Severity score for predicting pneumonia in inhalation injury patients.
Inhalation injuries contribute significantly to morbidity and mortality in both children and adults with burns. Pneumonia is a major compromising factor in these patients. The purpose of this article was to evaluate the characteristics, impact factors, incidence, morbidity, and mortality of pneumonia in inhalation injuries. Furthermore, a severity score has been formulated to help predict the probability of developing pneumonia following inhalation injuries. A retrospective study was performed of 214 patients, treated for inhalation injuries from 1999 to 2009 at the Burn Center in Chang Gung Memorial Hospital, Linkou, Taiwan. Patients' characteristics, length of hospitalization, total burn surface area, initial PaO2:FiO2 ratio, number of intubated days, bronchoscope grade, initial carboxyhemoglobin level (COHb) and mortality rate were recorded. A Student's t-test was used for comparison of inhalation injury patients with and without pneumonia and was also used for comparing a TBSA of >20% to those with a TBSA of ≤20% in patients with inhalation injury and pneumonia. Logistic regression analyses were utilized to create a severity score related to pneumonia. 129 patients with inhalation injury were included in the analysis. Overall, 38% (49/129) patients developed pneumonia. Pneumonia associated with inhalation injury occurred more often in patients with a TBSA>20% (P<0.05). The intubation days, bronchoscope grade and COHb level of pneumonia patients were significantly longer (P<0.05). Initial PaO2:FiO2 ratio (PaO2/FiO2) was significantly lower in patients with pneumonia (P<0.05). Mortality following pneumonia was increased sevenfold (P<0.05). Hospitalization days and intubation days were significantly longer in TBSA>20%. Logistic regression analysis was performed to find out the impact factors of pneumonia in inhalation injury patients and to set a severity score. Patients age >60 years, TBSA >20%, bronchoscope grade is 3 or 4, initial PaO2/FiO2≦300 and initial COHb level>10% showed a significant difference (P<0.05). The total severity scale was set at 5 points. Each impact factor was given one point and when the score ≥2 it means patients have high risk of development of pneumonia. This study had identified the significant risk factors for potential development of pneumonia in a group of inhalation injury patients. The impact of these risk factors should be validated in further prospective trials to improve outcome or at least reduce the incidence of the surrogate diagnosis of pneumonia.


Brownian dynamics simulation of restricted rotational diffusion.
The restricted rotational diffusion of an axially symmetric particle is simulated by the Brownian dynamics technique. In addition to the wobbling-in-a-cone model, several continuous potentials are considered. The particle studied is particularly simple: a sphere anchored to a point fixed in space. However, presenting the results in a convenient, reduced form, they are valid for any axially symmetric particle. From simulated rotational trajectories, we calculate (P2(cos alpha] as a function of t, where alpha is the angle between two orientations separated by time t and P2 is the second Legendre polynomial. This correlation function is closely related to time-resolved electro-optic and spectroscopic properties. Simulated results for the cone model are in excellent agreement with the quasiexact results of Lipari and Szabo (1981, J. Chem. Phys., 75:2971-2976). Thus we confirm the good performance of the simulation technique and the validity of our working conditions. Novel results are presented for continuous restricting potentials, V(theta). The (P2) results for V = 1/2K theta 2 and V = Q(1 - cos theta) are practically the same if K and Q are chosen so tht the long-time (P2) values coincide. Thus, the quadratic potential seems to be a good representation of any monotonically increasing potential. However, for an uniaxial potential such as V = Csin2 theta, the decay is appreciably faster. The (P2) decays simulated for the continuous potentials are analyzed by the monoexponential version of the cone model. We found that such an analysis produces an overestimation of the true rotational diffusion coefficient of approximately 15% only, although for uniaxial potentials the error may be larger.


Intermittent dietary carbohydrate restriction versus calorie restriction and cardiometabolic profiles: A randomized trial.
The aim of this study was to investigate the effectiveness of an intermittent low-carbohydrate diet (ILCD) versus calorie restriction (ICR) in young populations and potential mechanisms. Thirty-four participants aged 9 to 30 years with cardiometabolic risk were randomized to receive a self-administered 2-week ILCD (carbohydrate intake ≤ 50 g/d on seven nonconsecutive days) or ICR (500-600 kcal/d for two consecutive days per week). Differences in changes in obesity measures, glycemic and lipid profiles, gut microbiota composition, and three serum biomarkers were compared. The ILCD and ICR similarly reduced body weight, waist circumference, fasting glucose, insulin, postprandial glucose variation, monocyte chemoattractant protein-1, free fatty acid, and fibroblast growth factor 21, whereas ILCD produced significantly different alterations in the following outcomes compared with ICR: greater increases in low-density lipoprotein cholesterol and total cholesterol (-0.36 mmol/L, 95% CI: -0.68 to -0.04; -0.40 mmol/L, 95% CI: -0.73 to -0.06) and greater decrease in triglyceride (0.20 mmol/L, 95% CI: 0.04 to 0.37). Actinobacteria and Bifidobacterium reduced after ILCD but not ICR; and the reductions strongly correlated with changes in fasting glucose (both r = 0.84) and low-density lipoprotein cholesterol (r = -0.81 and -0.72). This study found no evidence of differences in changes from baseline in obesity measures, glucose regulation, and inflammation between ILCD and ICR, despite trends in reduction in those parameters. However, there seemed to be some differences in responses in lipids and gut microbiota.


Independent immunodominant and immunorecessive tumor-specific antigens on a malignant tumor: antigenic dissection with cytolytic T cell clones.
We have analyzed the complexity of a unique tumor-specific transplantation antigen expressed by the murine ultraviolet light-induced fibrosarcoma 1591-RE. This tumor is highly immunogenic and is regularly rejected by normal mice. We have derived a cloned cytolytic T cell line showing a reactivity pattern representative of the cytolytic response of the host rejecting this regressor tumor. Using this T cell line (anti-A), variants of 1591-RE (1591-A-) were selected in vitro that had lost the same antigen as progressor variants of 1591-RE selected by the host in vivo. The in vitro derived variant was then used to generate a second T cell clone (anti-B) that recognized an antigen on the parental tumor that had been retained by the variants derived in vitro. Host-selected progressor variants were also found to have retained this antigen. By selecting for variants in vitro from the parental tumor with the anti-B T cell line, it was shown that the two different antigens (A and B) present on the parental tumor were lost independently of each other. Despite the independence of these two antigens, the host T cell response to the parental regressor tumor was invariably restricted to only the "immunodominant" A antigen.


Differences in occupational, transportation, domestic, and leisure-time physical activities: do geographical location and socio-cultural status matter?
Researchers have recently expressed their concern for the health of Francophones and rural dwellers in Canada. Their levels of physical activity may explain part of the observed differences. However, little is known about the physical activity levels of these 2 groups. The purpose of this study was to assess levels of physical activity among a sample of Francophones and rural dwellers. The study also assessed the associations of various types of physical activity to measures of health status. A quota-based convenience sample of 256 adults from Northern Ontario was surveyed using the IPAQ and the SF-12. There were no significant differences in activity levels between language groups (P = .06) or geographical groups (P = .22) on the combined dependent variables based on MANOVA. Leisure-time physical activity scores were consistently associated to better physical component summary scores of the SF-12. Implications for practice include that leisure-time physical activities have been at the forefront of public health promotion, and our findings support this approach. Further, population specific interventions are indeed important, however, within this Canadian context when identifying target groups one must look beyond sociocultural status or geographical location.


Wiskott-Aldrich Syndrome in four male siblings from a consanguineous family from Lebanon.
Wiskott-Aldrich syndrome (WAS) is a rare X-linked primary immunodeficiency disorder (PID) characterized by microthrombocytopenia, bloody diarrhea, eczema, recurrent infections, and a high incidence of autoimmunity and malignancy. To investigate the mechanism of thrombocytopenia and infections in four boys of consanguineous parents from Lebanon. Patient gDNA was studied using Next Generation Sequencing and Sanger Sequencing. Protein expression was determined by immunoblotting, and mRNA expression by semi-quantitative RT-PCR. F-actin polymerization and cellular proliferation were assayed by flow cytometry. We identified a threonine to a methionine change at position 45 (T45M) of the WAS protein (WASp) that abolished protein expression and disturbed F-actin polymerization and T cell proliferation, but not B cell proliferation. In addition, the levels of the WAS-interacting protein (WIP) were significantly decreased in the patients. The mutation identified severely destabilizes WASp and affects the downstream signaling events important for T cell function, but not B cell function. It was previously known that the stability of WASp depends on WIP. In this manuscript, we report that the stability of WIP also depends on WASp. Finally, it is important to suspect X-linked PIDs even in consanguineous families. The patients are above the optimal age for transplant in WAS, and it is difficult to identify one or more donors for four patients, therefore, they represent ideal candidates for gene therapy or interleukin-2 therapy.


Vibrational spectroscopic investigation of structurally-related LiFePO4, NaFePO4, and FePO4 compounds.
Vibrational spectroscopy was utilized to investigate the local structure of LiFePO(4), NaFePO(4), and FePO(4). The factor group splitting of the intramolecular PO(4)(3-) vibrations is between 10 and 20 cm(-1) less for NaFePO(4) than for LiFePO(4). This is because Li(+) ions have a higher charge density than Na(+) ions and can form stronger coordinative bonds with the PO(4)(3-) anions. Thus, the internal modes are more perturbed in LiFePO(4) and exhibit larger factor group splitting effects. The similarity of the factor group multiplets for both LiFePO(4) and NaFePO(4), particularly the PO(4)(3-) bending modes, strongly suggests that the 506 and 470 cm(-1) bands of LiFePO(4) consist almost entirely of lithium translatory motion. There are marked differences between the vibrational spectrum of FePO(4) and those of LiMPO(4) (M=Mn, Fe, Co, or Ni) or NaFePO(4). The monovalent cations interact with the oxygen atoms of the phosphate groups, affecting the frequencies and intensities of the intramolecular PO(4)(3-) modes, in a manner that is absent in FePO(4).


