The association between hypoglycemia and hospital use, food insufficiency, and unstable housing conditions: a cross-sectional study among patients with type 2 diabetes in Sudan.
Hypoglycemia is associated with mortality and healthcare utilization. We aimed to assess hypoglycemia risk and Hospital use among Sudanese patients with type 2 diabetes. One hundred and fifty-nine patients with type 2 diabetes attending a diabetes center in Omdurman, Sudan during the period from June to September 2018were approached. A structured questionnaire based on hypoglycemia risk and Hospital use, Fasting plasma glucose (FPG) and the glycated hemoglobin (HbA1c) was used to interview the patients. Participants (age 58.13 ± 9.96 years), 4.4%, 14.5%, and 81.1% were at high, moderate, and low hypoglycemia respectively, 66% reported food insufficiency, while 15.1% had unstable housing conditions. No relationship was evident between the hypoglycemia risk, gender, unstable housing conditions, food insufficiency, fasting plasma glucose,HbA1c, and the duration since the diagnosis of diabetes. A considerable number (18.9%) of Sudanese patients with diabetes were at moderate/high risk of hypoglycemia and Hospital use, including hypoglycemia risk and hospital use assessment in the holistic care of diabetes are recommended.


Performance of creatinine-based estimates of GFR in kidney transplant recipients: a systematic review.
Glomerular filtration rate (GFR) commonly is estimated in kidney transplantation by using creatinine-based estimation equations. The performance of these equations in kidney transplant recipients is unclear, with conflicting results between studies. Systematic review. Stable adult kidney transplant recipients more than 6 months posttransplantation. Reporting of or ability to calculate from available data the GFR estimation equation bias (mean difference between measured GFR and estimated GFR) and percent accuracy (percentage of GFR estimates within 10%, 20%, or 30% of measured GFR). Creatinine-based GFR estimation equations (Cockcroft-Gault, 6-variable Modification of Diet in Renal Disease [MDRD] Study, 4-variable MDRD Study, and Nankivell). GFR determination using plasma or renal clearance of inulin, radioisotopes, or nonradiographic contrast. The search yielded 23 studies. For the 4-variable MDRD Study equation, bias ranged from -11.4 to +9.2 mL/min/1.73 m(2) (0.15 mL/s/1.73 m(2)). Only 76% of estimates were within 30% of measured GFR. For the Cockcroft-Gault equation, bias ranged from -4.0 to +16 mL/min/1.73 m(2) and 73% of estimates were within 30% of measured GFR. For the Nankivell equation, bias ranged from -1.4 mL/min to 36.3 mL/min with a 30% accuracy of only 68%. This review is limited by the inability to pool bias data, lack of calibration of serum creatinine in the majority of studies, and inclusion of nonindependent observations in many studies. Differences in patient populations, baseline GFRs of the study group, reference standard GFR used, and creatinine assay calibration likely account for the heterogeneity in results. These factors need to be considered by investigators and clinicians when interpreting estimates of GFR in kidney transplant recipients.


Heat-Induced Fragmentation and Adapter-Assisted Whole Genome Amplification Using GenomePlex® Single-Cell Whole Genome Amplification Kit (WGA4).
Whole genome amplification (WGA) is a widely used technique allowing multiplying picogram amounts of target DNA by several orders of magnitude. The technique described here is based on heat-induced random fragmentation yielding DNA strands mainly ranging from 0.1 to 1 kb in length. The fragmented DNA is then subjected to library generation by annealing of adaptor sequences to both ends of the DNA fragments. Using primers hybridizing to the adapter sequences, the DNA is amplified by thermal cycling. This amplification typically yields > 2 mg DNA from a single cell, is suited for amplifying DNA isolated from (partly) degraded samples [e.g. formalin-fixed paraffin-embedded (FFPE) material] and works well when used for array-comparative genome hybridization (array-CGH).


Influence of external magnesium ions on the NMDA receptor channel block by different types of organic cations.
The NMDA type of ionotropic glutamate receptors plays a unique role in synaptic functions because of high permeability for calcium and because of a voltage-dependent block by endogenous Mg(2+). Activity and voltage dependence of the NMDA receptor channel block by organic cations are strongly affected by competition with magnesium ions for the binding site in the channel pore. It complicates prediction of action of NMDA receptor channel blockers in vivo. In the present work we studied the NMDA receptor channel block in the presence of Mg(2+) by several organic blockers with different characteristics of voltage dependence and mechanism of action. The action of NMDA receptor channel antagonists was studied in native NMDA receptors of hippocampus CA1 pyramidal neurons isolated from rat brain slices. It was demonstrated that the IC(50) values of NMDA receptor channel blockers at -30 mV are increased 1.5-5 times compared with magnesium-free conditions. The voltage dependence of the channel block is decreased, abolished or even inversed in the presence of magnesium. Although simple competition between magnesium ion and organic channel blockers provides a general explanation of the observed effects, certain disagreements were revealed. Diversity in Mg(2+) effects on the NMDAR channel block by different organic cations reported herein likely reflects interaction of NMDAR channel blockers with additional binding site(s) and suggests that individual analysis in the presence of Mg(2+) is required for newly developed NMDAR channel blocking drugs.


Induction of ssDNA-binding autoantibody secreting B cell immunity during murine malaria infection is a critical part of the protective immune responses.
Although it has been hypothesized that autoimmune-like phenomena may play a critical role in the protective immune responses to both human and animal malaria, there are still no evidence-based data to support this view. In this study we demonstrate that the majority of anti-single stranded (ss) DNA autoantibody secreting B cells were confined to B220(+)CD21(+)CD23(-) cells and that these cells expanded significantly in the spleen of C57BL/6 mice infected with Plasmodium yoelii 17X non-lethal (PyNL). To determine the role of ssDNA-binding autoantibody secreting B cell responses in murine malaria, we conjugated generation 6 (poly) amidoamine dendrimer nanoparticles with ssDNA to deplete ssDNA-binding autoreactive B cells in vivo. Our data revealed that 55.5% of mice died after DNA-coated nanoparticle-mediated in vivo depletion of ssDNA-specific autoreactive B cells and subsequent challenge using PyNL. Adoptive transfer of B cells with ssDNA specificity to mice, followed by PyNL infection, caused a later appearance and inhibition of parasitemia. The possible mechanism by which the ssDNA-binding autoantibody secreting B cells is involved in the protection against murine malaria has also been demonstrated.


A case of minimal change nephrotic syndrome with immunoglobulin A nephropathy transitioned to focal segmental glomerulosclerosis.
A 50-year-old woman with a 1-month history of lower extremity edema and a 5 kg weight increase was admitted to our hospital with suspected nephrotic syndrome in October 1999. Urine protein level was 3.5 g per day, 10-15 erythrocytes in urine per high-power field, and serum albumin level 2.5 g/dl. Furthermore, an accumulation of pleural effusion was confirmed by chest X-ray. The results of a renal biopsy indicated slight mesangial proliferation in the glomeruli by light microscopy, and an immunofluorescence study confirmed the deposition of immunoglobulin (Ig) A and C3 in the mesangial area. Diffuse attenuation of foot processes and dense deposits in the mesangial area were observed by electron microscopy. Treatment with 40 mg/day of prednisolone was effective, and proteinuria was negative 1 month later. Because of this course, we diagnosed minimal change nephrotic syndrome complicated by mild-proliferative IgA nephropathy. In November 2000, there was a relapse of nephrotic syndrome, which was believed to be induced by an influenza vaccination, but response to increased steroid treatment was favorable, and proteinuria disappeared on day 13 of steroid increase. A second relapse in May 2001, showed steroid resistance with renal insufficiency, and an increase in the selectivity index to 0.195. Light microscopy revealed focal sclerotic lesions of the glomeruli, and an immunofluorescence study revealed attenuation of mesangial IgA and C3 deposition. These findings led to the diagnosis that minimal change nephrotic syndrome had transitioned to focal segmental glomerulosclerosis, whereby mesangial IgA deposition was reduced by immunosuppressive treatment. Subsequently, her renal function gradually worsened to the point of end-stage renal failure by 27 months after the second relapse of nephrotic syndrome.


Hysteroscopic rollerball endometrial ablation as an alternative treatment for adenomyosis with menorrhagia and/or dysmenorrhea.
The aim of this study was to assess the long-term effectiveness and safety of hysteroscopic rollerball endometrial ablation as a surgical management of adenomyosis with menorrhagia and/or dysmenorrhea. We compared the results of patients who underwent pretreatment with gonadotropin-releasing hormone (GnRH) agonist with the results of those who did not. A retrospective study included 190 adenomyotic patients who suffered from menorrhagia and/or dysmenorrhea and underwent hysteroscopic rollerball endometrial ablation. Main outcome measures were rates of successful operation, complications, improvement of abnormal uterine bleeding and pelvic pain after the surgery. The majority of the patients (142, 74.7%) underwent hysteroscopic rollerball endometrial ablation during the early proliferative phase of the menstrual cycle. The rest were operated on after GnRH agonist pretreatment for 6-8 weeks. Ablations were successfully performed on all patients in a day surgery setting. The average operation time was 36.3 ± 7.1 min. The mean glycine deficit was 583.4 ± 247.3 mL. The ablation in the no-pretreatment group took a significantly longer time and had more glycine absorption compared to the GnRH agonist pretreatment group (P < 0.0001). Mean postoperative follow-up duration was five years (range 1-10 years). A total of 187 patients (98.4%) who had undergone hysteroscopic endometrial ablation reported decreased bleeding: amenorrhea in 58 (30.5%), hypomenorrhea in 78 (41.1%), and eumenorrhea in 51 (26.8%) patients. Three patients (1.6%) underwent hysterectomy due to symptoms recurrence. A total of 165 (86.8%) patients with dysmenorrhea reported either reduced or no dysmenorrhea. There was no significant difference in the efficacy of hysteroscopic rollerball endometrial ablation between patients who underwent pretreatment with GnRH agonists and those who did not. No major complications related to the procedure were reported. Hysteroscopic rollerball endometrial ablation as a surgical management of menorrhagia and dysmenorrhea that develops in patients with adenomyosis is an effective and safe procedure. It can reduce the need for the unnecessary major surgery of hysterectomy.


