Simple systemic index associated with oxaliplatin-induced liver damage can be a novel biomarker to predict prognosis after resection of colorectal liver metastasis.
Oxaliplatin, an anticancer drug for advanced colorectal cancer, causes liver sinusoidal damage, sometimes with portal hypertension. We conducted a retrospective comparative study of the relationship of liver sinusoidal disorders and liver function with the prognosis in patients who underwent hepatectomy for colorectal liver metastasis (CRLM). In total, 158 patients who underwent hepatectomy for CRLM were included in the study, and the effect of chemotherapy-associated liver damage on the prognosis was examined. Preoperative oxaliplatin was used in 75 of 158 patients; of these 75 patients, 26 had intraoperative blue liver (BL). In a comparison of the BL group (n = 26) and non-BL group (n = 132), patients in the BL group had a significantly lower serum albumin concentration and a significantly higher indocyanine green test result, aspartate aminotransferase-to-platelet ratio index (APRI), and FIB-4 score. Operative morbidities were not significantly different between the two groups. The overall survival rate after hepatectomy was significantly worse in the BL group than in the non-BL group. In the univariate analysis, the serum albumin concentration, indocyanine green test, a high tumor burden score (TBS), and the APRI were statistically significant poor prognostic factors. In the multivariate analysis, the APRI and a high TBS were independent poor prognostic factors. The APRI and TBS in patients with CRLM are prognostic predictors after hepatectomy for metastatic liver cancer. This study indicated that liver damage in patients treated with preoperative oxaliplatin has an effect on the prognosis.


Clinically successful dentin and enamel bonding.
This manuscript highlights clinical applications of the Tenure dentin bonding agent. Research comparing diametral and bond strengths, and microleakage of Tenure and other dentin bonding agents is presented. The Light-cured Zionomer glass ionomer is shown to provide a superior dentin bond when compared to Vitrabond.


Inherent laxity in total knee prostheses.
The anterior-posterior and rotatory laxities of 14 total knee prosthesis designs were measured in a loading rig with compressive, shear, and torque loads representative of physiologic loads. The measured laxities covered a wide range, both greater and smaller than that of the anatomic knee. This range was mainly due to the curvature or flatness of the plastic tibial surface and conformity with the femoral component. Pressure patterns showed the corresponding contact track and area on the tibial surfaces. It is proposed that for normal function, the laxity of the device should complement the remaining anatomic structures to produce a combined laxity resembling that of the normal knee. Excessive prosthetic laxity will lead to the risk of instability, soft tissue attenuation, edge-loading on components, and high contact stresses on the plastic. Inadequate prosthetic laxity may lead to altered kinematics and excessive stresses at the interface, running the risk of long-term loosening. The authors show the laxities of many currently used devices, providing important background information for assessing the role intrinsic prosthetic constraint might play in total joint performance in clinical analyses.


Complications of dual chamber pacemaker implantation in the elderly. Pacemaker Selection in the Elderly (PASE) Investigators.
Pacemakers are frequently implanted, yet accurate prospective data on implant complications are limited. Elderly patients may be at increased risk of implant complications and are increasingly being referred for pacemaker implantation. The purpose of the present analysis was to define the incidence and possible predictors of serious complications of dual chamber permanent pacemaker implantation in the elderly. Therefore, we sought to prospectively identify the incidence and predictors of pacemaker implant complications in a large multicenter trial involving patients receiving a dual chamber pacemaker. The Pacemaker Selection in the Elderly (PASE) study was a prospective trial designed to evaluate quality of life in dual chamber pacemaker recipients age 65 years or older randomized to DDDR versus VVIR programming. In addition to being age 65 years or older, patients enrolled in this study were in normal sinus rhythm, and had standard indications for permanent pacemaker implantation. All patients received dual chamber pacemakers and were randomized to DDDR versus VVIR pacing. Pacemaker implant complications were collected on standardized forms which were completed at pacemaker implantation and during follow-up appointments. In this study of 407 patients, there were 26 complications occurring in 25 patients (6.1%). The most frequent complication was lead dislodgment which occurred in 9 patients. This was followed by pneumothorax (8 patients) and cardiac perforations (4 patients). In 18 patients (4.4%) repeat surgical procedures (including chest tubes) were required. Complications were noted prior to discharge in only 18 patients. There were no significant predictors of overall complications. Pneumothorax was more frequent in patients > or = 75 years old, and was observed only in patients with subclavian venous access. In conclusion, complications from pacemaker implantation in the elderly are seen in 6.1% of patients and 4.4% of patients require a repeat surgical procedure. Other than advanced age and lower weight predicting for pneumothorax, there are no significant clinical predictors of complications.


Transitions in the nuclear age: late adolescence to early adulthood.
College students, subjects in a 1983 study on reaction to that threat of nuclear war, participated in a follow-up study to investigate the changes that occur from late adolescence to early adulthood. The 41 subjects again completed the Nuclear War Attitude Survey (NWAS II) and, additionally, a second questionnaire and to 1 to 2 1/2 hour individual interview during which they were asked to explain changes in their answers to the NWAS II. Compared to their previous responses to the NWAS II, the responses of these young adults showed statistically significant decreases in the frequency they reported thinking about the possibility of nuclear war, their estimation of the likelihood of a nuclear war, and their intention to contact the news media to express their views. The researchers hypothesize that the major reasons for changes in response were (1) developmental differences, (2) the campus culture, (3) the political climate, (4) the media climate and (5) lack of engagement with the democratic process.


Fetal, Preterm, and Term Neonate Exposure to Remifentanil: A Systematic Review of Efficacy and Safety.
Owing to its pharmacodynamic properties, especially the rapid onset and short duration of its action, the use of remifentanil in obstetric anesthesia, as well as in neonatology, might be increasingly used. We conducted a systematic review to assess the efficacy and safety of remifentanil in preterm and term neonates. Outcomes of interest were neonatal adaptation after fetal exposure; neonatal pain, distress, and discomfort control during invasive procedures; and the occurrence of hemodynamic effects or respiratory depression induced by remifentanil infusion. Given the different contexts of use, we have organized this work into three parts: (A) use of remifentanil for labor or cesarean section, with exposure of the fetus before birth, (B) brief use for neonatal procedural analgesia, and (C) prolonged use for sedation/analgesia of neonates. The bibliographic search was conducted based on keywords using electronic medical databases (DATABASE, Cochrane Library, PubMed, and EMBASE) from 1 January 2000 until 31 December 2022. Twenty-two articles were included (10 in part A, 5 in part B and 7 in part C). Prospective, controlled, randomized, blinded, and intention-to-treat trials were retained. Neonates were well adapted after exposure to remifentanil in the fetal period. Pain, stress, and discomfort were controlled during a brief or prolonged invasive procedure when remifentanil was used for sedation/analgesia. The physiological parameters were stable and the procedures were straightforward. Chest wall rigidity appeared to be a common side effect, but this can be managed by slow and continuous infusion and by using the minimum effective dose. Remifentanil appears to be effective and safe in the short term in preterm and full-term neonates. However, its safety is compromised by the risk of chest wall rigidity. It should be used in appropriate neonatal units and in the presence of physicians able to monitor its side effects. Long-term outcomes have not been evaluated, to our knowledge.


PPAR-γ agonist, pioglitazone, reduced oxidative and endoplasmic reticulum stress associated with L-NAME-induced hypertension in rats.
Peroxisome proliferator-activated receptor γ (PPAR-γ) agonist, pioglitazone, is used clinically to improve the glycemic state in patients with type-2 diabetes mellitus. Independent of its blood glucose-lowering properties, pioglitazone ameliorates different cardiovascular disorders. The aim of the present study was to investigate the effect of pioglitazone on cardiovascular complications of N-nitro-L-arginine methyl ester (L-NAME)-induced hypertension and to determine the role of oxidative and endoplasmic reticulum (ER) stress in its activity. Nitric oxide (NO) deficiency induced by chronic L-NAME administration was associated with high blood pressure (BP) and cardiac hypertrophy. L-NAME induced oxidative stress as indicated by reduced glutathione (GSH) levels, superoxide dismutase (SOD) and catalase activities as well as increased malondialdehyde (MDA) levels. Furthermore, L-NAME increased the expression of ER stress markers, activating transcription factor-4 (ATF-4) and C/EPBα-homologous protein-10 (CHOP-10) in both heart and aorta of hypertensive rats. Activation of PPAR-γ by pioglitazone reduced BP, restored the blunted NO levels, increased endothelial NO synthase (eNOS) expression, and restored the antioxidant status of L-NAME-induced hypertensive rats. Moreover, the antihypertensive activity of pioglitazone was associated with a reduction in ER stress and this effect was PPAR-γ dependent. Interestingly, the effect of ER stress inhibitor, 4-phenylbutyric acid (4-PBA) and antioxidant, N-acetylcysteine (NAC), on BP, NO availability, oxidative stress and ER stress mimics the activity of pioglitazone. Taken together, our data suggests that PPAR-γ is a potential target to inhibit vascular complications and cardiac damage associated with NO-deficient HTN and puts more emphasis on the importance of ER stress in regulating PPAR-γ activity.


Human AP endonuclease (APE1/Ref-1) and its acetylation regulate YB-1-p300 recruitment and RNA polymerase II loading in the drug-induced activation of multidrug resistance gene MDR1.
The overexpression of human apurinic/apyrimidinic (AP) endonuclease 1 (APE1/Ref-1), a key enzyme in the DNA base excision repair (BER) pathway, is often associated with tumor cell resistance to various anticancer drugs. In this study, we examined the molecular basis of transcriptional regulatory (nonrepair) function of APE1 in promoting resistance to certain types of drugs. We have recently shown that APE1 stably interacts with Y-box-binding protein 1 (YB-1), and acts as its coactivator for the expression of multidrug resistance gene MDR1, thereby causing drug resistance. In this study, we show, to the best of our knowledge, for the first time that APE1 is stably associated with the basic transcription factor RNA polymerase II (RNA pol II) and the coactivator p300 on the endogenous MDR1 promoter. The depletion of APE1 significantly reduces YB-1-p300 recruitment to the promoter, resulting in reduced RNA pol II loading. Drug-induced APE1 acetylation, which is mediated by p300, enhances formation of acetylated APE1 (AcAPE1)-YB-1-p300 complex on the MDR1 promoter. Enhanced recruitment of this complex increases MDR1 promoter-dependent luciferase activity and its endogenous expression. Using APE1-downregulated cells and cells overexpressing wild-type APE1 or its nonacetylable mutant, we have demonstrated that the loss of APE1's acetylation impaired MDR1 activation and sensitizes the cells to cisplatin or etoposide. We have thus established the basis for APE1's acetylation-dependent regulatory function in inducing MDR1-mediated drug resistance.