Retinoblastoma in older patients: A retrospective comparative analysis of 100 consecutive patients based on age.
To describe comparative clinical features, treatment, and outcomes of retinoblastoma in patients initially diagnosed at age 4 or older. Retrospective case series. There were 101 eyes in 100 consecutive patients age ≥4 years diagnosed with retinoblastoma. Mean patient age at diagnosis was 6.6 years (median 5.3, range 4.0-41.0 years). Tumors were predominantly classified (International Classification of Retinoblastoma) as group D (31%) or E (65%). Patients were divided by age into 3 groups: young (4-6 years [65%]), middle (>6-8 years [23%]), and older (>8 years [12%]). Comparing by age group (young vs. middle vs. older), mean tumor basal diameter (19.9 vs. 17.3 vs. 17.0 mm, p = 0.05) and mean tumor thickness (11.0 vs. 9.4 vs. 7.0 mm, p < 0.01) were greatest in the youngest group. Distance to the optic nerve (1.5 vs. 1.7 vs. 5.0 mm, p = 0.01) and foveola (1.9 vs. 1.8 vs. 6.0 mm, p < 0.01) were greatest in the oldest age group. Objective findings of leukocoria and strabismus were more common in younger patients, while older patients complained of subjective findings, like decreased vision (19% vs. 30% vs. 60%, p < 0.01) and floaters (3% vs. 4% vs. 17%, p = 0.05). Primary treatment included enucleation (76%) and other modalities (24%). Globe salvage rate was 13%, with no significant difference by age. Comparison of globe salvage by revealed significant improvement between 1974-2008 (6%) and 2009-2017 (38%, p < 0.01). Retinoblastoma in older patients (>8 years) tends to be smaller and more peripherally located, with more subjective presenting symptoms.


Evaluation of twice-daily, low-dose trilostane treatment administered orally in dogs with naturally occurring hyperadrenocorticism.
To evaluate the effects of twice-daily oral administration of a low-dose of trilostane treatment and assess the duration of effects after once-daily trilostane administration in dogs with naturally occurring hyperadrenocorticism (NOH). Prospective study. 28 dogs with NOH. 22 dogs received 0.5 to 2.5 mg of trilostane/kg (0.23 to 1.14 mg/lb) orally every 12 hours initially. At intervals, dogs were reevaluated; owner assessment of treatment response was recorded. To assess drug effect duration, 16 of the 22 dogs and 6 additional dogs underwent 2 ACTH stimulation tests 3 to 4 hours and 8 to 9 hours after once-daily trilostane administration. After 1 to 2 weeks, mean trilostane dosage was 1.4 mg/kg (0.64 mg/lb) every 12 hours (n = 22 dogs; good response [resolution of signs], 8; poor response, 14). Four to 8 weeks later, mean dosage was 1.8 mg/kg (0.82 mg/lb) every 12 or 8 hours (n = 21 and 1 dogs, respectively; good response, 15; poor response, 5; 2 dogs were ill). Eight to 16 weeks after the second reevaluation, remaining dogs had good responses (mean dosages, 1.9 mg/kg [0.86 mg/lb], q 12 h [n = 13 dogs] and 1.3 mg/kg [0.59 mg/lb], q 8 h [3]). At 3 to 4 hours and 8 to 9 hours after once-daily dosing, mean post-ACTH stimulation serum cortisol concentrations were 2.60 and 8.09 Pg/dL, respectively. In dogs with NOH, administration of trilostane at low doses every 12 hours was effective, although 2 dogs became ill during treatment. Drug effects diminished within 8 to 9 hours. Because of potential adverse effects, lower doses should be evaluated.


Inhibition of N- and L-type calcium channels by muscarinic receptor activation in rat sympathetic neurons.
Modulation of N- and L-type Ca2+ channels by oxotremorine-M (oxo-M) acting on muscarinic receptors and norepinephrine (NE) acting on alpha-adrenergic receptors was studied in superior cervical ganglion neurons. Oxo-M depresses dihydropyridine-augmented tail currents in whole-cell recordings, whereas NE does not. This modulation of L-type Ca2+ channels by oxo-M is abolished by adding 20 mM BAPTA to the pipette solution. Oxo-M, acting via a diffusible messenger, reduces the probability of opening of single N- and L-type channels recorded in cell-attached patches. We conclude that a diffusible messenger signaling pathway activated by oxo-M inhibits both N- and L-type Ca2+ channels, whereas a membrane-delimited pathway activated by oxo-M and NE inhibits only N-type Ca2+ channels.


Nerve growth factor does not seem to be a biomarker for neurogenic lower urinary tract dysfunction after spinal cord injury.
To prospectively investigate the association of bladder function with the nerve growth factor (NGF) concentration in the urine of individuals with neurogenic lower urinary tract dysfunction (NLUTD) after spinal cord injury (SCI). Individuals with chronic SCI and NLUTD presenting for a routine urologic examination at a tertiary urologic referral center were recruited for the study. Patient characteristics, the current bladder evacuation method and urodynamic parameters were collected. As controls, individuals with normal bladder function were recruited from the staff of a SCI rehabilitation center. The urinary NGF concentration was measured in triplicates by enzyme linked immunosorbent assay with a minimal sensitivity of 10 pg/ml. The data of 10 and 37 individuals with normal bladder function and NLUTD, respectively, were analyzed. The urinary NGF concentration was below 10 pg/ml in all investigated samples. The urinary NGF concentration did not differentiate between individuals with normal bladder function and those with NLUTD. At least in patients with SCI, the urinary NGF concentration does not seem to be a clinically relevant biomarker for NLUTD. Neurourol. Urodynam. 36:659-662, 2017. © 2016 Wiley Periodicals, Inc.


Relationship between lipophilicity of BCS class III and IV drugs and the functional activity of peroral absorption enhancers.
Absorption enhancers (AEs) have been shown to be specific in permeation enhancement capabilities because of which they increase absorption of some drug molecules more than others. Present study was designed to investigate the relationship between lipophilicity of drug molecules and the absorption enhancement potential of AEs. Four drug molecules of different lipophilicity were selected as model compounds, namely, cefotaxime sodium, ceftazidime pentahydrate, lovastatin and cyclosporin A. Their apparent permeability coefficients in the absence and presence of three classes of AEs (fatty acids, cyclodextrins, and bile salts) were determined using in vitro everted rat intestinal sac absorption model. Significant relationship was observed between log P of drug and absorption enhancement ratios by AEs. This relationship was found to be functionally directly or indirectly proportional depending upon nature of AE and explain the mechanism of permeation enhancement.


Structural and functional characterization of colonization factors AIBI-CS6 and AIIBII-CS6 of enterotoxigenic Escherichia coli.
Over time, the structure and function of the broadly dispersed colonization factor (CF) CS6 of enterotoxigenic Escherichia coli (ETEC) have become more significant. CS6 is composed of tightly-associated subunits, CssA and CssB which due to presence of natural point mutation gave rise to CS6 subtypes. In contrast to the other ETEC CFs, CS6 is an afimbrial, spherical-shaped oligomers of (CssA-CssB)n complex where 'n' is concentration dependent. In this study, we have compared AIBI-CS6 and AIIBII-CS6 structurally and functionally. The Mw of CssAI was 18.5 kDa but Mw of CssAII was 15.1 kDa. Both CssBI and CssBII had Mw of 15.9 kDa. The substitution of Gly39 with Ala39 in CssAI leads to reduction in Mw from 18.5 to 15.1 kDa. Due to higher Mw of CssAI, the size of AIBI concentration-dependent oligomers should be higher. However, the Mw of AIIBII oligomers were higher and AIIBII also showed higher oligomeric forms compared to AIBI both in native PAGE and electron microscopy. The oligomers of both subtypes could withstand greater temperatures and denaturant concentrations. In terms of cellular response, the levels of inflammatory cytokines were significantly higher in case of AIBI-CS6 expressing ETEC as compared to AIIBII-CS6 expressing ETEC both in vitro and in vivo. When inflammatory cytokines were evaluated after infecting suckling mice with these ETEC strains, the results were consistent. In conclusion, even though there was subtle structural difference between AIBI-CS6 and AIIBII-CS6 due to natural point mutations but ETEC strains expressing these subtypes displayed great variability in pathogenicity.


Histoenzymological and ultrastructural study of a bifocal calcifying epithelial odontogenic tumor. Characteristics of epithelial cells and histogenesis of amyloid-like material.
A calcifying epithelial odontogenic tumor, simultaneously located in the two jaws (maxilla and mandible) was examined by histochemical and electron microscopic methods. Squamous tumor cells without secretory polarity were different from those of common ameloblastoma. High activities of alkaline phosphatase and ATPases were demonstrated by light and electron microscopy on the cytoplasmic membrane, findings similar to those in the stratum intermedium cells of the normal dental germ from which these tumor cells seem to arise. The tumor cells, like preameloblasts of the dental germ, also produce a granulo-filamentous material in intracytoplasmic vesicles and discharge it into the stroma. This "pseudo-amyloid" substance represents an abnormal protein of the enamel matrix and calcification, mainly occurring in that substance, might be an attempt at mineralization.


Treatment of urinary incontinence in children: the artificial sphincter versus other methods.
Urinary incontinence in children is a distressing problem that often is magnified during puberty, since the children then realize the full significance of the disorder. Although there are numerous methods of treatment described none offers the reliable combination of a normal body image and total urinary continence. We describe our experience with the AS792 artificial urinary sphincter in treating children with urinary incontinence of varying etiologies and compare it with other described methods.


[Effect of the supplementary administration of vitamins in the ration on metabolic indices in people under alpine conditions].
It was shown that polyvitamin supplemented diets in which animal proteins had the biggest share and part of malassimilated polysaccharides had been replaced by easily assimilated disaccharides, promoted maintenance of the higher A/G ratio, low blood concentrations of lactic and pyruvic acids, and improvement of the parameters of acid-base metabolism in the people living under alpine conditions. After veloergometric test this group showed a less increase in the blood lactic acid content.


Thyroid cancer in childhood.
Thyroid cancer in childhood is a relatively rare condition. Often it shows biological characteristics different from those seen in adults. Based upon 10 cases in our clinic and 57 cases collected from the Japanese literatures, clinical features, pathology, treatment and prognosis of thyroid cancer in childhood are discussed. Pathogenesis is most likely to be related to hormonal changes during adolescence and previous radiation of the neck region. Cervical lymph nodes swelling was the chief complaint in 84.6 per cent of the cases. On the other hand, pulmonary metastases were recognized in the early stages in 33.5 per cent of the cases. Radical excision of the tumor with modified radical neck dissection is the treatment most frequently employed even in the presence of lung metastases. However, hypoparathyroidism and recurrent nerve injuries should be avoided at all cost in view of long life expectancy and the difficulty in treating them satisfactorily. Prognosis could be as good for children as it is for adults except in cases with early lung metastases.


An integrated rural health project in Saradidi, Kenya.
In 1979 a community self help health development programme was initiated in Saradidi, Kenya, as the community's response to its problems. In line with the theoretical considerations made for the implementation of primary health care the community was involved in planning, organization, setting of priorities and objectives, implementation and evaluation of the programme. The Saradidi Health Development Project (SHDP) was initiated by people from the area with material assistance from within and outside Saradidi. Nearly 10 years since the beginning of the project, the SHDP still runs more or less on its own providing experiences for other projects and initiators.