Roles of RPS41 in Biofilm Formation, Virulence, and Hydrogen Peroxide Sensitivity in Candida albicans.
In eukaryotes, loss of cytoplasmic ribosomal proteins (RPs) results in a reduced growth rate and other phenotypic defects. The ability to transition from a unicellular budding yeast to a filamentous form is very important for biofilm formation and virulence in Candida albicans. Our recent study found that loss of the RPS41 (C2_10620W_A) gene but not its paralog RPS42 (C1_01640W_A) resulted in altered growth and filamentation changes in C. albicans, so we hypothesized that the RPS41 gene should play important roles in virulence and biofilm formation in this pathogen. We found that both virulence and the ability to form biofilms were defective due to deletion of the RPS41 gene. We also found that loss of the RPS41 gene increased sensitivity to hydrogen peroxide, and that hydrogen peroxide induced the expression of the RPS41 gene in a wild-type strain. These results suggested that the RPS41 gene plays important roles in C. albicans biofilm formation, virulence, and susceptibility to hydrogen peroxide.


Thermal ablation performed in a primary care setting: the South Warwickshire Experience.
To assess the feasibility of performing outpatient thermal ablation in a primary care setting. Prospective study. A small peripheral hospital in the UK used by local general practitioners and visiting hospital practitioners for its outpatient facilities. The area of South Warwickshire serves a population of 270,000. Two general practitioners were trained to perform outpatient thermal ablation using the Thermachoice thermal ablation system (Thermachoice II). The unit functioned autonomously with support from a local gynaecologist and radiologist, accepting referrals from hospital consultants and general practitioners. Severity of menstrual loss, premenstrual symptoms, dysmenorrhoea and quality of life assessed by visual analogue scales before treatment and at one month, two months, one year and two years. Eighty-seven women were treated. No major complications were encountered from the procedure. Reduction of menstrual loss or cure was reported by over 94% of women. Premenstrual syndrome (PMS) and symptoms of dysmenorrhoea were also improved by treatment. The majority of women were satisfied with the operation at one month (96%), two months (93%), one year (92%) and two years (94%). Thermal ablation is a simple procedure well suited to an outpatient setting. There are few complications as a result of the use of the thermal ablation catheters, and this study has shown that the procedure can be undertaken in a primary care setting with excellent results.


Cardiovascular activities of intravenous methionine-enkephalin-Arg6-Phe7 and methionine-enkephalin-Arg6-Gly7-Leu8 in the conscious dog.
The preproenkephalin A molecule from the adrenal medulla contains the opioid peptides methionine-enkephalin (Met-ENK), leucine-enkephalin (Leu-ENK), methionine-enkephalin-Arg6-Phe7 (heptapeptide), and methionine-enkephalin-Arg6-Gly7-Leu8 (octapeptide). In the conscious, chronically instrumented dog, Met-ENK and Leu-ENK simultaneously increase heart rate and systemic arterial pressure following intravenous administration. In 19 of 23 dogs, heptapeptide produced a response identical to Met-ENK and Leu-ENK, which was inhibited by naloxone but unaffected by the dipeptidyl carboxypeptidase inhibitor SQ20881. However, in four dogs, heptapeptide produced only a fall in systemic pressure associated with an increase in heart rate despite characteristic Met-ENK responses in the same dogs; naloxone did not appear to alter this hypotensive response. Octapeptide produced slight increases in systemic pressure and heart rate. These data suggest that heptapeptide may possess intrinsic cardiovascular activity at opiate receptors; however, in certain dogs, non-opiate mechanisms, perhaps histamine release, may predominate.


Reef-forming polychaetes outcompetes ecosystem engineering mussels.
In order to understand changes in the functioning and the community structure of intertidal ecosystem in sewage-impacted sites, a long-term monitoring coverage study (2004-2011) was carried out on abrasion platforms of the SW Atlantic. The intertidal zone is characterized by the mytilid Brachidontes rodriguezii, an ecosystem engineer. Since the austral spring of 2008, a demographic explosion of an invader polychaetes, Boccardia proboscidea, has produced massive biogenic structures around the sewage discharge outfall. Cover percentage of this polychaete reached almost 100% in sewage-impacted sites but low or no coverage at all in Reference Sites. The density of B. rodriguezii declined due to the biogenic reefs stifles these mytilids. The massive settlement of B. proboscidea among mussels, the rapid growth and the tube construction smothers the mussels in sewage-impacted sites.


Non-monotonic dependence of water reorientation dynamics on surface hydrophilicity: competing effects of the hydration structure and hydrogen-bond strength.
The reorientation dynamics of interfacial water molecules was recently shown to change non-monotonically next to surfaces of increasing hydrophilicity, with slower dynamics next to strongly hydrophobic (apolar) and very hydrophilic surfaces, and faster dynamics next to surfaces of intermediate hydrophilicities. Through a combination of molecular dynamics simulations and analytic modeling, we provide a molecular interpretation of this behavior. We show that this non-monotonic dependence arises from two competing effects induced by the increasing surface hydrophilicity: first a change in the hydration structure with an enhanced population of water OH bonds pointing toward the surface and second a strengthening of the water-surface interaction energy. The extended jump model, including the effects due to transition-state excluded volume and transition-state hydrogen-bond strength, provides a quasi-quantitative description of the non-monotonic changes in the water reorientation dynamics with surface hydrophilicity.


Design and preparation of sterol mimetics as potential antiparasitics.
We have previously shown that azasterols have activity against Trypanosoma brucei, Trypanosoma cruzi and Leishmania species, which are the causative agents of various neglected tropical diseases. In this paper, we discuss the replacement of the sterol core of the azasterols with sterol mimics. Various mimics were designed, and the structures were minimised to see if they could adopt a similar conformation to that of the azasterols. From this, two series of mimics were synthesised and then evaluated against the parasites. Compounds showed moderate activity.


Effects of egg washing and storage temperature on the quality of eggshell cuticle and eggs.
This study investigated the quality of washed and unwashed eggs stored at 7°C (WC and UC for washed and unwashed eggs, respectively) and 25°C (WR and UR for washed and unwashed eggs, respectively) for 4weeks. The results show that the Haugh unit, albumin pH, thick albumin ratio, yolk index, air cell size, and S-ovalbumin content of UC were significantly the most superior, followed by those of WC, WR, and UR, in that order. Scanning electron microscopy and cuticle staining confirmed the damages and decreased cuticle coverage caused by washing and extended storage. Attenuated total reflection Fourier transform infrared spectroscopy revealed that cuticle composition changed significantly after washing and storage (P<0.05). High correlations were observed between the quality parameters evaluated. In conclusion, storage temperature critically influenced egg quality, and egg washing reduced cuticle coverage.


Development and Evaluation of an Immunoglobulin Y-Based ELISA for Measuring Prostate Specific Antigen in Human Serum.
Measurement of serum prostate specific antigen (PSA) concentrations remains one of the leading methods for diagnosing prostate cancer. We developed and evaluated an immunoglobulin Y (IgY)-based ELISA to measure total PSA (tPSA) concentrations in human serum that could be used as an alternative to commercially available in vitro diagnostic assays that rely on mouse monoclonal IgG. A sandwich ELISA based on an anti-PSA IgY antibody was developed. We evaluated the ability of the anti-PSA IgY antibody to detect free and complexed PSA at the same molar ratio. The assay was optimized, and its analytical performance was verified by calculating limit of background (LoB), limit of detection (LoD), and limit of quantification (LoQ). We performed correlation and regression analyses between tPSA concentrations measured by our ELISA and those from commercial assays: Cobas 6000 (Roche Diagnostics, Warszawa, Poland) and PSA total ELISA (IBL International, Hamburg, Germany). LoB, LoD, and LoQ, were 0.061, 0.083, and 0.100 ng/mL, respectively, and linearity range was 0.100-3.375 ng/mL. tPSA concentrations from our IgY-based ELISA strongly correlated with those from the commercial assays. Our IgY-based ELISA is an efficient equivalent to the above commercial assays. The use of IgY as the detecting agent could reduce the risk of false positive results, as well as decrease the overall cost of analysis.


Neodymium doped hydroxyapatite theranostic nanoplatforms for colon specific drug delivery applications.
Theranostic nanoplatforms integrate therapeutic payloads with diagnostic agents, and help monitor therapeutic response. In this regard, stimuli responsive nanoplatforms further favour combinatorial therapeutic approach that can considerably improve efficacy and specificity of treatment. Herein, we present the engineering of a smart theranostic nanoplatform based on neodymium doped hydroxyapatite (HAN). The presence of neodymium endows the HAN nanoplatforms with near-infrared fluorescence capability. These HAN nanoparticles were then subsequently modified with alginic acid (HANA) to confer pH responsiveness to the synthesized nanoplatforms delivering them to the colon after oral administration. These nanoplatforms possessing optimum size, needle shaped morphology and negative zeta potential, are conducive to cellular internalization. On excitation at 410nm they exhibit near infrared emission at 670nm unraveling their theranostic capabilities. Cytotoxic effects systematically assessed using MTT and live dead assays reveal excellent viability. Raman microscopic imaging technique used to visualize uptake in HeLa cells demonstrate increased uptake from 4 to 16h, with growing cluster size and localization in the cytoplasm. Moreover the concomitant presence of alginic acid manifested advantages of augmented loading and pH dependent release profiles of the model drug, 4 acetyl salicylic acid (4ASA). We could thus establish a theranostic system for early tumour detection, targeted tumour therapy and monitoring of colon cancer that can be administered via the oral route.


Calcium channel blockers.
The calcium channel blockers initially were approved for the treatment of classical and variant angina pectoris. Recent studies indicate that these agents also are useful in such diverse conditions as pulmonary and systemic hypertension, hypertrophic cardiomyopathy, arrhythmias, asthma, Raynaud's syndrome, esophageal spasm, myometrial hyperactivity, cerebral arterial spasm, and migraine.


A multicenter randomized controlled open-label trial to assess the efficacy of compound kushen injection in combination with single-agent chemotherapy in treatment of elderly patients with advanced non-small cell lung cancer: study protocol for a randomized controlled trial.
With the aging of the global population, an increasing number of elderly are diagnosed with advanced non-small cell lung cancer. Although systematic chemotherapy has been one of the primary treatments for advanced non-small cell lung cancer worldwide, the elderly cannot always tolerate standard platinum-based doublet chemotherapy, thus resulting in treatment failure. To reduce toxicity, single-agent chemotherapy is often used to treat the elderly with non-small cell lung cancer; however, this may increase the risk of treatment failure due to an inadequate dose. It has been shown that compound kushen injection in combination with chemotherapy can enhance the efficacy and reduce the toxicity. The aim of this trial is to assess the clinical effectiveness and safety of compound kushen injection in combination with single-agent chemotherapy versus platinum-based doublet chemotherapy in the treatment of elderly patients with advanced non-small cell lung cancer. This multicenter study will be an open-label, randomized controlled trial. Three hundred seventy elderly patients with advanced non-small cell lung cancer will be randomly divided into experimental (n = 185) and control groups (n = 185) to receive compound kushen injection in combination with single-agent chemotherapy or standard platinum-based doublet chemotherapy for two cycles. After two cycles, the disease control rate, objective response rate, clinical symptoms, quality of life, Karnofsky Performance Status, and side effects will be assessed. Follow-up evaluations will be performed every 8 weeks to evaluate the progression-free and overall survival. Before the trial was designed, compound kushen injection was shown to be effective for lung cancer through basic experiments and clinical trials. This study will determine whether or not the efficacy of compound kushen injection in combination with single-agent chemotherapy is comparable to that of platinum-based doublet chemotherapy, and whether or not the toxicity of compound kushen injection in combination with single-agent chemotherapy is lower than that of platinum-based doublet chemotherapy. ChiCTR-IPR-14005484 (16 November 2014).