Ecology and application of haloalkaliphilic anaerobic microbial communities.
Haloalkaliphilic microorganisms that grow optimally at high-pH and high-salinity conditions can be found in natural environments such as soda lakes. These globally spread lakes harbour interesting anaerobic microorganisms that have the potential of being applied in existing technologies or create new opportunities. In this review, we discuss the potential application of haloalkaliphilic anaerobic microbial communities in the fermentation of lignocellulosic feedstocks material subjected to an alkaline pre-treatment, methane production and sulfur removal technology. Also, the general advantages of operation at haloalkaline conditions, such as low volatile fatty acid and sulfide toxicity, are addressed. Finally, an outlook into the main challenges like ammonia toxicity and lack of aggregation is provided.


Influence of different molecular species of phosphatidylcholine on cholesterol transport from lipoprotein recombinants in the rat.
Studies were performed to determine to what extent phosphatidylcholines (PCs) of different composition influence the turnover of lipoprotein cholesterol. Lipoprotein recombinants with the composition and structure of spherical high density lipoproteins (HDL-R) were prepared with apoproteins, 14C-labeled unesterified cholesterol (UC), a [3H]cholesteryl ester (CE), and one of four single molecular species of PC. PCs were selected to include relatively hydrophilic species (16:1-16:1 and 16:0-18:2 PCs) and relatively hydrophobic species (18:0-18:2 and 20:1-20:1 PCs). PCs were also selected to include molecules with novel acyl group pairs (16:1-16:1 and 20:1-20:1 PCs) that would permit the whole molecule to be traced during its clearance from the serum. Rats were injected with HDL-R as an intravenous bolus, and serum, liver, and bile samples were obtained for up to 2 h. The clearance from the serum of each PC was monoexponential with the two most hydrophilic species much more rapidly cleared than either of the two less hydrophilic species. Clearance of specific PCs was not accompanied by PC remodeling (i.e. transacylations), and in the main could not be attributed to the action of lecithin-cholesterol acyltransferase (LCAT). In incubations designed to simulate in vivo conditions, no more than 15% of the disappearance of 16:1-16:1 PC, one of the most rapidly cleared PCs, was due to the action of LCAT. With 20:1-20:1 PC, one of the least rapidly cleared PCs, no LCAT activity could be detected. The clearance of radiolabeled UC was multiexponential and closely corresponded to the rate of disappearance of each PC. The clearance of radiolabeled CE was linear and, in contrast to UC, was the same with the administration of different PCs. Uptake of radiolabeled UC by the liver and excretion of radiolabeled UC into bile took place in parallel and corresponded to the rapidity of turnover of UC (and PCs) in the serum. With administration of 16:1-16:1 PC, complete equilibration of serum, liver, and bile UC was achieved by about 90 min, whereas with 20:1-20:1 PC, serum UC had not equilibrated by the end of the study. These findings demonstrate that, in the live animal, the kinetic pattern of transport of different lipids from an HDL recombinant is highly disparate, the rate of PC clearance is more rapid with molecular species of greater hydrophilic strength, and the rates of PC and UC clearance are closely coordinated and largely independent of the clearance of CE.


Patulin degradation in saccharomyces cerevisiae: Sensitive mutants.
The present experiments (sensitive mutants and transient inhibition of growth) are compatible with the synthesis of an inductible detoxifying substance in the wild type strain. This substance could be glutathione because glutathione detoxification scheme essentially involves properties of the SH group and it is well known that patulin reacts with sulfhy dril groups.Studies are presently being carried out with sensitive mutants to establish definitively the relation between intracellular pool of glutathone and the resistance mechanism of a yeast to patulin.


Glycaemic control in type II diabetic tube-fed patients with a new enteral formula low in carbohydrates and high in monounsaturated fatty acids: a randomised controlled trial.
To investigate the effects of long-term treatment with a new enteral formula low in carbohydrates and high in monounsaturated fatty acids (MUFAs), in comparison with a standard formula, on glycaemic control in tube-fed type II diabetic patients. Randomised, double-blind, controlled, multi-centre trial. Early rehabilitation centres, primary care and nursing facilities. A total of 78 patients with insulin-treated type II diabetes with HbA(1C) > or =7.0% and/or fasting blood glucose >6.66 mmol/l, who required enteral tube feeding due to neurological dysphagia. Patients received 113 kJ (27 kcal)/kg of body weight of either test feed or an isoenergetic, isonitrogenous enteral formula (control) for 12 weeks. Glycaemic control (total daily insulin dosage (IU), fasting blood glucose, and HbA(1C)) and gastrointestinal tolerance were monitored daily. After 12 weeks, median values for changes from baseline were as follows (test group vs control group, 'data as available' analysis): total daily IUs -6.0 vs 0.0 (P=0.0024), fasting blood glucose (mmol/l) -1.59 vs -0.08 (P=0.0068); HbA(1C) (%) -0.8 vs 0.0 (P=0.0016). Both formulas were tolerated comparably. This study indicates that in tube-fed insulin-treated type II diabetic patients, the new low-carbohydrate, high MUFA formula results in a more effective glycaemic control than the standard diet, while being comparable in safety.


Stressful life events and obsessive-compulsive disorder: clinical features and symptom dimensions.
The potential role of stressful life events (SLEs) in the genesis of obsessive-compulsive disorder (OCD) has been suggested by several authors, but whether the number or the severity or the type of SLEs preceding the onset of OCD has a triggering effect is unclear. Further, sociodemographic and clinical features of OCD preceded by SLEs, and the relationship between type of SLEs and type of obsessive-compulsive symptomatology remain mainly unexplored. The aims of this study were to compare the clinical features of OCD with and without SLEs preceding it and to examine the relationship between type of SLEs and OCD symptom dimensions. The number and type of SLEs which occurred before the onset of OCD were determined in 329 patients: the raters had to decide whether an occurrence 12 months before the onset of OCD would fit any of the 61 items on Paykel's list, and each event reported was carefully investigated in order to determine the exact time of occurrence. At least one event preceded the onset of OCD in 200 patients (60.8%), and this was significantly associated with female gender, abrupt onset of the disorder and somatic obsessions. Moreover, LogReg Analysis identified three specific traumatic events ("hospitalization of a family member", "major personal physical illness", "loss of personally valuable object") significantly associated with a symptom dimension (symmetry obsessions, repeating, ordering/arranging, counting, and checking compulsions). Additional evidence regarding the association among SLE-preceded OCD, female gender, somatic obsessions and symmetry/ordering symptoms should be obtained to advance the understanding of OCD.


Subtractive screening with the Mycobacterium tuberculosis surface protein phage display library.
Surface proteins consist of secreted and membrane proteins and play a central role in the interaction of the pathogen with its environment, especially in the pathogenicity of Mycobacterium tuberculosis (MTB). Research on surface proteins in MTB has focused on 2D electrophoresis of culture filtrate proteins (CFP), extraction of transmembrane proteins with detergent and predicting their properties with a range of available algorithms. However, functional analysis of these secretomes is possible only if many proteins are expressed and purified individually, which limits a large number of studies to the function of the proteome. Here, we utilized a phage display system to construct a whole genomic surface protein phage display library of MTB, which can complete direct selection, identification, expression, purification and functional research of surface proteins of MTB. With this system we made a new serological approach involving iterative subtraction screening. Cross-reactivity of antibodies was reduced by preadsorption of the surface protein phage display library with the sera of healthy BCG-vaccinated individuals prior to studying their reactivity against the sera of tuberculosis (TB) patients. As a result six antigens were identified, three of which have not previously been reported as diagnosis antigens. The surface protein phage display library shows great promise in the study of MTB.


Seasonal changes in photosynthetic characteristics of Pachysandra terminalis (Buxaceae), an evergreen woodland chamaephyte, in the cool temperate regions of Japan.
Seasonal changes in photosynthetic capacity, and photosynthetic responses to intercellular CO2 concentration and irradiance were investigated under laboratory conditions on intact leaves of Pachysandra terminalis. Photosynthetic capacity and stomatal conductance under saturating light intensity and constant water vapor pressure deficit showed almost the same seasonal trend. They increased from early June just after the expansion of leaves, reached the maximum in late-Septemer, and then decreased to winter. In over-wintering leaves they recovered and increased immediately after snow-melting, reached a first maximum in late April, and then decreased to early July in response to the reduction of light intensity on the forest floor. There-after, they increased from mid August, reached a second maximum in late September, and then decreased to winter. The parallel changes of photosynthesis and stomatal conductane indicate a more or less constant intercellular CO2 concentration throughout the year. The calculated values of relative stomatal limitation of photosynthesis were nearly constant throughout the year, irrespective of leaf age. The results indicate that the seasonal changes in light-saturated photosynthetic capacity are not due to a change of stomatal conductance, but to a change in the photosynthetic capacity of mesophyll. Indeed, carboxylation efficiency assessed by the inital slope of the Ci-photosynthesis curve changed in proportion to seasonal changes of the photosynthetic capacity in both current-year and over-wintered leaves. High photosynthetic capacity in current-year leaves as compared with one-year-old leaves was also due to the high photosynthetic capacity of mesophyll. Nevertheless, stomatal conductance changed in proportion to photosynthetic capacity, indicating that stomatal conductance is regulated by the mesophyll photosynthetic capacity such that the intercellular CO2 concentrations are maintained constant. The quantum yield also changed seasonally parallel with that in the photosynthetic capacity.


A cilia-independent function of BBSome mediated by DLK-MAPK signaling in C. elegans photosensation.
Bardet-Biedl syndrome (BBS) is a genetic disorder that affects primary cilia. BBSome, a protein complex composed of eight BBS proteins, regulates the structure and function of cilia, and its malfunction causes BBS in humans. Here, we report a cilia-independent function of BBSome. To identify genes that regulate the C. elegans photoreceptor protein LITE-1 in ciliated ASH photosensory neurons, we performed a genetic screen and isolated bbs mutants. Functional analysis revealed that BBSome regulates LITE-1 protein stability independently of cilia. Through another round of genetic screening, we found that this cilia-independent function of BBSome is mediated by DLK-MAPK signaling, which acts downstream of BBSome to control LITE-1 stability via Rab5-mediated endocytosis. BBSome exerts its function by regulating the expression of DLK. BBSome also regulates the expression of LZK, a mammalian DLK in human cells. These studies identify a cilia-independent function of BBSome and uncover DLK as an evolutionarily conserved BBSome effector.