The effect of epitope density and antibody affinity on the ELISA as analysed by monoclonal antibodies.
The antibody titre and the optical density values in an ELISA are influenced by the epitope density of the antigen and the affinity of the antibody tested. This has major implications in the interpretation of ELISA results.


Editorial Commentary: Tibial Tubercle Osteotomy Complications Are Most Common With Complete Detachment of the Distal Periosteal Hinge.
Tibial tubercle osteotomy (TTO) is complex because flat osteotomy is indicated for instability whereas anteromedialization is indicated for osteoarthritis. Instability is associated with patella alta, which sometimes requires distalization, and sometimes pediatric considerations include incompletely ossified tibial tubercle and open growth plates. Complete detachment, as is required for distalization, results in the highest rate of complications after TTO.


Current concepts for the treatment of acute scaphoid fractures.
Fractures of the scaphoid are common injuries, accounting for approximately 80 % of carpal fractures. Differentiation between stable and unstable fractures (Herbert classification) cannot be made with conventional X-rays, so evaluation by computed tomography should additionally be performed. Under most circumstances, minimally invasive surgery with cannulated screws is the treatment of choice. A longer cast immobilization after minimal-invasive surgery is not necessary. Conservative treatment still has a place if the fracture is not dislocated nor unstable, but operative treatment can be offered to reduce the period of cast immobilization. Displaced fractures have a greater risk for nonunion and therefore should be treated operatively. Proximal pole fractures are definitely unstable, requiring treatment with screw fixation. The surgical approach depends on the location of the fracture and the preference of the surgeon.


Associations Between Patient Perceptions of Communication, Cure, and Other Patient-Related Factors Regarding Patient-Reported Quality of Care Following Surgical Resection of Lung and Colorectal Cancer.
The objective of the current study was to analyze various patient-related factors related to patient-reported quality of overall and surgical care following surgical resection of lung or colorectal cancer. Between 2003 and 2005, 3,954 patients who underwent cancer-directed surgery for newly diagnosed lung (30.3%) or colorectal (69.7%) cancer were identified from a population- and health system-based survey of participants from multiple US regions. Factors associated with patient-perceived quality of overall and surgical care were analyzed with multivariable logistic regression models. Overall, 56.7% of patients reported excellent quality of overall care and 67.9% of patients reported excellent quality of surgical care; there was no difference by cancer type (P > 0.05). Factors associated with lower likelihood to report excellent quality of overall and surgical care included female sex, minority race, and the presence of multiple comorbidities (all odds ratio [OR] <1, all P < 0.05). Patients who had higher levels of education (overall quality: OR 1.62; surgical quality: OR 1.26), higher annual income (overall quality: OR 1.29; surgical quality: OR 1.23), and good physical function (overall quality: OR 1.35; surgical quality: OR 1.24) were all more likely to report excellent quality of overall and surgical care (all P < 0.05). Furthermore, patients who reported their physician as having excellent communication skills (overall quality: OR 6.49; surgical quality: OR 3.74) as well as patients who perceived their cancer as likely curable (overall quality: OR 1.17; surgical quality: OR 1.11) were more likely to report excellent quality of overall and surgical care (all P < 0.05). Patient-reported quality of care is associated with several factors including race, income, and educational status, as well as physician communication and patient perception of likelihood of cure. Future studies are needed to more closely examine patient-physician relationships and communication barriers, particularly among minority patients and those with lower income and educational status.


Polyether ether ketone - As an alternative biomaterial for Metal Richmond crown-3-dimensional finite element analysis.
This study was aimed to analyze the stress generation and distribution for "polyether ether ketone (PEEK)" and metal cobalt-chromium (Co-Cr) at different locations of the tooth using finite element analysis (FEA), when they are casted-off as "Richmond crowns." The model of the tooth was designed using "computer-aided design/computer-aided manufacturing" followed by generating the "Mesh" of the tooth to analyze the stress caused by applying vertical and oblique loads of 100N and 40N, respectively, in cubical nodes for both PEEK and metal endodontic post-based Richmond crown. The "3-dimensional von Mises criteria" was used to compare stresses of both elements using FEA. The material properties for each component were designated by respective modulus of elasticity and Poisson's ratio. The statistical test of the stress generation in various locations of PEEK and Metal (Co-Cr) Richmond crown was done by independent t-test. From the FEA analysis of Richmond crown, it is evident that maximum stress was generated by "Metal" of about 66.418 MPa when compared to "PEEK" (15.826 MPa). "PEEK Richmond crown" produced minimal stress on the tooth and the other surrounding regions than "Metal Richmond crown" with a statistically significant difference (P < 0.05). The results proved that the "Metal Richmond crown" postsystem had a tendency to produce more stress on the tooth and the other surrounding regions than the PEEK. The FEA proved the pros of using "PEEK post Richmond crown," which is a big boon for the modern era dentistry.


Accuracy of PET-CT in predicting survival in patients with esophageal cancer.
Positron emission tomography (PET) is an integral part of tumor staging for patients with esophageal cancer. Recent studies suggest a role for PET scan in predicting survival in these patients, but this relationship is unclear in the setting of neoadjuvant therapy. We examined pretreatment maximum standard uptake value (SUV(max)) of the primary tumor in patients treated with and without neoadjuvant therapy. All patients undergoing esophagectomy with a preoperative PET scan over a nine-year period (2001-2010) were identified from a prospectively maintained database. Positron emission tomography data were obtained from computers housing the original PET scans. Overall survival was correlated with SUV(max) of the primary tumor. A total of 191 patients were identified, and 103 patients met inclusion criteria. Eighty-two had an adenocarcinoma (80%), and 21 (20%) had a squamous cell carcinoma. Fifty-seven (55%) patients received neoadjuvant therapy. In the surgery alone group, a SUV(max) of > 5.0 in the primary tumor was associated with poor prognosis [Hazard Ratio (HR) 0.32; p = 0.007], but this factor did not retain its significance on multivariate analysis (HR 0.65; p = 0.43). Pretreatment SUV(max) in patients who underwent neoadjuvant therapy was not significant in predicting overall survival (p = 0.10). This study does not support the use of SUV(max) on pretreatment PET scans as a prognostic tool for patients with esophageal cancer, especially in those who have received neoadjuvant therapy. Lymph node status is a more accurate predictor of outcome, and efforts to improve pretreatment staging should focus on this factor.


Dead space and CO₂ elimination related to pattern of inspiratory gas delivery in ARDS patients.
The inspiratory flow pattern influences CO₂ elimination by affecting the time the tidal volume remains resident in alveoli. This time is expressed in terms of mean distribution time (MDT), which is the time available for distribution and diffusion of inspired tidal gas within resident alveolar gas. In healthy and sick pigs, abrupt cessation of inspiratory flow (that is, high end-inspiratory flow (EIF)), enhances CO₂ elimination. The objective was to test the hypothesis that effects of inspiratory gas delivery pattern on CO₂ exchange can be comprehensively described from the effects of MDT and EIF in patients with acute respiratory distress syndrome (ARDS). In a medical intensive care unit of a university hospital, ARDS patients were studied during sequences of breaths with varying inspiratory flow patterns. Patients were ventilated with a computer-controlled ventilator allowing single breaths to be modified with respect to durations of inspiratory flow and postinspiratory pause (TP), as well as the shape of the inspiratory flow wave. From the single-breath test for CO₂, the volume of CO₂ eliminated by each tidal breath was derived. A long MDT, caused primarily by a long TP, led to importantly enhanced CO₂ elimination. So did a high EIF. Effects of MDT and EIF were comprehensively described with a simple equation. Typically, an efficient and a less-efficient pattern of inspiration could result in ± 10% variation of CO₂ elimination, and in individuals, up to 35%. In ARDS, CO₂ elimination is importantly enhanced by an inspiratory flow pattern with long MDT and high EIF. An optimal inspiratory pattern allows a reduction of tidal volume and may be part of lung-protective ventilation.


The significance of immunonutrition nutritional support in patients undergoing postoperative adjuvant chemotherapy for lung cancer: case-control study.
In this study, the effect of postoperative early nutritional supplementation on the course of the disease was investigated in patients who were operated for non-small cell lung cancer and received adjuvant chemotherapy. The study examined the data of patients who anatomical pulmonary resection for non-small cell lung cancer and who were treated with adjuvant chemotherapy at our clinic between January 2014 and January 2020. Patients who received early postoperative nutritional supplements and those who continued with a normal diet were compared in terms of complications, mortality, recurrence, and survival. The study sample consisted of 68 (84%) male and 13 (16%) female patients, and the mean duration of postoperative follow-up was 31.6 ± 17.9 (4-75) months. Metastasis was identified in eight (17.4%) patients in GrupNS (Nutritional Supplements) compared to 10 (28.6%) patients in GroupC (Control) (p = 0.231). Of the total, 11 (23.9%) patients died in GroupNS compared to 13 (37.1%) in GroupC (p = 0.196). Mean survival was 58.9 ± 3.8 (95% CI: 4.0-75.0) months in GroupNS compared to 43.5 ± 4.6 (95% CI: 6.0-66.0) months in GroupC (p = 0.045). Early nutritional supplements should be considered as having a positive effect especially on survival in this specific patient group involving factors with high catabolic effects, such as neoplasia, operation, and chemotherapy together.


New alpha-pyrrolidinonoids and glycosides from Euphorbia humifusa.
A phytochemical investigation on the constituents from Euphorbia humifusa Willd. has resulted in the isolation of three new alpha-pyrrolidinonoidal compounds, 5beta-methoxy-4beta-hydroxy-3-methylene-alpha-pyrrolidinone (1), 5beta-methoxy-4alpha-hydroxy-3-methylene-alpha-pyrrolidinone (2), and 5beta-butoxy-4alpha-hydroxy-3-methylene-alpha-pyrrolidinone (3), and three new glycosides including an indole glycoside, 3-(2-hydroxyethyl)-5-(1-O-beta-glucopyranosyloxy)-indole (4), an ionone glycoside, 3-oxo-7,8-dihydro-alpha-ionone-11-O-beta-glucoside (5), and a hemiterpene glycoside, 1-(4-hydroxy-2-methyl-2-buten-1-yl)-6- (3,4,5-trihydroxybenzoyl)-beta-d-glucose (6), along with 10 known compounds. Their structures were elucidated by analysis of 1D and 2D NMR spectral data. The structure of 1 was further confirmed by a single-crystal X-ray diffraction analysis.


