Entrainment and Phase-Shifting of the Circadian Rhythm of Cell Division by Calcium in Synchronous Cultures of the Wild-Type Z Strain and of the ZC Achlorophyllous Mutant of Euglena gracilis.
Cell division in exponentially increasing populations of the wild-type, photosynthetic Z strain of Euglena gracilis Klebs cultured autotrophically on an aerated, magnetically stirred, minimal mineral medium (pH 7.0) in constant light (LL) or in a light-dark 1 hour:1 hour cycle (LD:1,1) at 25 degrees C could be synchronized by a 10-hour:10-hour low (2 micromolar):normal (200 micromolar) cycle in the concentration of external calcium. Similar results were obtained with the photosynthesis-deficient, achlorophyllous ZC mutant cultured in darkness at 16 degrees C on mineral medium supplemented with 0.1% ethanol as a carbon source; even a single low-Ca(2+) (2 micromolar) pulse was effective in eliciting synchrony. In contrast, whereas the 20-hour entrained rhythm of cell division in ZC then free-ran with a circadian period (tau = 26 hours) for many cycles after the imposed calcium regimen was discontinued, division rhythmicity did not persist in the Z strain in LL. The rhythm in wild-type cultures (free-running in LD:1,1) could be phase-shifted by a single 2-hour increase (from 200 micromolar to 10 millimolar; HiCa) or decrease (from 200-2 micromolar; LoCa) in external Ca(2+) concentration (varied by the addition of CaCl(2) or EDTA, respectively, to the medium). Pulses were terminated by returning the cells to medium containing 200 micromolar Ca(2+) (the normal concentration), and the steady-state phase-shifts engendered (if any) after transients had subsided were calculated with reference to an unperturbed culture. For both HiCa and LoCa pulses given at different circadian times, strong (type 0) phase-response curves (PRCs) were obtained, but although the LoCa PRC was the same as that obtained for light signals, the HiCa PRC was the opposite (a mirror image). These results implicate calcium in clock function, although it is likely that only a small portion of the total intracellular Ca(2+) ion is playing a role since the period of the division rhythm in cultures grown in the continuous presence of excess Ca(2+) or under LoCa was not altered significantly.


Artery of Percheron Occlusion in China: A Case Report and Chinese Literature Review.
The artery of Percheron (AOP) is a rare anatomical variant in which bilateral paramedian thalami are supplied by a single vascular branch arising from the P1 segment of the posterior cerebral artery. We present a case of AOP occlusion presenting as loss of consciousness and summarize the literature in Chinese to find the clinical characteristics. An 83-year-old woman was found unconscious for 1 day at home and was sent to the hospital the next day. Cerebral magnetic resonance imaging on day 1 of the patient showed a recent bilateral paramedian thalamic infarction. Simultaneously, magnetic resonance angiography found evident artery stenosis of the right P1 segment of the posterior cerebral artery, suggesting that the patient was diagnosed with AOP occlusion. Since the patient has missed the best time for thrombolytic therapy, anticoagulant therapy was given immediately; as the patient was then found to have pulmonary infections, antibiotic therapy was also initiated. The neurological status of this patient improved very slow. In about 2 weeks, the patient becomes more conscious but still could not speak or move. Our report suggests that unusual mood disorder and language disorder of aged patients might indicate the AOP occlusion, and cerebral imaging of magnetic resonance imaging (better with magnetic resonance angiography) should be performed to establish the diagnosis of AOP occlusion. The fast and accurate diagnosis of stroke because of AOP occlusion could best benefit the patients.


The Arabidopsis pop2-1 mutant reveals the involvement of GABA transaminase in salt stress tolerance.
GABA (gamma-aminobutyric acid) is a non protein amino acid that has been reported to accumulate in a number of plant species when subjected to high salinity and many other environmental constraints. However, no experimental data are to date available on the molecular function of GABA and the involvement of its metabolism in salt stress tolerance in higher plants. Here, we investigated the regulation of GABA metabolism in Arabidopsis thaliana at the metabolite, enzymatic activity and gene transcription levels upon NaCl stress. We identified the GABA transaminase (GABA-T), the first step of GABA catabolism, as the most responsive to NaCl. We further performed a functional analysis of the corresponding gene POP2 and demonstrated that the previously isolated loss-of-function pop2-1 mutant was oversensitive to ionic stress but not to osmotic stress suggesting a specific role in salt tolerance. NaCl oversensitivity was not associated with overaccumulation of Na+ and Cl- but mutant showed a slight decrease in K+. To bring insights into POP2 function, a promoter-reporter gene strategy was used and showed that POP2 was mainly expressed in roots under control conditions and was induced in primary root apex and aerial parts of plants in response to NaCl. Additionally, GC-MS- and UPLC-based metabolite profiling revealed major changes in roots of pop2-1 mutant upon NaCl stress including accumulation of amino acids and decrease in carbohydrates content. GABA metabolism was overall up-regulated in response to NaCl in Arabidopsis. Particularly, GABA-T was found to play a pivotal function and impairment of this step was responsible for a decrease in salt tolerance indicating that GABA catabolism was a determinant of Arabidopsis salt tolerance. GABA-T would act in salt responses in linking N and C metabolisms in roots.


Negative effect of leptin on bone mass in type 1 diabetes.
Studies investigating the effect of leptin on bone mass were inconsistent and some related it to the effect of insulin. We intend in this cross-sectional study to investigate the effect of leptin on bone mass in type 1 diabetic patients. We recruited 42 patients with type 1 diabetes for which we determined weight, height, HbA1c, microalbuminuria, serum leptin, bone mineral content (BMC) and density (BMD), and body composition. The patients had an average age of 20.1 +/- 0.6 years, an average body mass index (BMI) of 23.6 +/- 0.5 kg/cm(2) and an average duration of diabetes of 9.1 +/- 1.0 years. The Z-score was not correlated with HbA1c or duration of the disease, and the average Z-score was not different in patients with microalbuminuria as compared to patients with no reported microalbuminuria. On the other hand, Z-score and BMC correlated negatively with leptin (r = -0.31; p = 0.04 and -0.60, p < 0.01, respectively). These correlations persisted after adjustment for fat mass. We conclude that not metabolic control of diabetes, but serum leptin has a negative effect on bone density in young patients with type 1 diabetes. This negative effect of leptin on bone density maybe, in part, due to deficiency of endogenous insulin secretion in these patients.


Factors associated with prolonged length of stay in older patients.
Prolonged stay in acute hospitals increases the risk of hospital-acquired infections in older patients, and disrupts patient flow and access to care due to bed shortages. We aimed to investigate the factors associated with prolonged length of stay (pLOS) among older patients (aged ≥ 78 years) in a tertiary hospital, to identify the potentially modifiable risk factors that could direct interventions to reduce length of stay (LOS). During a three-month period from January 2013 to March 2013, we identified 72 patients with pLOS (LOS ≥ 21 days) and compared their demographic and clinical variables with that of 281 randomly selected control patients (LOS < 21 days) using univariate and multivariate logistic regression analyses. The mean age of the patients was 85.30 ± 5.34 years; 54% of them were female and 72% were of Chinese ethnicity. Logistic regression revealed the following significant factors for increased LOS: discharge to intermediate and long-term care services (odds ratio [OR] 9.22, 95% confidence interval [CI] 3.56-23.89; p < 0.001); increased severity of illness (OR 2.41, 95% CI 1.12-5.21; p = 0.025); and presence of caregiver stress (OR 3.85, 95% CI 1.67-8.91; p = 0.002). Presence of caregiver stress and nursing home placement are potential modifiable risk factors of pLOS among older patients. Early identification and management of caregiver stress, as well as expediting discharge planning, may help to reduce the length of stay for this cohort.


Endothelial transcripts uncover a previously unknown phenotype: C4d-negative antibody-mediated rejection.
In the last decade, there has been a growing recognition of alloantibody responses in organ transplantation, but phenotypes related to antibody-mediated rejection (ABMR) remain incompletely defined. This article reviews recent molecular studies in kidney allograft tissues that decipher molecular burden and mechanisms of ABMR, leading to discovery of a new phenotype: 'C4d-negative ABMR'. High endothelial gene expression in kidney transplant biopsies with anti-human leukocyte antigen alloantibody indicates active antibody-mediated damage and poor graft survival, defining a previously unknown group of C4d-negative ABMR. C4d-negative ABMR is characterized by high intragraft endothelial gene expression, alloantibodies, histology of chronic ABMR (less frequently acute ABMR), and poor outcomes. Thus, endothelial molecular phenotype in biopsies with circulating antibody detects degree of active graft injury, and many of these transcripts reflect endothelial activation. C4d-negative ABMR is twice as common as C4d-positive ABMR. Recognition of this new phenotype reveals ABMR (C4d positive or negative) as the most common cause of late kidney transplant loss. C4d staining, although very useful, is insensitive for detecting ABMR. Measuring endothelial gene expression in biopsies from kidneys with alloantibody is a sensitive and specific method to diagnose ABMR and predict graft outcomes.


Helix packing in membrane proteins.
A survey of 45 transmembrane (TM) helices and 88 helix packing interactions in three independent transmembrane protein structures reveals the following features. (1) Helix lengths range from 14 to 36 residues with an average length of 26.4 residues. There is a preference for lengths greater than 20 residues. (2) The helices are tilted with respect to the bilayer normal by an average of 21 degrees, but there is a decided preference for smaller tilt angles. (3) The distribution of helix packing angles is very different than for soluble proteins. The most common packing angles for TM helices are centered around +20 degrees while for soluble proteins packing angles of around -35 degrees are the most prevalent. (4) The average distance of closest approach is 9.6 A, which is the same as soluble proteins. (5) There is no preference for the positioning of the point of closest approach along the length of the helices. (6) It is almost a rule that TM helices pack against neighbors in the sequence. Of the 37 helices that have a sequence neighbor, 36 of them are in significant contact with a neighbor. (7) An antiparallel orientation is more prevalent than a parallel orientation and antiparallel interactions are more intimate on average. The general features of helix bundle membrane protein architecture described in this survey should prove useful in the modeling of helix bundle transmembrane proteins.


Endoscopic management of Barrett's and early oesophageal neoplasia.
Barrett's oesophagus (BO) is the only known precursor to oesophageal adenocarcinoma (OAC). Dysplasia and intramucosal cancer arising in BO can safely be treated with endoscopic eradication therapy (EET) due to the low risk of subsequent lymph node metastasis. Treatment at an early stage is paramount due to the ongoing poor prognosis and outcomes of patients with advanced OAC. The mainstay of treatment is endoscopic resection of visible lesions for accurate staging followed by ablation therapy to all remaining columnar-lined epithelium, most commonly with radiofrequency ablation. Successful eradication of dysplasia can be achieved in >95% of patients with this EET combined approach.