Spontaneous hemorrhage from splenic tissue 13 years after total splenectomy: report of a case.
A 33-year-old man suffered sudden abdominal distension without traumatic episodes. He had undergone total splenectomy for hereditary spherocytosis 13 years ago. He was in shock, and his hemoglobin level was 10.5 g/dl. Contrast enhanced computed tomography revealed a giant mass in the left upper abdomen and extravasation of the contrast material into the mass. Excision of the mass was performed, and microscopic examination showed a giant hematoma surrounded by normal splenic tissue. We speculated that an accessory spleen or splenosis had enlarged for the 13 years and ruptured. The patient remained asymptomatic 4 months after the surgery. Spontaneous hemorrhage from accessory spleens or splenosis is extremely rare, and relevant case reports suggest that surgical resection of bleeding sites yields favorable prognosis although preoperative qualitative diagnosis seems to be difficult.


Update on Calcitonin Gene-Related Peptide Antagonism in the Treatment of Migraine.
The discovery of calcitonin gene-related peptide (CGRP) and its role in migraine has promoted a new era in migraine treatment: CGRP antagonism. Two classes of medications are currently available: small molecules targeting the CGRP receptor and monoclonal antibodies targeting the CGRP receptor or CGRP ligand. The revolution of these medications is represented by blurring the borders between acute and preventive treatments, episodic and chronic migraine, naïve and refractory patients and even between migraine and other headache disorders.


Monotropein inhibits colitis associated cancer through VDR/JAK1/STAT1 regulation of macrophage polarization.
Colorectal cancer (CRC) is a growing concern due to its high morbidity and mortality, and the search for effective and less toxic active substances against inflammatory bowel diseases has been a hot topic in the research and development of drugs against CRC. It is reported that monotropein isolated from the roots of Morinda officinalis, can improve Dextran Sodium Sulfate (DSS)-induced ulcerative colitis in mice, but its therapeutic effects and mechanisms for CRC treatment are still to be investigated. In the present study, we first used molecular docking, BLI, CESTA, and DARTS methods to detest whether monotropein targets VDR proteins. In addition, we used tumor cell conditioned co-culture and four models of macrophage polarisation to investigate the regulation of four macrophage polarisations by monotropein using RT-PCR, IF and western blot. Furthermore, we further validated the target of action of monotropein for the treatment of Azoxymethane (AOM)/DSS induced colitis associated cancer (CAC) using knockout animals. Meanwhile, we further explored the mechanism of action of monotropein in regulating polarisation by detecting JAK/STAT1-related genes and proteins. Molecular docking and biofilm interference techniques showed that monotropein bound to the VDR, and additional results from CESTA and DARTS suggested that VDR proteins are targets of monotropein. Furthermore, in tumor cell conditioned co-cultures or LPS + IFN-γ induced RAW264.7 cells, VDR translocation to the nucleus was reduced, JAK1/STAT1 signaling pathway proteins were up-regulated, and macrophages were polarised towards the M1-type after monotropein intervention. Animal models in which normal VDR or myeloid VDR was knocked out confirmed that JAK1 levels in intestinal tissues were increased after monotropein intervention, macrophages were polarised towards the M1 type, and CAC paracarcinomas were ameliorated. Taken together, the present study concluded that monotropein inhibited colitis-associated cancers through macrophage polarisation regulated by VDR/JAK1/STAT1.


Pleural effusion: beta-trace protein in diagnosing ventriculoperitoneal shunt complications.
Catheter dysfunction is a common complication with ventriculoperitoneal shunts. Apart from infection, obstruction, and leakage, migration of the shunt tip may cause particular problems. Pleural effusion is easily classified as a shunt complication if a transdiaphragmatic migration of a shunt can be demonstrated. If, however, the tip of the shunt is found adjacent to the diaphragm, it is difficult to decide if the effusion is caused by the ventriculoperitoneal shunt. Different diagnostic methods can be used in this situation. Below we report a case of pleural effusion-without shunt migration-which was revealed to be a shunt complication by quantifying beta-trace protein in the effusion.


Mechanisms of the association between PTSD and sexual arousal and lubrication functioning among trauma-exposed female service members/veterans.
The presence of a post-traumatic stress disorder (PTSD) diagnosis or higher PTSD severity is associated with higher overall sexual dysfunction in female service members/veterans. However, the mechanisms linking PTSD to specific components of women's sexual arousal function, like lubrication and mental arousal, are unknown. We conducted a survey among 464 women who reported probable Criterion A exposure for PTSD. Path analysis examined (1) the association of PTSD with sexual arousal, (2) whether specific PTSD symptom clusters were uniquely associated with sexual arousal, and (3) whether this association is indirect, through the effects of higher depression severity and lower romantic relationship satisfaction. Arousal was operationalized to measure both mental (subjective arousal) and physical (lubrication) experiences. Higher PTSD severity was associated with lower lubrication and arousal function. The association of PTSD severity with arousal was indirect, through lower romantic relationship satisfaction (estimate: -0.12; 95% CI: [-0.014, -0.007]) and higher depression (estimate: -0.08, 95% CI: [-0.012, -0.002]). The association of PTSD severity with lubrication was also indirect, but only through lower relationship satisfaction (estimate: -0.10, 95% CI: [-0.013, -0.006]). PTSD symptom clusters were not uniquely associated with arousal and lubrication through mediated pathways. Data were from a cross-sectional study using a convenience sample. Criterion A exposure could not be confirmed. PTSD may lead to arousal and lubrication dysfunction by contributing to higher depression severity and strained romantic relationships. Interventions targeting reductions in depressive symptoms and bolstering relationship satisfaction may minimize the burden of PTSD on sexual arousal concerns.


Consumer mobility and expenditure during the COVID-19 containments: Evidence from French transaction data.
This paper investigates the effects of the pandemic containment periods in France on individuals' movements, expenditure and adaptation to the shock, using billions of French bank card transactions measured before and during the COVID-19 pandemic. We measure not only the effect on consumer expenditure, but also on quantities directly related to the containment restrictions, such as consumer mobility, number of retailers visited, and inter-regional purchases. The results show large effects on these measures of consumers' movements, as well as on both online and offline measures of expenditure, particularly in the first containment period. We also find evidence that consumers adjusted rapidly during the first containment period, mitigating the effects of mobility restrictions via an increasing shift toward online purchasing, and that the nature of the adaptation differed for different types of purchase.


Cloning and expression pattern of a murine semaphorin homologous to H-sema IV.
The semaphorin/collapsin family of proteins comprises molecules thought to be important for the guidance of growing axons. All members of this family, which includes both secreted and cell-surface molecules, share a conserved domain of approximately 500 amino acids. Here, we report the cloning of a novel murine semaphorin, termed M-sema IV. It displays 96.3% identity to the human semaphorin H-sema IV and is therefore likely to be the respective murine homologue. In addition, an isoform was identified, which contains an additional 31 amino acids in the semaphorin domain. M-sema IV appears to be expressed ubiquitously in adulthood. During embryogenesis, in situ hybridization revealed M-sema IV expression in subregions of the central nervous system and various other tissues like skin, kidney, lung and intestine.


Parabens in aerobic granular sludge systems: Impacts on granulation and insights into removal mechanisms.
This work assessed the impact of methylparaben, ethylparaben, propylparaben, and butylparaben (200 μg L-1 each) on the granulation process as well as on the organic matter and nutrient removal of an aerobic granular sludge (AGS) system (6-h cycle). Additionally, some insights into the main paraben removal mechanisms were provided. In the presence of parabens, aerobic granules with good settleability, but with fragile and irregular structure, were grown. No significant effect of parabens on organic matter (>90%) and nitrogen (~70%) removal was evidenced. On the other hand, phosphorus removal was slightly impaired, although high removal efficiencies (~70%) were reached. High paraben removal efficiencies were achieved (>85%) in the AGS system, with methylparaben being the most recalcitrant compound. Concerning the removal mechanisms, biotransformation was the main mechanism in the removal of all parabens (85.5% for methylparaben and 100% for the others), whereas, apparently, adsorption played a role only in the removal of methylparaben. In addition, this compound was also suggested as a probable intermediate of the degradation of the larger alkyl-chain parabens. Lastly, regarding the microbial community, with the exception of Mycobacterium, the reactors shared the same genera, which may explain their comparable operational performances. Additionally, some genera that developed more in the presence of parabens may be related to their degradation. Therefore, although antimicrobial agents such as parabens compromised the granule structure, AGS system maintained a good operational performance and showed to be very efficient in paraben removal.


Downregulation of adiponectin system in granulosa cells and low levels of HMW adiponectin in PCOS.
The purpose of the study was to investigate changes in adiponectin system expression in granulosa cells (GCs) and high molecular weight adiponectin levels in serum and follicular fluid (FF) of 40 women with polycystic ovary syndrome (PCOS) compared to those in 40 women with normal ovary function. Adiponectin (Adipo), adiponectin receptor 1 (AdipoR1), and adiponectin receptor 2 (AdipoR2) messenger RNA (mRNA) expression levels were measured using quantitative real-time polymerase chain reaction (qRT-PCR). High molecular weight (HMW) adiponectin protein concentration was evaluated by ELISA method. Data were analyzed using Student's t test and one-way ANOVA in SPSS 21 software. At oocyte retrieval, FF was aspirated and GCs were obtained from a pooled collection of FF per each patient. PCR results showed expression of adiponectin, AdipoR1, AdipoR2, follicle-stimulating hormone receptor (FSHR), and luteinizing hormone receptor (LHR) in GCs. After controlling body mass index (BMI) values, qRT-PCR demonstrated a decreased expression of adiponectin system in GCs of PCOS patients compared to those in controls (p = 0.001). There was a strong positive correlation among AdipoR1 and AdipoR2 expression and also among FSH and LH receptor expression. (Both r = 0.8, p = 0.001). There were low levels of high molecular weight adiponectin in the serum of PCOS patients with controlled ovarian hyperstimulation (30.19 ± 4.3 ng/ml) compared to the controls (48.47 ± 5.9 ng/ml) and in the FF of PCOS patients with controlled ovarian hyperstimulation (7.86 ± 1.44 ng/ml) compared to the controls (14.22 ± 2.01 ng/ml; p = 0.02). Lower expression of adiponectin and its receptors in GCs might be an important manifestation in gonadotropin-stimulated PCOS patients which could influence the physiologic adiponectin roles such as interaction with insulin and LH in induction of GC gene expression.