Drug testing using a soft agar stem cell assay on patient and xenograft tumor material.
Since 1981 we have received 50 tumor samples from 10 different sites; over half were breast or ovary. Of the 27 that were considered suitable for cloning, 11 produced colony formation and 6 of these were drug tested. One ovarian granulosa cell tumor and its xenograft (V7) were tested against several cytotoxic agents. During a period of 16 months, sensitivity to cisplatin was relatively stable but sensitivity to vinblastine was markedly changed when the original tumor cells and original cells stored in liquid nitrogen were compared with xenograft cells. These changes may be related to patient treatments prior to tumor sample collection. This xenograft V7 exhibited chromosome karyotype and iso-enzyme Glucose-6-phosphate dehydrogenase consistent with it being of human origin. Gross histology of original tumor and xenograft were similar. Chemosensitization in vivo of a breast xenograft (Hx99) to melphalan by misonidazole was investigated. Misonidazole at a total dose of 0.5 g/kg given prior to melphalan (14 mg/kg) was an effective chemosensitizer.


Artificial intelligence-based education assists medical students' interpretation of hip fracture.
With recent transformations in medical education, the integration of technology to improve medical students' abilities has become feasible. Artificial intelligence (AI) has impacted several aspects of healthcare. However, few studies have focused on medical education. We performed an AI-assisted education study and confirmed that AI can accelerate trainees' medical image learning. We developed an AI-based medical image learning system to highlight hip fracture on a plain pelvic film. Thirty medical students were divided into a conventional (CL) group and an AI-assisted learning (AIL) group. In the CL group, the participants received a prelearning test and a postlearning test. In the AIL group, the participants received another test with AI-assisted education before the postlearning test. Then, we analyzed changes in diagnostic accuracy. The prelearning performance was comparable in both groups. In the CL group, postlearning accuracy (78.66 ± 14.53) was higher than prelearning accuracy (75.86 ± 11.36) with no significant difference (p = .264). The AIL group showed remarkable improvement. The WithAI score (88.87 ± 5.51) was significantly higher than the prelearning score (75.73 ± 10.58, p < 0.01). Moreover, the postlearning score (84.93 ± 14.53) was better than the prelearning score (p < 0.01). The increase in accuracy was significantly higher in the AIL group than in the CL group. The study demonstrated the viability of AI for augmenting medical education. Integrating AI into medical education requires dynamic collaboration from research, clinical, and educational perspectives.


Calcium Signaling in Neurons and Glial Cells: Role of Cav1 channels.
Calcium (Ca2+) is an essential component in intracellular signaling of brain cells, and its control mechanisms are of great interest in biological systems. Ca2+ can signal differently in neurons and glial cells using the same intracellular pathways or cell membrane structural components. These types of machinery are responsible for entry, permanence, and removal of Ca2+ from the cellular environment and are of vital importance for brain homeostasis. This review highlights the importance of Ca2+ in neuronal and glial cell physiology as well as aspects of learning, memory, and Alzheimer's disease, focusing on the involvement of L-type voltage-gated Ca2+ channels.


Novel_miR-1517 mediates CYP6CM1 to regulate imidacloprid resistance in Bemisia tabaci (Hemiptera: Gennadius).
Bemisia tabaci (Hemiptera: Gennadius) is a notorious pest that is capable of feeding on >600 kinds of agricultural crops. Imidacloprid is critical in managing pest with sucking mouthparts, such as B. tabaci. However, the field population of B. tabaci has evolved resistance because of insecticide overuse. The overexpression of the detoxification enzyme cytochrome P450 monooxygenase is considered the main mechanism of imidacloprid resistance, but the mechanism underlying gene regulation remains unclear. MicroRNAs are a type of endogenous small molecule compounds that is fundamental in regulating gene expression at the post-transcriptional level. Whether miRNAs are related to the imidacloprid resistance of B. tabaci remains unknown. To gain deep insight into imidacloprid resistance, we conducted on miRNAs expression profiling of two B. tabaci Mediterranean (MED) strains with 19-fold resistance through deep sequencing of small RNAs. A total of 8 known and 1591 novel miRNAs were identified. In addition, 16 miRNAs showed significant difference in expression levels between the two strains, as verified by quantitative reverse transcription PCR. Among these, novel_miR-376, 1517, and 1136 significantly expressed at low levels in resistant samples, decreasing by 36.9%, 60.2%, and 15.6%, respectively. Moreover, modulating novel_miR-1517 expression by feeding with 1517 inhibitor and 1517 mimic significantly affected B. tabaci imidacloprid susceptibility by regulating CYP6CM1 expression. In this article, miRNAs related to imidacloprid resistance of B. tabaci were systematically screened and identified, providing important information for the miRNA-based technological innovation for this pest management.


Simultaneous determination of lansoprazole and its metabolites 5'-hydroxy lansoprazole and lansoprazole sulphone in human plasma by LC-MS/MS: application to a pharmacokinetic study in healthy volunteers.
A highly sensitive and specific liquid chromatography coupled with tandem mass spectrometric (LC-MS/MS) method has been developed and validated for the simultaneous determination of lansoprazole and its metabolites 5'-hydroxy lansoprazole and lansoprazole sulphone. The detection was operated with multiple reaction-monitoring (MRM) using the electrospray ionization technique. The assay procedure involved precipitation of plasma samples with acetonitrile after indapamide was added as internal standard (IS). The chromatographic separation was achieved with a mixture of methanol-0.2% ammonium acetate and 0.1% methanoic acid in water (75:25, v/v) as mobile phase on an Inertsil ODS-3 column. The method was proved to be accurate and precise with linearity ranges of 10-4,000 ng/ml, 5.0-400 ng/ml, and 1.0-400 ng/ml for lansoprazole, 5'-hydroxy lansoprazole and lansoprazole sulphone, respectively, with the correlation coefficients (r) better than 0.999. The lower limits of quantification (LLOQ) were 2.0 ng/ml, 2.0 ng/ml, and 0.5 ng/ml for lansoprazole, 5'-hydroxy lansoprazole and lansoprazole sulphone, respectively. The intra- and inter-day precision and accuracy values were found to be within the assay variability limits (R.S.D.% within +/-15) in accordance with FDA guidelines. The validated LC-MS/MS method has been successfully applied for the determination of lansoprazole and its metabolites in human plasma.


Angiogenesis and antiangiogenic strategies in pancreatic cancer.
Despite numerous advances in the treatment of solid tumors, the prognosis of patients diagnosed with pancreatic cancer remains dismal. Results of both surgical and non-surgical treatment for pancreatic cancer have been extremely disappointing because of the tumors propensity to metastasize, failure of chemotherapy to achieve adequate levels within the tumor, and resistance of pancreatic cancer to cytotoxic agents. Current chemotherapeutic agents and radiation treatments rely on the rapidly dividing nature of tumor cells and are limited by their cytotoxic effects on normal cells. The need to exploit the difference between normal and malignant cells has resulted in an enormous amount of research into the process of tumor neovascularization. New agents are currently being developed that block tumor growth and metastasis through inhibition of angiogenesis. This article reviews the process of angiogenesis and antiangiogenic strategies with a special emphasis on pancreatic cancer.


Computed tomography demonstration of immediate and delayed complications of computed tomography-guided transthoracic percutaneous ethanol injection of hepatocellular carcinoma at the liver dome.
We conducted this study to correlate computed tomography (CT) images with the complications induced by CT-guided percutaneous ethanol injection (PEI) for the treatment of hepatocellular carcinoma (HCC). Twenty-two patients with ultrasonographically unreachable HCC were treated with CT-guided transthoracic PEI. The procedures and the CT findings were recorded to correlate with the various complications of PEI. After the ethanol injection, 3 patterns of CT images were identified according to the distribution of ethanol (ie, intratumoral, extrahepatic, and intrahepatic patterns). The intrahepatic pattern was further classified as the branch, tubular, and infiltrative types. During the follow-up period, 3 patients developed biliary stricture, portal vein thrombosis, or tumor seeding. The tubular type was associated with the development of biliary stricture, whereas the branch type was related to the occurrence of portal vein thrombosis. These complications were considered to be caused by a greater amount of ethanol leakage into bile ducts or portal veins than in cases without complications (median = 17 mL vs. 0 mL, P = 0.002). Ethanol leakage is not uncommon when performing PEI; however, it seems to be safe when the leakage is less than 15 mL. Injection of a small amount of ethanol or monitoring by CT may be helpful in preventing the development of these complications.


Variation in incidence of indinavir-associated nephrolithiasis among HIV-positive patients.
Nephrolithiasis may be an important consequence of indinavir therapy; however little has been published on the variation in incidence between different populations of patients or the possible mechanisms of calculus formation. To examine variation in the incidence of indinavir-associated nephrolithiasis (IAN) in HIV-positive patients in relation to hemophilia and hepatitis C virus (HCV) infection. Clinical data were abstracted retrospectively from the medical records of all adult patients treated with indinavir from September 1995 to September 1997. Occurrence of first IAN, defined as flank pain and hematuria after initiation of therapy, was analyzed in relation to hemophilia status and HCV infection. There were 17 episodes of IAN (22%) among 79 patients treated with indinavir. Of 10 patients with hemophilia, 50% developed IAN as compared with 17% of patients without hemophilia (P = 0.03). Median days to first IAN was 22 (range 7-110 days) for hemophiliacs and 156 (range 5-611 days) for those without hemophilia. Data for HCV status were available for 74 out of 79 patients: 10 out of 27 (37%) patients with HCV developed IAN compared with six out of 42 (14%) without HCV (P = 0.02). Overall incidence of IAN was higher than that previously reported and was significantly greater in hemophiliacs than in non-hemophiliacs. HCV may be a contributing factor.


Preoperative Evaluation and Cardiac Risk Assessment in Vascular Surgery.
We summarize epidemiologic trends, outcomes, and preoperative guidelines for vascular surgery patients from 2010 to 2022. Vascular surgery continues to evolve in technology and engineering to treat a surgical population that suffers from a high prevalence of comorbidities. Preoperative optimization seeks to characterize the burden of disease and to achieve medical control in the timeline available before surgery. Risk assessment, evaluation, optimization, and prediction of major adverse cardiac events is an evolving science where the Vascular Surgery Quality Initiative has made an impact. Ongoing investigation may demonstrate value for preoperative echocardiography, functional capacity, frailty, and mobility assessments.