Combined administration of platelet rich plasma and autologous bone marrow aspirate concentrate for spinal cord injury: a descriptive case series.
Administration of platelet rich plasma (PRP) and bone marrow aspirate concentrate (BMAC) has shown some promise in the treatment of neurological conditions; however, there is limited information on combined administration. As such, the purpose of this study was to assess safety and functional outcomes for patients administered combined autologous PRP and BMAC for spinal cord injury (SCI). This retrospective case series included seven patients who received combined treatment of autologous PRP and BMAC via intravenous and intrathecal administration as salvage therapy for SCI. Patients were reviewed for adverse reactions and clinical outcomes using the Oswestry Disability Index (ODI) for up to 1 year, as permitted by availability of follow-up data. Injury levels ranged from C3 through T11, and elapsed time between injury and salvage therapy ranged from 2.4 months to 6.2 years. Post-procedure complications were mild and rare, consisting only of self-limited headache and subjective memory impairment in one patient. Four patients experienced severe disability prior to PRP combined with BMAC injection, as evidenced by high (> 48/100) Oswestry Disability Index scores. Longitudinal Oswestry Disability Index scores for two patients with incomplete SCI at C6 and C7, both of whom had cervical spine injuries, demonstrated a decrease of 28-40% following salvage therapy, representing an improvement from severe to minimal disability. In conclusion, intrathecal/intravenous co-administration of PRP and BMAC resulted in no significant complications and may have had some clinical benefits. Larger clinical studies are needed to further test this method of treatment for patients with SCI who otherwise have limited meaningful treatment options. This study was reviewed and approved by the OhioHealth Institutional Review Board (IRB No. 1204946) on May 16, 2018.


Effect of Cu Doping on Structure and Physical Properties in the Antiferromagnetic Dirac Semimetal CaMnBi2.
The newly discovered AMnBi2 (A = Ca, Sr, Ba, Eu, and Yb) materials composed of two-dimensional Bi square nets provide an excellent platform to investigate the effect of magnetism on topological band structures. Effectively tuning the magnetic interaction in AMnBi2 is of great importance to advance this issue. Here, we describe an effective route to tune the magnetism in Dirac semimetal CaMnBi2 through Cu doping. Structural analysis on CaMn1-xCuxBi2 single crystals indicates that Cu atoms occupy the Mn sites randomly, with the maximum doping level of 25%. After Cu doping, the Bi square net in charge of the Dirac band is still retained, but the Bi-Bi bond distance is markedly shortened. The antiferromagnetic interaction of CaMnBi2 is strongly weakened in the Cu-doped crystals, with the transition temperature decreased from 260 to 85 K. On the contrary, the ferromagnetic component that originated from the canted AFM is enhanced, suggesting that the spin canting in this system is tunable. In addition, the magnetoresistance is decreased upon Cu doping, probably due to the disorder in structure. Our work suggests that the CaMn1-xCuxBi2 (0 ≤ x ≤ 0.25) system can offer a suitable playground to address the interplay between magnetism and the topological state.


MDIMP, a novel cardiac Ca(2+) channel blocker with atrial selectivity.
In cardiac muscle cells both T-and L-type Ca(2+) channels (TTCCs and LTCCs, respectively) are expressed, and the latter are relevant to a process known as excitation-contraction coupling (ECC). Evidence obtained from docking studies suggests that isoindolines derived from α-amino acids bind to the LTCC CaV1.2. In the present study, we investigated whether methyl (S)-2-(1,3-dihydroisoindol-2-yl)-4-methylpentanoate (MDIMP), which is derived from L-leucine, modulates both Ca(2+) channels and ECC. To this end, mechanical properties, as well as Ca(2+) transients and currents, were all investigated in isolated cardiac myocytes. The effects of MDIMP on CaV1.2 (transiently expressed in 293T/17 cells) were also studied. In this system, evidence was found for an inhibitory action that develops and recovers in min, with an IC50 of 450µM. With respect to myocytes: atrial-TTCCs, atrial-LTCCs, and ventricular-LTCCs were also inhibited, in that order of potency. Accordingly, Ca(2+) transients, contractions, and window currents of LTCCs were all reduced more strongly in atrial cells. Interestingly, while the modulation of LTCCs was state-independent in these cells, it was state-dependent, and dual, on the ventricular ones. Furthermore, practically all of the ventricular LTCCs were closed at resting membrane potentials. This could explain their resistance to MDIMP, as they were affected in only open or inactivated states. All these features in turn explain the preferential down-regulation of the atrial ECC. Thus, our results support the view that isoindolines bind to Ca(2+) channels, improve our knowledge of the corresponding structure-function relationship, and may be relevant for conditions where decreased atrial activity is desired.


Characterization of patient-reported outcomes in moderate to severe psoriasis.
The Patient Benefit Index (PBI) is a recently developed instrument to assess patient satisfaction with treatment. It has been applied to only a limited number of psoriasis patients. Characterization of patient-reported outcomes (PRO) in patients with moderate to severe psoriasis. 1787 patients with plaque psoriasis were documented. Psoriasis Area and Severity Index (PASI), body surface area (BSA), Dermatology Life Quality Index (DLQI) and PBI were determined. Correlations were calculated and the persistence of PBI improvement and strength of treatment effect were evaluated. A regression analysis was performed to characterize predictors of PBI and DLQI improvements. Significant correlations exist between ΔPASI/ΔBSA and ΔDLQI. Also, DLQI and PBI are correlated. Improvement in the skin condition has a positive and sustainable impact on all need dimensions of the PBI. The best early predictor for PBI was PASI 75 at treatment week 8, relevant factors predicting quality of life were PBI/subscale 4, (reducing physical impairment), ΔBSA and ΔPASI. Improvement in skin condition correlates with improvements in quality of life in patients with plaque psoriasis. Successful treatment leads to significant and sustainable patient benefit. While PBI subscale 4 is a good predictor for quality of life, more work is necessary to identify potential predictors for patient benefit.


[Ethics and the Federation of Swiss Physicians].
As a professional organization, the Federation of Swiss Physicians must make sure that generally admitted rules of ethics as well as professional regulations in this matter are recognized and observed by its members. In its statutes, it asserts itself for a high level medical care of the population; it requires not only a permanent renewal of professional aptitude as a duty in the widest meaning of the word, but also a great sense of responsibility for patients and society. Axioms on professional ethics are unfit as arguments for material requirements to fulfil the best possible all these duties. Credibility is only granted if ethical rules are really observed.


Life cycle of Hepatozoon mehlhorni sp. nov. in the viper Echis carinatus and the mosquito Culex pipiens.
Hepatozoon mehlhori sp. nov. and its developmental stages from the tissues of the Egyptian viper Echis carinatus and the mosquito Culex pipiens are described. The erythrocytic parasites were differentiated into the small form (trophozoite) measuring 14.5 +/- 0.6 x 4 +/- 0.12 micron and the mature form (gametocyte) measuring 17.2 +/- 1.6 x 5.4 +/- 0.5 micron. Merogony took place in the pulmonary endothelial cells and in the parenchyma cells of the liver and spleen of the infected vipers. Two types of meront were found. The large meronts (macromeronts) were 30.2 +/- 1.73 x 22.6 +/- 1.2 microns in size and yielded 16-40 (average, 28) micromerozoites measuring 17.2 +/- 0.7 x 5 +/- 0.15 microns. The small meronts (micromeronts) measured 18.2 +/- 0.6 x 13.5 +/- 0.5 microns and yielded 2-14 (average, 8) macromerozoites that were 15.1 +/- 0.12 x 6.2 +/- 0.8 microns in size. After syzygy in the haemocoel of the mosquito, the microgamont produced four uniflagellate microgametes (6.4 +/- 0.3 x 4.5 +/- 0.5 microns in size, with a short flagellum measuring 3.2 +/- 0.1 microns); on the 3rd day post-infection (p.i.)., one of these fertilized the macrogamete, giving rise to the zygote. The oocyst developed from the zygote on the 5th day p.i. and measured 135 +/- 2.6 x 120 +/- 1.8 microns. About 11-60 (average, 35) sporoblasts were formed by centripetal invaginations from each oocyst on the 8th day p.i. and developed into sporocysts on the 14th day p.i. Inside each sporocyst, 5-12 (average, 8) sporozoites, each measuring 12.6 +/- 1.2 x 4.1 +/- 0.3 microns, developed on the 16th day p.i. According to the above-mentioned characteristics the parasite was recorded as being a new species and was named Hepatozoon mehlhorni. Experimental transmission was accomplished by i.p. inoculation of the infectious stages (sporozoites) into uninfected vipers and led to the appearance of blood stages at 4-6 weeks p.i.


Extraordinary magnetoresistance in graphite: experimental evidence for the time-reversal symmetry breaking.
We report a highly anisotropic in-plane magnetoresistance (MR) in graphite that possesses in-plane parallel line-like structural defects. In a current direction perpendicular to the line defects (LD), MR is negative and linear in low fields with a crossover to a positive MR at higher fields, while in a current direction parallel to LD, we observed a giant super-linear positive MR. These extraordinary MRs are respectively explained by a hopping magnetoresistance via non-zero angular momentum orbitals, and by the magnetoresistance of inhomogeneous media. The linear negative orbital MR is a unique signature of the broken time-reversal symmetry (TRS). We discuss the origin of the disorder-induced TRS-breaking in graphite.


Common Building Motifs in Ba2Fe3(PO4)4·2H2O, BaFe3(PO4)3, and Na3Fe3(PO4)4: Labile Fe(2+)/Fe(3+) Ordering and Charge-Dependent Magnetism.
Two new mixed-valence Fe(2/3+) barium phosphates have been synthesized in hydrothermal conditions and characterized: Ba2Fe(2.66+)3(PO4)4·2H2O (compound 1, ratio Fe(3+)/Fe(2+) = 2:1, orthorhombic space group Pbca, a = 6.71240(10) Å, b = 10.6077(2) Å, c = 20.9975(5) Å, R1 = 3.39%) and BaFe(2.33+)3(PO4)3 (compound 2, ratio Fe(3+)/Fe(2+) = 1:2, orthorhombic, space group Imma with a = 10.5236(3) Å, b = 13.4454(4) Å, c = 6.6411(2) Å, R1 = 1.63%). 1 has a two-dimensional crystal structure built of [Fe(2.5+)2Fe(3+)1(PO4)4](4-) layers with charge segregation on two individual Fe crystal sites, in contrast to the single valence on these two sites found in similar layers of Na3Fe(3+)3(PO4)4. The crystal structure of 2 is formed of the same layers but condensed into a 3D [Fe(2+)2Fe(3+)1(PO4)3](2-) framework. The complete Fe(2+) vs Fe(3+) charge ordering on the two available sites differs from what was found in the two previous cases and denotes a remarkable charge adaptability of the common elementary units. Compared to the antiferromagnetic Na3Fe(3+)3(PO4)4 the partial iron reduction into Fe(2+) is responsible for strong ferromagnetic components along the c-easy axis for both 1 and 2. Additionally 1 shows multiple magnetization steps in the perpendicular direction, giving raise to atypical anisotropic magnetism into a complex magnetic phase diagram.