Transformation of 4-androsten-3,17-dione by growing cultures and cell extracts of Clostridium paraputrificum.
Growing cultures of Clostridium paraputrificum transformed 4-androsten-3,17-dione to 3 alpha-hydroxy-5 beta-androstan-17-one in a sequential manner with 5 beta-androstan-3,17-dione as an intermediate. The addition of 1.5 mM menadione to log-phase cultures which had formed 5 beta-androstan-3,17-dione resulted in a partial reoxidation of this steroid to 4-androsten-3,17-dione. However, this treatment also resulted in transient inhibition of culture growth. Resumption of growth was accompanied by complete reduction of 4-androsten-3,17-dione to 5 beta-androstan-3,17-dione. Cell extracts of C. paraputrificum were capable of carrying out these reductive transformations in the absence of added cofactors. However, Sephadex G-25 treated extracts required NADH or NADPH for these reactions. A flavin nucleotide, either FAD (plus NADH or NADPH) or FMN (plus NADH) was highly stimulatory for 4-androsten-3,17-dione reduction to 5 beta-androstan-3,17-dione. NADH was the preferred reduced pyridine nucleotide for reduction of the C4-C5 double bond, while time-course measurements suggested that NADPH was the preferred donor for reduction of the 3-keto group.


Combined Anterior-Posterior versus Posterior-Only Fixation of Stress-Positive Minimally Displaced Lateral Compression Type 1 (LC1) Pelvic Ring Injuries.
To compare hospital outcomes and late displacement between stress-positive minimally displaced lateral compression type 1 (LC1) pelvic ring injuries treated with combined anterior-posterior versus posterior-only fixation. Retrospective comparative cohort. Urban level-one trauma center. LC1 injuries managed operatively. Anterior-posterior versus posterior-only fixation. Physical therapy (PT) clearance, discharge location, hospital length of stay (LOS), inpatient morphine equivalent doses (MED), and fracture displacement at follow-up. Groups were similar in demographic and injury characteristics (age, high energy mechanism, ASA score, stress displacement, and rami/sacral fracture classifications). Anterior-posterior fixation resulted in longer operative times (median difference (MD): 27.0 minutes, 95% confidence interval (CI): 17.0 to 40.0, P < 0.0001) and had a trend of increased estimated blood loss (MD: 10 mL, CI: 0 to 30, P = 0.07). Patients with anterior-posterior fixation required less inpatient MEDs (MD: -180.0, CI: -341.2 to -15.0, P = 0.02), were more likely to clear PT by discharge (100% vs. 70%, proportional difference (PD): 30%, CI: 2.0%-57.2%, P = 0.02), were less likely to discharge to rehabilitation facilities (0% vs. 30%, PD: 30%, CI: 2.0%-57.2%, P = 0.02), and had a trend of less days to clear PT after surgery (MD: -1, CI: -2 to 0, P = 0.09) and decreased LOS (MD: -1, CI: -4 to 1, P = 0.17). Late fracture displacement did not differ between groups. Anterior-posterior fixation of LC1 injuries was associated with an improved early hospital course-specifically, reduced inpatient opioid use and an increased number of patients who could clear PT and discharge home. Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.


Wells' syndrome possibly caused by hematologic malignancy, influenza vaccination or ibrutinib: A case report.
Wells' syndrome (eosinophilic cellulitis) is an uncommon eosinophilic dermatosis of uncertain pathogenesis, characterized by clinical polymorphism and suggestive but nonspecific histopathologic traits. Its course is recurrent, and response to therapy is unpredictable. In a case in which the patient has a number of potential triggers for the manifestation of Wells' syndrome skin rash, the treating physician must decide or must make an assumption in order to establish the most likely clinical scenario. This is important for the patient's future treatment plans. We describe the clinical case of a 46-year-old female with chronic lymphocytic leukemia who had already received treatment for several months with ibrutinib. She was diagnosed with Wells' syndrome 10 d after an influenza vaccination containing thimerosal. Based on the literature, the patient was treated with a course of oral steroids. Resolution of clinical symptoms and rash were observed in response to the treatment. Ibrutinib was not discontinued. The etiology of Wells' syndrome remains unknown. Clinically, it resembles bacterial cellulitis. Lack of response to antibiotic treatment should lead the physician to consider a diagnosis of Wells' syndrome. Treating the underlying condition is important and may lead to resolution of the syndrome. However, the most common and effective treatment to limit the course of the disease are systemic steroids.


Mussel-inspired multifunctional surface through promoting osteogenesis and inhibiting osteoclastogenesis to facilitate bone regeneration.
Osteogenesis and osteoclastogenesis are closely associated during the bone regeneration process. The development of multifunctional bone repair scaffolds with dual therapeutic actions (pro-osteogenesis and anti-osteoclastogenesis) is still a challenging task for bone tissue engineering applications. Herein, through a facile surface coating process, mussel-inspired polydopamine (PDA) is adhered to the surface of a biocompatible porous scaffold followed by the immobilization of a small-molecule activator (LYN-1604 (LYN)) and the subsequent in situ coprecipitation of hydroxyapatite (HA) nanocrystals. PDA, acting as an intermediate bridge, can provide strong LYN immobilization and biomineralization ability, while LYN targets osteoclast precursor cells to inhibit osteoclastic differentiation and functional activity, which endows LYN/HA-coated hybrid scaffolds with robust anti-osteoclastogenesis ability. Due to the synergistic effects of the LYN and HA components, the obtained three-dimensional hybrid scaffolds exhibited the dual effects of osteoclastic inhibition and osteogenic stimulation, thereby promoting bone tissue repair. Systematic characterization experiments confirmed the successful fabrication of LYN/HA-coated hybrid scaffolds, which exhibited an interconnected porous structure with nanoroughened surface topography, favorable hydrophilicity, and improved mechanical properties, as well as the sustained sequential release of LYN and Ca ions. In vitro experiments demonstrated that LYN/HA-coated hybrid scaffolds possessed satisfactory cytocompatibility, effectively promoting cell adhesion, spreading, proliferation, alkaline phosphatase activity, matrix mineralization, and osteogenesis-related gene and protein secretion, as well as stimulating angiogenic differentiation of endothelial cells. In addition to osteogenesis, the engineered scaffolds also significantly reduced osteoclastogenesis, such as tartrate-resistant acid phosphatase activity, F-actin ring staining, and osteoclastogenesis-related gene and protein secretion. More importantly, in a rat calvarial defect model, the newly developed hybrid scaffolds significantly promoted bone repair and regeneration. Microcomputed tomography, histological, and immunohistochemical analyses all revealed that the LYN/HA-coated hybrid scaffolds possessed not only reliable biosafety but also excellent osteogenesis-inducing and osteoclastogenesis-inhibiting effects, resulting in faster and higher-quality bone tissue regeneration. Taken together, this study offers a powerful and promising strategy to construct multifunctional nanocomposite scaffolds by promoting osteo/angiogenesis and suppressing osteoclastogenesis to accelerate bone regeneration.


Physiological phenotyping of dementias using emotional sounds.
Emotional behavioral disturbances are hallmarks of many dementias but their pathophysiology is poorly understood. Here we addressed this issue using the paradigm of emotionally salient sounds. Pupil responses and affective valence ratings for nonverbal sounds of varying emotional salience were assessed in patients with behavioral variant frontotemporal dementia (bvFTD) (n = 14), semantic dementia (SD) (n = 10), progressive nonfluent aphasia (PNFA) (n = 12), and AD (n = 10) versus healthy age-matched individuals (n = 26). Referenced to healthy individuals, overall autonomic reactivity to sound was normal in Alzheimer's disease (AD) but reduced in other syndromes. Patients with bvFTD, SD, and AD showed altered coupling between pupillary and affective behavioral responses to emotionally salient sounds. Emotional sounds are a useful model system for analyzing how dementias affect the processing of salient environmental signals, with implications for defining pathophysiological mechanisms and novel biomarker development.


Clearance and maximum removal rate of liposomes in normal and impaired liver of rat.
In the present study the author described a new method for analysis of the reticuloendothelial system (RES) function, using blood clearance of liposomes containing encapsulated phenolsulfonphthalein as a marker. Various types and doses of liposomes were intravenously administered to rats and the clearance of liposomes from blood was observed. Large liposomes were cleared from blood at a faster rate than small ones. Large liposomes composed of phosphatidylcholine and cholesterol were mainly phagocytized with Kupffer cells. The rate of disappearance of liposomes from blood was able to be calculated. With increments of administered doses there was an associated decrease of the disappearance rate, which corresponded to the Lineweaver-Burk plot in the enzymatic process, and it was possible to calculate the maximum removal rate and Michaelis constant. Disappearance rates decreased after prior administration of large liposomes and the inhibitory mode was competitive. Disappearance rates decreased after pretreatment with dextran sulfate and the inhibitory mode differed from the competitive. In partially hepatectomized and CCl4 intoxicated animals, disappearance rates also decreased. Liposomes are easily prepared and non-toxic. The clearance test of liposomes is possible to evaluate the role of the phagocytic function of the RES, chiefly Kupffer cells, in various experimental and clinical conditions.


Luminal adrenergic agents modulate intestinal transport.
Intestinal transport is controlled by luminal solutes, neural pathways, and paracrine or humoral agents. The current study investigated the effect of luminally administered adrenergic agents on the intestinal transport of water and electrolytes. Dogs with 25-cm jejunal Thiry-Vella loops were studied. The loops were luminally perfused with an isotonic solution containing [14C]PEG, and the fluxes of H2O, Na+, and Cl- were calculated. Each experiment consisted of three 1-hr periods: basal, luminal agent infusion, and recovery. Luminal adrenergic agents did not alter heart rate. Norepinephrine (alpha 1 greater than alpha 2 and beta adrenergic agonist) and phenylephrine (alpha 1 adrenergic agonist) caused significant absorption of water and sodium. Clonidine (alpha 2 adrenergic agonist) and isoproterenol (beta adrenergic agonist) caused significant secretion of water, sodium, and chloride. Luminally administered adrenergic agents can influence small intestinal water and electrolyte transport. Alpha 1 agonists have a proabsorptive effect, while alpha 2 and beta agonists have a secretory effect. Luminally administered proabsorptive adrenergic agents may prove useful in pathologic secretory states such as diabetic diarrhea, small bowel transplantation, or diarrhea-associated endocrinopathies.