Massive chemotherapy with non-frozen autologous bone marrow transplantation in 13 cases of refractory Hodgkin's disease.
A group of 13 patients with advanced, diffuse Hodgkin's disease, poorly responding to the most widely employed primary chemotherapy regimens, were treated with massive chemotherapy (MCH) followed by rescue with non-frozen autologous bone marrow infusion (ABMT). Complete remission (CR) was obtained in 8/13 patients (61.5%) and partial remission in two. Hematopoietic recovery occurred in 12 cases. These preliminary results would seem to indicate that MCH with non-frozen ABMT may be successfully used in patients with resistant or relapsed Hodgkin's disease.


Prevalence of complications among second-generation Japanese-American men with diabetes, impaired glucose tolerance, or normal glucose tolerance.
In a study sample of 229 second-generation Japanese-American (Nisei) men, 79 with normal glucose tolerance, 72 with impaired glucose tolerance (IGT), and 78 with non-insulin-dependent diabetes, we have determined prevalence rates for certain conditions (ischemic heart disease, peripheral vascular disease, hypertension, retinopathy, neuropathy, and nephropathy) associated with diabetes. All subjects participated in a 75-g oral glucose tolerance test. World Health Organization (WHO) diagnostic criteria and information from the subject's medical history and personal physician were used to classify the subjects. Retinopathy was observed only in diabetic men in the study sample (11.5% of diabetic men). Furthermore, it was observed only in men who were receiving drug treatment for diabetes--40.0% of insulin-treated and 17.2% of sulfonylurea-treated men. Electrophysiologic evidence of peripheral neuropathy was observed in 46.2% of diabetic men and in 4.0% of nondiabetic (normal and IGT) men. For diabetic men with fasting serum glucose greater than or equal to 140 mg/dl, 63.8% had peripheral neuropathy and 19.1% had retinopathy, whereas for diabetic men with fasting serum glucose less than 140 mg/dl, 19.4% had neuropathy and none had retinopathy. For diabetic men with a diabetes duration of greater than or equal to 10 yr, 72.7% had neuropathy and 31.8% had retinopathy; with a diabetes duration of 5-9 yr, 70.6% had neuropathy and 11.8% had retinopathy; and with a diabetes duration of less than 5 yr, 20.5% had neuropathy and none had retinopathy. Nephropathy was distinctly uncommon, and among the measurements of kidney function, only proteinuria was clearly abnormal with diabetes. Prevalence rates of hypertension, peripheral vascular disease, and ischemic heart disease were highest in Nisei men with diabetes, lowest in men with normal glucose tolerance, and intermediate in men with IGT.(ABSTRACT TRUNCATED AT 250 WORDS)


Dynamic access of the glucocorticoid receptor to response elements in chromatin.
Transcriptional activation as a rate-limiting step of gene expression is often triggered by an environmental stimulus that is transmitted through a signaling cascade to specific transcription factors. Transcription factors must then find appropriate target genes in the context of chromatin. Subsequent modulation of local chromatin domains is now recognized as a major mechanism of gene regulation. The interactions of transcription factors with chromatin structures have recently been observed to be highly dynamic, with residence times measured in seconds. Thus, the concept of static, multi-protein complexes forming at regulatory elements in the genome has been replaced by a new paradigm that envisages rapid and continuous exchange events with the template. These highly dynamic interactions are a property of both DNA-protein and protein-protein interactions and are inherent to every stage of the transcriptional response. In this review we discuss the dynamics of a nuclear receptor, and its transcriptional response in the chromatin context.


Structured transverse orbital angular momentum probed by a levitated optomechanical sensor.
The momentum carried by structured light fields exhibits a rich array of surprising features. In this work, we generate transverse orbital angular momentum (TOAM) in the interference field of two parallel and counter-propagating linearly-polarised focused beams, synthesising an array of identical handedness vortices carrying intrinsic TOAM. We explore this structured light field using an optomechanical sensor, consisting of an optically levitated silicon nanorod, whose rotation is a probe of the optical angular momentum, which generates an exceptionally large torque. This simple creation and direct observation of TOAM will have applications in studies of fundamental physics, the optical manipulation of matter and quantum optomechanics.


Gene therapy researchers' assessments of risks and perceptions of risk acceptability in clinical trials.
Although recent clinical trials have demonstrated the increasing promise of gene therapy, they have also illustrated the difficulties of assessing risks, given the inherent uncertainty of trial outcomes. An international survey was conducted to investigate gene therapy researchers' perceptions and assessments of risks in clinical trials. Data from respondents (n = 156) demonstrated researchers' perceptions of clinical context and the strength of preclinical evidence strongly influenced risk assessments and judgments of acceptable risk levels. Professional experience in clinical care, and particularly care of children, predicted favorable attitudes toward nonanimal preclinical models and trial initiation when sub-optimal treatments were available. The potential for adverse events to impact negatively on the gene therapy field and on public trust were relevant considerations when planning a trial. Decisions about clinical trials appear to be influenced not only by the clinical context and preclinical evidence, but also subjective factors reflecting the experience of researchers, value-judgments about risk and benefit, and attitudes toward preclinical models, uncertainty, adverse events, and the perceived needs of patients. It is clear that risk assessment in clinical research involves moral and scientific judgment. Identifying moral assumptions and qualitative assessments underpinning the design and conduct of research may facilitate future decision-making in clinical trials.


Maternal uterine artery Doppler studies at high altitude and sea level.
To determine uterine artery impedance using Doppler in the second and third trimesters at sea level and at high altitude. Uterine artery resistance and pulsatility indices (RI and PI, respectively) were obtained by Doppler velocimetry from 242 women in Cerro de Pasco (4300 m altitude) and 200 women in Lima (sea level), all with normal singleton pregnancies between 14 and 40 weeks of gestation. Impedance indices at high altitude and sea level were compared using fractional polynomial regression analysis. Impedance to uterine artery blood flow was lower at high altitude than at sea level (for PI ratio Lima/Cerro de Pasco = 1.06; P = 0.011). If gestation bands were compared, the difference was significant up to 25 weeks. At high altitude, pregnancy is associated with lower uteroplacental impedance than at sea level. This may reflect a compensatory mechanism of uteroplacental development to lower oxygen tension associated with altitude.


Influence of dose, repeated treatment and batch of hormone on ovarian response in heifers treated with PMSG.
The effect of two dose levels (1000 and 2000 i.u.) of three different commercially available batches of PMSG on the ovarian response (ovulations and follicles greater than 10 mn) of 42 heifers was examined in a randomized incomplete block experiment. Each animal was subjected to two consecutive but different treatments. A significant effect of dose was observed and there were fewer ovulations, but no reduction in the number of follicles, after the second PMSG treatment. There was no evidence that the ovarian response was affected by the PMSG batch used.


Adenoma Malignum Presenting With Profound Hyponatremia.
Adenoma malignum of the cervix (also referred to as minimal deviation adenocarcinoma) is a rare malignancy. Although previous reports have described adenoma malignum presenting with mucinous vaginal discharge, no reports to our knowledge have described a presentation with profound hyponatremia due to fluid losses. We present a case of adenoma malignum in a 52-year-old woman who presented with substantial watery vaginal discharge and profound hyponatremia. Despite being a rare cervical tumour, adenoma malignum should be considered in the differential diagnosis of watery vaginal discharge. This tumour can present with severe electrolyte disturbances.


Blood lead levels and childhood asthma.
To measure blood lead levels in children (5-14 y) with bronchial asthma, and correlate with asthma severity. Cross-sectional analytical. Pediatric Allergy and Immunology Clinic of a Childrens hospital in Cairo, Egypt. 200 children (127 males) with bronchial asthma and 125 age- and sex-matched healthy controls (80 males). Blood lead levels were measured by atomic absorption spectrophotometer technique, and were subsequently correlated with asthma severity. No significant difference in mean (SD) blood lead levels was observed between children with asthma [13.3 (4.8) ug/dL] and control group [11.4 (3.9) ug/dL]. 190 children (58.5%) had elevated blood lead levels (>10 ug/dL), with no significant difference between patients (60%) and controls (56%). Patients with elevated blood lead levels had significantly higher frequency of eosinophilia (66.7%) and increased total immunoglobulin E (83.3%) compared to other patients with blood lead levels <10ug/dL (10% and 43.8%, respectively). Patients of asthma with elevated blood lead levels had higher grades of severity of asthma compared to those with blood lead levels <10 ug/dL. Blood lead levels are not significantly associated with diagnosis of asthma but elevated blood lead levels seem to be associated with increased asthma severity and higher frequency of eosinophilia and elevated immunoglobulin E levels.


Solvation and Ion-Pairing Effects of Choline Acetate Electrolyte in Protic and Aprotic Solvents Studied by NMR Titrations.
Choline-based electrolytes have been proposed as environmentally friendly and low-cost alternatives for secondary zinc air batteries. Choline acetate [Ch]+ [OAc]- in protic (D2 O) and aprotic (DMSO-d6 ) solvents has been studied by means of concentration-dependent 1 H NMR, viscosity, and density measurements. The viscosities have been calculated on the basis of the Jones-Dole equation and showed that the dominant contribution originates from short-range ion-solvent interactions. Site-specific association affinities were assigned from NMR chemical shift titrations. In DMSO-d6 , the hydroxyl group of choline was found to have the smallest dissociation constant followed by the methyl group of acetate. The corresponding Gibbs energies at low concentration were found to be in agreement with a solvent-separated ion pair (2SIP) configuration, whereas at concentrations above 300 mM, a solvent-shared ion pair (SIP) configuration was assigned. For [Ch]+ [OAc]- in D2 O, association effects were found to be weaker, attributed to the high dielectric constant of the solvent. On time scales on the order of 100 ms, NMR linewidth perturbations indicated a change in the local rotational dynamics of the ions, attributed to short-range cation-solvent interactions and not to solvent viscosity. At 184 mM, ∼ 40 % of the cations in DMSO-d6 and ∼ 10 % in D2 O were found to exhibit short-range interactions, as indicated by the linewidth perturbations. It was found that at about 300 mM, the ions in DMSO-d6 exhibit a transition from free to collective translational dynamics on time scales on the order of 400 ms. In DMSO-d6 , both ions were found to be almost equally solvated, whereas in D2 O solvation of acetate was stronger, as indicated by the obtained effective hydrodynamic radii. For [Ch]+ [OAc]- in DMSO-d6 , the results suggest a solvent-shared ion association with weak H-bonding interactions for concentrations between 0.3-1 M. Overall, the extent of ion association in solvents such as DMSO is not expected to significantly limit charge transport and hinder the performance of choline-based electrolytes.