Comprehensive treatment of extensively drug-resistant tuberculosis.
Extensively drug-resistant tuberculosis has been reported in 45 countries, including countries with limited resources and a high burden of tuberculosis. We describe the management of extensively drug-resistant tuberculosis and treatment outcomes among patients who were referred for individualized outpatient therapy in Peru. A total of 810 patients were referred for free individualized therapy, including drug treatment, resective surgery, adverse-event management, and nutritional and psychosocial support. We tested isolates from 651 patients for extensively drug-resistant tuberculosis and developed regimens that included five or more drugs to which the infecting isolate was not resistant. Of the 651 patients tested, 48 (7.4%) had extensively drug-resistant tuberculosis; the remaining 603 patients had multidrug-resistant tuberculosis. The patients with extensively drug-resistant tuberculosis had undergone more treatment than the other patients (mean [+/-SD] number of regimens, 4.2+/-1.9 vs. 3.2+/-1.6; P<0.001) and had isolates that were resistant to more drugs (number of drugs, 8.4+/-1.1 vs. 5.3+/-1.5; P<0.001). None of the patients with extensively drug-resistant tuberculosis were coinfected with the human immunodeficiency virus (HIV). Patients with extensively drug-resistant tuberculosis received daily, supervised therapy with an average of 5.3+/-1.3 drugs, including cycloserine, an injectable drug, and a fluoroquinolone. Twenty-nine of these patients (60.4%) completed treatment or were cured, as compared with 400 patients (66.3%) with multidrug-resistant tuberculosis (P=0.36). Extensively drug-resistant tuberculosis can be cured in HIV-negative patients through outpatient treatment, even in those who have received multiple prior courses of therapy for tuberculosis.


Interception of moving objects in karate: an experimental, marker-free benchmark.
karate requires an optimal interception of the opponent's attack. Particularly in unconstrained situations, normal, untrained, subjects solve this problem adopting rather different solutions. It is currently unknown if karate as show a more uniform selection of interception schemes due to their special training. here we applied a 3D scanner to study the movement reproducibility of skilled karate as in a natural setup, using an unconstrained interception task. Six right handed karatekas and six controls participated to the study. 3D motion tracking data of the upper limbs were obtained using the Microsoft Kinect sensor, a real-time 3D scanner. The interception task consisted of intercepting and stopping a moving stick which was directed towards the side of the subject in two different positions (upper and lower). the analysis of hand trajectories showed that the strategy of the movement was remarkably different between control subjects, whereas it was more uniform in karatekas. Moreover, we observed a significant difference in the variability of the interception point between control subjects and karatekas. the results confirm the presence of individual idiosincratic behavior in interception tasks also in ecologically realistic situations, and that experience and training (as in karatekas) play an important role in the trajectory in interceptive tasks.


Endoscopic Resection of a Massive Ossifying Fibroma in the Sinonasal Cavity.
An ossifying fibroma (OF) is a type of benign fibro-osteoma that rarely involves the sinonasal cavity. Recent developments in endoscopic sinus surgery allow the removal of large benign tumors from the nasal cavity and sinuses. Here, the athors report the case of a 48-year-old female who underwent endoscopic sinus surgery under general anesthesia to completely remove a large OF involving the sphenoid sinus and nasal cavity. No recurrence was noted during the recent 3-year follow-up. Endoscopic resection of OFs is an excellent choice for very experienced surgeons, affording the advantages of direct observation as well as visual enhancement and magnification, thus reducing intra- and post-operative morbidity.


Reflections on funding the National Health Service: from illusion to reality?
Opinions differ about how best we organise our services to promote and preserve it, meet their costs and apportion them between the individual and the state. The well-being of the NHS is imperilled and its development is impeded by underfunding, a state of affairs likely to persist as long as it depends exclusively on Exchequer monies. To break the impasse the public should reconsider its attitude to the imposition of health charges, the marketing of health services, and coll raboration between the NHS, public bodies and private groups. The able-bodied might well, within their means, bear some of the costs of the services they use. The NHS would profit from a rapprochement with private medicine. A more prompt and positive response by the NHS to clinical and social challenges might be facilitated if its ties to government were loosened and it was overseen by an independent agency. Free health is a Utopian ideal. In the real world the best we are likely to achieve is an up-to-date health service which gives a fair deal to patients, who are its raison d'etre, and to those who provide the money to pay for it; it should syncretise the art and science of medicine.


The role of histidine in the anemia of folate deficiency.
The amino acid histidine is metabolized to glutamic acid in mammalian tissue. Formiminoglutamic acid (FIGLU) is an intermediary in this reaction, and tetrahydrofolic acid is the coenzyme that converts it to glutamic acid. A test for folate deficiency concerns the measurement of urinary FIGLU excretion after a histidine load. It was observed that folate-deficient individuals receiving the histidine for the FIGLU test made hematological response that alleviated the anemia associated with this deficiency. This was unusual in that a biochemical test to determine the deficiency results in a beneficial effect for one aspect of the deficiency. The studies reported in this paper give a metabolic explanation for this phenomenon. Urine was collected for 24 hr from 25 folate-deficient subjects, 10 vitamin B(12)-deficient subjects, and 15 normal controls. Urinary excretion of histidine was a mean of 203 mg with a range of 130-360 mg for the folate-deficient subjects; 51.5 mg with a range of 30-76.6 mg for normal subjects; and 60.0 mg with a range of 32.3-93.0 mg for the vitamin B(12)-deficient subjects. All the folate-deficient subjects subsequently made a hematological response to the histidine administered for the FIGLU test. No hematological response was observed in the vitamin B(12)-deficient individuals. When folic acid was given to folate-deficient subjects who received no histidine, urinary histidine levels returned to normal levels rapidly and this was followed by a hematological response. Others have shown that volunteers fed a histidine-free diet developed anemia. In normal subjects, histidine is excreted much more in the urine than other essential amino acids are. Hemoglobin protein contains 10% histidine. Under normal conditions, dietary histidine can supply sufficient histidine to prevent anemia. When the dietary intake is diminished or the urinary excretion is greatly increased, anemia results. It is concluded that folate deficiency causes histidine depletion through increased urinary excretion of this amino acid. Feeding histidine replenishes tissue levels of histidine, resulting in hemoglobin regeneration. Folic acid administration results in return of histidine to normal urinary levels. Thus, a combination of folic acid histidine would be beneficial for folate deficient individuals.


The effects of subchronic chlorate exposure in Sprague-Dawley rats.
Male and female Sprague-Dawley rats were exposed to drinking water containing 3.0, 12.0 or 48.0 mM sodium chlorate. The mean drinking water consumption varied between exposure groups from 100-200 ml/kg/day. Female exposure groups consistently drank more water (23-42%) than male exposure groups thereby receiving more chlorate/kg/day at every exposure level. There were no compound related deaths; however, both males and females in the high exposure groups had significant weight loss during the 90-day exposure period. Also, in these same groups females had mild but significant decreases in the following relative organ weights; adrenals, thymus and spleen, while the relative brain weight was increased. In males, the heart, kidneys and liver were mildly decreased while the brain and testes were mildly increased. Red blood cell counts and percent hematocrit were decreased in both sexes in the high dose group. Pituitary gland (pars distalis) vacuolization and thyroid gland colloid depletion were prominent in both sexes in mid and/or high dose animals. A NOAEL of 0.36 mM chlorate/kg b.w./day in males and 0.50 mM chlorate/kg b.w./day in females were established.


Thiol-Rich fp-6 Controls the Tautomer Equilibrium of Oxidized Dopa in Interfacial Mussel Foot Proteins.
3,4-Dihydroxyphenylalanine (Dopa) is a versatile molecule that enables marine mussels to achieve successful underwater adhesion. However, due to its complicated redox chemistry and vulnerability to oxidation, controlling surface adhesion and cohesion has been a challenging issue to overcome. Foot protein type 6 (fp-6), a thiol-rich interfacial mussel adhesive protein, has been reported as a proteinaceous antioxidant for mussels that helps Dopa maintain surface adhesion ability. In this study, we focused on the role of fp-6 in oxidized Dopa. The effect on the tautomer equilibrium of oxidized Dopa was investigated using recombinant fp-6 (rfp-6) and Dopa-incorporated foot protein type 3 fast variant (drfp-3F), which were produced in bacterial cells. The redox chemistry of Dopa in drfp-3F and the role of rfp-6 were observed using a UV-vis spectrophotometer and a surface forces apparatus (SFA). We discovered that rfp-6 shifts the tautomer equilibrium to ΔDopa as a preferred tautomer for oxidized Dopa in drfp-3F and makes drfp-3F better on underwater surface adhesion.


Superior vena cava syndrome arising from subclavian vein port catheter implantation and paraneoplastic syndrome.
Central venous thrombosis is an important complication of venous catheterization. We presented a 49-year-old male patient who developed massive central venous thrombosis causing superior vena cava (SVC) syndrome after placement of a right subclavian vein port catheter. The patient had inoperable gastric cancer for which he had been receiving chemotherapy for two years. He had a six-month history of fixed port catheter placement into the right subclavian vein. Contrast-enhanced computed tomography (CT) of the chest showed complete obstruction of the SVC and CT angiography showed extensive thrombosis from the subclavian vein to the end of the SVC. Extensive lung and mediastinal metastases were also observed. Surgical intervention was not considered. Fibrinolytic therapy was instituted with 75 mg tissue plasminogen activator (tPA) infusion for 18 hours. The patient's symptoms and the signs of SVC syndrome disappeared and clinical parameters returned to normal within several hours. The day after completion of fibrinolytic therapy, repeat contrast CT angiography showed total resolution of SVC thrombosis. Slow infusion of tPA may be effective in the treatment of SVC syndrome caused by acute thrombosis.


Role of insulin in endogenous hypertriglyceridemia.
Dietary carbohydrate accentuation of endogenous triglyceride production has been studied in 33 patients. A broad and relatively continuous spectrum of steady-state plasma triglyceride concentrations was produced in 31 of the 33 subjects during 3 wk of a high carbohydrate (fat-free) liquid formula diet. Two patients developed plasma triglyceride concentrations in excess of 2000 mg/100 ml, and these were the only patients we have studied in which carbohydrate induction of hypertriglyceridemia seemed to be associated with a defect in endogenous plasma triglyceride removal mechanisms. In the remaining 31 patients the degree of hypertriglyceridemia was highly correlated with the insulin response elicited by the ingestion of the high carbohydrate formula (P < 0.005). No significant correlation existed between fasting plasma triglyceride concentration and either plasma glucose or free fatty acid concentrations after the high carbohydrate diet, nor was the degree of hypertriglyceridemia related to degree of obesity. It is suggested that hypertriglyceridemia in most subjects results from an increase in hepatic triglyceride secretion rate secondary to exaggerated postprandial increases in plasma insulin concentration.