CaMKII inhibition in the prefrontal cortex specifically increases the positive reinforcing effects of sweetened alcohol in C57BL/6J mice.
Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) is a multifunctional enzyme that is required for synaptic plasticity and has been proposed to be a primary molecular component of the etiology of alcohol addiction. Chronic alcohol intake upregulates CaMKIIα protein expression in reward-related brain regions including the amygdala and nucleus accumbens, and CaMKIIα activity in the amygdala is required for the positive reinforcing effects of alcohol, suggesting this system promotes consumption in the early stages of alcohol addiction. Alternatively, the medial prefrontal cortex (mPFC) is known to inhibit limbic activity via CaMKII-dependent excitatory projections and may, therefore, enable top-down regulation of motivation. Here we sought to remove that regulatory control by site-specifically inhibiting CaMKII activity in the mPFC, and measured effects on the positive reinforcing effects of sweetened alcohol in C57BL/6J mice. Infusion of the CAMKII inhibitor KN-93 (0-10.0 μg) in the mPFC primarily increased alcohol+sucrose reinforced response rate in a dose- and time-dependent manner. KN-93 infusion reduced response rate in behavior-matched sucrose-only controls. Importantly, potentiation of operant responding for sweetened alcohol occurred immediately after infusion, at a time during which effects on sucrose responding were not observed, and persisted through the session. These results suggest that endogenous CaMKII activity in the mPFC exerts inhibitory control over the positive reinforcing effects of alcohol. Downregulation of CaMKII signaling in the mPFC might contribute to escalated alcohol use.


Impact of Ventricular Assist Device-Specific Infections on Post-Heart Transplant Infections: A Retrospective Single-Center Study.
Patients with a ventricular assist device (VAD) who are awaiting heart transplant (HTx) are susceptible to infections. Such infections, especially at the site of the VAD, may increase the risk of severe post-transplant infections and mortality. Information on the characteristics of VAD-specific infections and outcomes in HTx recipients after prolonged periods of LVAD therapy is scarce. We aimed to assess the impact of active VAD-specific infections on the incidence of early post-transplant infections and patient survival. We conducted a retrospective review of adult HTx cases at our center between April 2011 and October 2020. Informed consent was waived due to study design. A total of 86 patients were included in this study, among whom 94.2% (n = 81) were bridged with a VAD, and the median VAD support period was 1089 days. Patients with active VAD-specific infections were significantly more likely to develop severe acute mediastinitis [odds ratio (OR) 14.8, 95% confidence interval (CI) 4.83-45.4, P < .01]. Active VAD infections were significantly related to increased length of intensive care unit stay (22.1 days vs 13.0 days, P = .016) and longer mechanical ventilation periods (324.7 hours vs 113.2 hours, P = .03). The 30-day survival rates for patients with and without post-transplant infections were 100% and 97.1%, respectively. Compared to other risk factors, the presence of active VAD-specific infections increases the risk of early post-heart transplant infections and morbidity, without affecting mortality.


Management of upper and lower limb spasticity in neuro-rehabilitation.
This article reviews the treatment of upper and lower limb spasticity in neurological rehabilitation. Botulinum toxin A proved effective in several placebo-controlled studies reducing muscle tone, easing hand hygiene and nursing, improving upper limb motor functions and gait ability. The effects are reversible and the toxin is well tolerated. Electrical stimulation, tonic stretch post injection and the active use of the treated extremity are means to increase the effectiveness of the costly therapy. Phenol 5% is an alternative in case of budget constraints, but the technique is demanding and side effects are more frequent. Further, task-specific repetitive therapy should follow the successful treatment of focal spasticity in eligible patients to get the maximum profit with regard to disability.


Stability of Trichomonas vaginalis DNA in urine specimens.
Trichomonas vaginalis is an important pathogen in both men and women. Culture is considered the diagnostic gold standard, although studies have shown that PCR is more sensitive than either culture or wet mount for the diagnosis of T. vaginalis infections. We sought to identify a simple method for stabilizing T. vaginalis DNA in urine samples that could be easily applied to molecular testing. The stability of T. vaginalis DNA in 40 urine samples was assessed by storage for various times at either 4 degrees C or room temperature with or without the Becton Dickinson urine preservative transport (UPT) kit. Overall, there was better stability of T. vaginalis DNA when specimens were stored at 4 degrees C than when they were stored at 20 to 22 degrees C and when the UPT system was used. T. vaginalis DNA was stable in specimens stored without using the UPT at 4 degrees C for about 3 days and at room temperature for only 1 day. For specimens placed in the UPT within 24 h (times of 1, 6, and 24 h) of collection, the DNA was stable for up to 30 days when stored at 4 degrees C. For specimens stored at room temperature, the urine should be added to the UPT ideally within 1 hour of collection, and in this case the DNA remained stable for up to 30 days. When storing specimens at room temperature, a delay of 24 h prior to adding to UPT led to an unacceptably high loss of assay sensitivity.


The caleosin CLO7 and its role in the heterotrimeric G-protein signalling network.
The investigation of the caleosin CLO7 in relation to heterotrimeric G-protein signalling in Arabidopsis showed that the gene plays a role in seed germination and embryo viability. The caleosin CLO7 belongs to a multi-gene family of calcium-binding proteins which are characterized by single EF-hand motifs. Other members of the caleosin gene family have been shown to affect transpiration and seed germination as well as play a role in both abiotic and biotic stress responses. The proteins are associated with lipid droplets/oil bodies and some members of the gene family have been shown to have peroxygenase activity. Members of the gene family have also been shown to interact with the α subunit of the heterotrimeric G protein complex. In this study, we further expand on the diversity of physiological responses in which members of this gene family play regulatory roles. Utilizing BiFC and Y2H protein-protein interaction assays, CLO7 is identified as an interactor of the heterotrimeric G protein α subunit, GPA1. The full-length CLO7 is shown to interact with both the wild-type GPA1 and its constitutively active form, GPA1QL, at the plasma membrane. Point mutations to critical amino acids for calcium binding in the EF-hand of CLO7 indicate that the interaction with GPA1 is calcium-dependent and that the interaction with GPA1QL is enhanced by calcium. Protein-protein interaction assays also show that CLO7 interacts with Pirin1, a member of the cupin gene superfamily and a known downstream effector of GPA1, and this interaction is calcium-dependent. The N-terminal portion of CLO7 is responsible for these interactions. GFP-tagged CLO7 protein localizes to the endoplasmic reticulum (ER) and to lipid bodies. Characterization of the clo7 mutant line has shown that CLO7 is implicated in the abscisic acid (ABA) and mannitol-mediated inhibition of seed germination, with the clo7 mutant displaying higher germination rates in response to osmotic stress and ABA hormone treatment. These results provide insight into the role of CLO7 in seed germination in response to abiotic stress as well as its interaction with GPA1 and Pirin1. CLO7 also plays a role in embryo viability with the clo7gpa1 double mutant displaying embryo lethality, and therefore the double mutant cannot be recovered.


Methylene blue is more toxic to erythroleukemic cells than to normal peripheral blood mononuclear cells: a possible use in chemotherapy.
Methylene blue (MB) is a phenothiazine with radio and photosensitizing properties and anti-tumoral activity. Our group has shown that MB was capable of inhibiting the in vitro growth of erythroleukemic cells with multidrug resistance (MDR). However, there are no studies comparing the cytotoxicity of this molecule for normal and tumoral cells. In this work, the cytotoxicity of MB was measured by MTT method in erythroleukemic and melanoma lineages, comparing it with that of normal cells:lymphocytes and melanocytes. MB was more cytotoxic for tumoral cells; however, there was no difference between erytroleukemic cells with or without MDR phenotype. Lymphocytes and erythroleukemic cells were much more sensitive to the effects of MB than melanoma cells and melanocytes. The proliferation of phytohemagglutinin-activated lymphocytes was inhibited when 3H-thymidine incorporation to DNA was measured. We tried to analyze whether the cells were dying, via apoptosis or necrosis, using Anexin-V and propidium iodide. Despite higher levels of Anexin-V, it was not possible to distinguish necrosis from apoptosis, as the fluorescence of MB is in the same channel as propidium iodide. The production of hydrogen peroxide was measured by cytometry using dihydrorhodamine 123 (DHR). Despite the erythroleukemic cells and lymphocytes being capable of producing free radicals, there was no relation between the production and the sensitivity of various cells to MB. Our results suggest that MB should be used as a chemotherapeutic agent, because of its preferential cytotoxic effects over tumor cells, considering the fact that MDR cells are also sensitive, and due to its radio and photosensitizing activities.


The feasibility of a home-based moderate-intensity physical activity intervention in obese children and adolescents.
To explore the feasibility of conducting a 10-week home-based physical activity (PA) programme and evaluate the changes in insulin sensitivity (S(I)) commensurate with the programme in obese young people. Open-labelled intervention. Home-based intervention with clinical assessments at a tertiary paediatric hospital. 18 obese (body mass index (BMI)>International Obesity Task Force age and sex-specific cut-offs) children and adolescents (8-18 years, 11 girls/7 boys) were recruited. 15 participants (nine girls/six boys, mean+/-SE age 11.8+/-0.6 years, BMI-SD scores (BMI-SDS) 3.5+/-0.1, six prepubertal/nine pubertal) completed the intervention. The programme comprised biweekly home visits over 10 weeks with personalised plans implemented aiming to increase moderate-intensity PA. Pedometers and PA diaries were used as self-monitoring tools. The goals were to (1) teach participants behavioural skills related to adopting and maintaining an active lifestyle and (2) increase daily participation in PA. Mean steps/day were assessed. S(I) assessed by the frequently sampled intravenous glucose tolerance test and other components of the insulin resistance syndrome were measured. Mean steps/day increased significantly from 10 363+/-927 (baseline) to 13 013+/-1131 (week 10) (p<0.05). S(I) was also significantly increased, despite no change in BMI-SDS, and remained so after an additional 10-week follow-up. The results suggest that such a home-based PA programme is feasible. S(I) improved without changes in BMI-SDS. More rigorous evaluations of such programmes are warranted.


Robotic Esophagectomy Compared With Open Esophagectomy Reduces Sarcopenia within the First Postoperative Year: A Propensity Score-Matched Analysis.
Sarcopenia is a known risk factor for adverse outcomes after esophageal cancer (EC) surgery. Robot-assisted minimally invasive esophagectomy (RAMIE) offers numerous advantages, including reduced morbidity and mortality. However, no evidence exists to date comparing the development of sarcopenia after RAMIE and open esophagectomy (OE). The objective was to evaluate whether the development of sarcopenia within the first postoperative year after esophagectomy is associated with the surgical approach: RAMIE versus OE. A total of 168 patients with EC were analyzed who either underwent total robotic or fully open Ivor Lewis esophagectomy in a propensity score-matched analysis. Sarcopenia was assessed using the skeletal muscle index (cm2/m2) and psoas muscle thickness per height (mm/m) on axial computed tomography scans during the first postoperative year; in total 540 computed tomography scans were evaluated. After 1-to-1 propensity score matching for confounders, 67 patients were allocated to RAMIE and OE groups, respectively. Skeletal muscle index in the OE group was significantly lower compared with the RAMIE group at the third (43.2 ± 7.6 cm2/m2 versus 49.1 ± 6.9 cm2/m2, p = 0.001), sixth (42.7 ± 7.8 cm2/m2 versus 51.5 ± 8.2 cm2/m2, p < 0.001) and ninth (43.0 ± 7.0 cm2/m2 versus 49.9 ± 6.6 cm2/m2, p = 0.015) postoperative month. Similar results were recorded for psoas muscle thickness per height. To our knowledge, this study is the first to suggest a substantial benefit of RAMIE compared with open esophagectomy in terms of postoperative sarcopenia. These results add further evidence to support the implementation of the robotic approach in multimodal therapy of EC.