Targeting cancer glycosylation repolarizes tumor-associated macrophages allowing effective immune checkpoint blockade.
Immune checkpoint blockade (ICB) has substantially improved the prognosis of patients with cancer, but the majority experiences limited benefit, supporting the need for new therapeutic approaches. Up-regulation of sialic acid-containing glycans, termed hypersialylation, is a common feature of cancer-associated glycosylation, driving disease progression and immune escape through the engagement of Siglec receptors on tumor-infiltrating immune cells. Here, we show that tumor sialylation correlates with distinct immune states and reduced survival in human cancers. The targeted removal of Siglec ligands in the tumor microenvironment, using an antibody-sialidase conjugate, enhanced antitumor immunity and halted tumor progression in several murine models. Using single-cell RNA sequencing, we revealed that desialylation repolarized tumor-associated macrophages (TAMs). We also identified Siglec-E as the main receptor for hypersialylation on TAMs. Last, we found that genetic and therapeutic desialylation, as well as loss of Siglec-E, enhanced the efficacy of ICB. Thus, therapeutic desialylation represents an immunotherapeutic approach to reshape macrophage phenotypes and augment the adaptive antitumor immune response.


Patterns of obsessive-compulsive symptoms and social function in schizophrenia.
Research has alternately found that obsessive and compulsive (OC) symptoms in schizophrenia are associated with graver and lesser levels of negative symptoms. One possible explanation is that there are two distinct groups of persons with OC symptoms: those with cognitive deficits and high levels of negative symptoms and those who generally function well and have low levels of negative symptoms. To examine this question, we performed a cluster analysis on 66 persons with schizophrenia spectrum disorders on the basis of their level of obsessive-compulsive phenomena and global psychosocial function. Four groups were found: high OC/good function (n=9), non-OC/poor function (n=25), non-OC/moderate function (n=20), and high OC/poor function (n=12). A MANCOVA controlling for age found significant group differences on assessments of negative symptoms, executive function and attention among groups. As predicted, the high OC/poor function group had significantly poorer attention than any other group and poorer executive function than either non-OC group. The high OC/good function had lower levels of negative symptoms than either non-OC group. Implications for research and rehabilitation are discussed.


Substrate specificity of feline and canine herpesvirus thymidine kinase.
The thymidine kinases from feline herpesvirus (FHV TK) and canine herpesvirus (CHV TK) were cloned and characterized. The two proteins are closely sequence-related to each other and also to the herpes simplex virus type 1 thymidine kinase (HSV-1 TK). Although FHV TK and CHV TK have a level of identity of 31 and 35%, respectively, with HSV-1 TK, and a general amino acid similarity of approximately 54% with HSV-1 TK, they do not recognize the same broad range of substrates as HSV-1 TK does. Instead the substrate recognition is restricted to dThd and pyrimidine analogs such as 1-beta-d-arabinofuranosylthymine (araT), 3'-azido-2',3'-dideoxythymidine (AZT) and (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU). FHV TK and CHV TK differ in substrate recognition from mammalian cytosolic thymidine kinase 1 (TK1) in that TK1 does not phosphorylate BVDU and they also differ from mammalian mitochondrial thymidine kinase 2 (TK2), which, in addition to thymidine and thymidine analogs also phosphorylates dCyd. Although the nucleoside analog BVDU was a good substrate for FHV and CHV TK, the compound was poorly inhibitory to virus-induced cytopathic effect in FHV- and CHV-infected cells. The reason is likely the poor, if any, thymidylate kinase activity of FHV and CHV TK, which in HSV-1 TK-expressing cells convert BVDU-MP to its 5'-diphosphate derivative.


A double-blind, placebo-controlled trial of topical I,25-dihydroxycholecalciferol in psoriasis.
In a double-blind trial of topical I,25-dihydroxycholecalciferol in 47 patients with psoriasis no benefit was shown compared with placebo.


Effect of bone cylinder length on distraction osteogenesis in the rabbit tibia.
The viability and osteogenic potential of bone cylinders for bone transport was investigated in one tibia of 18 mature male New Zealand rabbits. The length of the bone cylinder was equal to or twice that of the diameter of the tibia. The cylinder was cut subperiosteally with an externally cooled oscillating saw from a lateral approach, after a specific unilateral external fixator had been applied. To simulate bone transport, one end of the cylinder was fixed to the distal bone stump by a cerclage wire and healing and revascularization was prevented by an interposed expanded polytetrafluoroethylene membrane. The periosteum was re-adapted and sutured, and distraction began 10 days postoperatively at 0.25 mm/12 hours for 22 days. New bone formation in the distraction gap was quantified by dual energy x-ray absorptiometry and by computer-assisted histomorphometry of polyfluorochrome-labeled undecalcified bone sections and corresponding microradiographs. In half of the animals with each size cylinder, osseous bridging occurred, so the findings on distraction osteogenesis are reported only for the remaining nine animals. Generally, centripetal mineralization of the gap with two distinct zones of ripening bone structures and a central radiolucent fibrocartilaginous zone could be distinguished. Neither absorptiometry nor histomorphometry showed significant differences in the overall amount of this new bone formation for the bone cylinders of two different lengths. However, osteogenesis was significantly greater at the proximal end than at the cylinder. New bone was formed predominantly from endosteal sites in the smaller cylinders and from periosteal sites in the larger cylinders. Histologically, there was complete necrosis of both sizes of cylinders, followed by revitalization through newly formed vascular channels.(ABSTRACT TRUNCATED AT 250 WORDS)


Testosterone affects neural gene expression differently in male and female juncos: a role for hormones in mediating sexual dimorphism and conflict.
Despite sharing much of their genomes, males and females are often highly dimorphic, reflecting at least in part the resolution of sexual conflict in response to sexually antagonistic selection. Sexual dimorphism arises owing to sex differences in gene expression, and steroid hormones are often invoked as a proximate cause of sexual dimorphism. Experimental elevation of androgens can modify behavior, physiology, and gene expression, but knowledge of the role of hormones remains incomplete, including how the sexes differ in gene expression in response to hormones. We addressed these questions in a bird species with a long history of behavioral endocrinological and ecological study, the dark-eyed junco (Junco hyemalis), using a custom microarray. Focusing on two brain regions involved in sexually dimorphic behavior and regulation of hormone secretion, we identified 651 genes that differed in expression by sex in medial amygdala and 611 in hypothalamus. Additionally, we treated individuals of each sex with testosterone implants and identified many genes that may be related to previously identified phenotypic effects of testosterone treatment. Some of these genes relate to previously identified effects of testosterone-treatment and suggest that the multiple effects of testosterone may be mediated by modifying the expression of a small number of genes. Notably, testosterone-treatment tended to alter expression of different genes in each sex: only 4 of the 527 genes identified as significant in one sex or the other were significantly differentially expressed in both sexes. Hormonally regulated gene expression is a key mechanism underlying sexual dimorphism, and our study identifies specific genes that may mediate some of these processes.


Highly stable lithium sulfur batteries enhanced by flocculation and solidification of soluble polysulfides in routine ether electrolyte.
Lithium-sulfur batteries (LSBs) are among the most promising next-generation high energy density energy-storage systems. However, practical application has been hindered by fundamental problems, especially shuttling by the higher-order polysulfides (PSs) and slow redox kinetics. Herein, a novel electrolyte-based strategy is proposed by adding an ultrasmall amount of the low-cost and commercially available cationic antistatic agent octadecyl dimethyl hydroxyethyl quaternary ammonium nitrate (SN) into a routine ether electrolyte. Due to the strong cation-anion interaction and bridge-bonding with SN, rapid flocculation of the soluble polysulfide intermediates into solid-state polysulfide-SN sediments is found, which significantly inhibited the adverse shuttling effect. Moreover, a catalytic effect was also demonstrated for conversion of the polysulfide-SN intermediates, which enhanced the redox kinetics of Li-S batteries. Encouragingly, for cells with only 0.1 % added SN, an initial specific capacity of 783.6 mAh/g and a retained specific capacity of 565.7 mAh/g were found at 2C after 200 cycles, which corresponded to an ultralow capacity decay rate of only 0.014 % per cycle. This work may provide a simple and promising regulation strategy for preparing highly stable Li-S batteries.


Evaluation of clinicoradiological outcomes of lateral vertebral notch referred pedicular screws entry point in subaxial cervical spine by freehand technique.
Cervical pedicle screws (CPSs), though associated with complications and steep learning curve, have significantly increased strength and stability as compared to any other posterior instrumentation methods. Using anatomical referral techniques, pedicle screws can be inserted safely with a high accuracy rate obviating the need for anterior stabilization. Our present study aims to investigate the safety and outcomes of lateral vertebral notch (LVN) referred entry point for subaxial CPSs by freehand technique. We retrospectively studied 22 patients who underwent CPS fixation. Computed tomography (CT) scan with angiography was done in each case to know the anatomy, characteristics, and anomalies of each pedicle. Postoperative CT scan was done to look for any breach in cervical pedicles. We used free hand technique for insertion of subaxial cervical pedicles taking LVN as a reference point. The authors used the medial wall of the cervical pedicles as a safe guide for the probes that walked along it. Eighty screws were inserted in total in the study group. Mean angle of screw with sagittal axis of vertebrae was 23.43° ± 9.279°. Range of angle used was 6°-40°. Perforation occurred in 11 pedicle screws: C3 (2 out of 8, 25%), c5 (3 out of 20, 15%), and c4 (4 of 22, 18%). Out of 11 perforations, four were complete and seven were partial perforations. One complete medial perforation was associated with radiculopathy that required revision. The technique described in the study can be considered relatively safe, easy, and reliable method of inserting cervical pedicle screws with high accuracy (86.25%) and low complication rates (1.25%). However, meticulous preoperative planning is required.