Gait kinematics of subjects with ankle instability using a multisegmented foot model.
Many patients who sustain an acute lateral ankle sprain develop chronic ankle instability (CAI). Altered ankle kinematics have been reported to play a role in the underlying mechanisms of CAI. In previous studies, however, the foot was modeled as one rigid segment, ignoring the complexity of the ankle and foot anatomy and kinematics. The purpose of this study was to evaluate stance phase kinematics of subjects with CAI, copers, and controls during walking and running using both a rigid and a multisegmented foot model. Foot and ankle kinematics of 77 subjects (29 subjects with self-reported CAI, 24 copers, and 24 controls) were measured during barefoot walking and running using a rigid foot model and a six-segment Ghent Foot Model. Data were collected on a 20-m-long instrumented runway embedded with a force plate and a six-camera optoelectronic system. Groups were compared using statistical parametric mapping. Both the CAI and the coper group showed similar differences during midstance and late stance compared with the control group (P < 0.05). The rigid foot segment showed a more everted position during walking compared with the control group. Based on the Ghent Foot Model, the rear foot also showed a more everted position during running. The medial forefoot showed a more inverted position for both running and walking compared with the control group. Our study revealed significant midstance and late stance differences in rigid foot, rear foot, and medial forefoot kinematics The multisegmented foot model demonstrated intricate behavior of the foot that is not detectable with rigid foot modeling. Further research using these models is necessary to expand knowledge of foot kinematics in subjects with CAI.


Clusterin, a haploinsufficient tumor suppressor gene in neuroblastomas.
Clusterin expression in various types of human cancers may be higher or lower than in normal tissue, and clusterin may promote or inhibit apoptosis, cell motility, and inflammation. We investigated the role of clusterin in tumor development in mouse models of neuroblastoma. We assessed expression of microRNAs in the miR-17-92 cluster by real-time reverse transcription-polymerase chain reaction in MYCN-transfected SH-SY5Y and SH-EP cells and inhibited expression by transfection with microRNA antisense oligonucleotides. Tumor development was studied in mice (n = 66) that were heterozygous or homozygous for the MYCN transgene and/or for the clusterin gene; these mice were from a cross between MYCN-transgenic mice, which develop neuroblastoma, and clusterin-knockout mice. Tumor growth and metastasis were studied in immunodeficient mice that were injected with human neuroblastoma cells that had enhanced (by clusterin transfection, four mice per group) or reduced (by clusterin short hairpin RNA [shRNA] transfection, eight mice per group) clusterin expression. All statistical tests were two-sided. Clusterin expression increased when expression of MYCN-induced miR-17-92 microRNA cluster in SH-SY5Y neuroblastoma cells was inhibited by transfection with antisense oligonucleotides compared with scrambled oligonucleotides. Statistically significantly more neuroblastoma-bearing MYCN-transgenic mice were found in groups with zero or one clusterin allele than in those with two clusterin alleles (eg, 12 tumor-bearing mice in the zero-allele group vs three in the two-allele group, n = 22 mice per group; relative risk for neuroblastoma development = 4.85, 95% confidence interval [CI] = 1.69 to 14.00; P = .005). Five weeks after injection, fewer clusterin-overexpressing LA-N-5 human neuroblastoma cells than control cells were found in mouse liver or bone marrow, but statistically significantly more clusterin shRNA-transfected HTLA230 cells (3.27%, with decreased clusterin expression) than control-transfected cells (1.53%) were found in the bone marrow (difference = 1.74%, 95% CI = 0.24% to 3.24%, P = .026). We report, to our knowledge, the first genetic evidence that clusterin is a tumor and metastasis suppressor gene.


Assembly of the bacteriophage T4 replication machine requires the acidic carboxy terminus of gene 32 protein.
The acidic carboxy-terminal 89-amino acid fragment of bacteriophage T4 gene 32 protein was expressed in Escherichia coli to high levels from an inducible plasmid construct. Infection of induced cells by wild-type T4 phage results in impaired phage DNA synthesis. The time at which DNA synthesis begins and the diminution in DNA synthesis rates correlate with the amount of carboxy-terminal peptide that accumulates intracellularly prior to infection. Correspondingly, when induced cells are infected with viable phage containing a small deletion near the carboxy-terminus of 32 protein (delta PR201), the inhibition of phage DNA synthesis was much more severe. The mutant 32 protein competes less well against overproduced wild-type acid peptide than does wild-type 32 protein. The purified acid peptide, when used as the attached ligand for affinity chromatography, binds several T4 proteins from phage-infected cells, including 43 protein (T4 DNA polymerase), Dda protein (a DNA helicase), and UvsX protein (a Rec-like recombination protein). Furthermore, at 50- to 100-fold molar excess of acid peptide over intact 32 protein, phage DNA synthesis was specifically inhibited at the initiation step in an in vitro 5-protein DNA replication experiment. We propose that one or more phage replication proteins are titrated as non-productive protein-protein complexes at a site away from the DNA template. This implies that the carboxy-terminal domain of 32 protein is involved in an obligate step of replication machine assembly when the protein is properly attached to ssDNA in the vicinity of a primer-template junction. The assembly defect we observe is strikingly similar to the repression, or "squelching", of the activity of certain eukaryotic transcriptional activators.


Moiré Superlattice-Induced Superconductivity in One-Unit-Cell FeTe.
In this work, we demonstrate that the nonsuperconducting single-layer FeTe can become superconducting when its structure is properly tuned by epitaxially growing it on Bi2Te3 thin films. The properties of the single-layer FeTe deviate strongly from its bulk counterpart, as evidenced by the emergence of a large superconductivity gap (3.3 meV) and an apparent 8 × 2 superlattice (SL). Our first-principles calculations indicate that the 8 × 2 SL and the emergence of the novel superconducting phase are essentially the result of the structural change in FeTe due to the presence of the underlying Bi2Te3 layer. The structural change in FeTe likely suppresses the antiferromagnetic order in the FeTe and leads to superconductivity. Our work clearly demonstrates that moiré pattern engineering in a heterostructure is a reachable dimension for investigating novel materials and material properties.


A tungsten external heater for BX90 diamond anvil cells with a range up to 1700 K.
Resistive heating of a sample in a diamond anvil cell (DAC) can generate a homogeneous temperature field across the sample chamber with reliable temperatures measured by a thermocouple. It is of importance in experiments aiming at exploring phase diagrams and quantifying thermoelastic properties of materials. Here, we present a ring-heater design developed for BX90 diamond anvil cells (DACs). It is made of a ring-shaped aluminum oxide holder hosting a tungsten wire coil inside and coupled with Ar + 2% H2 gas to prevent oxidation during experiment. This modular plug-and-play design enables in situ studies of samples via x-ray diffraction up to a temperature of 1700 K. Temperature in the BX90 sample volume as measured through a thermocouple was calibrated using the melting point of gold. As an application of this design, we report the thermal expansion coefficient of MgO at 9.5(1) GPa.


[Significance of urinary uracil measurement following administration of DPD inhibitory fluoropyrimidine(DIF)products].
Individual differences in 5-FU metabolism are mainly attributed to individual differences in the activity of DPD, an enzyme that can metabolize more than 85% of 5-FU. Because urinary uracil is a reflection of DPD activity, it is measured to predict and prevent the occurrence of side effects caused by pyrimidine-type chemotherapeutic agents. From urinary uracil values measured in 84 gastrointestinal cancer patients, 0-60 mmol/g.creatinine was set as a standard. In patients whose urinary uracil values exceeded the standard, 5-FU tended to be accumulated when S-1, a DIF product, was administered and side effects, such as anorexia, vomiting and diarrhea occurred immediately after the start of S-1 administration. If an appropriate DIF product is selected and its dosage set based on the patient's urinary uracil value, the occurrence of side effects would be reduced. Subsequently, a continuation of medication would be possible.


Photodynamic Theranostics of Central Lung Cancer: Capabilities of Early Diagnosis and Minimally Invasive Therapy (Review).
The aim of the study was to assess the prospects for central lung cancer (CLC) screening using fluorescent diagnostics and its treatment by endobronchial photodynamic therapy (PDT). Bronchoscopic fluorescent diagnostics using chlorin e6 photosensitizers and a developed instrumental system enable to reveal tumor changes in large bronchi mucosa at early stages, and a developed PDT technique performed under fluorescent control helps achieve personalized treatment. Such an approach is considered as a theranostic technique - photodynamic theranostics. central lung cancer screening requires a fluorescent dye characterized by availability and can be used directly within the examination. Indocyanine green can be used as a dye, its peculiarity is the necessity to excite and record fluorescence in the near-infrared (NIR) wavelength band. First experiments using NIR bands to diagnose a bronchoscopic system showed the detectability of tumor areas using on-site bronchoscopic photodynamic theranostics, which consists in NIR imaging of tumor foci when a standard dose of indocyanine green is administered during the examination. Further progress of early diagnostics and minimally invasive CLC therapy will be determined by the development of new photosensitizers, which should be characterized by a high absorption band in NIR area, quick accumulation in a tumor, high yield of single oxygen in NIR illumination, bright fluorescence, high potential in terms of the induction of an anti-tumor immune response.


VX-322: a novel dual receptor tyrosine kinase inhibitor for the treatment of acute myelogenous leukemia.
In acute myelogenous leukemia (AML), the FLT3 receptor tyrosine kinase (RTK) is highly expressed with 30% of patients expressing a mutated, constitutively active form of this protein. To inhibit this receptor, VX-322 was developed and found to be very potent against both the FLT3 and c-KIT RTKs with enzyme K(i) values of <1 nM and a cellular IC(50) between 1 and 5 nM. It was efficacious in a FLT3-ITD dependent myeloproliferative mouse model, doubling survival compared to other FLT3 inhibitors, with 25% of the mice cured. Upon treatment of primary AML patient blast cells, the dual inhibition of FLT3 and c-KIT was superior to inhibitors targeting a single RTK. Thus, this compound may represent an improved pharmacologic and selectivity profile that could be effective in the treatment of AML.