Liver involvement in a large cohort of patients with hereditary hemorrhagic telangiectasia: echo-color-Doppler vs multislice computed tomography study.
Hepatic arterio-venous malformations (HAVMs) have been found in 74% of hereditary hemorrhagic telangiectasia (HHT) patients with multislice CT (MSCT). This single-blind study aimed to compare the diagnostic accuracy of echo-color-Doppler with MSCT and identify the most sensitive ultrasound criteria indicating hepatic shunts. One hundred and fifty-three HHT patients were systematically screened for HAVMs by biological tests, abdominal MSCT and echo-color-Doppler. Twenty-five normal subjects and 15 cirrhotic patients were also included as control groups. Both intrahepatic ("color spots" and hypervascularization) and extrahepatic parameters (diameter, flow velocity and tortuosity of hepatic artery and diameter and flow velocity of portal/hepatic vein) were utilized. "Color-spots" are defined as subcapsular vascular spots with a high-velocity arterial blood flow and low resistivity index and can identify extremely small HAVMs. CT was positive in 128/153 (84%) patients and Doppler color spots were found in 131/153 (86%) patients. The sensitivity, specificity and diagnostic accuracy of "color spots" compared to MSCT were 95.3%, 68.0% and 91.8%, respectively. The "color-spot" showed a greater correlation to CT (V(index)=0.655; p<0.0001) than extrahepatic criteria (V=0.317). In 20/29 (69%) subjects, echo-color-Doppler, confirmed by CT, identified the third criterion for definite HHT diagnosis. Intrahepatic criteria was superior to extrahepatic criteria for identification of HAVMs. A new Doppler parameter ("color-spots") with an optimal accuracy for detecting HAVMs is proposed for easy periodic screening of HHT patients.


Perceived stress and stressors among first-year undergraduate students at a private medical school in Nigeria.
Medical training has long been globally recognised as involving numerous stressors that can affect the well-being of students. This study, the first to be conducted among first-year medical students at a private university in Nigeria, aims to identify factors associated with students' perceived stress. An analytical cross-sectional design was employed. A semi-structured pretested and validated questionnaire was administered to first-year medical students. The data were analysed using IBM SPSS version 25.0. Descriptive and analytical statistics were presented as frequencies, percentages, means, and standard deviations. The chi-square test was also used to identify the associations between categorical variables. The majority of the respondents were females (72.2%) and Christians (85.8%). Sixty seven percent of the participants perceived medical school as being stressful. More females than males were stressed. Statistically, ethnicity and intrapersonal factors were correlated with perceived stress. In this study, the prevalence of perceived stress among first-year medical undergraduate students was high. Students should be prepared on how to cope with stress by developing coping strategies such as healthy lifestyle patterns, availing of social support, engaging in physical activity, and seeking counselling when needed.


Routine, direct measurement of aortic pressure in the conscious rabbit.
A method for preparation and application of an indwelling catheter for measurement of aortic pressure in conscious rabbits is described. The catheter is generally reliable for periods longer than one month and requires little interference with the normal circulation. The system utilizes coiled polyethylene tubing which has a tapered tip covered with silicone rubber tubing and, at its exterior end, a Velcro matrix for skin healing. The catheter tip is pulled into the abdominal aorta with a trocar, directed caudally. The exterior end is run subcutaneously to the nape of the neck. In 19 rabbits prepared by this method, mean pressure was determined to be 68 +/- 2 mm Hg and pulse pressure was 29 +/- 1 mm Hg two weeks after implantation. The catheters remained patent in 17 rabbits at the time of sacrifice, 12 to 120 days later. In an in vitro sweep-frequency test, maximal resonance of the catheter system was found to lie between 12-14 Hz, at which point the measured pressure amplitude exceeded control by 12.5%.


Severe COVID-19 Infection and Pediatric Comorbidities: A Systematic Review and Meta-Analysis.
There is limited information on the severity of COVID-19 infection in children with comorbidities. We investigated the effects of pediatric comorbidities on COVID-19 severity by means of a systematic review and meta-analysis of published literature. PubMed, Embase, and Medline databases were searched for publications on pediatric COVID-19 infections published January 1st to October 5th, 2020. Articles describing at least one child with and without comorbidities, COVID-19 infection, and reported outcomes were included. 42 studies containing 275,661 children without comorbidities and 9,353 children with comorbidities were included. Severe COVID-19 was present in 5.1% of children with comorbidities, and in 0.2% without comorbidities. Random-effects analysis revealed a higher risk of severe COVID-19 among children with comorbidities than for healthy children; relative risk ratio 1.79 (95% CI 1.27 - 2.51; I2 = 94%). Children with underlying conditions also had a higher risk of COVID-19-associated mortality; relative risk ratio 2.81 (95% CI 1.31 - 6.02; I2 = 82%). Children with obesity had a relative risk ratio of 2.87 (95% CI 1.16 - 7.07; I2 = 36%). Children with comorbidities have a higher risk of severe COVID-19 and associated mortality than children without underlying disease. Additional studies are required to further evaluate this relationship.


Fecal indicator bacteria, direct pathogen detection, and microbial community analysis provide different microbiological water quality assessment of a tropical urban marine estuary.
Urban marine estuaries are often impacted by microbiological contamination that impairs use and affects human health acutely, while limited is known about microbiological water quality in urban marine estuaries in the absence of reported sewage spills. This study used a tropical urban marine estuary, the Ala Wai Canal in Honolulu, Hawaii, as the model system to compare fecal indicator bacteria (FIB) concentrations, bacterial pathogen profiles, and microbial community structures. The FIB Escherichia coli exhibited higher geometric mean 132 CFU/100mL (n=28) than those of enterococci (18 CFU/100mL) and Clostridium perfringens (21 CFU/100mL). Amongst the four pathogens targeted by cultivation methods (Salmonella, Campylobacter, Listeria monocytogenes and Vibrio parahaemolyticus), only was V. parahaemolyticus detected and was detected at high frequency. Microbial community analysis through 16S rRNA gene amplicon sequencing also indicated the high prevalence of Vibrio in the water. The pathogen detection patterns and microbial community structure showed no significant correlation with FIB concentration profiles. Together, the results highlight the limitation of using traditional FIB in assessing water microbiological quality in the tropical urban marine estuary environment, indicating the need for more comprehensive microbial risk assessment approaches such as direct detection of pathogens.


Experimental models of hepatotoxicity related to acute liver failure.
Acute liver failure can be the consequence of various etiologies, with most cases arising from drug-induced hepatotoxicity in Western countries. Despite advances in this field, the management of acute liver failure continues to be one of the most challenging problems in clinical medicine. The availability of adequate experimental models is of crucial importance to provide a better understanding of this condition and to allow identification of novel drug targets, testing the efficacy of new therapeutic interventions and acting as models for assessing mechanisms of toxicity. Experimental models of hepatotoxicity related to acute liver failure rely on surgical procedures, chemical exposure or viral infection. Each of these models has a number of strengths and weaknesses. This paper specifically reviews commonly used chemical in vivo and in vitro models of hepatotoxicity associated with acute liver failure.


Liveable residential space, residential density, and hypertension in Hong Kong: A population-based cohort study.
Hypertension is a leading preventable risk factor of chronic disease and all-cause mortality. Housing is a fundamental social determinant of health. Yet, little is known about the impacts of liveable residential space and density on hypertension. This retrospective observational study (median follow-up of 2.2 years) leveraged the FAMILY Cohort, a large territory-wide cohort in Hong Kong, Special Administrative Region, People's Republic of China to quantify associations of objectively measured liveable space and residential density with blood pressure outcomes among adults aged ≥16 years. Blood pressure outcomes comprised diastolic blood pressure (DBP), systolic blood pressure (SBP), mean arterial pressure (MAP), and hypertension. Liveable space was measured as residential floor area, and density was assessed using the number of residential units per building block and neighborhood residential unit density within predefined catchments. Multivariable regression models examined associations of liveable floor area and residential density with prevalent and incident hypertension. We investigated effect modifications by age, sex, income, employment status, and housing type. Propensity score matching was further employed to match a subset of participants who moved to smaller residences at follow-up with equivalent controls who did not move, and generalized linear models examined the impact of moving to smaller residences upon blood pressure outcomes. Our fully adjusted models of prevalent hypertension outcomes comprised 30,439 participants at baseline, while 13,895 participants were available for incident models at follow-up. We found that each interquartile range (IQR) increment in liveable floor area was associated with lower DBP (beta [β] = -0.269 mm Hg, 95% confidence interval [CI]: -0.419 to -0.118, p < 0.001), SBP (β = -0.317 mm Hg, -0.551 to -0.084, p = 0.008), MAP (β = -0.285 mm Hg, -0.451 to -0.119 with p < 0.001), and prevalent hypertension (odds ratio [OR] = 0.955, 0.918 to 0.993, p = 0.022) at baseline. Each IQR increment in residential units per building block was associated with higher DBP (β = 0.477 mm Hg, 0.212 to 0.742, p = <0.001), SBP (β = 0.750 mm Hg, 0.322 to 1.177, p = <0.001), MAP (β = 0.568 mm Hg, 0.269 to 0.866, p < 0.001), and prevalent hypertension (OR = 1.091, 1.024 to 1.162, p = 0.007). Each IQR increase in neighborhood residential density within 0.5-mi street catchment was associated with lower DBP (β = -0.289 mm Hg, -0.441 to -0.137, p = <0.001), SBP (β = -0.411 mm Hg, -0.655 to -0.168, p < 0.001), MAP (β = -0.330 mm Hg, -0.501 to -0.159, p = <0.001), and lower prevalent hypertension (OR = 0.933, 0.899 to 0.969, p < 0.001). In the longitudinal analyses, each IQR increment in liveable floor area was associated with lower DBP (β = -0.237 mm Hg, -0.431 to -0.043, p = 0.016), MAP (β = -0.244 mm Hg, -0.444 to -0.043, p = 0.017), and incident hypertension (adjusted OR = 0.909, 0.836 to 0.988, p = 0.025). The inverse associations between larger liveable area and blood pressure outcomes were more pronounced among women and those residing in public housing. In the propensity-matched analysis, participants moving to residences of lower liveable floor area were associated with higher odds of incident hypertension in reference to those who did not move (OR = 1.623, 1.173 to 2.199, p = 0.002). The major limitations of the study are unmeasured residual confounding and loss to follow-up. We disentangled the association of micro-, meso-, and macrolevel residential densities with hypertension and found that higher liveable floor area and neighborhood scale residential density were associated with lower odds of hypertension. These findings suggest adequate housing in the form of provisioning of sufficient liveable space and optimizing residential density at the building block, and neighborhood levels should be investigated as a potential population-wide preventive strategy for lowering hypertension and associated chronic diseases.