Relationship between Treatment Burden, Health Literacy, and Medication Adherence in Older Adults Coping with Multiple Chronic Conditions.
A prospective study was conducted to investigate the impact of treatment burden and health literacy on medication adherence among older adults with multiple chronic conditions (MCC) and to explore the potential moderating effects of demographic and clinical factors. Face-to-face structured interviews were conducted among older adults aged 60 and above using the Burden of Treatment Questionnaire (TBQ-15), Short Form Health Literacy Questionnaire (HLS-SF12), and Malaysia Medication Adherence Assessment Tool (MyMAAT). This study included 346 older adults aged 60 years and above with two or more chronic conditions (n = 346). Hypertension (30.2%), hyperlipidemia (24.0%), and diabetes (18.0%) were the most reported chronic conditions among participants. The mean score of treatment burden was 53.4 (SD = 28.2), indicating an acceptable burden of treatment. The mean score of health literacy was 16.4 (SD = 12.6), indicating a limited health literacy level among participants; meanwhile, the mean score of medication adherence was 32.6 (SD = 12.3), indicating medication non-adherence among participants. Medication adherence was significantly correlated with treatment burden (r = -0.22, p < 0.0001), health literacy (r = 0.36, p < 0.0001), number of chronic conditions (r = -0.23, p < 0.0001), and age (r = -0.11, p < 0.05). The study findings emphasize that multimorbid older adults with high treatment burdens and low health literacy are more likely to have poor medication adherence. This underscores the importance for clinicians to address these factors in order to improve medication adherence among older adults with multiple chronic conditions (MCC).


Apolipoprotein E inhibition of vascular hyperplasia and neointima formation requires inducible nitric oxide synthase.
Previous studies have shown apolipoprotein E (apoE) recruitment to medial layers of carotid arteries after vascular injury in vivo and apoE activation of inducible nitric oxide synthase (iNOS) in smooth muscle cells in vitro. This investigation explored the relationship between medial apoE recruitment and iNOS activation in protection against neointimal hyperplasia. ApoE was present in both neointimal-resistant C57BL/6 mice and neointimal-susceptible FVB/N mice 24 h after carotid denudation, but iNOS expression was observed only in the neointimal-resistant C57BL/6 mice. However, iNOS was not observed in apoE-defective C57BL/6 mice. In contrast, overexpression of apoE in FVB/N mice activated iNOS expression in the injured vessels, resulting in protection against neointimal hyperplasia. ApoE and iNOS were colocalized in the medial layer of neointimal-resistant mouse strains. Endothelial denudation of carotid arteries in the iNOS-deficient NOS2(-/-) mice did not increase neointimal hyperplasia but significantly increased medial thickness and area. The iNOS-specific inhibitor also abrogated the apoE protective effects on vascular response to injury in apoE-overexpressing FVB/N mice. Thus, injury-induced activation of iNOS requires apoE recruitment. Moreover, both apoE and iNOS are necessary for the suppression of cell proliferation, and apoE recruitment without iNOS expression resulted in medial hyperplasia without cell migration to the intima.


Toxic and transforming effects of polycyclic hydrocarbons in fetal hamster lung-cell cultures. I. Benzo(alpha)pyrene.
When seeded at a low cell density in Petri dishes not pre-conditioned with feeder layers, fetal hamster lung cells at 2-4 passages grew with greatly varied plating efficiencies (PE). Addition of insulin to the serum-supplemented medium gave relatively constant PE. However, the presence of insulin in the medium enhanced the toxicity of benzo(alpha)pyrene (BP) on these cells. Cytotoxic and cell transforming effects of BP in the presence of insulin were studied.


Interrelation between luteal cell types in steroidogenesis in vitro of human corpus luteum.
Slices of human corpora lutea of menstruation at different stages, or of inner and outer layers consisting of pure granulosa lutein cells and combined theca and granulosa lutein cells respectively, were incubated with [4-14C]-pregnenolone or with [4-14C]-androstenedione respectively. Conversion of 14C-radioactivity to progestins, androgens and/or estrogens was assessed by the reverse dilution technique with recrystallization to constant specific activity. Although progesterone was the major steroid formed from pregnenolone, a transient increase in androgen formation with a concomitant decrease in estrogen formation in developing corpora lutea was followed by an increase in estrogen with a decrease in androgen formation in mature corpora lutea. The reciprocal relation between estrogen and androgen formation is associated with the behaviour of theca lutein cells since the cells disappeared at the former and clearly differentiated at the latter stages of corpora lutea. The outer layers consistently produced more 17-hydroxyprogesterone, androgens and estrogens from pregnenolone than the inner layers, while the inner layers converted constantly more androstenedione to estrogens than the outer layers. It is suggested that aromatase activity of granulosa lutein cells in co-existence with theca lutein cells is required by human corpora lutea for fulfillment of the function of estrogen synthesis.


Behavioral economic demand assessments in the addictions.
Behavioral economics in the addictions is the application of both economics and psychology to study multifaceted components of substance use decision-making behavior. One such component is demand: the relative value of a substance for a user (i.e., the association between drug use and cost). The degree to which a user values a substance can be measured via performance on hypothetical purchase tasks which replicate drug purchase and consumption. Demand has been evaluated across substances, including alcohol, marijuana, tobacco, and alternative tobacco products. Recent advances in the study of demand have greatly improved the assessment of drug value, including application to novel products, selection of optimal task unit, assessment of demand in naïve or potential future users, and the importance of instructional set specificity.


Fabrication of poly(lactic acid) foam with high expansion ratio and oriented cellular structure by restricting cold crystallization.
The foaming behavior of semi-crystalline polymers is significantly affected by their crystallization. To achieve high expansion ratio of poly(lactic acid) (PLA) foams, we thought its cold crystallization should be restricted. Therefore, we used a short soaking time of CO2 to fabricate high-expansion PLA foams. Dynamic mechanical analysis of unfoamed PLA showed that only one rubbery plateau was observed owing to complete cold crystallization under a soaking time of 40 min at 10 MPa. The crystal morphology demonstrated that a short soaking time of 3 min could restrict the cold crystallization of PLA. Owing to plasticization of CO2, PLA crystallization of was accelerated at low temperatures (40-80 °C) but hindered at high temperatures (80-130 °C) at 10 MPa. Foaming results showed that under a soaking time of 3 min, a high expansion ratio exceeding 10 was achievable over a wide foaming temperature range of 90 to 115 °C because more amorphous regions were preserved at 10 MPa. In addition, the prepared foams presented an oriented cellular structure. Compared with the isotropic foam, the anisotropic foam exhibited higher compressive strength and heat resistance. The prepared PLA foams have good application prospects in the fields such as cushioning, packaging, and construction.


Cancer specific mortality in patients with collecting duct vs. clear cell renal carcinoma.
Collecting duct carcinoma (CDC) is biologically more aggressive than clear cell renal cell carcinoma (ccRCC). We tested for differences in cancer specific mortality (CSM) rates according to CDC vs. ISUP (International Society of Urological Pathology) 4 ccRCC histological subtype. We hypothesized that the survival disadvantage still applies, even after most detailed adjustments. Within Surveillance, Epidemiology, and End Results database (2004-2018), we identified 380 CDC vs. 6273 ISUP 4 ccRCC patients of all stages. Propensity score matching (age, sex, race/ethnicity, T, N, and M stages, nephrectomy, and systemic therapy status), Kaplan-Meier plots and multivariable Cox regression models were used. All 380 CDC were matched (1:2) with 760 ISUP4 ccRCC patients. Prior to matching CDC patients exhibited higher rates of lymph node invasion (37.6 % vs. 14.7 %, p < 0.001), and of distant metastases (40.8 % vs. 30.4 %, p < 0.001). Systemic therapy rates were higher in CDC (29.5 % vs. 20.5 %, p < 0.001). However, nephrectomy rates were higher in ISUP4 ccRCC patients (97.5 % vs. 84.7 %, p < 0.001). After matching, in multivariable Cox regression models addressing CSM, CDC was associated with a HR of 1.5 (p < 0.001) in the overall population vs. 1.9 (p = 0.014) in stage I-II vs. 1.4 (p = 0.022) in stage III vs. 1.6 in stage IV (p < 0.001), relative to ISUP4 ccRCC. CDC patients exhibited 40-90 % higher CSM than their ISUP4 ccRCC counterparts in the overall analysis, as well as in stage specific analyses. The CSM disadvantage applies despite higher rates of systemic therapy in CDC patients.


Genetic determinants of plasma HDL-cholesterol levels in familial hypercholesterolemia.
The objective of this study was to determine the extent to which common genetic variants can explain the variation of high-density lipoprotein cholesterol (HDL-C) plasma levels in familial hypercholesterolemia (FH). FH is characterized by elevated low-density lipoprotein cholesterol levels and premature cardiovascular disease (CVD). Although low HDL-C levels have been shown to affect the severity of the clinical phenotype, little is known about the factors that determine HDL-C levels in these patients. A cohort of 1002 heterozygous FH patients was genotyped for polymorphisms in the genes encoding for ATP-binding cassette transporter A1, apolipoprotein (apo) AIV, apoCIII, apoE, cholesteryl transfer ester protein, hepatic lipase, lipoprotein lipase, and two paraoxonases. Multiple linear regression showed that, together, these polymorphisms explain only 3.9% of the variation of HDL-C plasma levels. When significant two-way interactions between the polymorphisms were also taken into account, the explained variation rose to 12.5%. In a regression model that also incorporated sex, smoking, alcohol use, body mass index, and concomitant beta-blocker use as covariates, the explained variation of HDL-C plasma levels even increased to 32.5%. This study provides direct evidence that multiple, modestly penetrant, but highly prevalent, polymorphisms can explain a substantial part of the variation of HDL-C plasma levels in a representative large cohort of heterozygous FH patients.


Pallidal DBS for dystonia in the age of personalized medicine.
In response to the correspondence by Albanese and co-workers, we discuss etiology as a factor predicting outcome of pallidal DBS in dystonia, reanalysing our dataset on causes of non-response to pallidal DBS in isolated dystonia by looking only at patients with a diagnosis of idiopathic dystonia at time of surgery.


Pancreatic islet cell adenocarcinoma: clinical and diagnostic features of six cases.
The clinicopathologic aspects of pancreatic islet cell adenocarcinoma in 6 dogs were compared. Diagnosis was based on insulin-glucose ratios in 5 dogs. Surgical excision of the tumor resulted in absence of clinical signs for at least 1 year in 3 dogs.