[Cystic meningioma].
Cystic meningioma represent a rare entity, accounting 1.7 to 11.7% from the total intracranial meningiomas. We present a 41 years old patients' case who suffered of an progressive bilateral visual acuity decreasing, more pronounced on the right side. The clinical examination revealed a severe reduction of vision, represented by difficulties in light perception on the right side. The MRI and CT scan showed an expansive, multi-lobular, fronto temporal process on the right side (87/58/63 mm), presenting a liquid signal, different from intra-cerebro-spinal fluid, without contrast enhancement at the level of the septae. The patient is operated on, the total resection of an polycystic and spongious tumour being accomplished together with the aspiration of the liquid from the giant peritumoral cyst. The postoperative evolution was favourable. The anatomo-pathological result: meningothelial meningioma. Several classifications, the etiology of intra and peritumoral cysts formation are discussed together with the therapeutical possibilities.


Lycopene bioaccessibility and starch digestibility for extruded snacks enriched with tomato derivatives.
To improve the nutritional value of energy-dense extruded snacks, corn grits were replaced with tomato paste and/or tomato skin powder at ratios of 5, 10, and 20% and extruded to make expanded snack foodlike products. Using a model digestion system, lycopene bioaccessibility and uptake from the snacks into Caco-2 cells were determined. The digestibility of the starch, the main nutrient component of the snacks, was also investigated. While extrusion cooking reduced the lycopene content of the snacks, the proportion of bioaccessible lycopene increased. Lycopene uptake by the Caco-2 cells from the extruded snacks exceeded that of the control in which the lycopene was not extruded, by 5% (p < 0.05). The digestibility of starch in the snacks varied depending on the type of tomato derivative and its concentration. Optimization of the extrusion cooking process and the ingredients can yield functional extruded snack products that contain bioavailable lycopene.


Exacerbation of atopic dermatitis symptoms by ustekinumab in psoriatic patients with elevated serum immunoglobulin E levels: Report of two cases.
Psoriasis is a chronic inflammatory skin disease mainly mediated by a T-helper cell subset, Th17 cells. Recently, increased levels of total serum immunoglobulin (Ig)E have been reported in a subset of psoriatic patients. Ustekinumab (UST) is one of the most commonly used biologic agents for the treatment of moderate to severe plaque psoriasis, and a previous report also documented effectiveness of UST for psoriatic patients with high serum IgE levels. We experienced two psoriatic patients with high serum IgE levels, in whom UST completely improved psoriasis but paradoxically provoked or exacerbated atopic dermatitis (AD)-like symptoms. This reciprocal phenomenon suggests the shift of Th balance toward Th2, along with altered profiles of inflammatory cytokines. It appears prudent to consider the possibility of such adverse effects when treating psoriatic patients with UST with concomitant AD symptoms, a history of AD or high serum IgE levels.


Central nervous system infection in the intensive care unit: Development and validation of a multi-parameter diagnostic prediction tool to identify suspected patients.
Central nervous system infections (CNSI) are diseases with high morbidity and mortality, and their diagnosis in the intensive care environment can be challenging. Objective: To develop and validate a diagnostic model to quickly screen intensive care patients with suspected CNSI using readily available clinical data. Derivation cohort: 783 patients admitted to an infectious diseases intensive care unit (ICU) in Oswaldo Cruz Foundation, Rio de Janeiro RJ, Brazil, for any reason, between 01/01/2012 and 06/30/2019, with a prevalence of 97 (12.4%) CNSI cases. Validation cohort 1: 163 patients prospectively collected, between 07/01/2019 and 07/01/2020, from the same ICU, with 15 (9.2%) CNSI cases. Validation cohort 2: 7,270 patients with 88 CNSI (1.21%) admitted to a neuro ICU in Chicago, IL, USA between 01/01/2014 and 06/30/2019. Prediction model: Multivariate logistic regression analysis was performed to construct the model, and Receiver Operating Characteristic (ROC) curve analysis was used for model validation. Eight predictors-age <56 years old, cerebrospinal fluid white blood cell count >2 cells/mm3, fever (≥38°C/100.4°F), focal neurologic deficit, Glasgow Coma Scale <14 points, AIDS/HIV, and seizure-were included in the development diagnostic model (P<0.05). The pool data's model had an Area Under the Receiver Operating Characteristics (AUC) curve of 0.892 (95% confidence interval 0.864-0.921, P<0.0001). A promising and straightforward screening tool for central nervous system infections, with few and readily available clinical variables, was developed and had good accuracy, with internal and external validity.


The CDCP1 Signaling Hub: A Target for Cancer Detection and Therapeutic Intervention.
CUB-domain containing protein 1 (CDCP1) is a type I transmembrane glycoprotein that is upregulated in malignancies of the breast, lung, colorectum, ovary, kidney, liver, pancreas, and hematopoietic system. Here, we discuss CDCP1 as an important hub for oncogenic signaling and its key roles in malignant transformation and summarize approaches focused on exploiting it for cancer diagnosis and therapy. Elevated levels of CDCP1 are associated with progressive disease and markedly poorer survival. Predominantly located on the cell surface, CDCP1 lies at the nexus of key tumorigenic and metastatic signaling cascades, including the SRC/PKCδ, PI3K/AKT, WNT, and RAS/ERK axes, the oxidative pentose phosphate pathway, and fatty acid oxidation, making important functional contributions to cancer cell survival and growth, metastasis, and treatment resistance. These findings have stimulated the development of agents that target CDCP1 for detection and treatment of a range of cancers, and results from preclinical models suggest that these approaches could be efficacious and have manageable toxicity profiles.


The SAR Payload Design and Performance for the GF-3 Mission.
This paper describes the C-band multi-polarization Synthetic Aperture Radar (SAR) sensor for the Gaofen-3 (GF-3) mission. Based on the requirement analysis, the design of working modes and SAR payload are given. An accurate antenna model is introduced for the pattern optimization and SAR performance calculation. The paper concludes with an overview of predicted performance which was verified by in-orbit tests.


Solvent extraction, ion chromatography, and mass spectrometry of molybdenum isotopes.
A procedure was developed that allows precise determination of molybdenum isotope abundances in natural samples. Purification of molybdenum was first achieved by solvent extraction using di(2-ethylhexyl) phosphate. Further separation of molybdenum from isobar nuclides was obtained by ion chromatography using AG1-X8 strongly basic anion exchanger. Finally, molybdenum isotopic composition was measured using a multiple collector inductively coupled plasma hexapole mass spectrometer. The abundances of molybdenum isotopes 92, 94, 95, 96, 97, 98, and 100 are 14.8428(510), 9.2498(157), 15.9303(133), 16.6787(37), 9.5534(83), 24.1346(394), and 9.6104(312) respectively, resulting in an atomic mass of 95.9304(45). After internal normalization for mass fractionation, no variation of the molybdenum isotopic composition is observed among terrestrial samples within a relative precision on the order of 0.00001-0.0001. This demonstrates the reliability of the method, which can be applied to searching for possible isotopic anomalies and mass fractionation.


Dynamic compressive loading enhances cartilage matrix synthesis and distribution and suppresses hypertrophy in hMSC-laden hyaluronic acid hydrogels.
Mesenchymal stem cells (MSCs) are being recognized as a viable cell source for cartilage repair, and there is growing evidence that mechanical signals play a critical role in the regulation of stem cell chondrogenesis and in cartilage development. In this study we investigated the effect of dynamic compressive loading on chondrogenesis, the production and distribution of cartilage specific matrix, and the hypertrophic differentiation of human MSCs encapsulated in hyaluronic acid (HA) hydrogels during long term culture. After 70 days of culture, dynamic compressive loading increased the mechanical properties, as well as the glycosaminoglycan (GAG) and collagen contents of HA hydrogel constructs in a seeding density dependent manner. The impact of loading on HA hydrogel construct properties was delayed when applied to lower density (20 million MSCs/ml) compared to higher seeding density (60 million MSCs/ml) constructs. Furthermore, loading promoted a more uniform spatial distribution of cartilage matrix in HA hydrogels with both seeding densities, leading to significantly improved mechanical properties as compared to free swelling constructs. Using a previously developed in vitro hypertrophy model, dynamic compressive loading was also shown to significantly reduce the expression of hypertrophic markers by human MSCs and to suppress the degree of calcification in MSC-seeded HA hydrogels. Findings from this study highlight the importance of mechanical loading in stem cell based therapy for cartilage repair in improving neocartilage properties and in potentially maintaining the cartilage phenotype.


[Analysis of 25 episodes of acute occupational poisoning accidents and studies on its preventive strategy].
To study the causes of the occurrence of severe acute occupational poisoning and its first-aid, and to improve its prevention and management. Data of labor health conditions in 25 episodes of poisoning during the past 13 years were collected and analyzed statistically according to industries, enterprises and toxicals. Twenty-five episodes of poisoning accidents involved 131 persons, with 22 deaths. The incidence rate of occupational poisoning accidents in township and town enterprises exceeded that in state-owned ones. Ten kinds of toxicants were involved in the poisoning, with the hydrogen sulfide, benzene, carbon monoxide, phosgene and organophosphorus pesticide at the top five places in the number of cases with poisoning they caused. There were another 131 persons intoxicated during their emergency action and eight deaths, with a higher incidence and mortality rates due to poisoning than those in the operation workers. The major causes of the poisoning accidents were lack of knowledge of prevention and protection from them. It laid a good foundation for the establishment of emergency rescuing system in the grassroots.


The STAGE technique (superficial tunica albuginea geometric-based excision) for the correction of biplanar congenital penile curvature.
Congenital penile curvature can present with both uniplanar and biplanar defects, the latter of which entails more technically demanding surgery. The study aims to demonstrate the efficacy and safety of our novel superficial tunica albuginea geometric-based excision (STAGE) technique based on multiple, small, superficial elliptical tunica albuginea excisions and geometrical principles for correcting biplanar congenital penile curvature. The study represents a retrospective analysis of 145 patients with disabling congenital biplanar ventrolateral (n = 131; 90.3%) or dorsolateral (n = 14; 9.7%) curvature of the penis, which underwent stepwise STAGEs between June 2006 and March 2012. Multiple 3-mm elliptical excisions of the superficial tunica albuginea were performed without compromising the inner layer of the tunica albuginea, thus resulting in a stepwise correction of the curvature and improved distribution of the bending force of the curvature. Functional outcome regarding penile straightening, erectile function, and patient satisfaction were evaluated. Furthermore, clinical data concerning the early postoperative outcome were analyzed retrospectively. The mean follow-up period was 21 months (range 6-62 months). Mean age at surgery was 23.8 years (range 15-47 years). Mean degree of curvature was 65° (range 45-90°). There was no recurrent curvature. Complete correction of the penile axis was obtained in 98.6% (n = 143). No change in erectile function according to International Index of Erectile Function-5 score was visible (P = 0.748). The mean loss of penile length was 0.7 cm (range 0.3-0.9 cm). The excellent functional outcomes resulted in a high level of patient satisfaction, including improved self-esteem, libido, sexual intercourse, and psychosexual relief. Two patients had a residual curvature of up to 30° requiring a reoperation. No intra- or postoperative complications were encountered. We recommend the STAGE technique as the optimal surgical intervention for correcting both uniplanar and biplanar congenital deviations.


