84%. There were no differences in locoregional control according to degree of primary surgical resection. The 5-year local control rate for metastatic sites was 74%. The 5-year PFS rates for patients with 0, 1, 2, and >3 postinduction MIBG sites were 66%, 57%, 20%, and 0% (P<.0001), respectively, whereas 5-year OS rates were 80%, 57%, 50%, and 0%, respectively (P<.0001). RT to the primary site and postinduction MIBG-positive metastatic sites was associated with 84% and 74% local control, respectively. The number of MIBG-avid sites present after induction chemotherapy and surgery was predictive of progression-free and overall survival.


Mitochondrial membrane potential is reduced in peripheral natural killer cells following partial hepatectomy.
The mechanism underlying immunosuppression after partial hepatectomy remains unclear. Hepatectomy induces lymphopenia, which is related to immunomodulation. The aim of this study was to determine whether peripheral blood lymphocytes (PBL) are susceptible to mitochondria-mediated apoptosis after hepatic resection. We compared the changes in mitochondrial membrane potential in lymphocytes from hepatectomized patients with metastatic liver tumor with the corresponding changes in lymphocytes from cholechystectomized patients, because changes in mitochondrial membrane potential have been reported to frequently occur during the early stages of apoptosis. Mitochondrial membrane potential, subpopulation, and apoptosis of lymphocytes were estimated with flow cytometry. Hepatectomy significantly (P<0.001) reduced postoperative mitochondrial membrane potential, while cholecystectomy slightly decreased it. Apoptosis of lymphocytes was increased on post-hepatectomy day, and this increase was correlated with the extent of mitochondrial membrane potential reduction. The major subset of lymphocytes with low mitochondrial membrane potential consisted of CD56(+) natural killer (NK) cells, and NK cell activity and cell counts significantly decreased after hepatectomy. Mitochondrial membrane potential of PBL was reduced after hepatectomy, and some lymphocytes underwent apoptosis through the mitochondrial pathway, which was one of the causes for lymphopenia. NK cells were more responsible for the decrease of mitochondrial membrane potential after hepatectomy than other lymphocytes, and the reduction in mitochondrial membrane potential in NK cells appeared to reflect modulation of the innate immune system.


Recurrence of endometrial carcinoma and the value of routine follow up.
To identify women treated for endometrial carcinoma with increased risk for recurrent disease, to examine how and when recurrences are discovered, and to assess the clinical benefit of routine follow up investigations. Retrospective case analysis. Hordaland county, Norway. All women treated for endometrial carcinoma in a demographically well defined area, in a 10-year period (1981-1990). Data concerning patient characteristics and course of the disease were collected through review of the medical records, correspondence with the primary physician and from the Norwegian Cancer Registry. Univariate and multivariate survival analysis. After curative surgical treatment 249 women diagnosed with endometrial carcinoma were followed for a median period of 9 years (range 4-16) or until death. Among these 249 radically treated patients, 47 had recurrent disease, 32 within the first two years. Ten of the recurrences were diagnosed at routine follow up, but only four were asymptomatic. In our follow up programme, one asymptomatic recurrence was detected for every 653 routine consultations. A low risk group, with FIGO Stage IA/IB or patient age below 60 years at primary operation was identified in multivariate recurrence-free survival analysis. No asymptomatic recurrences were found in this group. Low risk women should be considered for an alternative, less frequent follow up. The sensitivity for current practice of routine follow up in detecting asymptomatic recurrences is so low that other beneficial effects should be documented to defend the large resources spent on this programme.


Quantitative Assessment of Airway Pathology in Subjects With COPD Using Low-Dose High-Resolution Computed Tomography.
The purpose of this study was to correlate airway parameters of COPD determined by low-dose high-resolution computed tomography (HRCT) with pulmonary function testing (PFT) results. PFT data were collected for subjects with COPD and healthy controls. All subjects received inspiratory and expiratory phase low-dose HRCT. Bronchi in the apical segment of the right upper lobe (RB1), posterior segment of the right lower lobe (RB6), and lower lingual segment of the left upper lobe (LB5) were the target bronchi. Software automatically calculated airway wall area, inner area, and airway wall area percentage (percentage wall area for bronchial external area). A total of 75 COPD and 20 control subjects were included. The subjects with COPD were classified according to COPD stage, with 20 grade I, II, and III subjects, respectively, and 15 grade IV subjects. In COPD grade II, residual volume/total lung capacity was negatively correlated with airway wall area in LB5 (r = -0.51). In COPD grade III, FVC was negatively correlated with airway wall area percentage in LB5 (r = -0.49) but positively correlated with airway wall area in RB6 (r = 0.52); percent-of-predicted FEV1 was negatively correlated with airway wall area percentage in RB1 (r = -0.49); residual volume was negatively correlated with airway wall area (r = -0.47), and total lung capacity was negatively correlated with airway wall area in RB1 (r = -0.52) (all, P < .001). The results of this study suggest that airway parameters in different COPD grades have no uniform tendency of correlation with PFT, but some HRCT parameters are correlated to some PFT parameters.


The chemical structure of a tetrasaccharide containing N-acetylglucosamine obtained from bovine colostrum kappa-casein.
A tetrasaccharide consisting of D-galactose, N-acetylneuraminic acid, N-acetylglucosamine and N-acetylgalactosaminitol (1 : 1 : 1: 1) was obtained from bovine colostrum kappa-casein. It is the main carbohydrate portion of a caseinoglycopeptide formed by alkaline borohydride treatment. The carbohydrate sequence was analyzed by enzymatic and chemical methods and by mass spectrometry, and was shown to be N-acetylglucosaminyl-beta-1-3-galactosyl-beta-1-3[N-acetylneuraminyl-alpha-2-6- ]-N-acetylgalactosaminitol.


[3H]-Noncocaine and [3H]-pseudococaine: effect of N-demethylation and C2-epimerization of cocaine on its pharmacokinetics in the rat.
After i.v. injections of cocaine, norcocaine, pseudococaine to the rat, the T 1/2 in brain were 0.4, 0.6, 0.2 h respectively and in plasma 0.4, 0.5, 0.2 h respectively. Benzoylnorecgonine and norecgonine were the metabolites of norcocaine in brain. Pseudonorcocaine, pseudobenzoylnorecgonine, pseudobenzoylecgonine and pseudoecgonine were the metabolites of pseudococaine in rat brain. Benzolynorecgonine and pseudobenzoylecgonine had potent stimulant activity intracisternally in the rats.