A new approach to high sensitivity liquid chromatography-mass spectrometry of peptides using nanoflow solvent assisted inlet ionization.
Liquid chromatography (LC) solvent assisted inlet ionization (SAII) mass spectrometry (MS) was previously reported to give good chromatographic resolution and MS detection injecting 66 ng of a BSA tryptic digest. In analogy to nano-electrospray ionization (nESI), we extend SAII LC/MS to nano-SAII (nSAII) operating at nL min(-1) flow rates and demonstrate good quality ion chromatograms and mass spectra from injection of as little as 0.7 ng of BSA digest onto a capillary LC column. Data dependent fragmentation is demonstrated for injection of 7 ng of a BSA digest. This method has advantages over nESI in ease of use and low cost as it requires no voltage and is operational without the necessity of connectors or fragile nESI emitters, although similar constricted tips can be helpful in nSAII to stabilize the signal at low nanoliter flow. At a flow rate of 0.8 μL min(-1), the only requirement for nSAII is that the exit-end of the capillary LC column be adjusted near the aperture of the heated inlet of the mass spectrometer.


Valproic acid targets HDAC1/2 and HDAC1/PTEN/Akt signalling to inhibit cell proliferation via the induction of autophagy in gastric cancer.
Valproic acid (2-propylpentanoic acid, VPA) has been widely used as an anticonvulsant drug and is a choice drug for seizure treatment. VPA is also used as a short-chain fatty acid HDAC inhibitor that affects proliferation and differentiation and induces cell apoptosis in both solid and haematologic malignancies. Here, we observed that VPA treatment inhibited HDAC1/2 activity and induced autophagy in gastric cancer cells, leading to apoptosis. VPA-induced apoptosis occurred through inhibition of the HDAC1/PTEN/Akt signalling pathway and involved alterations in Bcl-2 and Beclin-1. The antitumour effects of VPA were verified in vivo using SGC-7901 xenograft models. Moreover, we evaluated the expression of HDAC1/2 in gastric cancer patient samples and revealed a positive correlation between HDAC1/2 overexpression and poor prognosis. These findings indicate that VPA may serve as a potential therapeutic agent for gastric cancer and that HDAC1/2 might be a promising therapeutic biomarker for the disease.


Development of a web-based modelling framework for harmful algal blooms transport simulation using open-source technologies.
Desktop-based modelling packages presented typical limitations in interactive simulation. This study presents a web-based modelling framework that fully consolidated the simulation work-flow into a WebGIS application, providing a one-step solution for HABs transport simulation within an intuitive and interactive modelling environment. An improved Lagrangian particle-tracking scheme was proposed using fractional Brownian motion technique. The presented model was devoted to quickly forecast the transport pathways in both temporal and spatial dimensions, and evaluate the approximate trends and qualitative understanding of HABs development in data-poor situations. The web modelling platform was developed using multiple open-source JavaScript libraries. The developed WebGIS application provides user-friendly interfaces to prepare inputs, configure simulation settings, visualize, analyse, and validate simulation results within the same framework. The feasibility, capacity, and advantage of the proposed framework were tested and evaluated in a real-world application of red tide transport simulation in the Qinhuangdao coastal waters. The model results showed qualitative agreement with the red tide observed from remote sensing. Our experimental results demonstrated that the developed web-based modelling prototype would present a useful performance for study cases related to HABs transport simulation.


[Enzymatic digestibility of peptides containing tert-butyltryptophan residues (author's transl)].
The effects of tert-butylation of tryptophan residues in peptide chains on the enzymatic digestibility were investigated. It was shown that replacement of tryptophan in position 9 of Corticotropin-(1--19)-nonadecapeptidamide by a mono- or tri-tert-butylated tryptophan enhances the resistance of the resulting analogue against proteolytic enzymes.


Automated MRI parcellation study of regional volume and thickness of prefrontal cortex (PFC) in antipsychotic-naïve schizophrenia.
Prefrontal cortical dysfunction is considered to be critical in the pathogenesis of schizophrenia. However, structural magnetic resonance imaging (MRI) studies on the PFC have yielded inconsistent results because of various confounding factors. In this study we examined the volume and thickness abnormalities of the PFC in antipsychotic-naïve schizophrenia patients (n = 51) in comparison with age-, sex-, and handedness-matched (as a group) healthy comparison subjects (n = 47) using a newly described automated MRI parcellation analysis. Schizophrenia patients showed i) significant volume deficits in bilateral lateral orbitofrontal and left medial orbitofrontal cortices as well as bilateral pars triangularis; and ii) significant thickness deficit in bilateral medial orbitofrontal cortices. Negative syndrome score had a significant negative correlation with the thickness of the left medial orbitofrontal cortex. The study findings emphasize that prefrontal deficit in schizophrenia is differential and involves primarily the regions essential for 'social cognition'.


Single-session endosonography and endoscopic retrograde cholangiopancreatography for biliopancreatic diseases is feasible, effective and cost beneficial.
Endoscopic ultrasonography (EUS) and Endoscopic Retrograde Cholangiopancreatography (ERCP) are often required in patients with pancreaticobiliary disorders. To assess the clinical impact and costs savings of a single session EUS-ERCP. Patient and intervention data from April 2009 to March 2012 were prospectively recruited and retrospectively analyzed from a database at a tertiary hospital. Indications, diagnostic yield, procedure details, complications and costs were evaluated. Fifty-five scheduled combined procedures were done in 53 patients. The accuracy of EUS-fine needle aspiration for malignancy was 90%. The main clinical indication was a malignant obstructing lesion (66%). The ERCP cannulation was successful in 67%, and in 11/15 failed ERCP (73%), drainage was completed thanks to an EUS-guided biliary drainage: 6 transmurals, 5 rendezvous. Eight patients (14%) had related complications: bacteremia (n = 3), pancreatitis (n = 2), bleeding (n = 2) and perforation (n = 1). The mean duration was 65 ± 22.2 min. The mean estimated cost for a single session was €3437, and €4095 for two separate sessions. The estimated cost savings using a single-session strategy was €658 per patient, representing a total savings of €36,189. Combined EUS and ERCP is safe, technically feasible and cost beneficial. Furthermore, in failed ERCP cases, the endoscopic biliary drainage can be completed with EUS-guided biliary access in the same procedure.


Tuberculosis affecting the oral cavity in Brazilian HIV-infected patients.
Tuberculosis (TB) affecting the oral cavity is a very rare disease. We reviewed the medical data of 18 HIV(1)-infected patients referred to the Stomatology Group, Ear, Nose, and Throat Department, São Paulo University Medical School, who had a diagnosis of oral tuberculosis, between 1991 and 2002. This retrospective study aimed to analyze the relationship between oral tuberculosis and HIV infection. The clinical records of the patients were reviewed to note age and gender, symptoms, and site and type of the lesions in the oral mucosa. Results of CD4+ T-lymphocyte count, sputum analysis, tuberculin skin test, histopathologic characteristics, cultures of the specimens (that were taken during the biopsy), chest x-ray findings, and the type of treatment they received were also reviewed. The most affected sites were palate and tongue. All patients had culture confirming tuberculosis. Patients with HIV and nonhealing oral lesions or papillomatous masses in the oral mucosa should be screened for the presence of pulmonary tuberculosis.


Cylindrical vector beam multiplexer/demultiplexer using off-axis polarization control.
The emergence of cylindrical vector beam (CVB) multiplexing has opened new avenues for high-capacity optical communication. Although several configurations have been developed to couple/separate CVBs, the CVB multiplexer/demultiplexer remains elusive due to lack of effective off-axis polarization control technologies. Here we report a straightforward approach to realize off-axis polarization control for CVB multiplexing/demultiplexing based on a metal-dielectric-metal metasurface. We show that the left- and right-handed circularly polarized (LHCP/RHCP) components of CVBs are independently modulated via spin-to-orbit interactions by the properly designed metasurface, and then simultaneously multiplexed and demultiplexed due to the reversibility of light path and the conservation of vector mode. We also show that the proposed multiplexers/demultiplexers are broadband (from 1310 to 1625 nm) and compatible with wavelength-division-multiplexing. As a proof of concept, we successfully demonstrate a four-channel CVB multiplexing communication, combining wavelength-division-multiplexing and polarization-division-multiplexing with a transmission rate of 1.56 Tbit/s and a bit-error-rate of 10-6 at the receive power of -21.6 dBm. This study paves the way for CVB multiplexing/demultiplexing and may benefit high-capacity CVB communication.


Supramalleolar osteotomies for degenerative joint disease of the ankle joint: indication, technique and results.
Patients with varus or valgus hindfoot deformities usually present with asymmetric ankle osteoarthritis. In-vitro biomechanical studies have shown that varus or valgus hindfoot deformity may lead to altered load distribution in the tibiotalar joint which may result in medial (varus) or lateral (valgus) tibiotalar joint degeneration in the short or medium term. The treatment of asymmetric ankle osteoarthritis remains challenging, because more than half of the tibiotalar joint surface is usually preserved. Therefore, joint-sacrificing procedures like total ankle replacement or ankle arthrodesis may not be the most appropriate treatment options. The shortand midterm results following realignment surgery, are very promising with substantial pain relief and functional improvement observed post-operatively. In this review article we describe the indications, surgical techniques, and results from of realignment surgery of the ankle joint in the current literature.


Soft tissue phenotype modification predicts gingival margin long-term (10-year) stability: Longitudinal analysis of six randomized clinical trials.
To assess the prognostic value of soft tissue phenotype modification following root coverage procedures for predicting the long-term (10-year) behaviour of the gingival margin. Participants from six randomized clinical trials on root coverage procedures at the University of Michigan were re-invited for a longitudinal evaluation. Clinical measurements were obtained by two calibrated examiners. A data-driven approach to model selection with Akaike information criterion (AIC) was carried out via multilevel regression analyses and partial regression plotting for changes in the level of the gingival margin over time and interactions with the early (6-month) results of soft tissue phenotypic modification. One-hundred and fifty-seven treated sites in 83 patients were re-assessed at the long-term recall. AIC-driven model selection and regression analyses demonstrated that 6-month keratinized tissue width (KTW) and gingival thickness (GT) influenced the trajectory of the gingival margin similarly in a concave manner; however, GT was the driving determinant that predicted significantly less relapse in the treatments, with stability of the treated gingival margin obtained beyond values of 1.46 mm. Among a compliant patient cohort, irrespective of the rendered therapy, the presence of at least 1.5 mm KTW and 1.46 mm GT was correlated with the long-term stability of the gingival margin.


Formation of gold nanoparticles via a thiol functionalized polyoxometalate.
A useful method for the synthesis of Au nanoparticles is presented. The synthesis of Au nanoparticles with various morphologies was carried out at room temperature using gamma radiolysis and NaBH4 reduction of HAuCl4 in N,N'-dimethylformamide:water solutions containing polyoxometalate (POM). The results demonstrated that by controlling the rate of reduction and ratio of DMF and water, metal particle size and shape can be further tailored. It is shown that gold nanoparticles with controllable size can be synthesized. In principle, the general finding of this work can be extended to other transition/noble metal nanoparticles.