Unification of T2a and T2b tumors to T2 tumors in non-small cell lung cancer staging.
We investigated the validation of the seventh edition of the TNM staging (2009) system for lung cancer, retrospectively. From January 1990 to March 2004, 1629 patients who underwent lung resection with systemic lymph node dissection for non-small cell lung cancer at Nippon Medical School and Saitama Cancer Center were included. The overall survivals after surgery by each pathological stage according to the 1997 and 2009 systems were statistically analyzed using Kaplan-Meier estimated survival curves, and the significance of the difference was analyzed by the log-rank test. The 2009 system had significant prognostic distinction between each T descriptor except for T2a and T2b, and between each M descriptor. The 2009 system had better prognostic distinction between each pathological stage except for stages IB and IIA, and stages IIIB and IV. In the simulation, we unified T2a and T2b tumors into T2 tumors, and T2bN0M0 and T2bN1M0 were moved to stages IB and IIA, respectively. This proposed system had significant prognostic distinction between the proposed IB, IIA, and IIB stages. The 2009 system provides better patient selection for surgery and prognostic distinction between each stage except for stages IB and IIA, and stages IIIB and IV, compared with the 1997 system. Unification of T2a and T2b tumors to T2 tumors can improve prognostic distinction between stages IB and IIA.


Artificial intelligence in healthcare: Proposals for policy development in South Africa.
Despite the tremendous promise offered by artificial intelligence (AI) for healthcare in South Africa, existing policy frameworks are inadequate for encouraging innovation in this field. Practical, concrete and solution-driven policy recommendations are needed to encourage the creation and use of AI systems. This article considers five distinct problematic issues which call for policy development: (i) outdated legislation; (ii) data and algorithmic bias; (iii) the impact on the healthcare workforce; (iv) the imposition of liability dilemma; and (v) a lack of innovation and development of AI systems for healthcare in South Africa. The adoption of a national policy framework that addresses these issues directly is imperative to ensure the uptake of AI development and deployment for healthcare in a safe, responsible and regulated manner.


Absolute molecular weight of polyaniline.
The absolute molecular weight of polyaniline in the pernigraniline, emeraldine, and leucoemeraldine oxidation states has been measured by light scattering and the exact number of aniline repeat units determined for the first time. Using potential-time profiling to monitor the chemical oxidative polymerization of aniline using ammonium peroxydisulfate oxidant, all three oxidation states of polyaniline can be synthesized in one step and the evolution of polymer molecular weight monitored. The pernigraniline intermediate formed during the chemical oxidative polymerization of aniline increases by 17-20% when it is converted to emeraldine, which is consistent with a two-step polymerization mechanism. These findings establish a solid experimental framework to chemically synthesize block copolymers of polyaniline by using different monomers to intercept the reaction at the pernigraniline oxidation state.


Postoperative complications in patients with human immunodeficiency virus disease. Clinical data and a literature review.
To compare complications after and outcome from surgical procedures between patients with human immunodeficiency virus (HIV) disease and a matched control population. Retrospective case review. 476-bed university tertiary care center. Of 343 patients diagnosed as having HIV disease between 1981 and September 1991, 26 (7.6 percent) were Walter Reed classifications system 3B or greater and underwent a surgical procedure with general anesthesia or, in the case of 2 patients, regional anesthesia, at the study hospital. These patients were matched to 26 control patients by severity of illness according to APACHE II severity of illness score and by age, sex, race, and anesthetic regimen. The postoperative occurrence of dysrhythmia, hypotension, hypoxia, hemorrhage, renal insufficiency, or infection was evaluated in the study and control groups. Deaths within 3 and 30 days of the procedure and duration of survival after discharge from the hospital were recorded. Frequency of complications and 3- and 30-day mortality did not differ between the 2 groups. Duration of survival after discharge from the hospital in patients with HIV disease (7.4 +/- 9.7 months) was approximately 25 percent that in control patients (30.6 +/- 35.9 months) (p = 0.02). HIV disease does not increase the risk of postprocedural complications, including death, up to 30 days postprocedure. Thereafter, patients with HIV disease classified by the Walter Reed System as > or = 3B may survive for a shorter time than do equally ill patients who do not have HIV disease. Thus, needed surgical intervention should not be limited based on HIV status and concern for subsequent complications.


The third intracellular loop of D1 and D5 dopaminergic receptors dictates their subtype-specific PKC-induced sensitization and desensitization in a receptor conformation-dependent manner.
We previously showed that phorbol-12-myristate-13-acetate (PMA) mediates a robust PKC-dependent sensitization and desensitization of the highly homologous human Gs protein and adenylyl cyclase (AC)-linked D1 (hD1R) and D5 (hD5R) dopaminergic receptors, respectively. Here, we demonstrate using forskolin-mediated AC stimulation that PMA-mediated hD1R sensitization and hD5R desensitization is not associated with changes in AC activity. We next employed a series of chimeric hD1R and hD5R to delineate the underlying structural determinants dictating the subtype-specific regulation of human D1-like receptors by PMA. We first used chimeric receptors in which the whole terminal region (TR) spanning from the extracellular face of transmembrane domain 6 to the end of cytoplasmic tail (CT) or CT alone were exchanged between hD1R and hD5R. CT and TR swaps lead to chimeric hD1R and hD5R retaining PMA-induced sensitization and desensitization of wild type parent receptors. In striking contrast, hD1R sensitization and hD5R desensitization mediated by PMA are correspondingly switched to PMA-induced receptor desensitization and sensitization following the IL3 swap between hD1R and hD5R. Cell treatment with the PKC blocker, Gö6983, inhibits PMA-induced regulation of these chimeric receptors in a similar fashion to wild type receptors. Further studies with chimeras constructed by exchanging IL3 and TR show that PMA-induced regulation of these chimeras remains fully switched relative to their respective wild type parent receptor. Interestingly, results obtained with the exchange of IL3 and TR also reveal that the D1-like subtype-specific regulation by PMA, while fully dictated by IL3, can be modulated in a receptor conformation-dependent manner. Overall, our results strongly suggest that IL3 is the critical determinant underlying the subtype-specific regulation of human D1-like receptor responsiveness by PKC.


Dietary soybean protein compared with casein damages colonic epithelium and stimulates colonic epithelial proliferation in rats.
Recently we showed that soybean protein compared with casein stimulates the fecal excretion of endogenous magnesium. In the present study we investigated whether this differential effect of soybean protein is due to intestinal epithelial cell damage and thus results in a compensating increase in proliferation of epithelial cells. Two groups of six rats were fed purified high fat, low calcium diets, differing only in the type of protein. When compared with casein feeding, soybean protein feeding stimulated the fecal excretion of magnesium, fat and fatty acids, but had no effect on the excretion of bile acids. In fecal water, the concentration of bile acids was lower when soybean protein was fed. In contrast, free fatty acid concentration, as well as luminal cytolytic activity, was higher in fecal water of rats fed soybean protein. Furthermore, epithelial cell damage and proliferation of colonic epithelium (measured as in vivo incorporation of tritiated thymidine into DNA) were greater in rats fed soybean protein. The stimulation of colonic proliferation by soybean protein is consistent with the observed increase in luminal cytolytic activity and epithelial cell damage. We conclude that the stimulatory effect of soybean protein on endogenous magnesium excretion is due to a soybean protein-specific damage of colonic epithelial cells, which results in a compensatory epithelial cell hyperproliferation.


[Correction of myopia with the intracorneal ring].
The Implantation of intracorneal ring segments (ICRS) offers the possibility of reversible, refractive surgery for correction of lower myopia up to -5.0 D. We report our first results 1 year after implantation of ICR segments. From April 1997 to August 1998 we implanted ICRS in 48 eyes of 31 patients (12 male, 19 female) to correct myopia. The preoperative refraction (spherical equivalent) was between -1.0 and -5.0 D (astigmatism < 1.0 D). The average age was 34.0 years (range 19-48 years). ICRS implantation was performed in peribulbar anaesthesia. All operations were done by the same surgeon. The average follow-up was 10 months (ranges 1-12 months). After 6 months the deviation from the target refraction of all eyes was < 1.5 D; 26 of 27 eyes (96.3%) showed a deviation of < or = 1.0 D. Six months after surgery, 18 of 27 eyes (66.6%) showed an uncorrected visual acuity of 20/20 or better, 23 of 26 eyes (88.4%) showed 20/25 or better, and 25 of 26 eyes (96.2) 20/40 and better. Only 1 of 16 eyes showed an uncorrected visual acuity of 20/50. In all eyes, the best-corrected visual acuity was 20/20 or better. In 2 eyes an ICRS exchange and implantation of a thicker ring was necessary because the target refraction could not be achieved with the first implanted ring. In 2 eyes an ICRS reposition was done to optimize the location of the ring within the cornea. In 4 eyes we explanted the ring due to double vision (1 x) and distorted vision (3 x) caused by induced astigmatism. After explantation the preoperative refraction (+/- 0.15 D) was reached within 1 to 1.5 months. There was no regression after 6 months (n = 27) or after 1 year (n = 7). Our 1-year results of ICRS implantation show that myopia correction with the advantage of reversibility and lower complication rate is possible by this refractive surgical method. Ring exchange and explantation are possible. Earlier postoperative complaints like photophobia, unstable visual acuity or discomfort usually disappear rapidly. The decision of 95.0% of the patients to have ICRS implantation also into the second eye shows the high degree of satisfaction.


Folk beliefs of cultural changes in China.
For the last several decades, Chinese society has experienced transformative changes. How are these changes understood among Chinese people? To examine this question, Part 1 in this research solicited folk beliefs of cultural change from a group of Chinese participants in an open-ended format, and the generated folk beliefs were rated by another group of participants in Part 2 to gage each belief's level of agreement. Part 3 plotted the folk beliefs retained in Part 2 using the Google Ngram Viewer in order to infer the amount of intellectual interests that each belief has received cross-temporarily. These analyses suggested a few themes in Chinese folk beliefs of cultural change (1) rising perceived importance of materialism and individualism in understanding contemporary Chinese culture and Chinese psychology relative to those of the past (2) rising perceived importance of freedom, democracy and human rights and (3) enduring perceived importance of family relations and friendship as well as patriotism. Interestingly, findings from Parts 2 and 3 diverged somewhat, illuminating possible divergence between folk beliefs and intellectual interests especially for issues related to heritage of Confucianism.