Quasi-bound states in an NPN-type nanometer-scale graphene quantum dot under a magnetic field.
We solve the quasi-bound state-energy spectra and wavefunctions of an NPN-type graphene quantum dot under a perpendicular magnetic field. The evolution of the quasi-bound state spectra under the magnetic field is investigated using a Wentzel-Kramers-Brillouin approximation. In numerical calculations, we also show that the twofold energy degeneracy of the opposite angular momenta breaks under a weak magnetic field. As the magnetic field strengthens, this phenomenon produces an observable splitting of the energy spectrum. Our results demonstrate the relation between the quasi-bound state-energy spectrum in graphene quantum dots and magnetic field strength, which is relevant to recent measurements in scanning tunneling microscopy.


[Pitched battle in Gueme between the Massa of Cameroon and Massa of Chad].
To avenge an act of adultery a pitched battle broke out between the Massa from Cameroon and the Massa from Chad, ending with 82 wounded people on the Cameroonian side, mainly skull, face and upper limbs injuries. Considering the importance of cattle in the social relations in the Massa society particularly in matrimonial exchanges, the battles are often triggered by robbery of cows or bay an act of adultery. Massa are familiar with this type of battle where two long lines of men armed with stones and sticks, confront each other encouraged by the lines of the women. Their accessories (club, battle helmet), their compliance with the rules of the battle (to collect the injured, not to strike a man on the ground or who is injured, end of the fighting at dusk), explain the great number of wounded people, the epidemiology, and the type of injuries. Injured people are usually in care of traditional healers performing distinct techniques using local resources. The role of the women in this type of fighting illustrates their place in the Massa society.


New Single Nucleotide Deletion In the SMPD1 Gene Causes Niemann Pick Disease Type A in a Child from Southwest Iran: A Case Report.
NIEMANN PICK DISEASE (NPD) TYPE A (NPA: MIM #257200) is a lipid storage disorder with an autosomal recessive inheritance and occurrs by defect of the SMPD1 gene encoding sphingomyelinase. Disruption of this enzyme leads to the accumulation of sphingomyelin in brain and liver, which in turn causes dysfunction or damage of tissue. We report firstly a 2.5 year old boy with NPA in southwest Iran. Initially, the diagnosis was resulted on the basis of clinical symptoms. The genomic DNA of the suspected individual was subjected to exon sequencing of the SMPD1 gene. According to the human reference sequence NM_000543.4, a novel single guanine deletion resulting in a frameshift mutation (p.Gly247Alafs*9) was observed in the SMPD1 gene that might be causative for the outcome of the disease. The present report is the first molecular genetics diagnosis of the NPA in southwest Iran. The detected deletion in the SMPD1 gene is remarkable because of its novelty. Despite similar morbidity SGA infants exhibited higher lethal complication rates following delayed meconium passage compared to AGA infants.


[Vulvar leiomyoma. Report of a case].
We report the case of a 44-year-old, who was resected of a vulvar tumor. The pathological report was leiomyoma with focal myxoid degeneration, which is an infrequent benign tumor.


Serotonin transporter clustering in blood lymphocytes as a putative biomarker of therapeutic efficacy in major depressive disorder.
Serotonin transporter (SERT) binding is decreased in lymphocytes of depression patients and this decrease is partially reversed by antidepressant medication. However, recent evidence has shown that clustering of SERT on cell membranes is very important for receptor functionality. Alteration in SERT clustering on peripheral lymphocytes does not affect symptoms severity. At the most it is associated or predicts responsivity to treatment. We collected blood samples from 38 untreated and newly diagnosed depression patients at the time of diagnosis and after 8weeks of pharmacological treatment and of 38 control subjects. We used the Hamilton Scale to quantify the level of depression in patients both before and after pharmacological treatment. We then used immunocytochemistry to assess SERT protein clusters in lymphocyte blood samples. We found an increase in SERT cluster size, but not the number of SERT clusters, in naïve depression patients compared to control subjects. Based on the distribution of SERT cluster size we differentiated the naïve depression patients into two groups (D-I and D-II). Naïve D-I and D-II patients initially showed similar Hamilton scores. However, after pharmacological treatment the D-II patients showed a greater decrease in Hamilton scores than did the D-I patients, and they had an increase in the number of SERT clusters. The data should be replicated in a larger cohort of patients and with a proper clinical trial. We propose that SERT clustering in blood lymphocytes may be a putative biomarker for antidepressant efficacy in major depressive disorder.


[Neurotropic, anti-inflammatory and antitumor properties of hopantenic acid: a chemoinformatic analysis of its molecule].
Hopantenic acid is a well-known nootropic drug similar in its chemical structure to pantothenic acid (vitamin B5). Neurotropic effects of hopantenic acid act through binding with delta- and kappa opioid receptors, modulation of acetylcholine secretion and relationship with dopamine receptors. Besides neurotropic effects, hopantenic acid may modulate the metabolism of prostaglandins, steroids and have antitumor effects.


Quantitative determination of perchlorate in bottled water and tea with online solid phase extraction high-performance liquid chromatography coupled to tandem mass spectrometry.
Due to the similarity in ionic radius, perchlorate has been reported to inhibit the iodide intake in the thyroid gland, which may lead to low heart rate, weight gain, and fatigue. In recent years, the presence of perchlorate in drinking water, surface water, soil, and food supplies in the United States has raised a great concern on establishing the maximum residue limit (MRL) for perchlorate to reduce its possible adverse influence on human health. US EPA currently puts perchlorate on the final third Contamination Candidate List (CCL3) and suggests a health reference level at 4.9 μg L⁻¹. The MRL of perchlorate was therefore set at 5.0 μg L⁻¹ by the authors for method validation. In this study, large volume injection (up to 1-mL) and online solid phase extraction (SPE) were utilized for pre-concentrating perchlorate ions and removing unretained matrix components prior to reversed-phase HPLC analysis using ESI-tandem MS under the negative mode. After eluting perchlorate from online SPE, 0.1% formic acid solution was utilized for isocratic HPLC analysis without any organic solvent. Multiple reaction monitoring (MRM) and the internal standard, Cl₁₈O₄⁻, were utilized for quantitatively determining perchlorate in bottled water and bottled tea samples. Two linear ranges, 0.05-0.50 μg L⁻¹ and 0.50-10.00 μg L⁻¹, were established to better estimate the residual amounts of perchlorate in bottled water samples with a method detection limit (MDL, signal-to-noise ratio of 3) of 0.01 μg L⁻¹. The linear range was 1.50-10.00 μg L⁻¹ for bottled tea samples with a MDL of 0.5 μg L⁻¹. In addition, the proposed method was further validated based on the EU Commission Decision 2002/657/EC, including within-laboratory reproducibility, decision limit (CCα), and detection capability (CCβ) for bottled water and bottled tea samples. The intra-day/inter-day precision and accuracy as well as within-laboratory reproducibility were determined by calculating the relative standard deviation (RSD) at three spiked levels (0.5 MRL, 1 MRL, 1.5 MRL). The within-laboratory reproducibility (n=18) for both bottled water and bottled tea samples, spiked at MRL (5.0 μg L⁻¹) of ClO₄⁻, was less than 10%. The values of CCα/CCβ were reported as 5.43/5.74 μg L⁻¹ and 5.03/5.75 μg L⁻¹ for bottled water and bottled tea samples, respectively.


Modulation of vascular tone by endothelin-1: role of preload, endothelial integrity and concentration of endothelin-1.
1. Endothelin-1 (ET-1) has been shown to exert both arterial relaxant and constrictor effects. To examine the mechanisms of these divergent effects, rat aortic rings were suspended in an organ bath (baseline preload, 5 g) and exposed to ET-1 (10(-11) to 10(-7) M). ET-1 contracted these rings in a concentration-dependent fashion. 2. When aortic rings were contracted with noradrenaline (NA) to 1 g of tension, ET-1 caused further contraction of these rings. In rings precontracted to 2 to 4 g of tension, low concentrations of ET-1 (10(-11) to 10(-9) M) caused a significant relaxation, but high concentrations (greater than or equal to 5 x 10(-9) M) caused a marked contraction, indicating both relaxant and contractile effects of ET-1 depending on the preload and ET-1 concentration. 3. To determine the mechanism of ET-1-induced relaxation, aortic rings were pretreated with the cyclo-oxygenase inhibitor indomethacin, NG-monomethyl-L-arginine (L-NMMA) an inhibitor of synthesis of endothelium-derived relaxing factor (EDRF), or oxyhaemoglobin (Hb) which decreases the activity of EDRF, prior to their exposure to ET-1. Both indomethacin and L-NMMA markedly (P less than 0.01) attenuated ET-1-induced relaxation, whereas Hb totally abolished it. Removal of the endothelium from aortic rings also abolished ET-1-mediated relaxation. 4. The relaxant effect of ET-1 in NA-precontracted rings was associated with marked accumulation of guanosine 3':5'-cyclic monophosphate (cyclic GMP), whereas ET-1-induced contraction of quiescent rings was not. 5.In manually stretched rings (4 g of tension), ET-l caused only concentration-dependent contraction, but no cyclic GMP accumulation.6. Thus, ET-1 contracts rat aortic rings with intact endothelium and those which are passively stretched. However, stimulation of rat aortic rings with NA to modest tension alters the contractile effect of ET-1 to a potent relaxant effect. The ET-l-mediated relaxation in this setting appears to be endothelium-dependent and is related to release of both cyclo-oxygenase products and EDRF.