Ferritinophagy-mediated iron competition in RUTIs: Tug-of-war between UPEC and host.
Uropathogenic Escherichia coli (UPEC) is the main pathogen of recurrent urinary tract infections (RUTIs). Urinary tract infection is a complicated interaction between UPEC and the host. During infection, UPEC can evade the host's immune response and retain in bladder epithelial cells, which requires adequate nutritional support. Iron is the first necessary trace element in life and a key nutritional factor, making it an important part of the competition between UPEC and the host. On the one hand, UPEC grabs iron to satisfy its reproduction, on the other hand, the host relies on iron to build nutritional immunity defenses against UPEC. Ferritinophagy is a selective autophagy of ferritin mediated by nuclear receptor coactivator 4, which is not only a way for the host to regulate iron metabolism to maintain iron homeostasis, but also a key point of competition between the host and UPEC. Although recent studies have confirmed the role of ferritinophagy in the progression of many diseases, the mechanism of potential interactions between ferritinophagy in UPEC and the host is poorly understood. In this paper, we reviewed the potential mechanisms of ferritinophagy-mediated iron competition in the UPEC-host interactions. This competitive relationship, like a tug-of-war, is a confrontation between the capability of UPEC to capture iron and the host's nutritional immunity defense, which could be the trigger for RUTIs. Therefore, understanding ferritinophagy-mediated iron competition may provide new strategies for exploring effective antibiotic alternative therapies to prevent and treat RUTIs.


Preparation of mesoporous titania solid superacid and its catalytic property.
Mesoporous titania (TiO(2)) was synthesized by hydrothermal method using cetyltrimethyl ammonium bromide (CTAB) as a template and using anhydrous ethanol and tetra-n-butyl titanate (TBOT) as raw materials. Mesoporous titania solid superacid and nanosized titania solid superacid catalysts were prepared by wet impregnation method. The structure and property of as-prepared samples were characterized by means of XRD, FT-IR and N(2) physical adsorption. The esterification of salicylic acid with isoamyl alcohol and the condensation of cyclohexanone with ethylene were used as model reactions to test the catalytic activities of the catalysts. On the other hand, the comparison of catalytic activities of the prepared solid superacid catalysts and the conventional liquid acid H(2)SO(4) was also carried out under the same experimental conditions. The results show that the catalytic activities of the prepared solid superacid catalysts were higher than that of the conventional liquid acid H(2)SO(4), and that the catalytic activity of mesoporous TiO(2) solid superacid is the highest among the three catalysts. Mesoporous TiO(2) solid superacid is a good catalyst for the synthesis of isoamyl salicylate or cyclohexanone ethylene ketal.


Results of ofloxacin therapy in andrologic patients suffering from therapy-requiring asymptomatic infections.
In 1990, microbiological ejaculate analyses were carried out on a routine basis on 125 andrological patients, in addition to the determination of the concentration, motility and morphology of the spermatozoa. Fourteen patients (11.2%) with therapy-requiring asymptomatic infections (TAI) > 10(4) CFU (colony-forming units) ml-1 were effectively treated with Ofloxacin (Tarivid) at 2 x 200 mg d-1 for a period of 20 d. Concentration, motility and morphology of the spermatozoa were determined before the Ofloxacin treatment and controlled 1, 3, and 6 months later and correlated to the values obtained before the treatment. Over the entire period of observation, the morphology did not change significantly, whilst initially 1 month after the treatment the concentration and the motility decreased significantly (P < 0.05). Three months later they again reached the starting values. After 6 months, a significant improvement occurred with regard to the motility, as compared to the starting values (P < 0.01), whilst the concentration remained at the level of the starting values. By this, Ofloxacin has been proved to be an effective medication for the treatment of TAI. In the end, it still remains an open question whether the improvement in sperm motility is primarily related to the Ofloxacin therapy.


Biobehavioral susceptibility for obesity in childhood: Behavioral, genetic and neuroimaging studies of appetite.
Modern food environments are conducive to overeating and weight gain, but not everyone develops obesity. One reason for this may be that individuals differ in appetitive characteristics, or traits, that manifest early in life and go on to influence their behavioral susceptibility to gain and maintain excess weight. Classic studies showing that eating behavior in children can be measured by behavioral paradigms such as tests of caloric compensation and eating in the absence of hunger inspired the development and validation of psychometric instruments to assess appetitive characteristics in children and infants. A large body of evidence now suggests that food approach traits increase obesity risk, while food avoidant traits, such as satiety responsiveness, decrease obesity risk. Twin studies and genetic association studies have demonstrated that appetitive characteristics are heritable, consistent with a biological etiology. However, family environment factors are also influential, with mounting evidence suggesting that genetic and environmental risk factors interact and correlate with consequences for child eating behavior and weight. Further, neuroimaging studies are revealing that individual differences in responses to visual food cues, as well as to small tastes and larger amounts of food, across a number of brain regions involved in reward/motivation, cognitive control and other functions, may contribute to individual variation in appetitive behavior. Growing evidence also suggests that variation on psychometric measures of appetite is associated with regional differences in brain structure, and differential patterns of resting state functional connectivity. Large prospective studies beginning in infancy promise to enrich our understanding of neural and other biological underpinnings of appetite and obesity development in early life, and how the interplay between genetic and environmental factors affects appetitive systems. The biobehavioral susceptibility model of obesity development and maintenance outlined in this narrative review has implications for prevention and treatment of obesity in childhood.


Pressure sores in nursing home patients.
One hundred and sixty-seven patients were part of a cross-sectional study examining pressure sores in patients in skilled nursing facilities. Every patient admitted to this study was physically examined for the presence or absence of pressure sores and evaluated according to a standardized procedure. Using logistic regression analysis, the variables most significantly associated with pressure sores included a history of hypertension, infection, unwelcome response to visitors, history of poor dietary intake and a pattern of slow or poor response to commands. Knowledge of these factors may lead to more intensive efforts to develop better methods of prevention and treatment of pressure sores.


Lipid-based nanoparticles as drug delivery systems for cancer immunotherapy.
Immune checkpoint inhibitors (ICIs) have shown remarkable success in cancer treatment. However, in cancer patients without sufficient antitumor immunity, numerous data indicate that blocking the negative signals elicited by immune checkpoints is ineffective. Drugs that stimulate immune activation-related pathways are emerging as another route for improving immunotherapy. In addition, the development of nanotechnology presents a promising platform for tissue and cell type-specific delivery and improved uptake of immunomodulatory agents, ultimately leading to enhanced cancer immunotherapy and reduced side effects. In this review, we summarize and discuss the latest developments in nanoparticles (NPs) for cancer immuno-oncology therapy with a focus on lipid-based NPs (lipid-NPs), including the characteristics and advantages of various types. Using the agonists targeting stimulation of the interferon genes (STING) transmembrane protein as an exemplar, we review the potential of various lipid-NPs to augment STING agonist therapy. Furthermore, we present recent findings and underlying mechanisms on how STING pathway activation fosters antitumor immunity and regulates the tumor microenvironment and provide a summary of the distinct STING agonists in preclinical studies and clinical trials. Ultimately, we conduct a critical assessment of the obstacles and future directions in the utilization of lipid-NPs to enhance cancer immunotherapy.


The role of a peri-urban forest on air quality improvement in the Mexico City megalopolis.
Air quality improvement by a forested, peri-urban national park was quantified by combining the Urban Forest Effects (UFORE) and the Weather Research and Forecasting coupled with Chemistry (WRF-Chem) models. We estimated the ecosystem-level annual pollution removal function of the park's trees, shrub and grasses using pollution concentration data for carbon monoxide (CO), ozone (O(3)), and particulate matter less than 10 microns in diameter (PM(10)), modeled meteorological and pollution variables, and measured forest structure data. Ecosystem-level O(3) and CO removal and formation were also analyzed for a representative month. Total annual air quality improvement of the park's vegetation was approximately 0.02% for CO, 1% for O(3,) and 2% for PM(10), of the annual concentrations for these three pollutants. Results can be used to understand the air quality regulation ecosystem services of peri-urban forests and regional dynamics of air pollution emissions from major urban areas.


Gross cystic disease of the breast.
The aetiology of fibrocystic disease of the human breast remains problematical. While oestrogens may cause cystic lesions and epithelial proliferation in the mammary glands of experimental animals and certain progestogens (chlormadinone acetate and medroxyprogesterone acetate) may induce severe myoepithelial hyperplasia in beagles, the classical oral contraceptives (oestrogens and progestogens) reduce the incidence of fibrocystic breast disease in women. The role of prolactin in human breast disease is far from clear despite the fact that in rodents mammary tumors fail to develop following oestrogen administration in the absence of prolactin. Because women with gross cystic disease of the breast are at four times greater risk of developing malignant breast disease, it is felt that the administration of courses of danazol, an impeded androgen derived from the progestin, 17 alpha-ethinyl testosterone, has proved effective in lessening fibrocystic disease of the breast, frequently obviating the need for breast biopsy. The study of the hormonal content of fluid aspirated from gross breast cysts should help elucidate the pathophysiology of breast disease. Breast cyst fluid is rich in androgens, particularly dehydroepiandrosterone sulfate; concentrations of polypeptide hormones like FSH, LH, TSH, PRL, and calcitonin are invariably present sometimes in less and at other times in greater amounts than that found in plasma. Of particular interest is the finding of measurable levels of beta-hCG in cyst fluid but not in the serum. The question arises whether the beta-hCG is biologically active or are the assay values merely the expression of radioimmunoassayable components? Preliminary (as yet unpublished) studies reveal excellent bioactivity as measured by testosterone production in Leydig cell cultures. Time will tell whether elevated levels of bioactive beta-hCG portend neoplastic potential.


Removal of organic debris with Er:YAG laser irradiation and microleakage of fissures sealants in vitro.
The current study was conducted to improve fissure sealing by pre-treatment with Er:YAG laser irradiation in order to remove organic debris. The surface morphology, surface roughness of fissure cavities, and the degree of microleakage after laser treatment were compared with those after bristle brush treatment in vitro. Sixty extracted human teeth were used in this study. The teeth were randomly divided into two groups of 30 each. Artificial fissures were prepared in all teeth into which artificial organic debris was placed. The debris in 30 teeth of one group was removed by means of Er:YAG laser system and the remaining 30 teeth were cleaned using a bristle brush with prophylaxis paste. Surface morphology and surface roughness of were analyzed in ten samples from each group by color laser three-dimensional (3D) microscopy and by scanning electron microscopic examination. The remaining samples were then filled with sealant and subjected to a microleakage test under thermocycling. Statistical analysis was performed using the Mann-Whitney U test; a value of p < 0.05 was considered significant. Morphologically, most of the debris was removed by Er:YAG laser treatment, whereas some fissures were not cleaned by bristle brush. However, microleakage test of both laser and etched brush methods showed similar results. Laser technique might facilitate good adaptation of resin sealant to enamel, because of an increase in surface roughness and favorable surface characteristics.