Pollen morphology and its taxonomic potential in some selected taxa of Caesalpiniaceae observed under light microscopy and scanning electron microscopy.
Pollen micromorphology is not only used to check the functional and structural evolution in plants but also to solve the taxonomic problem related to the classification of plants. Therefore, keeping in view the significance of pollen traits, selected taxa of the subfamily Caesalpiniaceae was collected from different geographical regions of Pakistan. The species were then analyzed under both light microscopy and scanning electron microscopy techniques to investigate the importance of micromorphological characters of pollen in the identification and classification of species. Great variation was recorded in equatorial shape, surface ornamentation, tectum, polar diameter, equatorial diameter, and exine thickness. However, little variation was observed in pollen type, polar shape, and fertility of pollen. The equatorial shape of five types was observed: prolate, prolate-spheroidal, spheroidal-subprolate, subspheroidal-prolate, and subspheroidal. Four types of surface ornamentation, psilate, granulate, clavate, and perforate, were recorded. Tectum of five types, intactate, reticulate regulate, medium reticulate, tactate, and striate, was observed. Sexine was thicker than nexine in all studied species. The largest polar diameter was observed in Caesalpinia pulcherrima 64.1 μm while the smallest in Parkinsonia aculeata 26.1 μm. The largest equatorial diameter was found in C. pulcherrima of 70.25 μm whereas the smallest in P. aculeata 27.57 μm. All the pollens analyzed were tricolporate. All studied species have a fertility ratio of more than 90%. A taxonomic key was developed to show the variation in pollen features and delimit species for the correct identification. In conclusion, the pollen traits were found useful to define species boundaries at various taxonomic ranks and will strengthen the taxonomy of this subfamily. Besides, this study also explored the palynological traits and their implication in the taxonomy of the subfamily Caesalpiniaceae.


Time-of-day and attentional-order influences on dichotic processing of digits in learning disabled and normal achieving children.
A heterogeneous group of 26 learning disabled (LD) and 30 normal achieving (NA) children, responded to a dichotic listening task using digits in morning and afternoon settings. Attentional order (i.e., right ear first versus left ear first) interacted with (1) Time-of-Day and (2) Group and Ear Attended. The first interaction revealed, as predicted, higher morning performance for subjects directed to attend right first. Subjects directed left first showed higher afternoon performance. These results are consistent with enhanced left hemisphere involvement after left hemisphere priming in the morning, and after right hemisphere priming in the afternoon. The second interaction indicated the LD had more difficulty than controls switching attention to the right ear when instructed to attend left first. The LD may activate the right hemisphere (via left hemispace attending) and have difficulty with subsequent right hemisphere inhibition, or left hemisphere activation, when shifting to right ear attending. Nonparametric tests revealed a greater incidence of lateralized responders in the morning for normal achievers attending left first. Findings are seen to augment previous research.


[Determination of 25 quinolones in cosmetics by liquid chromatography-tandem mass spectrometry].
An analytical method was developed for the simultaneous determination of 25 quinolones, including danofloxacin mesylate, enrofloxacin, flumequine, oxloinic acid, ciprofloxacin, sarafloxacin, nalidixic acid, norfloxacin, and ofloxacin etc in cosmetics using direct extraction and liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). Cosmetic sample was extracted by acidified acetonitrile, defatted by n-hexane and separated on Poroshell EC-C18 column with gradient elution program using acetonitrile and water (both containing 0. 1% formic acid) as the mobile phases and analyzed by LC-ESI-MS/MS under the positive mode using multiple reaction monitoring (MRM). The interference of matrix was reduced by the matrix-matched calibration standard curve. The method showed good linearities over the range of 1-200 mg/kg for the 25 quinolones with good linear correlation coefficients (r ≥ 0.999). The method detection limit of the 25 quinolones was 1.0 mg/kg, and the recoveries of all analytes in lotion, milky and cream cosmetics matrices ranged from 87.4% to 105% at the spiked levels of 1, 5 and 10 mg/kg with the relative standard deviations (RSD) of 4.54%-19.7% (n = 6). The results indicated that this method is simple, fast and credible, and suitable for the simultaneous determination of the quinolones in the above three types of cosmetics.


Heparanase inhibits osteoblastogenesis and shifts bone marrow progenitor cell fate in myeloma bone disease.
A major cause of morbidity in patients with multiple myeloma is the development and progression of bone disease. Myeloma bone disease is characterized by rampant osteolysis in the presence of absent or diminished bone formation. Heparanase, an enzyme that acts both at the cell-surface and within the extracellular matrix to degrade polymeric heparan sulfate chains, is upregulated in a variety of human cancers including multiple myeloma. We and others have shown that heparanase enhances osteoclastogenesis and bone loss. However, increased osteolysis is only one element of the spectrum of myeloma bone disease. In the present study, we hypothesized that heparanase would also affect mesenchymal cells in the bone microenvironment and investigated the effect of heparanase on the differentiation of osteoblast/stromal lineage cells. Using a combination of molecular, biochemical, cellular and in vivo approaches, we demonstrated that heparanase significantly inhibited osteoblast differentiation and mineralization, and reduced bone formation in vivo. In addition, heparanase shifts the differentiation potential of osteoblast progenitors from osteoblastogenesis to adipogenesis. Mechanistically, this shift in cell fate is due, at least in part, to heparanase-enhanced production and secretion of the Wnt signaling pathway inhibitor DKK1 by both osteoblast progenitors and myeloma cells. Collectively, these data provide important new insights into the role of heparanase in all aspects of myeloma bone disease and strongly support the use of heparanase inhibitors in the treatment of multiple myeloma.


Aging and urinary bladder carcinogenesis induced in rats by N-butyl-N-(4-hydroxybutyl)nitrosamine.
The effect of age on induction of carcinogenesis by N-butyl-N-(4-hydroxybutyl)nitrosamine [(BBN) CAS: 3817-11-6] in the urinary bladder epithelium was examined in 130 male and 130 female F344 rats. Rats of both sexes 6, 52, and 98 weeks old were given 0.025% BBN in their drinking water for 20 weeks. Then approximately half the rats were sacrificed, while the rest were maintained without further treatment for 10 weeks. Examination of the rats revealed an age-related increase in the induction of urinary bladder carcinoma, although the total intakes of BBN and urinary excretions of its proximate carcinogen were not age related. Rats treated with BBN at 98 weeks of age developed more squamous cell carcinomas and invasive carcinomas than the 2 younger groups. This study demonstrated an increased risk of urinary bladder carcinogenesis with age in animals.


Benchmarking Critical Care Well-Being: Before and After the Coronavirus Disease 2019 Pandemic.
Examine well-being, measured as burnout and professional fulfillment, across critical care healthcare professionals, ICUs, and hospitals within a health system; examine the impact of the coronavirus disease 2019 pandemic. To complement a longitudinal survey administered to medical critical care physicians at the end of an ICU rotation, which began in May 2018, we conducted a cross-sectional survey among critical care professionals across four hospitals in December 2018 to January 2019. We report the results of the cross-sectional survey and, to examine the impact of the coronavirus disease 2019 pandemic, the longitudinal survey results from July 2019 to May 2020. Academic medical center. Four-hundred eighty-one critical care professionals, including 353 critical care nurses, 58 advanced practice providers, 57 physicians, and 13 pharmacists, participated in the cross-sectional survey; 15 medical critical care physicians participated in the longitudinal survey through the coronavirus disease 2019 pandemic. None. Burnout was present in 50% of ICU clinicians, ranging from 42% for critical care physicians to 55% for advanced practice providers. Professional fulfillment was less common at 37%, with significant variability across provider (p = 0.04), with a low of 23% among critical care pharmacists and a high of 53% among physicians. Well-being varied significantly at the hospital and ICU level. Workload and job demand were identified as drivers of burnout and meaning in work, culture and values of work community, control and flexibility, and social support and community at work were each identified as drivers of well-being. Between July 2019 and March 2020, burnout and professional fulfillment were present in 35% (15/43) and 58% (25/43) of medical critical care physician responses, respectively. In comparison, during the coronavirus disease 2019 pandemic, burnout and professional fulfillment were present in 57% (12/21) and 38% (8/21), respectively. Burnout was common across roles, yet differed across ICUs and hospitals. Professional fulfillment varied by provider role. We identified potentially modifiable factors related to clinician well-being that can inform organizational strategies at the ICU and hospital level. Longitudinal studies, designed to assess the long-term impact of the coronavirus disease 2019 pandemic on the well-being of the critical care workforce, are urgently needed.


RiboCAT: a new capillary electrophoresis data analysis tool for nucleic acid probing.
Chemical and enzymatic probing of RNA secondary structure and RNA/protein interactions provides the basis for understanding the functions of structured RNAs. However, the ability to rapidly perform such experiments using capillary electrophoresis has been hampered by relatively labor-intensive data analysis software. While these computationally robust programs have been shown to calculate residue-specific reactivities to a high degree of accuracy, they often require time-consuming manual intervention and lack the ability to be easily modified by users. To alleviate these issues, RiboCAT (Ribonucleic acid capillary-electrophoresis analysis tool) was developed as a user-friendly, Microsoft Excel-based tool that reduces the need for manual intervention, thereby significantly shortening the time required for data analysis. Features of this tool include (i) the use of an Excel platform, (ii) a method of intercapillary signal alignment using internal size standards, (iii) a peak-sharpening algorithm to more accurately identify peaks, and (iv) an open architecture allowing for simple user intervention. Furthermore, a complementary tool, RiboDOG (RiboCAT data output generator) was designed to facilitate the comparison of multiple data sets, highlighting potential inconsistencies and inaccuracies that may have occurred during analysis. Using these new tools, the secondary structure of the HIV-1 5' untranslated region (5'UTR) was determined using selective 2'-hydroxyl acylation analyzed by primer extension (SHAPE), matching the results of previous work.


Anti-Inflammatory Pyranochalcone Derivative Attenuates LPS-Induced Acute Kidney Injury via Inhibiting TLR4/NF-κB Pathway.
Treatment of septic acute kidney injury (AKI) has still been beyond satisfaction, although anti-inflammatory therapy is beneficial for sepsis-induced AKI. Compound 5b was derived from natural pyranochalcones and exhibited potent anti-inflammatory activity in adjuvant-induced arthritis. In this study, we aimed to investigate the renoprotective effects and potential mechanism of 5b against lipopolysaccharide (LPS)-induced AKI. C57BL/6 mice and human renal proximal tubule cell line (HK-2 cell) were treated with LPS, respectively. Compound 5b was orally administrated at a dose of 25 mg/kg/day for 5 days before LPS (10 mg/kg) intraperitoneal injection. Cells were pretreated with 25 μg/mL 5b for 30 min before LPS (1 μg/mL) treatment. Pretreatment with 5b markedly alleviated tubular injury and renal dysfunction in LPS-induced AKI. The expression of IL-1β, IL-6, and TNF-α both in renal tissue of AKI mice and in the LPS-stimulated HK-2 cell culture medium were reduced by 5b treatment (p < 0.05). The results of immunohistochemistry staining showed that 5b reduced the expression of NF-κB p65 in kidneys. Similarly, 5b decreased the LPS-induced levels of NF-κB p65 and TLR4 proteins in kidneys and HK-2 cells. These data demonstrated that a potent pyranochalcone derivative, 5b, exhibited renoprotective effect against LPS-induced AKI, which was associated with anti-inflammatory activity by inhibiting the TLR4/NF-κB pathway.