A Comparative Study of Different Stem Cell Transplantation for Spinal Cord Injury: A Systematic Review and Network Meta-Analysis.
In the present study, we evaluated the efficacy and safety of different stem cell types for spinal cord injury (SCI) therapy to determine the superior treatment of SCI. A systematic literature search was performed using PubMed, Embase, the Cochrane Library, Web of Science, VIP, Chinese National Knowledge Infrastructure, and Wan Fang databases from initiation to January 30, 2021. A Bayesian network meta-analysis was performed using ADDIS (Aggregate Data Drug Information System) software. The PROSPERO registration number was CRD42020129635. We included 12 studies with 642 patients in the present study. A network meta-analysis revealed that bone mesenchymal stem cells (BMSCs) combined with rehabilitation training were significantly more effective than rehabilitation training alone in improving the American Spinal Injury Association (ASIA) impairment scale grade (odds ratio, 94.25; 95% confidence interval [CI], 6.71-9321.95), ASIA motor score (weighted mean difference [WMD], 6.67; 95% CI, 0.83-12.73), ASIA sensory functional score (WMD, 12.41; 95% CI, 3.42-21.72), and Barthel index (WMD, 7.24; 95% CI, 0.21-14.30). However, no statistically significant differences were observed between bone marrow mononuclear cells (MNCs) combined with rehabilitation training, umbilical cord-derived mesenchymal stem cells (UCMSCs) combined with rehabilitation training, or UCMSCs alone and rehabilitation alone for all indicators. In terms of safety, there were no serious and permanent adverse effects after transplantation of BMSCs, MNCs, or UCMSCs. BMSCs plus rehabilitation might be superior to other stem cell treatments of SCI in improving the ASIA impairment scale grade, ASIA motor score, ASIA sensory functional score, and Barthel index. The therapeutic effects of UCMSCs and MNCs remain to be confirmed.


A study of the incorporation of cytochrome oxidase into planar synthetic membranes.
Cytochrome oxidase molecules were incorporated into black lipid membranes and into a new form of planar synthetic membrane. Studies of these membranes indicated that the incorporation of large membrane bound enzymes into black lipid membranes involves difficulties fundamental to this technique. On the other hand the new method described in this paper is more promising.


Optimizing the cooling block for the quick freeze method.
It is important for future ultrastructural preservation studies to freeze biological specimens as rapidly as possible. Finite element numerical techniques have been used to compare different cooling block materials used in the quick freeze 'slamming' method. It is concluded that a pure silver block at an optimum initial temperature of about 15.6 K will produce the quickest cooling and will give rates approximately 50% higher than if the block were initially cooled to 4.2 K. A copper block will produce the fastest cooling rates when the block is initially at liquid nitrogen temperature of 77.3 K provided the section being studied is taken no more than about 30 microns from the specimen-block interface. Composite metal blocks can further reduce the total specimen cooling time compared to a mono-block at the same initial temperature but the cooling rate near the interface will be slower. Future methods for specifying cooling rates within thin biological samples should be standardized and must be based on a combination of finite element numerical analysis and the measured temperature at the rear surface of the sample. Thermal contact resistance between cooling block and specimen and between specimen and the rear face temperature sensor must be minimal.


N-Hydroxysuccinamide functionalized iron oxide nanoparticles conjugated with 5-flurouracil for hyperthermic therapy of malignant liver cancer cells by DNA repair disruption.
Magnetized iron oxide nanoparticles are ideal materials for biological and biomedical applications due to their biocompatibility, super paramagnetic behavior, surface capability, and chemical stability. This research article is narrating the overview of methodologies of preparation, functionalization, characterization and applications of Fe3O4 nanoparticles. Super paramagnetic nanoparticles are studied for their hyperthermia properties. The proposed mechanism behind the hyperthermia was damaging the proteins responsible for DNA repair thereby, directly accelerating the DNA damages on cancer cells by increasing the temperature in the vicinity of the cancer cells. In this study, super paramagnetic iron oxide (Fe3O4) nanoparticles (SPIONs) and anti-cancer drug, 5-fluorouracil, functionalized with N-Hydroxysuccinimide organic molecules. A specific absorption rate at 351 nm can be achieved using UV analysis. The magnetic Fe3O4 nanoparticles had a cubic crystalline structure. FE-SEM(field emission scanning Electron microscopy) with EDAX(energy dispersive X-ray analysis) analysis shows that the size of the SPION was about 30-100 nm range and the percentage of chemical compositions was higher in the order of Fe, O, C. for particle size analysis, the SPION were positively charged derived at +9.9 mV and its conductivity is measured at 0.826 mS/cm. In-vitro anti-cancerous activity analysis in Hep-G2 cells (liver cancer cells) shows that the 5-fluorouracil functionalized SPIONs have higher inhibition rate than the bare Fe3O4 nanoparticles. The Fe3O4 nanoparticles were studied for their hyperthermic abilities at two different frequencies such as 3.05 × 106 kAm-1s-1 and 4.58 × 106 kAm-1s-1.The bare Fe3O4 at low magnetic field, 10 mg was required to raise the temperature above 42°- 45 °C and at high magnetic field, 6 mg was enough to raise the same temperature. The 5-fluorouracil functionalized Fe3O4 shows that at low magnetic field, 6 mg is required to raise the hyperthermia temperature and at high magnetic field, 3 mg is required to raise the temperature above 42°- 45 °C. the rate of heating and the temperature achieved with time can be tuned with concentrations as well as magnetic component present in the Fe3O4 nanoparticles. Beyond this concentration, the rate of cell death was observed to increase. The saturation and low residual magnetization were revealed by the magnetization analysis, making them well suited for clinical applications.


Surgical anatomy of the nuchal muscles in the posterior cervicothoracic junction: significance of the preservation of the C7 spinous process in cervical laminoplasty.
An anatomic study investigated the attachment of the nuchal muscles to the spinous process. To investigate the anatomic details of the attachment of the nuchal muscles to the spinous process, and which muscles are spared, and to what extent, when the C7 spinous process is preserved in the cervical laminoplasty. In previous studies, it was reported that the incidence of postoperative axial pain was lower in C3-C6 laminoplasty than in C3-C7 laminoplasty, emphasizing the effectiveness of the former procedure where discission of the nuchal muscles that are attached to the C7 spinous process is avoided. However, there have been no detailed anatomic studies of the attachment of the nuchal muscles to the spinous process at the cervicothoracic junction. The anatomy of the speculum rhomboideum of the trapezius, rhomboideus minor, rhomboideus major, serratus posterior superior, splenius capitis, and splenius cervicis to the spinous processes of the cervicothoracic junction were studied using 50 cadavers. The possibility of total discission of the speculum rhomboideum of the trapezius was 0% with C3-C6 laminoplasty and 18% with C3-C7 laminoplasty. More than 50% preservation of the speculum rhomboideum of the trapezius is possible in 72% in C3-C6 laminoplasty and 16% in C3-C7 laminoplasty. In C3-C7 laminoplasty, the possibility of partial preservation of the rhomboideus minor, serratus posterior superior, and splenius capitis at the spinous process was 0%, 66%, and 29%, respectively. The rhomboideus major in 16% and the splenius cervicis in 56% could be completely preserved without partial discission of the muscle attachment. On the other hand, in C3-C6 laminoplasty, the muscles that were spared without complete discission of the muscular attachment at the spinous process were the rhomboideus minor in 35%, the serratus posterior superior in 100% and the splenius capitis in 67%. The rhomboideus major in 76% and the splenius cervicis in 80% were completely spared without partial discission of the muscular attachment. The current study confirmed that C3-C6 laminoplasty in which the C7 spinous process is preserved reduces invasion of the nuchal muscles.


Stable, site-specific fluorescent tagging constructs optimized for burkholderia species.
Several vectors that facilitate stable fluorescent labeling of Burkholderia pseudomallei and Burkholderia thailandensis were constructed. These vectors combined the effectiveness of the mini-Tn7 site-specific transposition system with fluorescent proteins optimized for Burkholderia spp., enabling bacterial tracking during cellular infection.


Expression of matrix metalloproteinases in human glioma cell lines in the presence of IL-10.
Matrix metalloproteinases have been implicated to play a vital role in glioma invasion as they degrade extracellular matrix to facilitate the subsequent migration of tumor cells into the surrounding brain tissue. The cytokine Interleukin-10 (IL-10) was detected recently in glial tumors in vivo. Expression of specific IL-10 mRNA as well as blood serum levels of IL-10 in glioma patients increased with malignancy suggesting a functional role of IL-10 in glioma progression. Moreover, glioma cell migration in vitro was enhanced in the presence of IL-10. We therefore investigated the expression of the matrix metalloproteinases (MMPs) stromelysin-1 (MMP-3), 72-kDa collagenase (MMP-2), 92-kDa collagenase (MMP-9), matrilysin (MMP-7) and the human macrophage metalloelastase (MMP-12). In addition, a possible relation between exposure of glioma cells to IL-10 and invasiveness of these cells due to MMP expression was analyzed. Experiments with Matrigel coated Boyden chambers revealed a pronounced dose dependent effect of IL-10 on glioma invasiveness. The synthetic MMP-inhibitor Marimastat markedly reduced cell invasion in the Boyden chambers confirming the significance of MMPs in the process of invasion. Subsequently, the expression level of MMPs and the serine protease uPA was investigated in 7 glioma cell lines (U373, GaMG, U251, GHE, SNB19, U138 and D54) by RT-PCR. In all but one cell line no enhancement of MMP expression by IL-10 was detected. Matrilysin in U373 cells was the only protease found to be upregulated in the presence of IL-10 dependent on cell density. The present data suggest that IL-10 related effects on the invasive properties of the cell lines are not directly mediated by an upregulation of matrix metalloproteinase expression.


The Maternal-to-Zygotic Transition in Flowering Plants: Evidence, Mechanisms, and Plasticity.
The maternal-to-zygotic transition (MZT) defines a developmental phase during which the embryo progressively emancipates itself from a developmental control relying largely on maternal information. The MZT is a functional readout of two processes: the clearance of maternally derived information and the de novo expression of the inherited, parental alleles enabled by zygotic genome activation (ZGA). In plants, for many years the debate about whether the MZT exists at all focused on the ZGA alone. However, several recent studies provide evidence for a progressive alleviation of the maternal control over embryogenesis that is correlated with a gradual ZGA, a process that is itself maternally controlled. Yet, several examples of zygotic genes that are expressed and/or functionally required early in embryogenesis demonstrate a certain flexibility in the dynamics and kinetics of the MZT among plant species and also intraspecific hybrids.


[The future and the past of surgery for the complicated spine trauma].
The state of art of the spine and spinal cord trauma is highlighted. The thorough literature review was performed. Main trends of the spine surgery, both adopted long ago, and new experimental theories were represented. Problems of medical help organization were also stressed.