Deletion of autophagy related, ATG1 and F-box motif encoding YDR131C, together, lead to synthetic growth defects and flocculation behavior in Saccharomyces cerevisiae.
Ubiquitin proteasome system (UPS) and autophagy both pathways are involved in clearing the nonessential cellular components and also crosstalk during cellular response to normal and stress conditions. The F-box motif proteins constitute the SCF-E3 ligase complex of the UPS pathway in Saccharomyces cerevisiae and are involved in the substrate recruitment for ubiquitination. The ATG1 encoded Atg1p, a conserved serine-threonine kinase is crucial for the autophagy process. Here in this study, we report that loss of F-box motif encoding YDR131C and ATG1 together results in growth defects, floc formation, sensitivity to hydroxyurea, methyl methanesulfonate, and hydrogen peroxide. Both the genes also interact with the flocculation-related genes (FLO) and associate with gene ontology terms "ubiquitin-protein transferase activity" and "cellular catabolic process." Based on in silico analysis and experimental evidence we conclude that YDR131C and ATG1 function in parallel pathways to regulate the growth, flocculation, and stress response.


Mismatch negativity in common marmosets: Whole-cortical recordings with multi-channel electrocorticograms.
Mismatch negativity (MMN) is a component of event-related potentials (ERPs) evoked by violations of regularity in sensory stimulus-series in humans. Recently, the MMN has received attention as a clinical and translatable biomarker of psychiatric disorders such as schizophrenia, and for the development animal models of these psychiatric disorders. In this study, we investigated the generation of MMN in common marmosets, which are an important non-human primate model with genetic manipulability. We recorded the electrocorticograms (ECoGs) from two common marmosets with epidurally implanted electrodes covering a wide range of cortical regions. ECoG recordings were conducted in a passive listening condition with a roving oddball paradigm. We compared the ERPs evoked by repeatedly presented standard stimuli and those evoked by the deviant stimuli. Significant differences in the ERPs were observed in several cortical areas. In particular, deviant stimuli elicited larger negative activity than standard stimuli in the temporal area. In addition, the latency and polarity of the activity were comparable to human MMNs. This is thus the first report of MMN-like activity in common marmosets. Our findings have the potential to advance future gene-manipulation studies that aim to establish non-human primate models of schizophrenia.


Ontogenesis of immunocytochemically demonstrable somatotrophs in the adenohypophyseal pars distalis of the developing chick embryo.
Growth hormone (GH)-containing cells in the hypophyseal pars distalis of the chick embryo were identified immunohistochemically using anti-chicken GH sera. GH cells are first demonstrable in Rathke's Pouch as early as Day 4.5 of incubation. By Day 9.5, when the two lobes (rostral and caudal) of the pars distalis are easily recognized, GH cells are confined exclusively to the caudal lobe. Although the number of GH cells increases gradually during embryonic development, there is a statistically significant difference between Days 10.5 and 12.5 in both the cellular density and the percentage of somatotrophs. GH cells, which contain coarse granules evenly distributed throughout the cytoplasm, varied in diameter from 9.3 micron on Day 4.5 to 11.8 micron on Day 20.5, while the nuclear diameter of these cells increased from 2.8 micron on Day 4.5 to 4.9 micron on Day 20.5. There was a statistically significant difference in the nuclear/cytoplasmic ratio between Days 4.5 and 13.5 and between Days 13.5 and 20.5 of incubation. Aspects of the regulation of growth hormone synthesis and secretion in the chick embryo are discussed.


Prediction of tubulo-interstitial injury by Doppler ultrasound in glomerular diseases: value of resistive and atrophic indices.
Doppler ultrasound is increasingly used in Nephrology for diagnosis of renovascular hypertension and evaluation of allograft dysfunction. However, its utility in glomerular disease remains controversial. Using Doppler Ultrasound, we prospectively tested the role of resistive and atrophic indices in predicting tubulointerstitial lesions in patients with glomerular disease as demonstrated by renal biopsy. Seventy one patients with primary or secondary glomerular diseases were examined by Doppler ultrasonography immediately before renalbiopsy. The resistive and atrophic indices (RI & AI) were calculated and compared with histologic changes in biopsy specimen. Receiver Operator Characteristics analysis showed RI of 0.60 as an optimal value for discriminating tubulointerstitial changes with sensitivity of 82.7% and specificity of 92%. An AI of 0.65 was shown to be optimal for discriminating tubulointerstitial injury with sensitivity of 69.2% and specificity of 85%. The combination of the two indices had not been found to be superior to either index alone. There was a significant correlation between atrophic and resistive indices. (r=0.358, p< 0.01). It was observed that older age, smoking, elevated AI and RI, low GFR, high serum cholesterol and Hypertension were found to be significantly associated with the presence of tubulointerstitial injury in the univariate analysis whereas only elevated AI and RI were found to predict tubulointerstitial injury in multivariate analysis. Measurement of RI by Doppler ultrasound can be considered as a supplementary diagnostic tool in glomerular diseases to predict the severity of tubulointerstitial injury.


MDM2, MDMX, and p73 regulate cell-cycle progression in the absence of wild-type p53.
The p53 tumor suppressor protein, known to be critically important in several processes including cell-cycle arrest and apoptosis, is highly regulated by multiple mechanisms, most certifiably the Murine Double Minute 2-Murine Double Minute X (MDM2-MDMX) heterodimer. The role of MDM2-MDMX in cell-cycle regulation through inhibition of p53 has been well established. Here we report that in cells either lacking p53 or expressing certain tumor-derived mutant forms of p53, loss of endogenous MDM2 or MDMX, or inhibition of E3 ligase activity of the heterocomplex, causes cell-cycle arrest. This arrest is correlated with a reduction in E2F1, E2F3, and p73 levels. Remarkably, direct ablation of endogenous p73 produces a similar effect on the cell cycle and the expression of certain E2F family members at both protein and messenger RNA levels. These data suggest that MDM2 and MDMX, working at least in part as a heterocomplex, may play a p53-independent role in maintaining cell-cycle progression by promoting the activity of E2F family members as well as p73, making them a potential target of interest in cancers lacking wild-type p53.


Dosages of Nutrient Supplements and Potential Long-Term Toxicity in Attention-Deficit/Hyperactivity Disorder Micronutrient Study.
We read with interest the article by Johnstone et al.1 reporting their vitamin-mineral randomized trial that found that children with attention-deficit/hyperactivity disorder (ADHD) showed global benefit over placebo by blinded clinician rating, but not by parent-report CASI-5 composite rating in a population with ADHD and irritability. Because some of the mineral dosing was in potentially toxic ranges, we sought to examine the trial findings. Given that the producing company is promoting their supplement for long-term use,2 the scientific and consumer communities might value some additional information about potential toxicity from long-term dosing.


Prolactin, cortisol, and antidepressant treatment.
In four depressed patients with abnormal dexamethasone suppression test results before treatment, plasma prolactin levels significantly increased after successful amitriptyline therapy. Such an increase did not take place in five depressed patients with normal dexamethasone suppression test findings.


[European Academy for Medicine of Ageing (EAMA)].
The European Academy for Medicine of Ageing was founded in 1995 by a nucleus group of European professors: Duursma (Utrecht, NL), Evans (Oxford, GB), Michel (Geneve, CH) and Stähelin (Basel, CH). The aim was to get an adequate postgraduate training under the auspices of an international faculty. A whole curriculum consists of four one-week sessions over a period of two years. In each session student's state of the art lectures, group discussions followed by plenary presentations, as well as the lectures of members of the Executive Board and invited experts are scored and analyzed. Meanwhile EAMA is in its sixth session. The evaluation (comparison of first with last part) shows its great success with an overall improvement of 32%, content of take home messages (28%), scientific lectures (31%) and techniques of presentation (37%). The EAMA has achieved one of its major goals to attract young geriatricians not only from Europe but also from North and Latin America, Africa and Near East. Several networking groups have been established on special fields of interest (e. g. falls, dementia, diabetes mellitus). A recently performed survey showed that about two thirds of the former students have meanwhile taken over a leading (academic) position in geriatrics in their countries.


Stability and Differences in Empathy Between Men and Women Medical Students: a Panel Design Study.
Empathy is central to the physician-patient relationship, and affects clinical outcomes. There is uncertainty about the stability of empathy in medical students over the course of medical school, as well as differences in empathy between men and women. A panel study design was used to follow first year through fourth year medical students (MS1-4) during the 2018-2019 school year. Empathy was measured using the interpersonal reactivity index (IRI), a self-report scale that separates empathy into a cognitive perspective taking (PT) and affective empathic concern (EC) component. A total of 631 (359 women and 272 men) from 970 students (65% response rate) responded to a baseline survey, and a total of 536 students (300 women and 236 men) from 970 students (55% response rate) responded to surveys throughout the year. At baseline, women had significantly higher EC scores than men (p < 0.0001), with no significant PT difference between men and women (p > 0.05). These differences were stable for all MS cohorts. Women had self-reported higher affective empathy (EC component) than men, while there were no differences in cognitive empathy (PT component). We discuss these data in the context of defining gender vs. sex, socialized gender stereotypes, and implications for future research.


Estimating fetal age using multiple parameters: a prospective evaluation in a racially mixed population.
This study was designed to evaluate the accuracy of regression models for menstrual age prediction using single versus multiple fetal ultrasonographic measurements (biparietal diameter, head circumference, abdominal circumference, and femur length). The models tested had been previously developed from a study of middle-class white patients in a private hospital. The current study population consisted of 300 indigent black and Hispanic patients seen in a county hospital. This study demonstrated prospectively that the use of multiple parameters in estimating fetal age offers a significant advantage over any single parameter used alone and that the regression equations developed from a middle-class white population appear to be applicable to fetuses from a population with different socioeconomic and racial characteristics.


Genotoxicity of three pyridine compounds to L5178Y mouse lymphoma cells.
The L5178Y mouse lymphoma assay was used to examine the potential mutagenicity of three halogenated pyridine compounds. Position effects of the halogen moiety and the role of metabolic activation were analyzed based on induced mutant frequency, gross chromosome aberrations, and micronuclei. Without activation, 2-chloropyridine, 3-chloropyridine, and 2-chloro-5-trifluoromethylpyridine produced a small increase in mutant frequency; only the 2-chloropyridine activity was significantly increased with activation. All three compounds were also clastogenic as demonstrated by increases in chromosome aberrations and micronuclei (except for 2-chloro-5-trifluoromethylpyridine which did not induce micronuclei either with or without activation).