Body Randomization Reduces the Sim-to-Real Gap for Compliant Quadruped Locomotion.
Designing controllers for compliant, underactuated robots is challenging and usually requires a learning procedure. Learning robotic control in simulated environments can speed up the process whilst lowering risk of physical damage. Since perfect simulations are unfeasible, several techniques are used to improve transfer to the real world. Here, we investigate the impact of randomizing body parameters during learning of CPG controllers in simulation. The controllers are evaluated on our physical quadruped robot. We find that body randomization in simulation increases chances of finding gaits that function well on the real robot.


Data mining reveal the association between diabetic foot ulcer and peripheral artery disease.
Diabetic foot ulcer (DFU) and peripheral artery disease (PAD) are common diseases that seriously affect the quality of life and bring a huge economic burden to society. Although mounting evidence supports a close link between the two disorders, the mechanisms of comorbidity remain to be fully elucidated. The gene expression profiles of DFU (GSE80178) and PAD (GSE100927) were downloaded from the Gene Expression Omnibus (GEO) database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) performed pathway enrichment analysis for common differentially expressed genes (DEGs) present in DFU and PAD. Subsequently, we constructed a protein-protein interaction (PPI) network using the STRING database and detected core modules and hub genes in the network. Finally, we analyzed the co-expression network and the TF-miRNA-mRNA regulatory network of hub genes. A total of 167 common DEGs (91 up-regulated genes and 76 down-regulated genes) was selected for subsequent analyses. Functional analysis emphasizes the important role of chemokines and cytokines in these two diseases. Finally, six hub genes were identified using cytoHubba, including CXCL8, IL1RN, MMP1, CD68, CCR7 and CCL3. The hub genes and signaling pathways involved can regulate both diseases simultaneously, suggesting a close relationship between the molecular mechanisms of the two diseases and possible targets for drugs that intervene in both diseases.


Enteral nutrition in patients with pancreatitis.
Nutritional support in the form of total parenteral nutrition (TPN) or enteral nutrition (EN) is successfully used in patients with pancreatitis, in whom the goal is to provide optimal nutrition while minimizing pancreatic exocrine activity. Controversy continues as to whether TPN or EN is more appropriate. Although TPN is traditionally preferred in acute pancreatitis, EN offers some advantages, being more physiologic, safer, and more cost-effective. A review of available animal and human studies suggests that elemental diets may be effective in patients with mild acute pancreatitis. In patients who have no clinical indication for restricting the gastrointestinal tract, EN may be preferred.


Molecular detection and characterization of zoonotic Anaplasma species in domestic dogs in Lusaka, Zambia.
Although tick-borne pathogens, Anaplasma platys and Anaplasma phagocytophilum are recognized as zoonotic agents associated with appreciable morbidity and mortality in dogs and humans worldwide, there is limited information on these infections in many African countries, including Zambia. The purpose of this study was to detect, identify and phylogenetically characterize Anaplasma species from dogs in Chilanga District in Lusaka Province, Zambia. A total of 301 blood samples were collected from apparently healthy and semi-confined dogs. Initial screening by polymerase chain reaction with specific primers targeting the 16S rRNA gene of Anaplasma species revealed that 9% (27/301) of our samples were positive. Subsequent sequence and phylogenetic analysis of a longer fragment of the 16S rRNA and citrate synthase (gltA) genes of four positive samples showed the presence of A. platys and an Anaplasma species, which was closely related to those detected in dogs in South Africa. This is the first report on molecular identification and characterization of canine-associated zoonotic Anaplasma species in Zambia.


Eco-evolutionary feedbacks can rescue cooperation in microbial populations.
Bacterial populations whose growth depends on the cooperative production of public goods are usually threatened by the rise of cheaters that do not contribute but just consume the common resource. Minimizing cheater invasions appears then as a necessary mechanism to maintain these populations. However, that invasions result instead in the persistence of cooperation is a prospect that has yet remained largely unexplored. Here, we show that the demographic collapse induced by cheaters in the population can actually contribute to the rescue of cooperation, in a clear illustration of how ecology and evolution can influence each other. The effect is made possible by the interplay between spatial constraints and the essentiality of the shared resource. We validate this result by carefully combining theory and experiments, with the engineering of a synthetic bacterial community in which the public compound allows survival to a lethal stress. The characterization of the experimental system identifies additional factors that can matter, like the impact of the lag phase on the tolerance to stress, or the appearance of spontaneous mutants. Our work explains the unanticipated dynamics that eco-evolutionary feedbacks can generate in microbial communities, feedbacks that reveal fundamental for the adaptive change of ecosystems at all scales.


Diagnosis of arteriogenic impotence: efficacy of duplex sonography as a screening tool.
The results of duplex sonography of the cavernosal artery were compared with the results of pharmacoarteriography in a series of impotent men in order to assess the validity of sonography as a screening tool for the diagnosis of arteriogenic impotence. Duplex sonography was performed in 30 impotent men after intracavernosal injection of papaverine and phentolamine. Maximal acceleration, peak systolic velocity, and resistive index were determined for the cavernosal artery. All patients had selective pharmacoarteriography and cavernosometry, which were used to diagnose arterial disease (bilateral hemodynamically significant stenoses or occlusions), suspected arteriolar dysfunction (inconspicuous helicine arterioles), or venoocclusive insufficiency (pharmacologic maintenance erectile flow greater than 25 ml/min). Seventeen patients had arterial insufficiency, four had arteriolar dysfunction, and nine had no significant arterial disease. Significant differences in Doppler measurements were found between patients without significant arterial disease and those with arterial insufficiency, including peak systolic velocity (50 +/- 25 cm/sec vs 33 +/- 17 cm/sec, p = .04), acceleration (524 +/- 261 cm/sec2 vs 199 +/- 111 cm/sec2, p < .001), and resistive index (88 +/- 12% vs 73 +/- 11%, p = .002). Differences were also noted between the group without significant arterial disease and the group with arteriolar dysfunction. When peak systolic velocity of less than 25 cm/sec or acceleration less than 400 cm/sec2 was used as an indication of inadequate arterial patency, the sensitivities were 35% and 100%, the specificities were 61% and 46%, and the negative predictive values were 42% and 100%, respectively, in the diagnosis of arterial insufficiency. Duplex sonography of the cavernosal arteries may be a useful screening tool in patients with suspected arteriogenic impotence only when acceleration is evaluated in addition to peak systolic velocity. The specificity of the method may be partially limited by the inability to distinguish between arterial and arteriolar disease.


Epidemiological Findings of Alcohol Misuse and Dependence Symptoms among Adolescent Girls and Young Women Involved in High-Risk Sexual Behavior in Kampala, Uganda.
Alcohol-related harms may be increased among adolescent girls and young women (AGYW) involved in sex work, yet data on alcohol misuse among AGYW in sub-Saharan Africa are still scarce. We conducted a cross-sectional study among 15-24-year-old AGYW from January 2013 to December 2018 in Kampala, Uganda and used the Alcohol Use Disorder Identification Test (AUDIT) to study alcohol use patterns and dependence symptoms (dependence score ≥4). Of 1440 participants (median age 21 years), 83.1% had less than secondary education, 79.8% reported ≥10 paying sexual partners in the past month, 46.0% had ever experienced intimate partner violence (IPV), and 20.6% were living with HIV. Overall, 59.9% scored ≥8 and 29.4% scored ≥16 on the AUDIT. Of 277 (15.8%) with dependence symptoms, 69.1% were screened alcohol dependent. An AUDIT score ≥8 was associated with older age, illicit drug use, experiencing IPV, inconsistent condom use with paying partners, and HIV sero-negativity. All factors remained associated with a higher score ≥16 except HIV status. Similarly, illicit drug use, experiencing IPV and inconsistent condom use were associated with dependence symptoms and, in addition, a higher number of paying sexual partners. Alcohol misuse is high in this population, they urgently need harmful substance use reduction interventions.


[Effects of insecticides on insect pest-natural enemy community in early rice fields].
This paper studied the effects of triazophos, shachongshuang, abamectin, and Bt + imidacloprid on the insect pest-natural enemy community in early rice fields in the Yangtze-Huaihe region of Anhui Province. The results showed that all of the test insecticides had significant effects in controlling the growth of major insect pest populations. The average value of insect pest-natural enemy community diversity under effects of triazophos, shachongshuang, abamectin, and Bt + imidacloprid was 1.545, 1.562, 1.691 and 1.915, respectively, while that in control plot was 1.897. After two weeks of applying insecticides, the plots applied with shachongshuang and abamectin had a similar composition of insect pest-natural enemy community, but the community composition was significantly different between the plots applied with triazophos and Bt + imidacloprid. From the viewpoints of community stability and pest control, Bt + imidacloprid had the best effect, and shachongshuang and abamectin were better than triazophos.


[Bilateral giant scrotal hydrocele in an adult].
Bilateral giant hydrocele in an adult is a rare clinical entity. A 31-year-old man presented with painless bilateral scrotal swelling that had appeared at age 13 years and had increased very slowly since. Computed tomography and ultrasonography revealed collection of fluid on both sides of the scrotum. Giant scrotal hydrocele were diagnosed, and surgical excision was performed. The fluid volume was 1,050 ml in right, 645 ml in left. No inguinal hernia was found. Pathologic examination of the resected portion of the tunica vaginalis testis revealed inflammatory changes, and fluid cytology was negative. Eight months has passed, and there has been no evidence of recurrence.


Nanotube Active Water Pump Driven by Alternating Hydrophobicity.
Water transport must be efficiency controlled for the future sustainability of life. Various water transport systems using carbon nanotubes have been proposed in recent years. Although these systems are more permeable than aquaporins, their water transport is passive. In this study, we successfully demonstrate an active water pump driven by simple hydrophobic interaction through computer simulation. Even in the absence of a pressure- or density-gradient, the proposed pump can actively transport water molecules by alternately switching the hydrophobicity of the pump surface. The water transport rate can be easily controlled by varying the time interval of switching. The pump with optimized switching time exhibits prominent water permeance. The results obtained herein can be applied in various water transport technologies because of the simple mechanics. The proposed water pump has the potential to realize an effective device such as a low-energy artificial purification system.