A myocybernetic model of the jaw system of the rat.
A dynamic model of the jaw system of the rat has been formulated. The model consists of several units: (1) A static muscle fiber model, relating force with fiber length, based on sarcomere morphometric information. (2) A static skeletal muscle model, relating muscle force with muscle length based on myomorphometric information and the static fiber model. (3) A dynamic skeletal muscle model, relating muscle force with muscle length, contraction velocity and stimulation rate, based on fiber type data, calcium dynamics and velocity-force relations and on the static skeletal muscle model. (4) A kinematic model of the jaw system, relating the possible movements of the jaw system with the morphometrics of the bones, joints and connective tissue. (5) A three-dimensional reconstruction package, devised to analyze and display the morphometrics of the jaw system and to show the model results in terms of force vectors, positions and movements of the jaw system. EMG data of chewing rats and myomorphometric data (from unit 5) are fed into unit 3 resulting in muscle forces. The trajectories of the lower jaw and hyoid resulting from these velocity-dependent forces are calculated using unit 4, taking inertias and gravity into account. The calculated movements are remarkably similar to those that have been observed experimentally. The force-velocity relation of the muscles is highly important in stabilizing the velocities of the elements.


Improvement and application research of the SRM in alpine regions.
The simulation of snowmelt runoff in alpine mountainous areas is of great significance not only for the risk assessment of snowmelt flood in spring and summer, but also for the development and management of water resources in the basin. An improved snowmelt runoff model (SRM) is constructed based on the analysis of change characteristics of climate, runoff, and snow and ice cover in the middle and upper reaches of the Taxkorgan River in Xinjiang Province, China. Because of the large evaporation in the study basin, the evaporation loss is added to the model. The SRM and the improved SRM are calibrated and verified by using data such as temperature, precipitation, water vapor pressure, and snow-covered area (SCA) ratio in the study basin from 2002 to 2012. The results show that, compared with the SRM, the average Nash-Sutcliffe coefficient (NSE) of annual runoff simulation increases from 0.80 to 0.86 in the calibration and increases from 0.74 to 0.83 in the validation through the improved model, and the average runoff error reduces from - 12.8 to 1.32% in the calibration and reduces from - 20.0 to - 11.51% in the validation. After adding the measured flow rate for real-time correction, the average NSE of annual runoff simulation increases from 0.91 to 0.93 and the average annual runoff error reduces from - 7.76 to - 3.91% in the calibration. The average NSE increases from 0.85 to 0.89 and the average runoff error reduces from - 12.35 to - 2.76% in the validation. It indicates that the SRM structure with increased evaporation loss is more in line with the actual situation. The short-term simulation effect of the model is greatly improved by adding the measured flow rate for real-time correction. At the same time, the improved SRM and the hypothetical climate change scenario are used to analyze the impact analysis of the snowmelt runoff simulation in the partial wet year. The results show that in the case of rising temperature, the ice and snow ablation period is prolonged, and the annual runoff also changes significantly in time distribution. It is of guiding significance for the influence of climate change on the runoff of recharged rivers with ice-snow meltwater in the other alpine regions.


Left atrioventricular valve repair after primary atrioventricular canal surgery: Predictors of durability.
Acute outcomes after atrioventricular canal defects (AVCD) surgery in the current era are excellent; yet despite surgical advances, ∼15% of patients require future left atrioventricular valve (LAVV) repair. Among patients with AVC who undergo LAVV repair after primary AVC surgery, we sought to characterize the durability of these repairs. Specifically, we aimed to determine predictors for reintervention following an LAVV repair in patients with repaired AVCD, with a focus on postoperative transesophageal echocardiography (TEE). We reviewed all patients undergoing LAVV repair (after a primary AVCD surgery) at Boston Children's Hospital between 2010 and 2020. Competing risk analysis was performed to evaluate cumulative incidence of LAVV reinterventions. Predictors of LAVV reintervention were evaluated using multivariable Cox regression. A total of 137 LAVV repairs following primary AVCD surgery were performed in 113 patients. Median age and weight at LAVV repair were 25 months (interquartile range, 12-76 months) and 11.1 kg (interquartile range, 7.8-19.4 kg). Original anatomy was complete AVCD in 87 (63%), transitional AVCD in 27 (20%), and partial AVCD in 23 (17%) cases. Over a median follow-up of 12 months (interquartile range, 1.3 months-4 years), 47 (34%) of the LAVV repairs required LAVV reintervention. Reinterventions included a total of 27 LAVV re-repairs and 20 LAVV replacements. In multivariable analysis, age at LAVV repair younger than 72 months, partial AVCD anatomy, left ventricle dysfunction, mean LAVV stenosis gradient ≥5 mm Hg, and multiple jets of regurgitation on postoperative LAVV repair TEE were associated with LAVV reintervention. Grade of LAVV regurgitation on postoperative TEE was not an independent risk factor, but reintervention rates were high when residual LAVV stenosis gradient was ≥5 mm Hg and residual mild LAVV regurgitation was present on postoperative TEE (47%) and even higher when residual LAVV stenosis gradient was ≥5 mm Hg and LAVV regurgitation was greater than mild (73%). Reintervention rates remain high for LAVV repairs that occur after primary AVCD surgery, particularly for patients with LAVV stenosis gradient ≥5 mm Hg and mild or greater LAVV regurgitation on postoperative TEE.


Characterizing molecular probes for diffusion measurements in the brain.
Brain diffusion properties are at present most commonly evaluated by magnetic resonance (MR) diffusion imaging. MR cannot easily distinguish between the extracellular and intracellular signal components, but the older technique of real-time iontophoresis (RTI) detects exclusively extracellular diffusion. Interpretation of the MR results would therefore benefit from auxiliary RTI measurements. This requires a molecular probe detectable by both techniques. Our aim was to specify a minimum set of requirements that such a diffusion probe should fulfill and apply it to two candidate probes: the cation tetramethylammonium (TMA(+)), used routinely in the RTI experiments, and the anion hexafluoroantimonate (SbF(6)(-)). Desirable characteristics of a molecular diffusion probe include predictable diffusion properties, stability, minimum interaction with cellular physiology, very slow penetration into the cells, and sufficiently strong and selective MR and RTI signals. These properties were evaluated using preparations of rat neocortical slices under normal and ischemic conditions, as well as solutions and agarose gel. While both molecules can be detected by MR and RTI, neither proved an ideal candidate. TMA(+) was very stable but it penetrated into the cells and accumulated there within tens of minutes. SbF(6)(-) did not enter the cells as readily but it was not stable, particularly in ischemic tissue and at higher temperatures. Its presence also resulted in a decreased extracellular volume. These probe properties help to interpret previously published MR data on TMA(+) diffusion and might play a role in other diffusion experiments obtained with them.


Cloning and functional characterization of related TC10 isoforms, a subfamily of Rho proteins involved in insulin-stimulated glucose transport.
Insulin stimulates glucose transport via phosphatidylinositol 3-kinase-dependent and -independent pathways. The phosphatidylinositol 3-kinase-independent pathway involves activation of the G protein TC10. A cDNA encoding the mouse homolog of TC10 was cloned, and its gene was mapped at the distal end of chromosome 17. Additionally, a second gene was discovered with approximately 70% sequence identity to TC10. We refer to this gene as TC10beta. Both isoforms of TC10 were activated by insulin upon transfection in 3T3L1 adipocytes. Cotransfection of cells with TC10alpha or beta plus a dominant negative form of the c-cbl-associated protein CAP prevented the activation by insulin, implicating the CAP/Cbl pathway. Interestingly, both forms of TC10 were also localized in lipid raft fractions in transfected adipocytes. However, although overexpression of TC10alpha completely blocked glucose transport, TC10beta only partially inhibited this process. Furthermore, TC10alpha overexpression disrupted adipocyte cortical actin, whereas TC10beta had little if any effect. Thus, there are two isoforms of this key signaling intermediate, both of which are activated by insulin, but they may play different roles in initiating downstream effectors that influence glucose transport.


Differential forskolin activation of rat heart and lung adenylate cyclase. Dependence on membrane-protein interactions.
We have investigated whether the greater ability of forskolin to activate adenylate cyclase (EC 126.96.36.199) from rat heart compared with rat lung is due to interactions between G-proteins and catalytic units, isoforms of catalytic units or membrane-protein interactions. Interactions between Gs and catalytic units were found to be similar in both tissues with 10 microM Gpp(NH)p increasing activity up to 5-fold. While MnCl2 increased the response of the lung enzyme to forskolin, it reduced the response of the cardiac enzyme and uncoupled Gs from the cardiac catalytic units indicating that Gs interactions potentiate the response to forskolin. After enzyme solubilisation with n-octyl-beta-D-glucopyranoside, the response to forskolin was identical in heart and lung whether assayed with magnesium or manganese chloride, and not significantly different from the heart membrane enzyme. Overall, the results show that the relatively poor response of lung adenylate cyclase to forskolin is due to specific inhibitory interactions between the enzyme and lung membrane constituents.


Temporally restricted activation of IFNβ signaling underlies response to immune checkpoint therapy in mice.
The biological determinants of the response to immune checkpoint blockade (ICB) in cancer remain incompletely understood. Little is known about dynamic biological events that underpin therapeutic efficacy due to the inability to frequently sample tumours in patients. Here, we map the transcriptional profiles of 144 responding and non-responding tumours within two mouse models at four time points during ICB. We find that responding tumours display on/fast-off kinetics of type-I-interferon (IFN) signaling. Phenocopying of this kinetics using time-dependent sequential dosing of recombinant IFNs and neutralizing antibodies markedly improves ICB efficacy, but only when IFNβ is targeted, not IFNα. We identify Ly6C+/CD11b+ inflammatory monocytes as the primary source of IFNβ and find that active type-I-IFN signaling in tumour-infiltrating inflammatory monocytes is associated with T cell expansion in patients treated with ICB. Together, our results suggest that on/fast-off modulation of IFNβ signaling is critical to the therapeutic response to ICB, which can be exploited to drive clinical outcomes towards response.