Assessing the decoupling of economic growth from environmental impacts in the European Union: A consumption-based approach.
Pursuing a responsible and sustainable development, the United Nations urged to decouple economic growth from environmental impacts. Several European Union (EU) policies have been implemented towards such goal. Although multiple authors have evaluated the decoupling of the economic growth from the resource use or environmental concerns, the environmental assessment mostly focused on pressures rather than impacts, and used single indicators assumed to be a proxy of the overall effects on the environment. Furthermore, no studies were found using a process-based life cycle approach to quantify the environmental impacts of consumption. To solve such research gap, this paper assesses the decoupling in the EU focusing on potential environmental impacts, complementing a production-based approach with two options for accounting for the impacts of consumption. The aim of this paper is to evaluate the decoupling of the economic growth (in terms of Gross Domestic Product) from the environmental impacts due to EU-28 consumption, assessed by means of life cycle assessment (LCA). The decoupling is then assessed in impact terms rather than limited to pressures by using the Environmental Footprint (EF2017) indicators, which allows assessing 16 different impacts. The Consumption Footprint indicator quantified the environmental impacts of EU apparent consumption, including the territorial impacts (Domestic Footprint) and the embodied impacts in both imports and exports (Trade Footprint). The inventory of pressures for the trade component is compiled either with a bottom-up approach (process-based LCA of representative traded goods) or a top-down approach (input-output-based LCA). Methodological aspects influencing the decoupling assessment and the resulting outputs are presented and discussed. According to the results, the environmental impacts of EU-28 consumption showed decoupling during the last decades (2005-2014), between relative to absolute decoupling depending on the inventory modeling approach taken. Some countries showed higher decoupling levels than others displaying a heterogeneous map of EU-28 decoupling, which was led by acidification, particulate matter, land use and eutrophication impacts. Notwithstanding current limitations, the assessment of decoupling using consumption-based environmental indicators is very promising for supporting policy-making towards addressing the actual impacts driven by the EU production and consumption system.


Reversal of alcohol dependence-induced deficits in cue-guided behavior via mGluR2/3 signaling in mice.
Alcohol use disorders are associated with deficits in adaptive behavior. While some behavioral impairments that are associated with alcohol use disorders may predate exposure to drugs of abuse, others may result directly from exposure to drugs of abuse, including alcohol. Identifying a causal role for how alcohol exposure leads to these impairments will enable further investigation of the neurobiological mechanisms by which it acts to dysregulate adaptive behavior. In the present study, we examined the effects of chronic intermittent ethanol exposure (CIE) on the use of reward-paired cues to guide consummatory behaviors in a mouse model, and further, how manipulations of mGluR2/3 signaling-known to be dysregulated after chronic alcohol exposure-may alter the expression of this behavior. Adult male C57B/6J mice were trained to self-administer 10 % ethanol and exposed to CIE via vapor inhalation. After CIE exposure, mice were trained in a Pavlovian task wherein a cue (tone) was paired with the delivery of a 10 % sucrose unconditioned stimulus. The use of the reward-paired cue to guide licking behavior was determined across training. The effect of systemic mGluR2/3 manipulation on discrimination between cue-on and cue-off intervals was assessed by administration of the mGluR2/3 agonist LY379268 or the antagonist LY341495 prior to a testing session. Exposure to CIE resulted in reductions in discrimination between cue-on and cue-off intervals, with CIE-exposed mice exhibiting significantly lower consummatory behavior during reward-paired cues than air controls. In addition, systemic administration of an mGluR2/3 agonist restored the use of reward-paired cues in CIE-exposed animals without impacting behavior in air controls. Conversely, administration of an mGluR2/3 antagonist mimicked the effects of CIE on cue-guided licking behavior, indicating that mGluR2/3 signaling can bidirectionally regulate the ability to use reward-paired cues to guide behavior. Together, these data suggest that chronic ethanol exposure drives impairments in the ability to use reward-paired cues to adaptively regulate behavior and that mGluR2/3 receptors represent a therapeutic target for restoration of these deficits in behavioral control in the alcoholic.


Percutaneous Cryoablation for Recurrent Head and Neck Tumors.
To report techniques and results of 16 cryoablation procedures in 11 patients treated for recurrent head and neck cancer. This retrospective study reviewed 11 consecutive patients with head and neck cancer recurrence after primary treatment by surgery and radiotherapy, treated with cryoablation between 2016 and 2020. Efficacy was measured by local control rate evaluated on MRI or/and PET. Tumor characteristics, number of cryoprobes, thermoprotective measures and complications were documented. Sixteen cryoablation procedures were performed in 11 patients with head and neck cancer recurrence after surgery or radiotherapy, deemed ineligible for classic salvage treatment. Among 11 patients, four were treated for an epidermoid carcinoma, four for an adenocarcinoma and three for other types: 1 muco-epidermoid carcinoma, 1 adenoid cystic carcinoma and 1 esthesioneuroblastoma, 10/11 patients had prior surgery, 7/11 patients had prior chemotherapy and 3/11 patients had prior radiotherapy. Median number of cryoprobes was 4, [IQR, 3-6 cryoprobes], thermoprotective measures to protect surrounding organs were required for 10/16 procedures. After cryoablation, local control rate was 45.4% at a mean follow-up of 11.7 months (range 3-34 months). Among the 16 cryoablation procedures, four resulted in complications, two were considered major complications: one septic shock on inhalation pneumopathy during extubation, requiring intensive care; and one dysphonia due to a recurrent nerve injury. Cryoablation as a salvage treatment for recurrence of head and neck tumors after surgery and/or radiotherapy is an effective option, especially for patients that cannot benefit from salvage surgery.


Lysobacter sedimenti sp. nov., Isolated from the Sediment, and Reclassification of Luteimonas lumbrici as Lysobacter lumbrici comb. nov.
A bacterium, designated 50T was isolated from the sediment of a pesticide plant in Shandong Province, PR China. The strain was non-motile, Gram stain-negative, rod shaped and grew optimally on NA medium at 30 °C, pH 7.5 and with 0% (w/v) NaCl. Strain 50T showed the highest 16S rRNA gene sequence similarity with Lysobacter pocheonensis Gsoil 193T (96.7%), followed by Luteimonas lumbrici 1.1416T (96.5%). Phylogenetic analyses based on 16S rRNA indicated that strain 50T and Luteimonas lumbrici 1.1416T were clustered with the genus of Lysobacter and formed a subclade with Lysobacter pocheonensis Gsoil 193T. In the phylogenetic analysis based on the genome sequences, strain 50T and Luteimonas lumbrici 1.1416T were also clustered with the type strains of the genus Lysobacter. The obtained ANI and the dDDH value between 50T and Luteimonas lumbrici 1.1416T were 80.6% and 24.0%, respectively. The respiratory quinone was ubiquinone-8 (Q-8), and the major cellular fatty acids were iso-C15: 0 (31.7%), summed feature 9 (iso-C17:1 ω9c or C16:0 10-methyl) (23.7%), iso-C17:0 (14.3%) and iso-C16:0 (12.6%). The major polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine and unidentified aminophospholipid, unidentified phospholipid and unidentified lipid. The genomic DNA G + C content was 69.5 mol%. According to the phenotypic, chemotaxonomic and phylogenetic analyses, strain 50T represents a novel species of the genus Lysobacter, for which the name Lysobacter sedimenti sp. nov. is proposed, with strain 50T (= KCTC 92088T = CCTCC AB 2022035T) as the type strain. In this study, it is also proposed that Luteimonas lumbrici should be transferred to the genus Lysobacter as Lysobacter lumbrici comb. nov. The type strain of Lysobacter lumbrici is 1.1416T (= KCTC 62979T = CCTCC AB 2018348T).


Attracting Enantiomers: Chiral Analytes That Are Simultaneously Shift Reagents Allow Rapid Screening of Enantiomeric Ratios by NMR Spectroscopy.
The rapid and direct determination of enantiomeric ratios is of increasing interest due to the significantly reduced effort compared to chromatographic methods and the large number of analytes, for instance in enantioselective catalysis. Current strategies include colorimetric assays, (a)chiral solvating reagents for NMR spectroscopy and metal complexes for CD sensing. We report the determination of enantiomeric ratios based on the self-induced diastereomeric anisochronism (SIDA) effect. Alanine derivatives that represent chiral products of enantioselective catalysis, such as the well-established hydrogenation of dehydroamino acids, were investigated. The SIDA effect was significantly enhanced by attachment of 3,5-dinitrobenzoyl π-π interactions sites. This simple modification enabled simultaneous determination of enantiomeric ratios and conversions by NMR spectroscopy.


Preparation of magnetic graphene @polydopamine @Zr-MOF material for the extraction and analysis of bisphenols in water samples.
In this work, a simple method for the extraction and analysis of bisphenols in environmental samples was presented. And the prepared zirconium-based magnetic MOFs (magG@PDA@Zr-MOF) were used as the sorbents for the magnetic solid-phase extraction. With the simple solvothermal reaction and sol-gel method, the prepared material showed great characteristics of large surface area, homogeneous pore size, good magnetic responsivity and super-hydrophilicity. The large surface area provided abundant sites to extract target compounds; the magnetic property could simplify the whole extraction procedure; and the hydrophilicity improved the dispersibility of the material in matrix. Here, various extraction parameters were optimized, including amounts of sorbents, adsorption time, species of elution solvents and desorption time. The whole extraction procedure could be accomplished in 30 min. And under the optimized conditions, method validations were also studied, such as linearity, the limit of detection and recovery. Finally, the prepared material was used in real water samples. The results showed this material had good potential as the sorbent for the extraction of targets in environmental water samples.


Listeriosis: an uncommon opportunistic infection in patients with acquired immunodeficiency syndrome. A report of five cases and a review of the literature.
Between January 1985 and March 1986, five cases of listeriosis were reported in Los Angeles County in patients with the acquired immunodeficiency syndrome (AIDS). All patients were homosexual men with no other risk factors for AIDS. Two patients had sepsis only, two patients had sepsis and meningitis, and one patient had sepsis and signs of meningitis. Sixty percent of the cases (three patients) had a prior or concurrent gastrointestinal illness. Eighty percent of the cases (four patients) also had no prior history of antibiotic administration. Both of these findings may have predisposed these AIDS patients to be at increased risk for listeriosis. Although listeriosis is an infrequent illness in AIDS patients, people with AIDS or human immunodeficiency virus infection should probably refrain from ingesting food items associated with listeriosis. These food items include improperly pasteurized dairy products, and raw fruits and vegetables not properly washed.


Enantiomeric 8,4'-type oxyneolignans from the root barks of Ailanthus altissima (Mill.) Swingle and their neuroprotective effects against H2O2-induced SH-SY5Y cells injury.
Ailanthus altissima Swingle is a deciduous tree, belonging to the Simaroubaceae family. Phytochemical investigation of the root barks of A. altissima showed the presence of eight pairs of enantiomeric 8,4'-type oxyneolignans (1a/1b-8a/8b) including nine undescribed compounds (1b, 2a, 3a/3b, 4a/4b, 5b, 7b, 8a). Their structures were elucidated by comprehensive spectroscopic analyses, and their absolute configurations were determined by comparison of the experimental and quantum chemical calculations of electronic circular dichroism (ECD) curves. In addition, their neuroprotective effects against H2O2-induced oxidative stress in human neuroblastoma SH-SY5Y cells were investigated. Among them, 4a, 4b, and 8b exhibited moderate neuroprotective activity.