Foliar δ13C within a temperate deciduous forest: spatial, temporal, and species sources of variation.
Foliar 13C-abundance (δ13C) was analyzed in the dominant trees of a temperate deciduous forest in east Tennessee (Walker Branch Watershed) to investigate the variation in foliar δ13C as a function of time (within-year and between years), space (canopy height, watershed topography and habitat) and species (deciduous and coniferous taxa). Various hypotheses were tested by analyzing (i) samples collected from the field during the growing season and (ii) foliar tissues maintained in an archived collection. The δ13C-value for leaves from the tops of trees was 2 to 3%. more positive than for leaves sampled at lower heights in the canopy. Quercus prinus leaves sampled just prior to autumn leaf fall had significantly more negative δ13C-values than those sampled during midsummer. On the more xeric ridges, needles of Pinus spp. had more positive δ13C-values than leaves from deciduous species. Foliar δ13C-values differed significantly as a function of topography. Deciduous leaves from xeric sites (ridges and slopes) had more positive δ13C-values than those from mesic (riparian and cove) environments. On the more xeric sites, foliar δ13C was significantly more positive in 1988 (a dry year) relative to that in 1989 (a year with above-normal precipitation). In contrast, leaf δ13C in trees from mesic valley bottoms did not differ significantly among years with disparate precipitation. Patterns in foliar δ13C indicated a higher ratio of net CO2 assimilation to transpiration (A/E) for trees in more xeric versus mesic habitats, and for trees in xeric habitats during years of drought versus years of normal precipitation. However, A/E (units of mmol CO2 fixed/mol H2O transpired) calculated on the basis of δ13C-values for leaves from the more xeric sites was higher in a wet year (6.6±1.2) versus a dry year (3.4±0.4). This difference was attributed to higher transpiration (and therefore lower A/E) in the year with lower relative humidity and higher average daily temperature. The calculated A/E values for the forest in 1988-89, based on δ13C, were within ±55% of estimates made over a 17 day period at this site in 1984 using micrometeorological methods.


Immunogenicity and protective efficacy of adenoviral and subunit RSV vaccines based on stabilized prefusion F protein in pre-clinical models.
Respiratory Syncytial Virus (RSV) remains a leading cause of severe respiratory disease for which no licensed vaccine is available. We have previously described the derivation of an RSV Fusion protein (F) stabilized in its prefusion conformation (preF) as vaccine immunogen and demonstrated superior immunogenicity in naive mice of preF versus wild type RSV F protein, both as protein and when expressed from an Ad26 vaccine vector. Here we address the question if there are qualitative differences between the two vaccine platforms for induction of protective immunity. In naïve mice, both Ad26.RSV.preF and preF protein induced humoral responses, whereas cellular responses were only elicited by Ad26.RSV.preF. In RSV pre-exposed mice, a single dose of either vaccine induced cellular responses and strong humoral responses. Ad26-induced RSV-specific cellular immune responses were detected systemically and locally in the lungs. Both vaccines showed protective efficacy in the cotton rat model, but Ad26.RSV.preF conferred protection at lower virus neutralizing titers in comparison to RSV preF protein. Factors that may contribute to the protective capacity of Ad26.RSV.preF elicited immunity are the induced IgG2a antibodies that are able to engage Fcγ receptors mediating Antibody Dependent Cellular Cytotoxicity (ADCC), and the induction of systemic and lung resident RSV specific CD8 + T cells. These data demonstrate qualitative improvement of immune responses elicited by an adenoviral vector based vaccine encoding the RSV preF antigen compared to the subunit vaccine in small animal models which may inform RSV vaccine development.


CD163(+) M2-type tumor-associated macrophage support the suppression of tumor-infiltrating T cells in osteosarcoma.
Osteosarcoma is one of the most common childhood cancers with high numbers of cancer-related deaths. Progress in conventional therapies is showing limited improvement. An adaptive T cell-based immunotherapy represents a promising new therapeutic option, but to improve its efficacy, regulatory mechanisms in osteosarcoma need further elucidation. Here, to evaluate the regulatory effect of tumor microenvironment of T cells in osteosarcoma, we examined the peripheral blood (PB) and tumor infiltrating (TI) T cells, and their correlations with PB and tumor immune characteristics. We found that TI T cells contained significantly higher levels of TIM-3(+)PD-1(-) and TIM-3(+)PD-1(+) cells than their PB counterparts. Similar to that in chronic HIV and HCV infections, these TIM-3(+)PD-1(-) and TIM-3(+)PD-1(+) T cells presented reduced proliferation and proinflammatory cytokine secretion in response to stimulation. Presence of M2-type (CD163(+)) macrophages exacerbated T cell immunosuppression, since frequencies of CD163(+) tumor-associated macrophages were directly correlated with the frequencies of suppressed TIM-3(+)PD-1(+) T cells. Moreover, depletion of CD163(+) macrophages significantly improved T cell proliferation and proinflammatory cytokine production. Overall, our data presented an intratumoral T cell-specific immunosuppression that was amplified by M2-type tumor-associated macrophages.


Guidelines, "minimal requirements" and standard of care in glioblastoma around the Mediterranean Area: A report from the AROME (Association of Radiotherapy and Oncology of the Mediterranean arEa) Neuro-Oncology working party.
Glioblastoma is the most common and the most lethal primary brain tumor in adults. Although studies are ongoing, the epidemiology of glioblastoma in North Africa (i.e. Morocco, Algeria and Tunisia) remains imperfectly settled and needs to be specified for a better optimization of the neuro-oncology healthcare across the Mediterranean area and in North Africa countries. Over the last years significant therapeutic advances have been accomplished improving survival and quality of life of glioblastoma patients. Indeed, concurrent temozolomide-radiotherapy (temoradiation) and adjuvant temozolomide has been established as the standard of care associated with a survival benefit and a better outcome. Therefore, considering this validated strategy and regarding the means and some other North Africa countries specificities, we decided, under the auspices of AROME (association of radiotherapy and oncology of the Mediterranean area; www.aromecancer.org), a non-profit organization, to organize a dedicated meeting to discuss the standards and elaborate a consensus on the "minimal requirements" adapted to the local resources. Thus, panels of physicians involved in daily multidisciplinary brain tumors management in the two borders of the Mediterranean area have been invited to the AROME neuro-oncology working party. We report here the consensus, established for minimal human and material resources for glioblastoma diagnosis and treatment faced to the standard of care, which should be reached. If the minimal requirements are not reached, the patients should be referred to the closest specialized medical center where at least minimal requirements, or, ideally, the standard of care should be guaranteed to the patients.


Impact of COVID-19 and lockdown on COPD admissions to Christchurch Hospital, New Zealand 2020-2021: a combined quantitative and qualitative study.
During the year following New Zealand's first COVID-19 lockdown, a 33% reduction in chronic obstructive pulmonary disease (COPD)-related admissions occurred and persisted beyond this period at Christchurch Hospital. To identify contributing factors which may have resulted in a persistent decrease in COPD hospitalisation rates at Christchurch Hospital following the 2020 COVID-19 lockdown. Using an explanatory sequential mixed-methods research design, we (i) retrospectively analysed hospital admissions and primary healthcare access by people with COPD (n = 1358) in Canterbury before, during and after COVID lockdown (24 March 2019 to 2021) and (ii) undertook individual interviews from a sample of patients (n = 14). Patients who were not re-admitted following the COVID-19 lockdown had fewer general practice encounters, acute primary care access, antibiotic and prednisone prescriptions. Proportionally fewer Māori and more Pacific patients were admitted with COPD following lockdown. Positive contributing factors at a primary care level included improvements in primary care interactions and medication management. At a patient and community level, there were improvements in lifestyle, self-management practices, social support and contact precautions. However, a subgroup of patients described negative effects such as social isolation. A combination of patient, primary care and community-level factors led to an overall persistent decrease in COPD admissions following the COVID-19 lockdown. Future targeted and individualised measures focusing on these modifiable factors may decrease future COPD-related hospital admissions. The study design facilitated further explanation about factors that contributed to the persistent decrease in hospital admissions among people living with COPD and has underscored the importance of social support, patient empowerment and reduction in barriers in accessing care in admission reduction.


Activity measurement and effective dose modelling of natural radionuclides in building material.
In this paper the assessment of natural radionuclides' activity concentration in building materials, calibration requirements and related indoor exposure dose models is presented. Particular attention is turned to specific improvements in low-level gamma-ray spectrometry to determine the activity concentration of necessary natural radionuclides in building materials with adequate measurement uncertainties. Different approaches for the modelling of the effective dose indoor due to external radiation resulted from natural radionuclides in building material and results of actual building material assessments are shown.


Transformation by concanavalin A of the response of molluscan neurones to L-glutamate.
Concanavalin A causes in all Aplysia and Helix neurones a depolarising response to L-glutamate. The Con A-induced glutamate response is pharmacologically distinct from the three cell-specific glutamate responses (two inhibitory, one excitatory) that can be elicited from untreated molluscan neurones. The transformation in glutamate sensitivity brought about by Con A does not seem to be related to the lectin's capacity to produce redistribution of receptor sites in cell membranes.


Presence of constipation predicts the therapeutic efficacy of pembrolizumab in metastatic urothelial cancer patients.
To study bowel function in urothelial cancer patients treated with pembrolizumab and to assess its association with treatment efficacy. This retrospective study was analyzed for patients with metastatic urothelial cancer who received immune checkpoint inhibitor treatment between December 2017 and June 2019 at Nagoya University and affiliated hospitals in Japan. The association between bowel dysfunction (defined as constipation or need for laxatives) and treatment efficacy was investigated. We retrospectively enrolled 73 patients with metastatic urothelial cancer who received immune checkpoint inhibitor treatment. All patients received pembrolizumab at 200 mg per bodyweight administered intravenously every 3 weeks. Performance status was 0-1 in 58 patients (79.5%), and liver metastasis was detected in 22 patients (30.1%). The median age was 72 years (range 40-89 years). A total of 45 patients had constipation. The median progression-free survival and overall survival from the start of immune checkpoint inhibitor treatment was 4.0 months (95% confidence interval 1.0-17.3) and 6.6 months (95% confidence interval 1.0-18.0), respectively. Patients with constipation had a significantly higher risk of disease progression (P = 0.005). There was no significant association between constipation and overall survival (P = 0.131). However, complete response was observed among two patients treated with immune checkpoint inhibitor, both of whom did not present constipation. The presence of constipation might be a prognostic factor for urothelial cancer patients undergoing immune checkpoint inhibitor treatment.


A Prospective Study of Employee Response to Bullying in a Workplace Environment: Does Assertiveness Actually Help or Hurt?
The aim of the present two-wave prospective study was twofold: (1) to identify the role of assertiveness in exposure to workplace bullying and (2) to determine causal and reverse causal long-term associations between workplace bullying exposure, working conditions and assertiveness. In the present two-wave panel design study (N = 128), with a six-month lag, high assertiveness predicted exposure to bullying. Furthermore, in line with the work environment hypothesis, the results indicate that negative workplace conditions in the first wave led to workplace bullying exposure. The findings suggest that assertive communication may be inappropriate in the case of workplace bullying. As such, we argue that functional assertiveness could be useful.