NLRP2 inhibits cell proliferation and migration by regulating EMT in lung adenocarcinoma cells.
Nucleotide-binding oligomerization domain-like receptors (NLRs) are crucial types of innate immune sensors and well known for their critical roles in the immune system. However, how NLRP2 functions in the progression of cancer is largely unknown. Here, we identified NLRP2 as an antioncogene in lung adenocarcinoma (LUAD) cells. Gain- and loss-of-function studies revealed that NLRP2 silencing promoted cell proliferation and migration by stimulating NF-kB signaling in the microenvironment, which induced epithelial-to-mesenchymal transition (EMT) phenotype and cytoskeleton reorganization in LUAD cells. The addition of the NF-kB inhibitor rescued the function of NLRP2 on EMT. Moreover, NLRP2 increased the level of cofilin phosphorylation and repressed subsequent F-actin reorganization. Consistently, the in vivo study showed that NLRP2 played an inhibitory role in forming metastasis foci. Taken together, NLRP2 inhibited cell proliferation and migration by regulating EMT in LUAD cells, demonstrating the essential function of NLRP2 in the development of LUAD.


Effect of age at cochlear implantation and at exposure to Cued Speech on literacy skills in deaf children.
The aim of this study was to investigate how age at cochlear implantation (CI) and age at exposure to Cued Speech (CS, Manual system that resolves the ambiguity inherent lipreading) could impact literacy skills in deaf children. Ninety deaf children fitted with CI (early vs late) and exposed to CS (early vs late) from primary schools (from Grade 2 to Grade 5) took part in this study. Five literacy skills were assessed: phonological skills through phoneme deletion, reading (decoding and sentence comprehension), word spelling and vocabulary. The results showed that both age at CI and age at first exposure to CS had some influence on literacy skills but there was no interaction between these factors. This implies that the positive effects of age at CI, especially on all literacy skills in the younger children, were not strengthened by age at exposure to CS.


Erratum: Schillaci MA. 2015. Letter to the Editor: Body Mass as a Confounding Variable When Predicting Group Size from Orbit Diameter and Neocortex Ratio. Am J Phys Anthropol. 158:170-171. DOI: 10.1002/ajpa.22781.
In Table 2 of the original publication the first column was incorrectly labeled as the variable sexual size dimorphism (SSD), rather than orbital aperture diameter (OAD). The corrected Table appears below.


Method for estimation of apoptotic cell fraction of cytotherapy using in vivo fluorine-19 magnetic resonance: pilot study in a patient with head and neck carcinoma receiving tumor-infiltrating lymphocytes labeled with perfluorocarbon nanoemulsion.
Adoptive transfer of T cells is a burgeoning cancer therapeutic approach. However, the fate of the cells, once transferred, is most often unknown. We describe the first clinical experience with a non-invasive biomarker to assay the apoptotic cell fraction (ACF) after cell therapy infusion, tested in the setting of head and neck squamous cell carcinoma (HNSCC). A patient with HNSCC received autologous tumor-infiltrating lymphocytes (TILs) labeled with a perfluorocarbon (PFC) nanoemulsion cell tracer. Nanoemulsion, released from apoptotic cells, clears through the reticuloendothelial system, particularly the Kupffer cells of the liver, and fluorine-19 (19F) magnetic resonance spectroscopy (MRS) of the liver was used to non-invasively infer the ACF. Autologous TILs were isolated from a patient in their late 50s with relapsed, refractory human papillomavirus-mediated squamous cell carcinoma of the right tonsil, metastatic to the lung. A lung metastasis was resected for T cell harvest and expansion using a rapid expansion protocol. The expanded TILs were intracellularly labeled with PFC nanoemulsion tracer by coincubation in the final 24 hours of culture, followed by a wash step. At 22 days after intravenous infusion of TILs, quantitative single-voxel liver 19F MRS was performed in vivo using a 3T MRI system. From these data, we model the apparent ACF of the initial cell inoculant. We show that it is feasible to PFC-label ~70×1010 TILs (F-TILs) in a single batch in a clinical cell processing facility, while maintaining >90% cell viability and standard flow cytometry-based release criteria for phenotype and function. Based on quantitative in vivo 19F MRS measurements in the liver, we estimate that ~30% cell equivalents of adoptively transferred F-TILs have become apoptotic by 22 days post-transfer. Survival of the primary cell therapy product is likely to vary per patient. A non-invasive assay of ACF over time could potentially provide insight into the mechanisms of response and non-response, informing future clinical studies. This information may be useful to developers of cytotherapies and clinicians as it opens an avenue to quantify cellular product survival and engraftment.


Photo-curable carboxymethylcellulose composite hydrogel as a promising biomaterial for biomedical applications.
A series of carboxymethylcellulose (CMC) functionalized with glycidyl methacrylate (GMA) was successfully synthesized for producing of CMC-g-GMA copolymer. Water-soluble CMC-g-GMA copolymer was photo-crosslinked while Irgacure-2959 was used as a UV-photo-initiator at 365 nm. On the other hand, cellulose nanocrystals (CNCs) from sugarcane were graft-copolymerized in an aqueous solution utilizing cerium ammonium nitrate (CAN) as an initiator in a redox-initiated free-radical approach. CNCs were grafted with GMA to enhance their physicochemical and biological characteristics. Factors affecting hydrogel formation, e.g. CMC-g-GMA copolymer concentration, irradiation time and incorporation of different concentration of CNCs-g-GMA nano-filler, were discussed in dependance on the swelling degree and gel fraction of the produced hydrogels. Notably, the addition of CNCs-g-GMA nanofillers increased progressively thermal stability of the prepared hydrogel. CMC-g-GMA filled with CNCs-g-GMA composite hydrogel showed antimicrobial activity against multidrug resistance pathogens. Thus, CMC-g-GMA filled with CNCs-g-GMA composite hydrogel could be endorsed as compatible biomaterials for versatile biomedical applications.


Post-acquisition correction of NMR spectra distorted by dynamic and static field inhomogeneity of cryogen-free magnets.
Post-acquisition correction of NMR spectra is an important part of NMR spectroscopy that enables refined NMR spectra to be obtained, clean from undesirable out-phasing, broadening and noising. We describe analytical and numerical mathematical methods for post-acquisition correction of NMR spectra distorted by static and dynamic magnetic field inhomogeneity caused by imperfections of main superconducting coils and the cold head operation, typical for cryogen-free magnets. For the dynamic inhomogeneity, we apply a variant of the general reference deconvolution method, complemented with our mathematical analysis of spectral parameters. For the static inhomogeneity, we apply the method of a delayed Fourier transform, also supported with our analytical calculations. We verify our approach by correction processing of high-field experimental liquid-state 1H NMR spectra of water and ethanol as well as solid-state 13C MAS NMR spectra of adamantane and obtain good results for both static and dynamic field distortions. This work complements our previous work on instrumental suppression of dynamic distortions caused by the cold head operation. The results presented contribute well to the general field of processing NMR spectra and serve towards a more extensive use of cryogen-free magnets in high-resolution NMR spectroscopy.


Controlling faecal incontinence (including constipation and bowel dysfunction).
Spina bifida may affect faecal continence in many ways. An understanding of the issues can assist general practitioners in supporting their patients through the process of learning to effectively management specialist centres.


One-Dimensional Magnetic Order Stabilized in Edge-Reconstructed MoS2 Nanoribbon via Bias Voltage.
Low-dimensional nanostructures are expected to play an important role in spintronics. However, in low-dimensional systems, thermal fluctuations become more significant, which makes long-range magnetic ordering thermodynamically unfavorable. For example, as predicted by the Ising model, 1D magnetic order cannot survive, even at an arbitrary low finite temperature. In this study, utilizing a nanoproximity effect, we design a MoS2 nanoribbon material to stabilize 1D magnetic order without requiring the explicit application of an external magnetic field. The designed MoS2 nanoribbon has a new edge-reconstruction pattern, which is much more stable than previously reported structures. As a novel electronic property, one edge is nonmagnetic but conductive, and the opposite edge contains a magnetic moment in the predicted reconstruction pattern. Therefore, a bias voltage can drive a current along the former edge, which then generates a magnetic field at the opposite edge to stabilize the 1D magnetic order there. This result opens a new avenue to realize the integrated electrical control of magnetism.


Transient giant R waves--a manifestation of potentially reversible acute severe myocardial ischaemia.
A patient with acute severe myocardial ischaemia manifested with transient giant R waves and ST segment elevation during chest pain. This probably represents transient complete occlusion of a major coronary artery, the left anterior descending in this case. Myocardial infarction was prevented by aggressive medical and surgical management.


Dietary phosphate restriction attenuates polycystic kidney disease in mice.
Studies in rodents with reduced nephron mass have suggested a strong positive correlation between dietary phosphate consumption and CKD progression. Prior work by our group demonstrated that dietary phosphate restriction can prevent tubular injury and microcyst formation in rodents with glomerulonephritis. Tubular injury and cystic dilation of tubules are key contributors to kidney function decline in polycystic kidney disease (PKD). Here, we determined whether dietary phosphate restriction slows renal cyst growth and fibrosis in a mouse model of PKD. Pcy/pcy mice received a normal phosphate (0.54%) or a phosphate-restricted (0.02%) diet (n = 10/group) from 7 to 20 wk of age. All of the other major dietary constituents, including protein source and content, were comparable between the two diets. At 20 wk, body weight, kidney weight-to-body weight ratio (KW/BW), cystic area, cyst number, and kidney fibrosis were quantified. Pcy/pcy mice fed a phosphate-restricted diet had lower serum phosphate, fibroblast growth factor 23, and parathyroid hormone levels, along with elevated serum calcium levels and increased kidney Klotho gene expression compared with mice that consumed the control diet. Dietary phosphate restriction resulted in a 25% lower KW/BW ratio and reduced the cyst number, cystic index, and gene expression for the tubular injury markers neutrophil gelatinase-associated lipocalin and interleukin-18. Mice fed the phosphate-restricted diet exhibited lower kidney expression for pathways involved in collagen deposition and myofibroblast activation (collagen type I-α1, phosphorylated SMAD3, and α-smooth muscle actin); however, histological differences in kidney fibrosis were not appreciated. Dietary phosphate restriction slows cystogenesis and inhibits the activation of key pathways in the generation of kidney fibrosis in PKD mice.